US20020156531A1 - Biomaterial system for in situ tissue repair - Google Patents

Biomaterial system for in situ tissue repair Download PDF

Info

Publication number
US20020156531A1
US20020156531A1 US10/167,372 US16737202A US2002156531A1 US 20020156531 A1 US20020156531 A1 US 20020156531A1 US 16737202 A US16737202 A US 16737202A US 2002156531 A1 US2002156531 A1 US 2002156531A1
Authority
US
United States
Prior art keywords
composition
biomaterial
cured
prosthesis
balloon
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/167,372
Inventor
Jeffrey Felt
Mark Rydell
Richard Zdrahala
Alexander Arsenyev
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/239,248 external-priority patent/US5556429A/en
Priority claimed from US08/590,293 external-priority patent/US5888220A/en
Priority to US10/167,372 priority Critical patent/US20020156531A1/en
Application filed by Individual filed Critical Individual
Publication of US20020156531A1 publication Critical patent/US20020156531A1/en
Priority to CA002473858A priority patent/CA2473858A1/en
Priority to JP2003561468A priority patent/JP4324478B2/en
Priority to US10/500,929 priority patent/US20040247641A1/en
Priority to EP03703997A priority patent/EP1474071B1/en
Priority to PCT/US2003/002142 priority patent/WO2003061522A2/en
Priority to US10/935,041 priority patent/US20050043808A1/en
Priority to AU2010200382A priority patent/AU2010200382A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40High-molecular-weight compounds
    • C08G18/48Polyethers
    • C08G18/4854Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/16Bone cutting, breaking or removal means other than saws, e.g. Osteoclasts; Drills or chisels for bones; Trepans
    • A61B17/17Guides or aligning means for drills, mills, pins or wires
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/68Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
    • A61B17/70Spinal positioners or stabilisers ; Bone stabilisers comprising fluid filler in an implant
    • A61B17/7097Stabilisers comprising fluid filler in an implant, e.g. balloon; devices for inserting or filling such implants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30756Cartilage endoprostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/441Joints for the spine, e.g. vertebrae, spinal discs made of inflatable pockets or chambers filled with fluid, e.g. with hydrogel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442Intervertebral or spinal discs, e.g. resilient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4601Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for introducing bone substitute, for implanting bone graft implants or for compacting them in the bone cavity
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4603Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof
    • A61F2/4611Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof of spinal prostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04Macromolecular materials
    • A61L29/041Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04Macromolecular materials
    • A61L29/06Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/08Processes
    • C08G18/10Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/67Unsaturated compounds having active hydrogen
    • C08G18/69Polymers of conjugated dienes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00163Optical arrangements
    • A61B1/00165Optical arrangements with light-conductive means, e.g. fibre optics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00234Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/16Bone cutting, breaking or removal means other than saws, e.g. Osteoclasts; Drills or chisels for bones; Trepans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00535Surgical instruments, devices or methods, e.g. tourniquets pneumatically or hydraulically operated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • A61F2/07Stent-grafts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30988Other joints not covered by any of the groups A61F2/32 - A61F2/4425
    • A61F2/3099Other joints not covered by any of the groups A61F2/32 - A61F2/4425 for temporo-mandibular [TM, TMJ] joints
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/38Joints for elbows or knees
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/40Joints for shoulders
    • A61F2/4081Glenoid components, e.g. cups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/42Joints for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes
    • A61F2/4202Joints for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes for ankles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/94Stents retaining their form, i.e. not being deformable, after placement in the predetermined place
    • A61F2/945Stents retaining their form, i.e. not being deformable, after placement in the predetermined place hardenable, e.g. stents formed in situ
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/30004Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
    • A61F2002/30016Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis differing in hardness, e.g. Vickers, Shore, Brinell
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/30004Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
    • A61F2002/30024Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis differing in coefficient of friction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006Properties of materials and coating materials
    • A61F2002/3008Properties of materials and coating materials radio-opaque, e.g. radio-opaque markers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108Shapes
    • A61F2002/30199Three-dimensional shapes
    • A61F2002/30224Three-dimensional shapes cylindrical
    • A61F2002/30235Three-dimensional shapes cylindrical tubular, e.g. sleeves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30563Special structural features of bone or joint prostheses not otherwise provided for having elastic means or damping means, different from springs, e.g. including an elastomeric core or shock absorbers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30576Special structural features of bone or joint prostheses not otherwise provided for with extending fixation tabs
    • A61F2002/30578Special structural features of bone or joint prostheses not otherwise provided for with extending fixation tabs having apertures, e.g. for receiving fixation screws
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30581Special structural features of bone or joint prostheses not otherwise provided for having a pocket filled with fluid, e.g. liquid
    • A61F2002/30583Special structural features of bone or joint prostheses not otherwise provided for having a pocket filled with fluid, e.g. liquid filled with hardenable fluid, e.g. curable in-situ
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30601Special structural features of bone or joint prostheses not otherwise provided for telescopic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A61F2002/30841Sharp anchoring protrusions for impaction into the bone, e.g. sharp pins, spikes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2002/30929Special external or bone-contacting surface, e.g. coating for improving bone ingrowth having at least two superposed coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • A61F2/30942Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
    • A61F2002/30957Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques using a positive or a negative model, e.g. moulds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/42Joints for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes
    • A61F2/4225Joints for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes for feet, e.g. toes
    • A61F2002/4233Joints for wrists or ankles; for hands, e.g. fingers; for feet, e.g. toes for feet, e.g. toes for metatarso-phalangeal joints, i.e. MTP joints
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442Intervertebral or spinal discs, e.g. resilient
    • A61F2002/444Intervertebral or spinal discs, e.g. resilient for replacing the nucleus pulposus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4603Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof
    • A61F2002/4625Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof with relative movement between parts of the instrument during use
    • A61F2002/4627Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof with relative movement between parts of the instrument during use with linear motion along or rotating motion about the instrument axis or the implantation direction, e.g. telescopic, along a guiding rod, screwing inside the instrument
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2002/4635Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor using minimally invasive surgery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0085Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof hardenable in situ, e.g. epoxy resins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063Three-dimensional shapes
    • A61F2230/0069Three-dimensional shapes cylindrical
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0019Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in hardness, e.g. Vickers, Shore, Brinell
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0021Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in coefficient of friction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0096Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers
    • A61F2250/0098Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers radio-opaque, e.g. radio-opaque markers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/38Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/2305Mixers of the two-component package type, i.e. where at least two components are separately stored, and are mixed in the moment of application
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S606/00Surgery
    • Y10S606/907Composed of particular material or coated
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S606/00Surgery
    • Y10S606/907Composed of particular material or coated
    • Y10S606/91Polymer

Definitions

  • the present invention relates to methods, apparatuses, materials and systems for the repair of musculoskeletal injury, and in particular, for bone and cartilage repair and replacement.
  • the invention in another aspect, relates to polymeric compositions, and to minimally invasive methods and materials for the preparation of prosthetic implants and the replacement or repair of joints and joint surfaces within the body.
  • the invention in situ curable compositions, such as polymer compositions, useful for such purposes.
  • the present invention relates to medical prostheses for use in in vivo applications, to methods of preparing and delivering such prostheses, and to materials useful for fabricating or preparing prostheses.
  • the invention relates to the preparation of prostheses in situ.
  • the musculoskeletal system is subject to injury caused by traumatic events as well as by a number of diseases, such as osteoarthritis and rheumatoid arthritis.
  • the joints of the body can be classified as between those that provide immovable articulations (synarthroidal), mixed articulations (amphiarthroidal), and movable articulations (diarthroidal).
  • the ability of amphiarthroidal and diarthroidal joints to provide effective and pain-free articulation, and/or to serve their weight-bearing function, is generally dependent on the presence of intact, healthy cartilage (e.g., fibrocartilage or hyaline cartilage) within the joint.
  • Total joint replacement is indicated under conditions in which the cartilage surface between the bones forming a joint has degenerated. Often it has degenerated to a point where there is significant pain during locomotion, as well as during translation and rotation of joint components.
  • Such degenerative joint disease is commonly treated by a technique known as total joint replacement arthroplasty, which is typically an invasive procedure that involves replacement of the original surfaces with artificial weight bearing materials in the form of implants.
  • Hip replacement generally involves the implantation of a femoral component in the form of a ball mounted on a shaft, together with an acetabular component in the form of a socket into which the ball sits.
  • Total knee replacement is somewhat more difficult than hip replacement because of the complex loading pattern of the knee.
  • the tibial component of a total knee replacement is fixed in the cancellous bone of the tibia.
  • the femoral component is typically fixed to the cortical bone of the femoral shaft using a suitable cement.
  • the tibial portion of a knee prosthetic device generally involves the insertion of a broad plateau region covering the tibia, after bone of the subchondral plate is removed.
  • a composite material is provided, involving a metal support underlying a polymeric, or fiber-reinforced polymeric tray.
  • the article describes a number of materials currently used for orthopedic applications, including metals (iron, cobalt, and titanium), degradable polymers, self-reinforced compositions of polyglycolic acid, stronger polymers such as polydioxanone, and ceramic materials such as hydroxyapatite and certain glasses.
  • the Peppas et al. article refers to the potential usefulness of polymers that can be triggered to undergo a phase change.
  • the article itself does not identify such polymers, but instead postulates that materials that are initially liquid might be administered through a minimally invasive surgical device and then triggered to solidify or gel in the presence of ultraviolet light, visible light, or ionic change in vivo.
  • the article cites an article of Hill-West, et al., Obstet. Gynecol. 83(1):59-64 (1994).
  • the Hill-West et al. article describes the use of a conformable, resorbable hydrogel barrier for preventing postoperative adhesions in animals.
  • the article describes the formation of the hydrogel barrier in situ by photopolymerizing a solution of a macromolecular prepolymer using UV light.
  • the hydrogel barrier is not described as being useful in weight-bearing, orthopedic applications, and in fact, was completely resorbed within 7 days after application.
  • a related drawback of an arthrotomy involves the need to cut through skin, nerves, vessels, muscles, ligaments, tendons, and/or joint capsules. Certain procedures can also require the use of either general or spinal anesthesia. They may also require blood transfusions and significant recovery time accompanied by post-surgical pain and discomfort. Lastly, prolonged physical therapy is typically required to strengthen operative areas and prevent contractures. Such therapy can often last up to six weeks or more.
  • a number of approaches, and in turn compositions, are currently employed for such purposes as preparing prosthetic implants and repairing damaged joints and joint cartilage.
  • Such approaches include the widespread use of artificial prosthetic implants that can be formed of an array of materials such as metals, ceramics, and bioerodible or resorbable materials. Indeed, the manufacture and use of such implants has grown exponentially in recent decades. See, for instance, “New Challenges in Biomaterials”, Science, 263:1715-1720 (1994), Peppas et al.
  • Applicant's U.S. Pat. No. 5,556,429 describes a joint resurfacing system which, in a preferred embodiment, involves the use of minimally invasive means to access and prepare a joint site, such as a knee, and to deliver a curable biomaterial to the prepared site and cure the biomaterial in apposition to the prepared site.
  • the system includes the use of curable biomaterials such as silicone polymers and polyurethane polymers.
  • Polyurethanes themselves have been developed and used since at least the 1940's for the preparation of a variety of materials, including cast polyurethane rubbers and millable gums.
  • Cast polyurethane rubbers can be subdivided into four general groups, including 1) unstable prepolymer systems, 2) stable prepolymer systems, 3) quasi-prepolymer systems, and 4) “oneshot” systems. See, for instance, “Polyurethanes and Polyisocanurates”, Chapter 27 in Plastics Materials , J. Brydson, ed., 6 th ed.Butterworth Heeinemann (1995).
  • compositions involve the reaction of a polyhydroxy material (polyol) with an isocyanate to provide a polyurethane material.
  • polyol polyhydroxy material
  • isocyanate an isocyanate
  • a limited number of references describe the use of components such as hydroxyl-terminated butadiene in the context of a polyurethane.
  • Khalil, et al. U.S. Pat. No. 5,288,797
  • the list of polyols described as being useful for forming the prepolymer is said to include polybutadiene having at least two terminal primary and/or secondary hydroxyl groups.
  • Graham et al. (U.S. Pat. No. 4,098,626) describes a hydroxy terminated polybutadiene based polyurethane bound propellant grains
  • Chapin et al. (U.S. Pat. No. 4,594,380) describe an elastomeric controlled release article having a matrix formed of a polyurethane that itself is the reaction product of an isocyanate and a polyol selected from a group that includes hydroxyl-terminated polybutadiene.
  • implantable medical devices have grown dramatically over past decades. Correspondingly, those developing new and useful biomaterials for use in fabricating such devices have attempted to keep pace.
  • the implantable medical devices can themselves take a wide variety of forms and purposes.
  • prostheses are used to replace or repair orthopedic joints.
  • the joints of the body can be classified as between those that provide immovable articulations (synarthroidal), mixed articulations (amphiarthroidal), and movable articulations (diarthroidal).
  • the ability of amphiarthroidal and diarthroidal joints to provide effective and pain-free articulation, and/or to serve their weight-bearing function, is generally dependent on the presence of intact, healthy cartilage within the joint.
  • the delivery of such biomaterials can take the shape of the prepared site, or can further incorporate the use of a mold, e.g., in the manner described in Applicant's corresponding PCT Patent Application No. PCT/US97/00457.
  • a mold is provided in the form of a balloon that can be delivered to the site of an intervertebral disc space, and there filled with biomaterial in order to serve as a replacement disc.
  • Implanted or implantable devices include Kuslich (U.S. Pat. No. 5,571,189); Kuslich (U.S. Pat. No. 5,549,679); Parsons et al. (U.S. Pat. No. 5,545,229); Oka (U.S. Pat. No. 5,458,643); Baumgartner (U.S. Pat. No. 5,171,280); Frey et al. (U.S. Pat. No. 4,932,969); Ray et al. (U.S. Pat. No. 4,904,260); Monson (U.S. Pat. No. 4,863,477); and Froning (U.S. Pat. No. 3,875,595).
  • Implantable medical prostheses can take other forms as well, including other traditional types that are fabricated and packaged prior to use, and implanted in either a transitory, temporary or permanent fashion within the body. Such prostheses can be used, for instance, as or in connection with passageways within the body such as catheters, such as stents and shunts. Other examples of devices implantable on at least a transitory basis include catheters such as balloon catheters. See, for example, the following U.S. patents to Walinsky (U.S. Pat. No. 5,470,314); Saab (U.S. Pat. No. 5,411,477); Shonk (U.S. Pat. No. 5,342,305); Trotta et al.
  • stents have become accepted as a means for preventing abrupt vessel closure and restenosis following balloon angioplasty and over the past decade has grown dramatically as problems inherent in early designs have been overcome.
  • stents are constructed from nonthrombogenic materials of sufficient flexibility (in their unexpanded state) to allow passage through guiding catheters and tortuous vessels.
  • Such stents are typically radiopaque to allow fluoroscopic visualization.
  • most coronary stents have been constructed from either stainless steel or titanium, e.g., in the form of an expandable mesh, wire coil, slotted tube, or zigzag design.
  • 5,334,201 describes a stent made of a crosslinkable material, by a method that involves encapsulating an uncured stent in a biologically compatible film, transluminally inserting the stent/film into position, and curing the stent.
  • Preformed catheters and grafts have also been used in the treatment of abdominal aortic aneurysms.
  • the ultimate goal in the treatment of aortic aneurysms is to exclude the aneurysm from the aortic bloodstream without interfering with limb and organ perfusion.
  • Direct surgical repair of such aneurysms is associated with high morbidity and mortality.
  • the technique of placing a prosthetic graft into the opened aneurysm and suturing it to “normal” aorta above and below requires extensive intraabdominal or retroperitoneal dissection, as well as interruption of blood flow during completion of the anastomoses, under general anesthesia.
  • Implantable prostheses as described above, can be contrasted to those used in the burgeoning dental field, in which polymers play an important role as ingredients of composite restorative materials, cements and adhesives, cavity liners and protective sealants. See, for instance, Brauer and Antonucci, “Dental Applications” pp 257-258 in Concise Encyclopedia of Polymer Science and Engineering.
  • a number of problems that continue to affect the further development of some or all of the above-described implanted prostheses include problems that affect the preparation of the prostheses themselves, their delivery to the site of use, and their interactions with the host or surrounding tissue in the course of their use.
  • the physician cannot correct the size and shape of the prostheses once it has been introduced to the body; therefore, all measurements and adjustments of size must be made preoperatively.
  • the aorta may continue to enlarge and thus pull away from the fixation stent. Problems associated with the healing interface between the stent, the graft, and the aorta is not known, and the graft may dislodge and migrate, causing acute iliac occlusion. The aneurysm may continue to function despite an intact functioning endovascular graft.
  • the present invention overcomes the drawbacks associated with the prior art by providing a method, and related composition and apparatus for repairing or resurfacing the site of injured tissue by minimally-invasive means.
  • the method of the present invention comprises the steps of:
  • the method of the invention lends itself to a corresponding system that comprises curable biomaterial, in combination with minimally invasive means for preparing the tissue site; delivering the biomaterial to the prepared tissue site; curing the biomaterial in situ; and contouring the cured biomaterial.
  • the individual components of such a system, and particularly means for delivering and curing biomaterial in a minimally invasive fashion are considered novel as well.
  • a system comprising: (a) an arthroscopic surgical instrument; and (b) a fluid delivery cannula capable of delivering a flowable, curable biomaterial under arthroscopic visualization, the biomaterial comprising a curable polymer and hydrogel.
  • the preferred system can be used to perform a method that comprises the steps of:
  • the cured, shaped biomaterial can be treated or modified in order to improve one or more desirable properties, for instance, it can be coated with a permanent interface material in order to improve the biocompatibility or coefficient of friction of the final implant.
  • the present invention provides a curable polyurethane composition
  • a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, one or more catalysts, and optionally, other ingredients such as an antioxidant and dye.
  • the composition is sufficiently flowable to permit it to be delivered to the body by minimally invasive means, and there fully cured under physiologically acceptable conditions.
  • the component parts are themselves flowable, or can be rendered flowable, in order to facilitate their mixing and use.
  • Applicants have discovered, inter alia, that the presence of the reactive hydrophobic additive of the prepolymer provides several unexpected and desirable features, both in the formulation and use of the prepolymer itself, as well as in the mixed composition. These features include an improved combination of such properties as moisture cure characteristics, crosslinking, viscosity, compression fatigue, and stability.
  • the use of the polymer significantly lessens, and can avoid altogether, the appearance of bubbles seen previously with polyurethane compositions cured in vivo in the presence of moisture.
  • the polyether component is present at a concentration of between about 2% and about 10%, and preferably between about 4% and about 8% by weight, based on the weight of the composition, and is selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polytetramethylene oxide (polyoxytetramethylene), and copolymers thereof.
  • a particularly preferred polyol is polytetramethylene oxide, preferably of relatively low molecular weights in the range of 250 to 2900, and combinations thereof.
  • the isocyanate is present in excess in the prepolymer component, e.g., at a concentration of between about 30% and about 50%, and preferably between about 35% and about 45%, by weight.
  • the isocyanate is preferably an aromatic (poly)isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate (MDI), and combinations thereof.
  • the reactive polymer additive itself is present at a concentration of between about 1% and about 50% by weight, and is selected from the group consisting of hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisoprene, polyisobutylene, silicones, polyethylenepropylenediene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures of the above.
  • the additive comprises hydroxyl-terminated polybutadiene, present at a concentration of between about 5% and about 30%, by weight, and preferably between about 5% and about 20% by weight.
  • the polyether polyol of the curative component is as described above with regard to the prepolymer and is present at a final concentration of between about 20% and 60%, and preferably between about 30% and about 45%, by weight.
  • the chain extender comprises a combination of linear (e.g., cyclohexane dimethanol (“CHDM”)) and branched (e.g, trimethyloyl propane (“TMP”) chain extenders, with the former being present at a final concentration of between about 1% and 20% (and preferably between about 5% and about 15%), and the latter being present at a final concentration of between about 1 % and about 20%, and preferably between about 1% and about 10%, by weight of the final composition.
  • CHDM cyclohexane dimethanol
  • TMP trimethyloyl propane
  • the composition provides improved properties, including an improved combination of such properties as hardness, strength and/or cure characteristics (particularly in the presence of moisture), as compared to compositions previously known. More surprisingly, Applicants have discovered that such improvement can be achieved without detrimental effect on other desired properties, including those that arise (a) prior to delivery, (b) in the course of delivery (including whatever mixing, curing, and/or shaping that may occur), and finally, (c) following cure and in the course of extended use in the body.
  • the invention provides a cured composition, prepared as the reaction product of a plurality of parts as described herein.
  • the invention provides a kit that can be used to prepare a composition and/or that itself includes a composition as a component part.
  • a kit may take the form of a composition (or its components) in combination with pre-formed device components or accessories, such as an implantable mold apparatus for shaping and restraining the composition.
  • a kit can also include a composition (or its components or parts) in combination with a delivery device adapted to deliver the composition to the site of tissue injury.
  • kits may also take the form of a composition, either as its component parts and/or in combination with other ingredients or materials, such as a filler or hydrogel (used to form a matrix), or together with an implantable prosthetic device.
  • a kit may include one or more protocols or instructions for use.
  • the invention provides a method of preparing and a method of using such a composition.
  • the invention provides a cured composition (optionally within a mold apparatus), for use in apposition to a joint surface, as well as the combination of such a joint surface with a cured composition (optionally within a mold apparatus) in apposition thereto.
  • the present invention provides an apparatus and method for forming a prosthesis, in situ, the method, in a preferred embodiment, comprising the steps of:
  • an implantable mold apparatus comprising a cavity adapted to receive and contain a flowable biomaterial and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial
  • the apparatus provides an implantable mold apparatus comprising an expandable cavity adapted to receive and contain a flowable biomaterial in a geometry, configuration and/or position optimal for the intended purpose, and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial.
  • the conduit is preferably removable from the filled cavity, e.g., by cutting it at or near the point where it joins the cavity.
  • the apparatus further includes means for providing positive or negative air pressure within or to the biomaterial cavity, in order to facilitate the delivery of biomaterial and/or to affect the final shape of the cured mold.
  • the apparatus and method can be used for a variety of applications, including for instance, to provide a balloon-like mold for use preparing a solid or intact prosthesis, e.g., for use in articulating joint repair or replacement and intervertebral disc repair.
  • the method can be used to provide a hollow mold, such as a sleeve-like tubular mold for use in preparing implanted passageways, e.g., in the form of catheters, such as stents, shunts, or grafts.
  • the invention provides a mold apparatus useful for performing a method of the invention, e.g., in the form of an inflatable balloon or tubular mold, preferably in combination with the conduit used to deliver biomaterial.
  • the invention further provides a system useful at the time of surgery to prepare an implanted prosthesis in vivo, the system comprising a mold apparatus (e.g., cavity and conduit) in combination with a supply of curable biomaterial, and optionally, with a source of positive and/or negative air pressure.
  • the invention provides a corresponding prosthesis formed by a method of the present invention, including for instance, an implanted knee prosthesis, intervertebral disc prosthesis, and a tubular prosthesis for use as a catheter, such as a stent, shunt, or graft (e.g., vascular graft).
  • the present invention further provides surgical kits that include a mold apparatus as presently described, in combination with a corresponding drilling template, and a kit in which a mold apparatus is provided in combination with a supply (e.g., sufficient for a single use) of biomaterial itself.
  • FIG. 1 shows a top plan view of a mold apparatus including a balloon cavity and biomaterial delivery conduit for use in intervertebral disc replacement.
  • FIG. 2 shows the apparatus of FIG. 1 with the balloon in its collapsed form contained within an outer sheath, suitable for insertion and positioning within the disc space.
  • FIG. 3 shows a mandrel used for forming the balloon of FIG. 1 by dip-coating the mandrel in a suitable solution of curable polymer.
  • FIG. 4 shows a balloon as formed upon the mandrel shown in FIG. 3
  • FIG. 5 shows the balloon of FIG. 1 positioned within the disc space and in the course of filling with biomaterial.
  • FIG. 6 shows a preferred embodiment of a mold apparatus for use in the repair or replacement of knee cartilage.
  • FIG. 7 shows a drilling template for use in connection with the apparatus of FIG. 6.
  • FIG. 8 shows a preferred embodiment of a mold apparatus, in uninflated and unfilled form, in the form of a tubular system for preparing an implanted passageway in situ.
  • FIG. 9 shows the mold of FIG. 8 in a form wherein relevant portions have been filled with air and biomaterial.
  • FIG. 10 shows a cross section of the mold apparatus of FIG. 9, taken along lines 10 - 10 .
  • the present invention provides a method and system for the repair of natural tissue that involve the delivery of a biomaterial composition using minimally invasive means, the composition being curable in situ in order to provide a permanent replacement for natural tissue.
  • the biomaterial is delivered to a mold apparatus that is positioned by minimally invasive means and filled with biomaterial composition, which is then cured in order to retain the mold and cured composition in situ.
  • repair will refer to the use of a composition to augment, replace or provide some or all of the structure or function of natural tissue in vivo, for instance, to provide an implant such as a catheter, or to repair (e.g., reconstruct or replace) cartilage, such as fibrocartilage or hyaline cartilage present in a diarthroidal or amphiarthroidal joint. Repair can take any suitable form, e.g., from patching the tissue to replacing it in its entirety, preferably in a manner that reconstructs its natural or other desired dimensions;
  • curable and inflections thereof, will refer to any chemical, physical, and/or mechanical transformation that allows a composition to progress from a form (e.g., flowable form) that allows it to be delivered to the joint site, into a more permanent (e.g., cured) form for final use in vivo.
  • curable can refer to uncured composition, having the potential to be cured in vivo (as by catalysis or the application of a suitable energy source), as well as to a composition in the process of curing (e.g., a composition formed at the time of delivery by the concurrent mixing of a plurality of composition components).
  • the cure of a composition can generally be considered to include three stages, including (a) the onset of gelation, (b) a period in which gelation occurs and the composition becomes sufficiently tack-free to permit shaping, and (c) complete cure to the point where the composition has been finally shaped for its intended use.
  • minimally invasive means refers to surgical means, such as microsurgical or endoscopic or arthroscopic surgical means, that can be accomplished with minimal disruption of the pertinent musculature, for instance, without the need for open access to the tissue injury site or through minimal incisions (e.g., incisions of less than about 4 cm and preferably less than about 2 cm).
  • Such surgical means are typically accomplished by the use of visualization such as fiberoptic or microscopic visualization, and provide a post-operative recovery time that is substantially less than the recovery time that accompanies the corresponding open surgical approach;
  • endoscopic/arthroscopic surgical instrument refers to the controllers and associated hardware and software necessary for performing conventional endoscopic or arthroscopic surgery
  • delivery cannula shall mean a cannula or other delivery device capable of being operated in a minimally invasive fashion, e.g., under arthroscopic visualization, and optionally together with associated connective tubing and containers for the operable and fluid attachment of the cannula to a source of composition for the storage, delivery, and recovery of compositions of the present invention.
  • mold will refer to the portion or portions of an apparatus of the invention used to receive, constrain, shape and/or retain a flowable biomaterial in the course of delivering and curing the biomaterial in situ.
  • a mold may include or rely upon natural tissues (such as the annular shell of an intervertebral disc) for at least a portion of its structure, conformation or function.
  • the mold is responsible, at least in part, for determining the position and final dimensions of the cured prosthetic implant.
  • its dimensions and other physical characteristics can be predetermined to provide an optimal combination of such properties as the ability to be delivered to a site using minimally invasive means, filled with biomaterial, and optionally, then remain in place as or at the interface between cured biomaterial and natural tissue.
  • the mold material can itself become integral to the body of the cured biomaterial.
  • a mold apparatus will generally include both a cavity for the receipt of biomaterial and a conduit for the delivery of biomaterial to that cavity. Some or all of the material used to form the cavity will generally be retained in situ, in combination with the cured biomaterial, while some or all of the conduit will generally be removed upon completion of the method.
  • An implanted prosthesis in turn, can be used to replace, provide, or supplement the structure or function of natural tissue in vivo.
  • the prosthesis can take any suitable form, e.g., including patching, repairing or replacing tissue (such as knee or intervertebral disc), supporting existing tissue (as by a stent, for instance), or creating new material having a tissue like function (as by a shunt).
  • biomaterial will be used interchangeably with the word “composition”, when used in the context of the present invention, and will generally refer to a material that is capable of being introduced to the site of a joint and cured to provide desired physical-chemical properties in vivo.
  • the term will refer to a material that is capable of being introduced to an site within the body using minimally invasive means, and cured or otherwise modified in order to cause it to be retained in a desired position and configuration.
  • biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 1 mm to about 6 mm inner diameter, and preferably of about 2 mm to about 3 mm inner diameter.
  • Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration.
  • the present invention provides a method and related materials and apparatus for repairing diarthroidal and amphiarthroidal joints by minimally invasive means.
  • the method involves the use of minimally invasive means to prepare the site of injury, deliver a curable biomaterial to the joint site, and to cure the biomaterial in situ in order to repair hyaline cartilage and/or fibrocartilage.
  • a liquid phase polymeric composite material (e.g., formed of a two-part polyurethane system) is applied through a cannula under arthroscopic visualization.
  • the composite is cured and contoured in situ to effectively resurface a damaged joint.
  • the cured polymer composite exhibits physical/chemical characteristics analogous to those of human cartilage, and demonstrates an optimal combination of such properties as load bearing, shear stress resistance, impact absorption, and wear characteristics.
  • the surface of the cured composite can optionally be modified after curing and contouring, e.g., in order to reduce its coefficient of friction.
  • the method of the present invention comprises the step of providing a curable biomaterial comprising a curable polymer, optionally in combination with a hydrogel.
  • Biomaterials suitable for use in the present invention include those materials that are capable of being delivered by means of a cannula, as described herein, and cured in situ in order to form a replacement material for bone or cartilage.
  • Natural cartilage is a non-vascular structure found in various parts of the body, and particularly articular cartilage, which exists as a glycosamine matrix with a fibrillar scaffold of Type II collagen. Chondrocytes are typically interspersed in the matrix. Its natural elasticity enables it to break the force of concussions, while its smoothness affords ease and freedom of movement. In terms of thickness, cartilage tends to take on the shape of the articular surface on which it lies. Where this is convex, the cartilage is thickest at the center, where the greatest pressure is received. The reverse is generally true in the case of concave articular surfaces.
  • Preferred biomaterials are intended to mimic many of the physical-chemical characteristics of natural cartilage.
  • Preferred biomaterials are composites of two or more individual materials, and particularly those comprising two phase systems formed from a polymeric matrix and a hydrogel filler.
  • Particularly preferred biomaterials are polyurethane systems of the type described herein.
  • the method of the invention can be used to repair a number of tissues, including a variety of joints, and is particularly useful for diarthroidal and amphiarthroidal joints.
  • suitable amphiarthroidal joints include the synphysoidal joints, such as the joints between bodies of the vertebrae. Such joints provide surfaces connected by fibrocartilage, and have limited motion.
  • Other examples include syndesmoidal joints, having surfaces united by an interosseous ligament, as in the inferior tibio-fibular joint.
  • Suitable diarthroidal joints include the ginglymus (a hinge joint, as in the interphalangeal joints and the joint between the humerus and the ulna); throchoides (a pivot joint, as in superior radio-ulnar articulation and atlanto-axial joint); condyloid (ovoid head with elliptical cavity, as in the wrist joint); reciprocal reception (saddle joint formed of convex and concave surfaces, as in the carpo-metacarpal joint of the thumb); enarthrosis (ball and socket joint, as in the hip and shoulder joints) and arthrodia (gliding joint, as in the carpal and tarsal articulations).
  • ginglymus a hinge joint, as in the interphalangeal joints and the joint between the humerus and the ulna
  • throchoides a pivot joint, as in superior radio-ulnar articulation and atlanto-axial joint
  • condyloid ovoid head with elliptical cavity, as in the wrist
  • the method and system of the present invention are used to resurface a joint selected from the group consisting of enarthroidial (“ball and socket”) joints, and in particular the hip and shoulder joints, and ginglymo-arthroidal (“hinge”) joints, and in particular the temporo-mandibular joint.
  • joints provide a particularly unique advantage in that one or more components of the natural joint can themselves be temporarily repositioned in order to contour the biomaterial as it cures.
  • a degenerative shoulder joint is repaired, for instance, by resurfacing either the humeral head, or preferably, the glenoid fossa.
  • the glenoid fossa is arthroscopically exposed and the residual cartilage is removed by burrs and cutters.
  • the humeral head is smoothed and all roughened cartilage surfaces removed.
  • a curable biomaterial is delivered allowed to flow smoothly into the glenoid fossa.
  • the humeral head With the polymer in a non-tacky, but moldable stage of cure the humeral head is repositioned into the glenoid for use in molding the polymer as it continues to cure.
  • the process can be performed using invasive surgical procedures, given the unique qualities of the biomaterial.
  • a degenerative hip joint is repaired in a similar manner, for instance, by resurfacing either the femoral head, or preferably, the acetabular cup.
  • the cup is arthroscopically exposed and the residual cartilage is removed by burrs and cutters.
  • the femoral head is smoothed and all roughened cartilage surfaces removed.
  • a curable biomaterial is delivered allowed to flow smoothly into the acetabular cup.
  • the femoral head With the polymer in a non-tacky, but moldable stage of cure the femoral head is repositioned into the acetabulum for use in molding the polymer as it continues to cure.
  • the process can be performed using invasive surgical procedures, given the unique qualities of the biomaterial.
  • a degenerative temporo-mandibular joint can be arthroscopically repaired using two small portals. Through one portal a needle arthroscope is placed for visualization of the temporomandibular joint. Through the second portal the surface of the maxillar portion is prepared and the mandible ramus surface is smoothed. Optionally, anchor points are cut in the maxilla. With the patient suitably positioned, a curable biomaterial is delivered and allowed to flow smoothly into the covered socket. With the polymer in a non-tacky, but moldable stage of cure the ramus of the mandible is repositioned and compressed into the socket for use in molding the polymer as it continues to cure. As an alternative to the use of minimally invasive means, each of these processes can be performed using invasive surgical procedures, given the unique qualities of the biomaterial.
  • the musculoskeletal system and more often its articulating joints, are subject to injury caused by traumatic events or diseases such as osteoarthritis and rheumatoid arthritis.
  • Inherent lubricity ofjoint's connective tissue, the cartilage is affected.
  • the non-functioning cartilage causes, in turn, abnormal wear and tear of both the connective tissue and bones. This process often results in progressive, crippling pain.
  • the polymer system one must have certain key characteristics: (1) it should be amenable to microphase separation and domain formation to mimic the cartilage; (2) the system must be liquid at delivery; (3) polymerization kinetics must be fast and fully controllable; (4) no toxic or otherwise harmful by-products can be released; (5) resultant polymer must have broad range of mechanical properties, excellent loan bearing, fatigue and wear resistance; (6) the system should be amenable to form microcellular structure; (7) lastly, the polymer must biodurable. Polyurethanes could be the chosen one.
  • aromatic polyurethanes based on polycarbonate polyols are considered most resistant to stress- and oxidation-driven Environmental Stress Cracking, we have selected PTMO-based polyols recognized for their superb hydrolytic resistance.
  • a two component system with MDI-quasi-prepolymer component “A” and OH-terminated intermediates as component “B” was used.
  • Blend of polyols was the choice to keep their melting temperature close to the ambient.
  • the “delayed action” fast curing kinetics was achieved with Tin compound/tertiary amine based catalyst system. Gel times of 10-40 sec. With predominant cure of 2-5 min. are required to mix, deliver, cure and shape the polyurethane.
  • Natural cartilage is a non-vascular structure found in various parts of the body. Articular cartilage tends to exist as a fine granular matrix forming a thin incrustation on the surfaces of joints. The natural elasticity of articular cartilage enables it to break the force of concussions, while its smoothness affords ease and freedom of movement.
  • a preferred composition is intended to mimic many of the physical, chemical and/or mechanical characteristics of natural cartilage.
  • a composition of this invention provides a useful implant in the form of a catheter, e.g., a stent, graft or shunt, by the use of a mold apparatus as described above. In such an embodiment the cured composition provides a number of characteristics, including _iocompatibility, strength, and the like.
  • compositions can be provided as one component systems, or as two or more component systems that can be mixed (or partially mixed) prior to or during delivery, or at the site of repair.
  • Such compositions are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter.
  • Such compositions are also curable, to enable them to be polymerized or otherwise modified, in situ, during delivery and/or at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration.
  • suitable materials can be homogeneous, providing the same physico-chemical properties throughout, or they can be heterogeneous and exhibit varying features or properties.
  • An example of a suitable homogeneous composition as presently used for knee joint repair, is described below.
  • An example of a heterogeneous composition e.g., for use as an intervertebral disc replacement, is a composition that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and an more liquid interior core (akin to the nucleus).
  • Such heterogeneous compositions can be prepared by the use of a single composition, e.g., by employing varying states of cure and/or by the use of a plurality of compositions, including varying compositions of the same ingredients used to form the composition.
  • Suitable compositions for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use.
  • such properties include processability, and the ability to be safely sterilized and stored.
  • suitable materials exhibit an optimal combination of such properties as flowability, moldability, and in vivo curability.
  • suitable compositions exhibit an optimal combination of such properties as cured strength (e.g., tensile and compressive), softness/stiffness ratio, _iocompatibility and biostability.
  • the compositions demonstrate an optimal combination of properties, particularly in terms of their conformational stability and retention of physical shape, dissolution stability, _iocompatibility, and physical performance, as well as physical properties such as density and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, shear strength, shear fatigue, impact absorption, wear characteristics, and surface abrasion.
  • properties such as density and surface roughness
  • mechanical properties such as load-bearing strength, tensile strength, shear strength, shear fatigue, impact absorption, wear characteristics, and surface abrasion.
  • Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of materials and polymers in general.
  • a preferred composition in its cured form, exhibits mechanical properties that approximate or exceed those of the natural tissue it is intended to provide or replace.
  • compositions, and compositions themselves are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by chemical catalysis, by exposure to an energy source such as ultraviolet light, or by chemical reaction producing exotherm. Thereafter the cured composition is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of its use in the body the cured, contoured composition exhibits physiological, physical-chemical and mechanical properties suitable for use in extended in vivo applications.
  • a “polymer system”, as used herein refers to the component or components used to prepare a polymeric composition of the present invention.
  • a polymer system comprises the components necessary to form two parts: Part I being an isocyanate-functional polyurethane pre-polymer (optionally referred to as an “isocyanate quasi-polymer”).
  • the quasi-polymer of Part I typically includes a polyol component in combination with a hydrophobic additive component and an excess of an isocyanate component.
  • 5 Part II of the two component system can include one long-chain polyols, chain extenders and/or cross-linkers, together with other ingredients (e.g., catalysts, stabilizers, placticizers, antioxidants, dyes and the like).
  • Such adjuvants or ingredients can be added to or combined with any other component thereof either prior to or at the time of mixing, delivery, and/or curing.
  • a polymer system of this invention is provided as a plurality of component parts and employs one or more catalysts.
  • the component parts, including catalyst can be mixed to initiate cure, and then delivered, set and fully cured under conditions (e.g., time and exotherm) sufficient for its desired purpose.
  • the resultant composition Upon the completion of cure, the resultant composition provides an optimal combination of properties for use in repairing or replacing injured or damaged tissue.
  • a suitable composition provides a bulk exotherm (within samples sizes suitable for in vivo use) of between about 100 degrees C. and about 140 degrees C., and preferably between about 110 degrees C. and about 130 degrees C., and a surface exotherm of between about 50 degrees C. and about 80 degrees C., and preferably between about 60 degrees C. and about 70 degrees C.
  • a composition of this invention can be expressed in terms of both: (1) the free isocyanate number (“FNCO”) (also known as the isocyanate equivalent), which can be defined as the average molecular weight of the isocyanate divided by the number of isocyanate functional groups, and (2) the average hydroxyl number (also know as hydroxyl equivalent weight), which can be defined as the average molecular weight of the polyol(s) divided by the average number of reactive hydroxyl groups per mole of polyol(s).
  • FNCO free isocyanate number
  • hydroxyl number also know as hydroxyl equivalent weight
  • the isocyanate component can be provided in any suitable form, examples of which include 2,4′-diphenylmethane diisocyanate, 4,4′-diphenylmethane diisocyanate, and mixtures or combinations of these isomers, optionally together with small quantities of 2,2′-diphenylmethane diisocyanate (typical of commercially available diphenylmethane diisocyanates).
  • Other examples include aromatic polyisocyanates and their mixtures or combinations, such as are derived from phosgenation of the condensation product of aniline and formaldehyde.
  • an isocyanate that has low volatility such as diphenylmethane diisocyanate, rather than more volatile materials such as toluene diisocyanate.
  • An example of a particularly suitable isocyanate component is the 4,4′-diphenylmethane diisocyanate (“MDI”), preferably provided in liquid form as a combination of 2,2′-, 2,4′- and 4,4′-isomers of MDI.
  • MDI 4,4′-diphenylmethane diisocyanate
  • the stoichiometery between Parts I (quasi prepolymer) and II (curative component), expressed in terms of the NCO:OH ratio of the isocyanate pre-polymer (Part I) and the polyol components (Part II) is preferably within the range of about 0.8 to 1 to about 1.2 to 1, and more preferably between about 0.9 to 1 to about 1.1 to 1. It has been found that NCO:OH ratios of less than about 0.8 to 1 tend to provide less than desired cure kinetics or physical-mechanical properties upon cure. Those ratios greater than about 1.1 to 1, in turn, tend to increase the potential for cytotoxicity or for adverse tissue reaction characterized by over crosslinking via internal allophanate or biuret links, generated by an excess of FNCO groups.
  • the polyol component can be provided in any suitable form as well.
  • polyol includes virtually any functional compound having active hydrogens in accordance with the well-known Zerevitinov test, as described for instance in Chemistry of Organic Compounds by Carl R. Noller, Chapter 6, pp. 121-122 (157), the disclosure of which is incorporated herein by reference.
  • amine terminated polyethers and polyolefins, thiols, polyimines, and polyamines can also be used as polyols in the present invention.
  • the NCO:active hydrogen ratio of the isocyanate to the active hydrogen compound will preferably fall within the same ranges as disclosed herein for the NCO:OH ratios.
  • Suitable polyols for use in preparing a composition of this invention include polyalkylene ethers derived from the condensation of alkylene oxides (e.g., ethylene oxide, propylene oxide, and blends thereof), as well as tetrahydrofuran based polytetramethylene ether glycols, polycaprolactone polyols, polycarbonate polyols and polyester polyols.
  • suitable polyols include polytetrahydrofuran polyol (“PTHF”, also known as polytetramethylene oxide (“PTMO”) or polytetramethylene ether glycol (“PTMEG”).
  • the polyol component can be provided in the form of a blend of two or more different molecular weights selected from the commercially available group consisting of 250, 650, 1000, 1400, 2000, and 2900. Materials having different molecular weights can be blended, e.g., using between 10:1 and 1:10 equivalent weights of a lower and higher molecular weight component (e.g., 250 and 1000 MW components), respectively, and preferably between about 2:1 and about 1:2 equivalent weights.
  • a lower and higher molecular weight component e.g., 250 and 1000 MW components
  • the optimal combination of components, as well as the absolute and relative proportions thereof, are selected to provide a polymer system that, upon mixing an/or heating, is sufficiently “flowable” under ambient or other selected controlled conditions (e.g., temperature) to permit it to be sterilized, mixed, delivered, and cured, e.g., using minimally invasive means, to provide the properties desired for in vivo applications as described herein.
  • selected controlled conditions e.g., temperature
  • a preferred polymer system of this invention also includes the use of one or more chain extenders.
  • Suitable chain extenders for use in the present invention provide an optimal combination of such properties as hard segment molecular weight and molecular weight distribution, phase separation and domain formation, virtual cross-linking by hard segment domains. In cases in which more than two functional extenders are used, their combination also provides an optimal or desire level of chemical crosslinking between both hard segment chains and hard and soft segment chains.
  • An example of a particularly preferred chain extender is a combination of a linear (e.g., two-functional) chain extender, such as 1,4-butanediol (“BDO”), together with a cross-linking (e.g., tri- or higher-functional) chain extender such as trimethylol propane (“TMP”).
  • BDO 1,4-butanediol
  • TMP trimethylol propane
  • Such chain extenders can be prepared in any suitable combination to produce a unique degree of crosslinking, predominantly in the hard segment domains but also crossing the phase boundaries.
  • Additional cross-linking in the hard segment augments the virtual cross-links generated by the hard segment domains and provides higher cross-link density and efficiency, resulting in the reinforcement of non cross-linked segments.
  • This can be particularly useful in relatively soft polyurethanes, such as those suitable for the repair of damaged cartilage. Reinforcement by virtual cross-links alone may not generate sufficient strength for in vivo performance in certain applications.
  • Additional cross-linking from the soft segment, potentially generated by use of higher functional polyols can be used to provide stiffer and less elastomeric materials. In this manner a balancing of hard and soft segments, and their relative contributions to overall properties can be achieved.
  • a polymer system of the present invention preferably contains one or more, and more preferably two or more, biocompatible catalysts that can assist in controlling the curing process, including the following periods: (1) the induction period, (2) the setting period, and finally, (3) the final cure of the biomaterial. Together these three periods, including their absolute and relative lengths, and the rate of acceleration or cure within each period, determine the cure kinetics or profile.
  • induction refers to the time period between mixing or activation of one or more polymer components (under conditions suitable to begin the curing process), and the onset of gelation. In a method of the present invention, this period generally corresponds with the delivery of the biomaterial to the site of ultimate use.
  • the induction period is characterized by infinitesimal or limited increase in viscosity of reacting mixture and relatively flat exotherm profile.
  • a biomaterial of this invention is simultaneously mixed just prior to actual delivery into the joint site, providing the surgeon with sufficient time to add and position material (e.g., into anchor points) before gelation causes the material to become less easily workable.
  • surgeon can leave the material in place as it sets, e.g., for on the order of three to twenty minutes, before placing instruments back into the site to finish sculpting the implant, or performing other desired steps such as positioning the femoral condyles to shape the implant.
  • set time (or gel time), as used herein, is determined from the initial mixing of components, and refers to the time needed for a mixed and delivered system to set to the point where it can be shaped. This period is characterized by a rapid rise in the slope of the reaction exotherm at the end of the period. By the end of this period, the surface of the gelled biomaterial is preferably tack free and will allow shaping, e.g., by positioning of the condyles.
  • the “cure time”, as used herein, is determined from the initial mixing, and refers to the total time needed to mix, shape and fully cure the biomaterial to the desired extent under the conditions used. Preferred polymer systems of this invention preferably provide an induction period that ends within about thirty seconds to two minutes following mixing of the components, followed by a set time of about 3 to about 15 minutes following mixing.
  • the polymer system preferably exhibits an exotherm compatible for its intended use, e.g., preferably an exotherm of less than about 70 to about 90 C, and more preferably less than about 80 C.
  • an exotherm compatible for its intended use e.g., preferably an exotherm of less than about 70 to about 90 C, and more preferably less than about 80 C.
  • Catalysts suitable for use in compositions of the present invention provide an optimal combination of such properties as set time, cure time, and in turn, viscosity (and flowability) of the curing polymer system.
  • the selection of catalyst and other ingredients provides a cure profile that exhibits both synergistic and “delayed action” kinetics, in which induction of cure begins immediately upon mixing the polymer components, and is relatively “flat” during the induction period, without significant increase of viscosity of reaction mixture.
  • This period permits delivery of the “flowable” polymer to the tissue injury site, and is followed by a setting period characterized by variable increase in slope (in a plot of temperature vs. time) that is designed to quickly drive the curing process to completion, and in turn, to quickly provide a set polymer that is sufficiently strong and tack-free to permit final shaping.
  • Suitable catalyts include tin compounds (such as tin esters, tin alkylesters, and tin mercaptides), amines, such as tertiary amines and the like.
  • An example of a suitable catalyst system is a combination of a tin catalyst (e.g., “Cotin 222”, available under the trademark “Cotin 222” from Cascam, Company, Bayonne N.J.) and a tertiary amine (e.g., DABCO(TEDA), a triethylene diamine catalyst available from Air Products, Allentown, Pa.
  • a tin catalyst e.g., “Cotin 222”, available under the trademark “Cotin 222” from Cascam, Company, Bayonne N.J.
  • a tertiary amine e.g., DABCO(TEDA)
  • these components can be used in any suitable ratio, e.g., between about 1:1 parts and about 1:5 parts of
  • antioxidants such as vitamin E, which can be used as a biocompatible antioxidant and mediator of macrophage attack designed to destroy the implant in vivo.
  • dyes such as “Green GLS Dye” (available from Clarian Corp., Charlotte, N.C.) that can be added (e.g., at a concentration of about 0.01% to about 0.05%, by weight) to facilitate the ability to visualize the polymer in the course of delivery to the “repair” site.
  • Preferred dyes are stable to change in the course of sterilization, e.g., by irradiation such as gamma or Electron-beam.
  • inorganic fillers such as calcium carbonate, titanium dioxide or barium sulfate can be added as well, in about 0.5 to about 20 percent (by weight) to affect the viscosity and thixotropic properties of the resultant mixture, to modify or increase the load bearing ability of the polymer and/or to render the implanted biomaterial radiopaque.
  • composition of the present invention can be delivered and cured within the body, preferably by minimally invasive means.
  • the composition is used to resurface or repair a joint, such as a knee or intervertebral disc.
  • the composition is used to form an implant in situ, e.g., in the form of a catheter such as a stent, graft, or shunt.
  • compositions capable of being delivered to the injury site, preferably via minimally invasive means.
  • the composition is provided as a system having a plurality of parts, e.g., a two-part system, wherein the two parts are capable of being separately prepared, sterilized, and packaged, such that the parts can be mixed in the operating room and at the time of use in order to initiate the curing process.
  • the static mixer can be used in a system having an application cannula, an application tip, and a cartridge having two or more chambers, each containing a separate component of the composition system.
  • a hand-powered, pneumatically, or electrically controlled extrusion gun can be used to extrude or eject the components through, for example, the static mixer, in order to completely mix them and thereby begin the process of curing.
  • the composition system then flows through the cannula and to the joint site or surface through the application tip.
  • the length, diameter, and vein design of the mixing element can be varied as necessary to achieve the desired mixing efficiency.
  • the composition of the present invention can be delivered to a site within the body, and there cured, preferably using minimally invasive means, in order to repair (e.g., reconstruct or resurface) tissue such as cartilage, and particularly cartilage associated with diarthroidal and amphiarthroidal joints.
  • repair e.g., reconstruct or resurface
  • the composition can be delivered and cured within an implanted mold device.
  • minimally invasive means a composition can be delivered to a site within the body, e.g., to a mold or a site of damaged or diseased cartilage, to be cured in situ in order to provide an implant or repair the cartilage without undue surgical trauma.
  • the invention provides compositions, including polymer systems, useful for performing such a method, as well as methods of preparing and using such compositions.
  • the invention provides a joint, e.g., a diarthroidal or amphiarthroidal joint, having interposed therein a composition that has been delivered and cured in situ.
  • compositions of the present invention provide improvement in one or more of the following properties as compared to those previously known, without detrimental effect on other desirable properties described herein.
  • Applicants have discovered a composition that provides significantly improved hardness and strength during stage ⁇ identified above, while also providing improved cure kinetics during stage (b), all without undue effect on other desirable properties.
  • a suitable composition of the present invention provides a hardness of about 60 Shore to about 95 Shore, as determined by ASTM Test Method D2240 set forth herein.
  • the fully cured composition provides improved tensile strength as well, as determined by ASTM Test Method D412 herein.
  • a preferred composition of this invention provides a tensile strength (measured in the dry state) of about 6,000 psi to about 10,000 psi.
  • composition provides a “wet” tensile strength (e.g., as determined after soaking the sample in saline for one week) of about 3,000 psi to about 5,000 psi.
  • a preferred composition of this invention provides a biphasic cure pattern, as depicted and described with respect to FIG. 1 herein.
  • a preferred fully cured composition of this invention provides a tensile strength of about 6,000 psi to about 10,000 psi, as determined by ASTM Test Method D412 herein.
  • the present invention provides a curable polyurethane composition
  • a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts.
  • the reactive hydrophobic additive comprises an hydroxyl- or amine-terminated polymer or copolymer selected from the group consisting of poybutadiene, polyisobutylene, silicone, polyisoprene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof, and particularly preferred is a composition wherein the additive comprises hydroxyl-terminated polybutadiene.
  • the hydroxyl-terminated polybutadiene can be present at a concentration of between about 5% and about 20%, by weight, based on the weight of the composition, and more preferably between about 8% and about 15% by weight.
  • compositions as described herein wherein the polyether component is l selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polyoxytetramethylene, and copolymers thereof, e.g., wherein the polyether component is present in the prepolymer component at a concentration of between about 2% and about 10% by weight, and is present in the curative component at a final concentration of between about 25% and 45%, based on the weight of the composition.
  • An example of such a composition is one in which the polyether component comprises polytetramethylene oxide having a molecular weight in the range of 250 to 1000.
  • composition which the isocyanate component comprises an aromatic isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate, and combinations thereof, preferably where the isocyanate is present in excess in the prepolymer component, at a concentration of between about 30% and about 50% by weight, based on the weight of the composition.
  • aromatic isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate, and combinations thereof, preferably where the isocyanate is present in excess in the prepolymer component, at a concentration of between about 30% and about 50% by weight, based on the weight of the composition.
  • the invention provides a curable polyurethane composition
  • a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including:
  • polyether polyols selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polyoxytetramethylene, and copolymers thereof,
  • one or more reactive hydrophobic additives comprising hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisobutylene, silicones, polyisoprene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof, and
  • the catalysts in combination with the remaining components, are sufficient to permit the composition to cure upon mixing at physiological temperature with a cure profile that comprises sequentially an onset period, a gelation period, and a complete cure period.
  • the invention provides a cured polyurethane implant suitable for extended use in vivo, the implant being formed as the reaction product of a composition that comprises: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts.
  • Such an implant exhibits improved Shore Hardness and tensile strength, as compared to an implant prepared from a comparable composition lacking hydrophobic additives, e.g., a Shore hardness of between about 60 and about 95 Shore, as determined by ASTM Test Method D2240, and a dry tensile strength of between about 6000 psi and about 10,000 psi, as determined by ASTM Test Method D412.
  • the invention also provides such an implant according positioned in permanent or temporary contact with a joint surface in vivo, and preferably positioned in permanent contact with the surface of subchrondral bone in the knee joint.
  • the invention also provides a kit comprising a plurality of sterile, flowable parts capable of being mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts.
  • the kit further comprises a delivery device for use in mixing the quasi-prepolymer component and curative component, and delivering the mixture to a tissue site using minimally invasive means.
  • Common polymeric materials for use in medical devices include, for example, polyvinyl chlorides, polyethylenes, stryrenic resins, polypropylene, thermoplastic polyesters, thermoplastic elastomers, polycarbonates, acrylonitrile-butadiene-styrene (“ABS”) resins, acrylics, polyurethanes, nylons, styrene acrylonitriles, and cellulosics.
  • ABS acrylonitrile-butadiene-styrene
  • Suitable matrix materials for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use.
  • properties include processability and the ability to be stably sterilized and stored.
  • properties include hydrogel compatibility and capacity, flowability, and in vivo curability.
  • properties include moldability, cured strength (e.g., tensile and compressive), elongation to break, and _iocompatibility.
  • suitable matrix materials include, but are not limited to, silicone polymers and polyurethane polymers.
  • the biomaterial matrix is formed of a silicone polymer, i.e., polymer containing a repeating silicon-oxygen backbone together with organic R groups attached to a significant portion of the silicon atoms by silicon-carbon bonds.
  • a silicone polymer i.e., polymer containing a repeating silicon-oxygen backbone together with organic R groups attached to a significant portion of the silicon atoms by silicon-carbon bonds.
  • Silicone polymers are commercially available in at least three general classes, namely as homopolymers, silicone random polymers, and silicone-organic (block) copolymers. Homopolymers in the form of polydimethyl siloxanes are preferred, and constitute the largest volume of homopolymers produced today.
  • the biomaterial matrix is formed of a polyurethane polymer.
  • Polyurethanes e.g, thermoplastic polyurethanes (“TPU”)
  • TPU thermoplastic polyurethanes
  • the isocyanate and long-chain diol form a “soft” segment, while the isocyanate and short-chain diol form a “hard” segment. It is the interaction of soft and hard segments that determines and provide the polymer with rubber-like properties.
  • the polyurethane chains are linear and assume the configuration into which they are formed, such as by injection molding, or in the case of the present invention, by arthroscopic application.
  • the hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber.
  • TPU's for medical use are presently based on the use of a diisocyanate such as diphenylmethane diisocyanate (“MDI”), a glycol such as polytetramethylene ether glycol, and a diol such as 1,4-butanediol.
  • MDI diphenylmethane diisocyanate
  • glycol such as polytetramethylene ether glycol
  • diol such as 1,4-butanediol.
  • Natural cartilage is a non-vascular structure found in various parts of the body.
  • the natural elasticity of articular cartilage enables it to break the force of concussions, while its smoothness affords ease and freedom of movement.
  • cartilage tends to take on the shape of the articular surface on which it lies.
  • Biomaterials are intended to mimic many of the physical-chemical characteristics of natural cartilage.
  • Biomaterials can be provided as one component systems, or as two or more component systems that can be mixed prior to or during delivery, or at the site of repair.
  • Such biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 1 mm to about 6 mm inner diameter, and preferably of about 2 mm to about 3 mm inner diameter.
  • Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration.
  • preferred materials can be homogeneous (i.e., providing the same chemical-physical parameters throughout), or they can be heterogeneous.
  • An example of a heterogeneous biomaterial for use as a disc replacement is a biomaterial that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and a more liquid (e.g, cushioning or softer) interior core (akin to the nucleus).
  • biomaterials can be used that provide implants having varying regions of varying or different physical-chemical properties. With disc replacement, for instance, biomaterials can be used to provide a more rigid, annulus-like outer region, and a more fluid, nucleus-like core.
  • Such di-or higher phasic cured materials can be prepared by the use of a single biomaterial, e.g., one that undergoes varying states of cure, or a plurality of biomaterials.
  • Common polymeric materials for use in medical devices include, for example, polyvinyl chlorides, polyethylenes, styrenic resins, polypropylene, thermoplastic polyesters, thermoplastic elastomers, polycarbonates, acrylonitrile-butadiene-styrene (“ABS”) resins, acrylics, polyurethanes, nylons, styrene acrylonitriles, and cellulosics. See, for example, “Guide to Medical Plastics”, pages 41-78 in Medical Device & Diagnostic Industry , April, 1994, the disclosure of which is incorporated herein by reference.
  • Suitable biomaterials for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use.
  • properties include processability, and the ability to be stably sterilized and stored.
  • properties include flowability, moldability, and in vivo curability.
  • properties include cured strength (e.g., tensile and compressive), stiffness, _iocompatibility and biostability.
  • suitable biomaterials include, but are not limited to, polyurethane polymers.
  • the biomaterial comprises a polyurethane polymer.
  • Polyurethanes e.g, thermoplastic polyurethanes (“TPU”)
  • TPU thermoplastic polyurethanes
  • the isocyanate and long-chain diol form a “soft” segment
  • the isocyanate and short-chain diol form a “hard” segment.
  • the hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber. It is the interaction of soft and hard segments that determines and provides the polymer with rubber-like properties.
  • TPU's for medical use are presently based on the use of a diisocyanate such as diphenylmethane diisocyanate (“MDI”), a glycol such as polytetramethylene ether glycol, and a diol such as 1,4-butanediol.
  • MDI diphenylmethane diisocyanate
  • glycol such as polytetramethylene ether glycol
  • diol such as 1,4-butanediol.
  • Biomaterials of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • optional adjuvants and additives such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • the biomaterials When cured, the biomaterials demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, dissolution stability, _iocompatibility, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, shear strength, fatigue, impact absorption, wear characteristics, and surface abrasion.
  • physical performance e.g., physical properties such as density, thickness, and surface roughness
  • mechanical properties such as load-bearing strength, tensile strength, shear strength, fatigue, impact absorption, wear characteristics, and surface abrasion.
  • Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of biomaterials.
  • preferred biomaterials in the cured form, exhibit mechanical properties that approximate those of the natural tissue that they are intended to replace.
  • preferred cured composites exhibit a load bearing strength of between about 50 and about 500 psi (pounds per square inch), preferably between about 100 and about 300 psi, and more preferably between about 100 and 200 psi.
  • Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints.
  • Such composites also exhibit a tensile strength of between about 3500 and about 6000 psi, and preferably between about 4000 and about 5000 psi, using test methods generally available to those skilled in the art, for instance using an “Instron” tensile tester.
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications.
  • the biomaterial is a polyurethane provided as a two-part prepolymer system comprising a diisocyanate, a polyalkylene oxide and low molecular diols as chain extenders.
  • the final polymer having a hard segment content of about 25 to about 50% by weight, and preferably of about 30 to about 40% by weight, based on the weight of the diisocyanate and chain extender.
  • one or more catalysts are incorporated into one or more components of the biomaterial, in order to cure the biomaterial in the physiological environment within a desired length of time.
  • biomaterials of the present invention are able to cure (i.e., to the point where distraction means can be removed and/or other biomaterial added), within on the order of 5 minutes or less, and more preferably within on the order of 3 minutes or less.
  • means are employed to improve the biostability, i.e., the oxidative and/or hydrolytic stability, of the biomaterial in vivo, thereby extending the life of the implant.
  • biostability i.e., the oxidative and/or hydrolytic stability
  • means are employed to improve the biostability, i.e., the oxidative and/or hydrolytic stability, of the biomaterial in vivo, thereby extending the life of the implant.
  • Suitable means for improving biostability include the use of an aliphatic macrodiol such as hydrogenated polybutadiene (HPDI).
  • HPDI hydrogenated polybutadiene
  • judicious choice of the corresponding diisocyanate (e.g., MDI) and chain extender (e.g., ethylenediamine) those skilled in the art will be able to achieve the desired packing density, or crystallinity, of the hard segments, thereby improving the hydrolytic stability of the cured polyurethane.
  • Biomaterials provided as a plurality of components can be mixed at the time of use using suitable mixing techniques, such as those commonly used for the delivery of two-part adhesive formulations.
  • suitable mixing device involves, for instance, a static mixer having a hollow tube having a segmented, helical vein running through its lumen.
  • a two-part polyurethane system can be mixed by forcing the respective components through the lumen, under pressure.
  • the static mixer can be used in a system having an application cannula, an application tip, and a cartridge having two or more chambers, each containing a separate component of the biomaterial system.
  • a hand-powered or electrically controlled extrusion gun can be used to extrude the components through the static mixer, in order to completely mix them and thereby begin the process of curing.
  • the biomaterial system then flows through the cannula and to the joint site or surface through the application tip.
  • the length, diameter, and vein design of the mixing element can be varied as necessary to achieve the desired mixing efficiency.
  • Hydrogels suitable for use in composites of the present invention are water-containing gels, i.e., polymers characterized by hydrophilicity and insolubility in water. See, for instance, “Hydrogels”, pages 458-459 in Concise Encyclopedia of Polymer Science and Engineering , Eds. Mark et al., Wiley and Sons, 1990, the disclosure of which is incorporated herein by reference. Although their use is optional in the present invention, the inclusion of hydrogels is highly preferred since they tend to contribute a number of desirable qualities. By virtue of their hydrophilic, water-containing nature, hydrogels assist the cured composite with load bearing capabilities of the cured composite. They also tend to decrease frictional forces on the composite and add thermal elasticity.
  • the hydrogel is a fine, powdery synthetic hydrogel. Suitable hydrogels exhibit an optimal combination of such properties as compatibility with the matrix polymer of choice, and _iocompatibility.
  • Suitable hydrogels swell to an equilibrium volume in water, but preserve their shape.
  • Synthetic hydrogels suitable for use in forming a composite of the present invention include those based on methacrylic and acrylic esters, (meth)acrylamide hydrogels, and those based on N-vinyl-2-pyrrolidinone.
  • Preferred hydrogels include those formed from monomeric hydroxyalkyl acrylates and methacrylates, copolymerized with a suitable cross-linking agent, such as ethylene dimethacrylate (“EDMA”).
  • EDMA ethylene dimethacrylate
  • the matrix polymer is a siloxane (i.e., silicone polymer), and preferably one selected from the group consisting of alpha, omega-dihydroxypoly(dimethylsiloxane) and poly(dimethylsiloxane) with 0.2 mol % of vinylmethyl-siloxane units.
  • Dispersed as the hydrogel component in the preferred polymer is 15% to 30% (by weight based on the weight of the uncured composite) of a lightly cross-linked hydrogel aggregate.
  • a preferred hydrogel aggregate is formed by 2-hydroxyethyl methacrylate (HEMA) cross-linked by ethylene dimethacrylate (EDMA) at a concentration of 2%-5% by weight, based on the weight of the hydrogel.
  • HEMA 2-hydroxyethyl methacrylate
  • EDMA ethylene dimethacrylate
  • hydrogel/matrix combinations and concentrations can be altered based on their intended application. For instance, a stiffer composite with a low hydrogel concentration, e.g., 10% based on the final weight of the composite, would be suitable for intervertebral disc replacement.
  • biomaterials will preferably contain a hydrogel phase at a concentration of between about 15 and 50 weight percent, and preferably between about 10 and about 50 weight percent, and preferably between about 15 and about 30 weight percent, based on the weight of the combination of matrix and hydrogel.
  • Composites of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • optional adjuvants and additives such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • Cured polymer-hydrogel composites demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, dissolution stability, _iocompatibility, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, static shear strength, fatigue of the anchor points, impact absorption, wear characteristics, and surface abrasion.
  • physical performance e.g., physical properties such as density, thickness, and surface roughness
  • mechanical properties such as load-bearing strength, tensile strength, static shear strength, fatigue of the anchor points, impact absorption, wear characteristics, and surface abrasion.
  • Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of biomaterials.
  • preferred composite materials in the cured form, exhibit mechanical properties approximating those of the natural tissue that they are intended to replace.
  • preferred cured composites exhibit a load bearing strength of between about 50 and about 200 psi (pounds per square inch), and preferably between about 100 and about 150 psi.
  • Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints.
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications.
  • Biomaterials for use in a method of this invention include, but are not limited to, those described in Applicant's co-pending PCT Application Nos. PCT/US97/00457.
  • Biomaterials can be provided as one component systems, or as two or more component systems that can be mixed prior to or during delivery, or at the site of repair.
  • Such biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter.
  • Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration.
  • Preferred biomaterials are intended to mimic many of the physical-chemical characteristics of natural tissue.
  • preferred materials can be homogeneous (i.e., providing the same chemical-physical parameters throughout), or they can be heterogeneous.
  • An example of a heterogeneous biomaterial for use as a disc replacement is a biomaterial that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and a more liquid (e.g., cushioning or softer) interior core (akin to the nucleus).
  • Suitable biomaterials for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use.
  • properties include processability, and the ability to be stably sterilized and stored.
  • properties include flowability, moldability, and in vivo curability.
  • properties include cured strength (e.g., tensile and compressive), stiffness, _iocompatibility and biostability.
  • suitable biomaterials include, but are not limited to, polyurethane polymers.
  • Biomaterials of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • optional adjuvants and additives such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose.
  • preferred biomaterials in the cured form, exhibit mechanical properties that approximate those of the natural tissue that they are intended to replace.
  • preferred cured composites exhibit a load bearing strength of between about 50 and about 500 psi (pounds per square inch), and preferably between about 100 and about 200 psi.
  • Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints.
  • Such composites further exhibit a tensile strength of between about 4,000 psi and about 10,000 psi, and preferably between about 6,000 psi and about 8,000 psi.
  • Cured biomaterials for use in non-orthopedic applications, e.g., as catheters can generally exhibit strength and stress parameters that are appreciably lower than those used in more demanding applications.
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery conduit to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications.
  • a biomaterial composition of the present invention can be provided in a heterogeneous form, e.g., having two or more portions that independently provide one or more properties that differ between the portions.
  • the present teaching can be employed in the following manner to provide a joint resurfacing implant having improved anchoring and tear resistance.
  • Reactive liquid polyurethanes as described above, can be mixed during delivery and polymerized in situ and in vivo in order resurface or restore damaged body joint.
  • such an implant can be immobilized in the joint by means of one or more anchoring holes drilled into the implant site.
  • Biomaterials having a surface hardness of about 65 to about 85 Shore A are relatively soft, and can be used to simulate the cushioning properties of articulating cartilage they target to replace.
  • the implant be even more firmly and permanently immobilized within the joint, in order to resist a “carpeting effect” that can otherwise be caused by load forces as well as frictional and/or twisting movements typical in the joint. Such an effect can serve to create extensive wear on the implant, leading to premature failure of the implant and even dislodging of the implant itself or portions thereof.
  • compositions described herein can be made with an optimal combination of hardness, stiffness and strength, in order to resist deformation. Such properties, in turn, will permit the anchor points to better resist deformation, or failure. In turn, such biomaterials can provide improved immobilization of the implant, patient healing, and joint acceptance and performance. Harder implants, however, tend to experience significantly greater wear when introduced between surfaces of communicating or articulating bones.
  • the implant can be provided in the form of a heterogeneous composition, including a harder portion for use as anchor points, and a softer portion for cushioning.
  • a multiphasic bulk morphology of the implant can be produced using an Interpenetrating Polymer Network (IPN), by bringing together softer and harder polymer networks while being polymerized.
  • IPN Interpenetrating Polymer Network
  • the present invention therefore provides a in situ formed composite that provides an optimal combination of anchoring and cushioning properties considered valuable for implant performance.
  • a thin layer (e.g., about 0.01 mm to about 1.0 mm) of strong, stiff and tough polyurethane, having the surface hardness of 55-75 Shore D is deposited into the lesion, filling completely the anchoring holes.
  • This layer is preferably either solid or microcellular, neat or enhanced with all potentially available biologicals to augment integration and immobilization into the surrounding environment; e.g. bone, cartilage, synovium, etc.
  • the anchoring is improved by increased resistance to deformation and thus the “pullout”, stemming from the harder and stiffer material.
  • aspects of biodurability vs. biodegradation can be considered for this anchoring layer. Given the present teaching, those skilled in the art will be able to provide suitable formulations to fulfill these needs.
  • the second layer in the form of a softer, cartilage-like polyurethane, is delivered and formed over the anchoring layer to form the composite.
  • This softer layer provides the functional requirements of the joint restoring implant.
  • the system described herein can be used to provide a joint implant having a mushroom-like appearance, in which “head” represents the implant; the “stem” represents the anchoring system.
  • head represents the implant
  • stem represents the anchoring system.
  • Such an implant will flow with the force-field acting upon it to extend its durability in the joint, and is particularly useful for indications where the necessary lesion as taught in U.S. Pat. No. 5,556,429 is impractical or impossible.
  • Reactive liquid polyurethanes mixed during delivery and polymerized in situ and in vivo are used to resurface or restore damaged body joint as described herein.
  • the in situ polymerized implant based on polyurethanes having the surface hardness between 60-95 Shore A, is immobilized in the joint, in the prepared lesion, via drilled anchoring holes in the selected implant site.
  • Anchoring holes are drilled at the “periphery” of the lesion. At least three holes are drilled to anchor the implant.
  • biomaterials are relatively soft, and are designed to simulate the properties of articulating cartilage they target to replace. Furthermore, these materials provide cushioning effect between respective bones of the respective joint.
  • anchor holes be drilled, essentially conical in shape and placed in a staggered pattern, to be filled with curable biomaterial and become an integral part of the implant. It is difficult to drill the holes in “toe-nail” fashion with the bottom tip of the hole pointing toward the periphery of the lesion. This diminishes the “holding” power of the anchoring hole system.
  • increasing numbers of anchor holes can serve to weaken the bone surface plateau (e.g. tibial plateau of the knee joint) causing potential “cave in” of the tibial plateau under the load. Holes can also serve to retain whatever folds might be brought on in the course of a carpeting effect, thereby potentially accelerating implant failure.
  • a preferred method includes the following steps:
  • a single, conically-shaped and center-located anchoring hole is drilled or otherwise generated within the joint surface to be restored.
  • a thin layer of 0.01 mm to 1.0 mm of strong, stiff and tough polyurethane, having the surface hardness of about 55 to about 75 Shore D is delivered to the plateau surface or the lesion, filling completely the anchoring hole, in order to generate the “stem” of the “mushroom”.
  • This stem layer can be provided in any suitable form, e.g., solid, microcellular, neat or enhanced with one or more biologicals to augment integration and immobilization into the surrounding environment; e.g. bone, cartilage, synovium, etc.
  • the anchoring will be improved by increased resistance to deformation and thus the “pullout”, stemming from the harder and stiffer material.
  • a second layer is delivered, e.g., in the form of a softer, cartilage-like polyurethane, which forms over the anchoring layer to form the composite in the form of “the head” of the “mushroom”.
  • one or more layers can be delivered, in any suitable order and using any suitable materials, in order to provide a multi-layered stem and/or head.
  • both the head and stem, and each layer therein are provided in the form of a single material (e.g., polyurethane) in a manner that permits delivered in a single or multi-layered fashion.
  • a single material e.g., polyurethane
  • the method of the invention involves an initial step of providing an implantable mold apparatus comprising a cavity adapted to receive and contain a flowable biomaterial and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial,
  • a cavity can take any suitable form, e.g., a unitary balloon-like cavity capable of being partially or completely filled with biomaterial in order to provide an intact prosthesis, or a shell-like or tubular cavity used to form a corresponding tubular prostheses.
  • the mold can be of any suitable shape or dimension, and can itself include a plurality of cavities and/or other chambers or conduits, such as those suitable for the delivery of air or vacuum, as described herein.
  • the method can be used for a variety of applications, including for instance, for the preparation of an integral prostheses, e.g., for use in articulating joint repair or replacement and intervertebral disc repair.
  • the method can be used to provide a hollow mold, such as a tubular mold for use in preparing implanted passageways, e.g., in the form of catheters, such as stents, shunts, or grafts.
  • the method of the invention is used in the course of intervertebral discectomy.
  • an amphiarthroidal joint such as the lumbar joint of the back, the vertebra are separated by an intervertebral disc formed of cartilage.
  • Applicant's copending PCT Application No. PCT/US97/00457 (the entirety of which is incorporated herein by reference), inter alia, describes a method for repairing an intervertebral disc that comprises the steps of:
  • the distraction of the disc space is accomplished by the use of suitable distraction means, such as an inflatable balloon or bladder.
  • suitable distraction means such as an inflatable balloon or bladder.
  • the balloon can be delivered in deflated form to the interior of the annulus and there inflated, as by the delivery of biomaterial, in order to distract the disc space and retain the biomaterial.
  • FIG. 1 An improved inflatable device for used in intervertebral disc repair will be described with reference to the Drawing, and in particular FIGS. 1 through 4.
  • an apparatus ( 10 ) is shown having balloon portion ( 12 ) and biomaterial conduit ( 14 ).
  • the balloon is dimensioned to be positioned within the annular shell following discectomy, and there filled with biomaterial in order to provide a replacement disc.
  • conduit ( 14 ) includes a venting system ( 16 ) that includes air passageway ( 18 ) passing from a distal point along the conduit, into and through its wall ( 20 ) in order to pass along the interior of the conduit.
  • Air passageway ( 18 ) terminates at a point at or near the proximal end of balloon ( 12 ), where it can be used to provide gas under pressure (e.g., in order to position the balloon and/or distract the joint) and where it can optionally be used to vent gas (e.g., air) within the balloon as the balloon is filled with biomaterial.
  • the air passageway ( 18 ) is preferably provided with one or more vent holes ( 22 ) at locations within the balloon, which serve to facilitate the delivery of biomaterial by improving venting of gas from within the balloon.
  • Conduit ( 14 ), including the air passageway, can be severed from balloon portion at or near the point ( 24 ) where they attach to or pass through the wall of the balloon. In this manner the conduit can be removed from the balloon as or after the biomaterial cures.
  • the balloon is preferably provided in a form collapsed or rolled within sheath ( 26 ), which can be drawn back in situ in order to release the balloon.
  • Sheath ( 26 ), conduit ( 14 ) and air passageway ( 18 ) can each prepared from materials commonly used for such purposes, such as polyurethane catheters, and suitably dimensioned to provide the respective functions.
  • the conduit portion for instance, will preferably be about 10 cm to about 30 cm in length, more preferably between about 15 cm to about 25 cm in length, and about 0.1 cm to about 10 cm, and more preferably about 0.3 cm to about 0.7 cm in outer diameter.
  • the air passageway in contrast, will typically be about 1 mm to about 3 mm in outer diameter, and of sufficient length to extend about 2 cm to about 4 cm beyond the proximal end of the conduit (and therefore into the balloon).
  • the balloon in turn, will typically be about 2 cm to about 3 cm in its longest dimension, about 1.5 cm to about 2.5 cm in width, and about 0.5 cm to about 1.5 cm in thickness, once filled with biomaterial.
  • Both the biomaterial conduit ( 14 ) and air passageway ( 18 ) are preferably provided with controllable and adjustable valves ( 28 ) and ( 30 ), for use in adjusting the flow of biomaterial and gas, respectively, between the two.
  • air passageway ( 18 ) can be provided such that it terminates at point substantially at or near where it meets the balloon, i.e., such that it does not extend into the balloon itself. In this manner it has been found that the balloon can still be adequately evacuated, yet in a manner that avoids the need to keep the distal portion of the air passageway permanently encased in cured biomaterial within the implant.
  • the mold apparatus can include means for positioning the balloon in situ, e.g., in the form of a vascular guide wire that can be placed through the delivery conduit itself, or preferably through an air passageway that terminates at or near the point of contact with the balloon.
  • the guide wire can be designed to substantially assume the curved contour of the extended but unfilled balloon, and to provide a plane of orientation, in order to both facilitate placement of the balloon and provide an outline of the periphery of the balloon in position and prior to filling. Thereafter the guide wire can be removed from the site prior to delivery of the biomaterial and air evacuation.
  • the use of a guide wire in this manner is particularly facilitated by the use of an air passageway that is unconnected to, and positioned outside of, the biomaterial conduit.
  • the invention further provides a rod, e.g., a plastic core material, dimensioned to be placed within the balloon, preferably by extending the rod through the conduit.
  • a vacuum can be drawn on the balloon through the air passageway in order to collapse the balloon around the rod.
  • the balloon can also be twisted or otherwise positioned into a desired conformation to facilitate a particular desired unfolding pattern when later inflated or filled with biomaterial.
  • a suitable vacuum source the step of collapsing the balloon in this manner can be accomplished at any suitable time, including just prior to use.
  • balloon materials that may tend to stick together or lose structural integrity over the course of extended storage in a collapsed form.
  • balloon materials can be provided with a suitable surface coating, e.g., a covalently bound polymeric coating, in order to improve the lubricity of the surface and thereby minimize the chance that contacting balloon surfaces will adhere to each other.
  • Mold cavities of the present invention can be formed by any suitable means.
  • the balloon is fabricated by dipcoating a suitably shaped mandrel into a curable polymer solution.
  • suitable materials include low melting point fusible materials, such as bismuth alloys that are commercially available from a number of sources (e.g., as Part nos. E-LMA-117, 158, 255 and 281 from Small Parts, Inc. Miami Lakes, Fla.).
  • Such an alloy begins to melt at about 117 degrees C., and solidifies at room temperature, expanding slightly in the process of cooling. The allow can be melted out in hot water and collected for re-use.
  • FIG. 3 shows a mandrel ( 32 ) covered with newly formed balloon ( 34 ) and held in chuck ( 36 ).
  • the solid mandrel ( 32 ) is used to form a balloon by dipcoating it in a suitable solution (not shown) as described herein. Once cast, the mandrel can be melted in order to remove it from the balloon by dipping the combination in water at about 120 degrees C. for about 5 to 15 minutes. As the mandrel _iocompat it can be poured and/or squeezed out of the balloon and reformed for further use.
  • FIG. 4 shows the resultant balloon ( 34 ), after removal of the mandrel, formed by this process.
  • the balloon retains an integral stem portion ( 38 ) that provides an attachment site for the conduit shown in FIG. 1.
  • a preferred balloon provides an optimal combination of such properties as extendibility and strength.
  • a balloon that is substantially non-extendible, but strong can be used to distract the disc space upon delivery of biomaterial, and by virtue of the biomaterial delivery pressure.
  • Preferred materials for use in preparing balloons of the present invention include, for instance, block copolymers such as castable thermoplastic polyurethanes, for instance those available under the tradenames ESTANE (Goodrich), PELLETHANE (Dow), TEXIN (Bayer), Roylar (Uniroyal), and ELASTOTHANE (Thiocol), as well as castable linear polyurethane ureas, such as those available under the tradenames CHROMOFLEX AR (Cardiotech), BIONATE (Polymer Technology Group), and BIOMER (Thoratec).
  • block copolymers such as castable thermoplastic polyurethanes, for instance those available under the tradenames ESTANE (Goodrich), PELLETHANE (Dow), TE
  • Preferred elastomeric polymers provide an optimal combination of such properties as flexibility under static and dynamic conditions, strength, tensile strength, elongation, elastic modulus during cyclic deformation, ductility, stability and durability, compliance, porosity, and patency. See generally, M. Szycher, J. Biomater. Appl. “Biostability of polyurethane elastomers: a critical review”, 3(2):297-402 (1988); A. Coury, et al., “Factors and interactions affecting the performance of polyurethane elastomers in medical devices”, J. Biomater. Appl.
  • a remoldable bismuth mandrel is formed having desired shape and dimensions. Balloons can be cast to achieve any desired final thickness, preferably on the order of 0.005 inches (0.01 cm) to about 0.015 (0.05 cm) inches thick, and preferably between about 0.008 inches (0.02 cm) to about 0.012 inches (0.03 cm).
  • the balloon itself is preferably cleaned, e.g., by the use of suitable solvents.
  • reinforcing materials such as meshes formed of natural or synthetic materials can be incorporated into the balloon, e.g., by layering them onto various portions while still wet, and covering the mesh with subsequent dip coats.
  • a mesh can be cut in a form sufficient to extend around the perimeter of the balloon, for instance, in order to provide added strength in the course of filling the balloon and distracting the space.
  • Suitable materials for preparing meshes include polyamide (e.g., NYLON), polyester (e.g., tradenames DACRON and HYTREL), polyethylene, and polypropylene, as well as liquid crystal polymers available under the tradename VECTRA.
  • a balloon, conduit and air passageway can be individually prepared and assembled by attaching the balloon to an end of the conduit, e.g., by gluing or sonic welding, and positioning the air passageway within or alongside the conduit and extending into the balloon. Thereafter the sheath can be applied to the conduit and slid over the balloon in its collapsed or rolled configuration.
  • Other materials or means can be incorporated into the apparatus, such as radioopaque portions, to facilitate the surgeons ability to orient the balloon in situ.
  • various joints and junctures between the parts of the apparatus can be sealed by the use of suitable adhesives or other materials.
  • FIG. 5 shows the balloon portion ( 12 ) in place, with sheath ( 26 ) retracted, within a reamed annular shell ( 70 ).
  • a curable biomaterial ( 72 ) is delivered into the balloon at the same time that air is withdrawn from the balloon through vent holes ( 22 ) of air passageway ( 18 ).
  • the apparatus can be inserted into the body through minimally invasive means in order to position the proximal end at the site of intended use, e.g., within the disc space. Once positioned, the sheath can be withdrawn in order to release the balloon.
  • air or other suitable gas can be delivered to the balloon through the air passageway in order to position the balloon and/or distract the joint. Thereafter, the valve can be opened to begin the flow of curable biomaterial.
  • gas in the balloon can be vented through air passageway by drawing a slight vacuum on the distal end of the passageway, as by the use of a syringe or other suitable vacuum source.
  • the biomaterial continues to fill the balloon, which in turn serves to distract (or assist in distracting) the space, until desired dimensions are obtained, whereupon the flow of biomaterial is stopped, the biomaterial is allowed to continue to fully cure (harden), and the balloon severed from the conduit.
  • the method and apparatus of the invention can also be used to repair other joints, including diarthroidal and amphiarthroidal joints.
  • suitable diarthroidal joints include the ginglymus (a hinge joint, as in the interphalangeal joints and the joint between the humerus and the ulna); throchoides (a pivot joint, as in superior radio-ulnar articulation and atlanto-axial joint); condyloid (ovoid head with elliptical cavity, as in the wrist joint); reciprocal reception (saddle joint formed of convex and concave surfaces, as in the carpo-metacarpal joint of the thumb); enarthrosis (ball and socket joint, as in the hip and shoulder joints) and arthrodia (gliding joint, as in the carpal and tarsal articulations).
  • the mold ( 40 ) includes a generally ovoid inflatable portion ( 42 ), preferably having protruding foot portions ( 44 ) extending therefrom and flowably attached to biomaterial conduit ( 46 ).
  • the foot portions, or footpads, ( 44 ) can be implanted into corresponding anchor sites drilled into the bone, in order to provide improved attachment thereto.
  • template ( 50 ) for use in drilling the holes that will correspond with foot portions ( 44 ).
  • template ( 50 ) includes both a substantially planar, disc-like, template portion ( 52 ) and an extendable delivery probe ( 54 ) useful for positioning the template by minimally invasive means.
  • the disc portion is provided with one or more, and preferably several apertures of predetermined spacing and diameter, to correspond with the foot portions of a corresponding inflatable portion.
  • a template such as that shown is considered novel in its own right, and particularly in the context of a system in which a mold and template are packaged or paired together to facilitate the delivery and placement of the mold in situ.
  • One or more footpads are formed or formable in a manner integral with the balloon or are attached thereto in any suitable manner.
  • the footpads can themselves be solid, or can be part of the cavity and filled with biomaterial.
  • the footpads are dimensioned to be positioned into corresponding anchor points within the bone, to further secure the mold to the site of tissue injury.
  • the underside of the balloon may have multiple fenestrations (e.g., micro holes) sufficient to permit the biomaterial to traverse the barrier of the balloon in order to contact the subchondral bone and/or fill the anchor points.
  • the apparatus can also be provided with means, such as a _iocompat air lumen or other means sufficient to evacuate the balloon in the course of biomaterial delivery, thereby facilitating the process further.
  • the cavity provided by an apparatus of this invention can be in a form sufficient to provide a hollow, e.g., tubular biomaterial upon cure.
  • the apparatus can be used to form an internal passageway, for instance, to support (internally or externally) an existing passageway (such as a vessel), to provide a replacement for natural vessel, and/or to provide a new passageway such as a shunt, between areas not previously or naturally connected.
  • a tubular mold can be used to form a catheter, which in turn, can serve as a prosthethic device for a variety of applications.
  • a catheter of the present invention can take a variety of forms, including, for instance, as an angiographic catheter, ureteral catheter, central venous catheter, _iocompati catheter, bladder catheter, intracardiac catheter, pacing catheter, and prostatic catheter.
  • a catheter of this invention can also serve as a shunt, to provide a diversion or bypass of accumulations of fluid to an absorbing or excreting system.
  • Suitable applications include, for instance, the use of a catheter as an arteriovenous shunt, Blalock shunt (subclavian artery to pulmonary artery), cavopulmonary shunt, distal splenorenal shunt, jejunoileal shunt, “left-to-right” shunt (e.g., in the heart as through a septal defect, or from the systemic circulation to the pulmonary), mesocaval shunt, peritoneovenous shunt, portacaval shunt, portasystemic shunt, renal-splenic shunt, “right-to-left” shunt (e.g., in the heart as through a septal defect, or from the pulmonary artery into the aorta), Scribner shunt (artery, generally radial, to cephalic vein
  • the catheter can be used to form a graft for abdominal aortic aneurysms, and in micro form as a graft for cerebral aneurysms.
  • a mold of this invention can be used to prepare a solid (e.g., curved and/or straight) rod, such as a medullary rod for internal fixation of various fractures.
  • a solid rod e.g., curved and/or straight
  • the balloon, and in turn rod can also be placed by minimally invasive means.
  • a catheter of this invention can be used in a variety of applications.
  • the invention provides a stent formed by a method of the present invention.
  • Stents of the present invention can be used in a variety of applications, including for peripheral vasculature, abdominal aortic aneurysms, and applications in connection with the prostate, esophagus, trachea, bile or biliary tract, and intestine.
  • a stent of this invention can lay within the lumen of a tubular structure to provide support during or after anastomosis, or to assure patency of an intact but contracted lumen.
  • apparatus ( 60 ) comprises an inner fluid passageway ( 62 ), surrounded by a generally concentric and inflatable air chamber ( 64 ), the air chamber being surrounded by a generally concentric and sealed or sealable biomaterial cavity ( 66 ).
  • the fluid passageway is adapted to permit the flow of a bodily fluid such as blood in the course of insertion and delivery of the apparatus.
  • the air chamber is adapted for attachment to a source of positive or negative air pressure
  • the biomaterial chamber is adapted to be attached to a source of flowable biomaterial which can be cured in situ to form a tubular prosthetic implant such as a catheter.
  • means can be provided to vent or evacuate the biomaterial chamber in the course of filling with biomaterial, e.g., by the application of slight vacuum using a separate and additional lumen (not shown).
  • the fluid passageway ( 62 ) and air chamber ( 64 ) are separated by a first barrier ( 68 ), while air chamber ( 64 ) and biomaterial cavity ( 66 ) are separated by a second barrier ( 70 ).
  • Outermost wall ( 72 ) provides the external surface of the biomaterial cavity and generally serves as an outer wall of the apparatus.
  • fluid passageway is sufficiently long to permit it to be delivered to a desired site within the body.
  • the air chamber and biomaterial cavity are provided along a portion of the fluid passageway, and generally need only be sufficiently long to serve their purpose in the preparation of a prosthetic implant.
  • the air chamber can be inflated with air (or other suitable material) to a desired position and dimensions, whereupon the biomaterial can be delivered to fill the biomaterial cavity and cured in situ to form an implanted catheter.
  • the air chamber can be inflated before, during and/or after delivery and/or cure of the biomaterial. Thereafter the air chamber can be deflated and, together with the fluid passageway, removed from the body leaving the cured biomaterial in place as a catheter.
  • a mold apparatus of the type shown in FIG. 10 can be provided with means for venting the biomaterial chamber, e.g., in the course of filling that chamber with biomaterial.
  • Venting means can be provided in a manner analogous to that described above with respect to the intervertebral disc balloon, that is, by the use of a separate air passageway operably attached to the biomaterial chamber on its proximal end, and attached or attachable to a vacuum source or source of pressurized air (or gas) on its opposite end.
  • FIG. 10 The cross-sectional view provided in FIG. 10 demonstrates the manner in which fluid passageway ( 62 ) serves to permit the continued flow of fluid within the body in the course of use. Adjacent or surrounding the passageway is one or more air passageways ( 64 ) that can be used to inflate biomaterial cavity ( 66 ) and establish it in a desired position with respect to the body and the passageway.
  • the present invention provides a method for forming a prosthesis in situ, the method comprising the steps of:
  • a mold apparatus comprising an inner fluid passageway, a portion of the passageway being surrounded by a circumferential inflatable air chamber, a portion of the air chamber being surrounded by a circumferential biomaterial cavity, the fluid passageway being adapted to permit the flow of a bodily fluid or substance in the course of insertion and delivery of the catheter, the air chamber being adapted for operable attachment to a source of positive or negative air pressure, and the biomaterial chamber being adapted for operable attachment to a source of flowable, curable biomaterial which can be cured in situ to form a catheter, wherein the air chamber, upon inflation serves to define the inner dimensions of the catheter, and upon deflation allows free separation and removal of the passageway and air chamber, leaving the newly formed biomaterial prosthesis in place,
  • the invention provides a mold apparatus comprising a inner fluid passageway, a portion of which is surrounded by a circumferential, radially expansible, and inflatable air chamber, a portion of the air chamber being surrounded by a circumferential, radially expansible, biomaterial cavity, the fluid passageway being adapted to permit the flow of bodily fluid or substances in the course of insertion and delivery of the catheter, the air chamber being adapted for operable attachment to a source of positive or negative air pressure, and the biomaterial chamber being adapted to be flowably attached to a source of biomaterial which can be cured in situ to form an implanted prosthesis.
  • the biomaterial passageway can itself be contoured or shaped in any suitable manner, e.g., to provide a helical or spiral flow path along the length of the mold apparatus, e.g., in order to provide improved control over the flow of biomaterial and/or to provide improved dimensional stability to the cured implant.
  • the biomaterial passageway can be branched or segmented in any suitable fashion, e.g., to provide a “Y” shaped configuration to accommodate vascular branch points such as that of the aorta.
  • the fluid passageway of this embodiment can be provided by any material suitable to provide an optimal combination of such properties as nontoxicity, the ability to be bonded or otherwise attached to the material(s) used to form the air chamber and/or biomaterial cavity.
  • a suitable material for forming the fluid passageway is polyethylene.
  • the air chamber and biomaterial can be formed from any suitable material, or combination of materials.
  • the air chamber will be formed having, as its interior surface, the exterior surface of the fluid passageway.
  • the remaining surface of the air chamber is preferably fabricated from a different, and expandable, material capable of being sealed to the passageway at its ends, and contacting and expanding the dimensions of the biomaterial cavity upon inflation.
  • the outer wall of the fluid passageway therefore, is preferably of sufficient strength to maintain its patency and integrity in order to withstand the pressure used to inflate the air chamber.
  • the biomaterial cavity in turn, can similarly share a common wall (its interior) with the exterior wall of the air chamber, particularly if measures are taken to ensure that desired portions of the apparatus can be withdrawn from the cured biomaterial in a manner that permits the cured biomaterial to remain within the body.
  • the barrier between the air chamber and biomaterial cavity is formed of two or more layers, one serving as the exterior, and expandable, wall of the air chamber, and the other laying substantially adjacent that wall and serving as the interior wall of the biomaterial cavity, and in turn, of the implanted prosthetic.
  • the outer and inner walls of the biomaterial cavity can themselves be integrally attached (e.g., tacked) together in a spiral configuration in order to strengthen the cylindrical geometry and facilitate both the evacuation of air and biomaterial delivery.
  • the walls of the fluid passageway, air chamber and biomaterial cavity are each of suitable dimensions (e.g., thickness and length) for their intended purpose.
  • the walls of the fluid passageway will be on the order of 0.02 inches (about 0.05 cm) or less in thickness, with the outer walls of the chamber and cavity being appreciably thinner, e.g., on the order of 0.01 inches (about 0.02 cm) or less and 0.005 inches (about 0.01 cm) or less, respectively.
  • the overall diameter of the fluid passageway can be adapted to its desired purpose, but is generally between about 0.1 cm and about 3 cm, and preferably between about 0.2 cm and about 2 cm.
  • the diameters of the air chamber and biomaterial cavity can also be adapted to their desired purpose, but will generally be between about 0.5 cm and about 5 cm (and preferably between about 1 cm and about 3 cm) for the overall diameter of the inflated air chamber and filled biomaterial cavity.
  • the biomaterial cavity can be used to form an implanted catheter of any suitable inner and outer diameter, with a corresponding wall thickness of between about 0.1 mm and about 5 mm, and preferably between about 0.5 mm and about 2 mm. In its uninflated and unfilled condition the diameter of the entire assembly is generally less than that of the vessel into which it will be inserted.
  • the various materials and/or portions used to fabricate such an apparatus can be secured in any suitable fashion, e.g., by the use of appropriate medical-grade adhesives, by the use of multiple wraps of fine thread or suture, by heat sealing, sonic welding, and the like.
  • the fluid passageway will be provided in the form of a cylindrical body, having the air chamber and biomaterial cavity similarly formed and positioned as cylindrical and concentric bodies, with the chamber configured to taper down at its ends for attachment to the outer surface of the fluid passageway, and the biomaterial cavity also tapered down at its ends for attachment to the outer surface of the air chamber.
  • At least two lumens are mounted as integral parts of the catheter body, including an air lumen ( 74 ) and a biomaterial lumen ( 76 ).
  • the air lumen is connected to an inflation port that passes through the outside wall and into the air chamber.
  • the opposite end of the air lumen passes along the distal length of the catheter to be controllably connected to an air or vacuum source.
  • the biomaterial lumen is flowably connected to an inflation port that passes through the outside wall and into the biomaterial cavity, with its opposite end passing along the distal length of the catheter to be controllably connected to a biomaterial source.
  • the apparatus is dimensioned to be delivered through minimally invasive means to a desired position within the body.
  • the inflatable air chamber and fillable biomaterial cavity can both be stored and inserted in a collapsed condition adjacent the outside surface of the fluid passageway.
  • the apparatus can be covered by a removable sheath (not shown) or other means suitable to facilitate its delivery to the desired position.
  • the apparatus can be inserted through minimally invasive means through an artery or other bodily vessel to a desired point within the body, for instance, to a stenosed region of a blood vessel.
  • positive air pressure is applied in order to inflate the air chamber to a desired dimension.
  • the outer and surrounding biomaterial cavity is suitably positioned for the receipt of biomaterial. As biomaterial fills the cavity, the pressure in the air chamber can be reduced in order to accommodate the increasing pressure and volume of biomaterial.
  • the air pressure can be further reduced in the air chamber, to the point where a vacuum can be drawn if desired, and the delivery conduit (fluid passageway and deflated air chamber) can be removed from the site.
  • the outer wall of the air chamber is distinct from the inner wall of the biomaterial cavity, such that the air chamber can be readily separated from the filled cavity, and axially removed therefrom.
  • Suitable materials for preparing a mold apparatus of the present invention are those that are presently used for such purposes as balloon angioplasty. Suitable materials provide an optimal combination of such properties as compliance, biostability and _iocompatibility, and mechanical characteristics such as elasticity and strength.
  • a mold apparatus can be provided in any suitable form, including having a plurality of layers and/or a plurality of compartments when expanded.
  • a useful apparatus will include the balloon or other biomaterial cavity itself, together with a delivery catheter (optionally having a plurality of lumen extending longitudinally therewith), and fluid or gas pressure delivery means.
  • mold material can be rendered porous or fenestrated in order to permit it to become saturated with the biomaterial and/or to permit tissue to growth into the material or attach itself thereto.
  • the mold material can be chemically or biochemically treated, e.g., coated, to enhance the function or prevent unwanted interactions with the surrounding biological environment. Suitable coatings can be used, for instance, to render the mold material lubricious, biocompatible. Such coatings can be attached in any suitable manner, e.g., covalently attached or passively adsorbed, and in a manner that is either permanent in nature or slowly releasable or replaceable over time.
  • the tissue injury site is prepared for receipt of the biomaterial.
  • Those skilled in the art will appreciate the manner in which computer analysis of subchondral bone mass can allow the operator to customize the mechanical properties of the polymer-hydrogel composite to match the adjacent subchondral bone. This can be accomplished by adjusting the size of the hydrogel aggregates and by changing the percentage of the hydrogel in the polymer composite.
  • the patient is first prepped and draped as per routine arthroscopic procedure.
  • the first area to by resurfaced is then positioned horizontally and facing upright. If the opposing bone requires resurfacing the joint can be repositioned after the initial application has cured. This will allow gravity to assist in filling the anchor points and distributing the liquid composite evenly over the surface to be covered. Based on the present description, all the necessary maneuvers will typically be carried out using only two or three access portals.
  • the surface to be bonded is first cleaned of inflammatory synovia and frayed or damaged cartilage using a laser knife and/or other instruments, such as an arthroscopic shaver.
  • the surface is then be prepared in order to improve its ability to accept and retain biomaterial.
  • the subchondral bone is roughened by a burr and any osteophytes removed, also by the use of a burr.
  • the bone is then irrigated to remove debris and the site suctioned dry.
  • the bone can also be abraded in order to roughen its surface, or it can be coated with a suitable cement or other interface material.
  • anchoring points are created in the supporting joint tissue.
  • inverted pyramidal or inverted T-shaped (A) anchor points can be cut into the subchondral bone using specially designed arthroscopic drill bits or by laser means.
  • the prepared bone surface can be treated with high molecular weight hyaluronic acid.
  • This will improve adhesion of the polymer and act to inhibit inflammation and local osteoporosis.
  • High molecular weight hyaluronic acid has also been shown to be an effective stimulator of osteophytes (i.e., bone-forming cells) as well as an inhibitor of Interleukin-1 (Il-1). As an IL-1 inhibitor, the acid will tend to decrease the inflammatory response in the area around the new insert.
  • a desired quantity of the curable biomaterial is delivered by minimally invasive means to the prepared site.
  • Uncured biomaterial either in bulk or in the form of separate reactive components, can be stored in suitable storage containers, e.g., sterile, _iocom-lined metal canisters.
  • the biomaterial can be delivered, as with a pump, from a storage canister to the delivery cannula on demand.
  • Biomaterial can be delivered in the form of a single composition, e.g., including both polymer matrix and hydrogel, or can be delivered in the form of a plurality of components or ingredients.
  • polymer matrix and hydrogel can be separately stored and suitably mixed or combined either in the course of delivery or at the injury site itself.
  • An example of a delivery system that can serve as a model for the delivery of uncured biomaterials is one presently sold by Dyonics, Inc. as the “InteliJET Fluid Management System”. This system involves the a low pressure, high flow rate delivery of saline to a site, and combines delivery with suction that is automatically adjusted to specific blade styles.
  • a preferred delivery system of the present invention will typically include a motor drive unit, with a remote controller, associated tube sets, a nonscope inflow delivery cannula, having independent fluid dynamics pressure and flow rate adjustments, an energy source for curing, attachments for the flush, vacuum, waste canister, overflow jars.
  • the application cannula will then be inserted into the joint and under visualization from the fiberoptic scope the polymer composite will be applied to the subchondral bone.
  • the flow of the liquid phase polymer composite will be controlled by the operator via a foot pedal connected to the pumping mechanism on the polymer canister.
  • the liquid phase polymer composite will flow from the tip of the application catheter to fill the anchor points and subsequently cover the subchondral bone.
  • the delivered biomaterial is cured by minimally invasive means and in such a manner that the cured biomaterial is retained in apposition to the prepared site.
  • the biomaterial can be cured by any suitable means, either in a single step or in stages as it is delivered.
  • Preferred biomaterials are curable by the application of ultraviolet light, making them particularly amenable to a system that delivers such light by minimally invasive means.
  • polymerization can be initiated by any suitable means, e.g., by the use of an ultraviolet light source at the tip of the application cannula. After the composite has cured (polymerized) the surface can be contoured as needed by other arthroscopic instruments. The joint will then be irrigated and the instruments removed from the portals.
  • the steps of preparing the joint surface and contouring the cured biomaterial, as described herein, can be accomplished using conventional arthroscopic instruments and tools. Stryker, Inc., Zimmer, Inc. and Dyonics, Inc. for instance, produce a wide array of arthroscopic surgical blades and instruments. Representative products are described in Dyonics' U.S. Pat. Nos. 4,274,414, 4,203,444, 4,705,038, 4,842,578, 4,834,729, and 4,983,179, the disclosure of each of which is incorporated herein by reference.
  • the cured, retained biomaterial is contoured to achieve a desired conformation approximating that of natural tissue.
  • the preferred composite is heat moldable, allowing for sculpting with a probe that can be introduced through an arthroscopic portal.
  • a probe will typically have a retractable, flat spatula-shaped end.
  • the tip of the spatula can be heated to about 100 degrees centigrade, at which temperature the surface of the composite can be sculpted to the desired contour. As the composite cools, it will have sufficient memory to retain the shape it was given.
  • the implant can later be resculpted to cover the worn area without the need to repeat the entire process described above. Instead, the heat probe can simply be re-inserted under the arthroscopic visualization and the insert remolded to provide adequate size or properties in the needed area.
  • the steps described herein can be performed or combined in any suitable fashion. For instance, it is contemplated that the delivery, curing and contouring of biomaterial can be accomplished simultaneously and in a single step, for instance, by the use of a mold that retains a biomaterial in a desired shape as it is delivered and cured.
  • the final biomaterial can be subjected to further physical/chemical modifications, e.g., in order to enhance it performance, _iocompatibility, and the like.
  • calcitonin and inflammatory inhibiting molecules such as Interleuken I inhibitors can be attached to the bone composite surface to prevent local osteoporosis and local inflammatory response which cause loosening.
  • the surface of the cured composite can optionally be modified in order to reduce the coefficient of friction.
  • a computer program can be used that is based on existing and ideal articulation angles.
  • the program can assist the operator in producing a component having an optimal combination of physical characteristics, for instance contour and thickness, in order to provide optimal alignment of the involved joint.
  • a holographic image can be generated through the arthroscope to aid the operator in producing the optimal thickness and contour of the polymer composite.
  • Small joint applications e.g., for wrists and ankles, as well as for metacarpal phalangeal joints, proximal interphalangeal joints, metatarsal phalangeal joints, and first carpalmetacarpal joints can also be developed.

Abstract

A method, and related composition and apparatus for repairing a tissue site. The method involves the use of a curable polyurethane biomaterial composition having a plurality of parts adapted to be mixed at the time of use in order to provide a flowable composition and to initiate cure. The flowable composition can be delivered using minimally invasive means to a tissue site and there fully cured provide a permanent and biocompatible prosthesis for repair of the tissue site. Further provided are a mold apparatus, e.g., in the form of a balloon or tubular cavity, for receiving a biomaterial composition, and a method for delivering and filling the mold apparatus with a curable composition in situ to provide a prosthesis for tissue repair.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is filed as a continuation application of U.S. Ser. No. 09/193,973, filed Nov. 18, 1997, which is a divisional application of U.S. Ser. No. 08/993,468, filed Dec. 18, 1997, issued Oct. 23, 2001 as U.S. Pat. No. 6,306,177, which is a continuation application of International Patent Application Serial No. PCT/US97/20874, filed Nov. 14, 1997; and a continuation-in-part of U.S. patent application Serial No. 60/056,624, filed Aug. 20, 1997; and a continuation-in-part of U.S. patent application Ser. No. 08/749,429, filed Nov. 15, 1996, which is a continuation-in-part of application Ser. No. 08/742,444, filed on Nov. 1, 1996, issued Aug. 18, 1998 as U.S. Pat. No. 5,795,353, which is a File Wrapper Continuation of application Ser. No. 08/474,113 filed on Jun. 7, 1995, which is a divisional of prior application Ser. No. 08/239,248, filed on May 6, 1994, now U.S. Pat. No. 5,556,429, issued Sep. 17, 1996; and a continuation-in-part of U.S. patent application Ser. No. 08/903,455, filed Jul. 30, 1997, which is a continuation-in-part of application Ser. No. 08/590,293, filed Jan. 23, 1996, issued Mar. 30, 1999 as U.S. Pat. No. 5,888,220.[0001]
  • TECHNICAL FIELD
  • The present invention relates to methods, apparatuses, materials and systems for the repair of musculoskeletal injury, and in particular, for bone and cartilage repair and replacement. [0002]
  • In another aspect, the invention relates to polymeric compositions, and to minimally invasive methods and materials for the preparation of prosthetic implants and the replacement or repair of joints and joint surfaces within the body. In another aspect the invention relates to in situ curable compositions, such as polymer compositions, useful for such purposes. [0003]
  • In yet another aspect, the present invention relates to medical prostheses for use in in vivo applications, to methods of preparing and delivering such prostheses, and to materials useful for fabricating or preparing prostheses. In a further aspect, the invention relates to the preparation of prostheses in situ. [0004]
  • BACKGROUND OF THE INVENTION
  • The musculoskeletal system is subject to injury caused by traumatic events as well as by a number of diseases, such as osteoarthritis and rheumatoid arthritis. [0005]
  • Repair of connective tissue of the musculoskeletal system is commonly performed using materials such as natural or synthetic tendons and ligaments. Joint repair and replacement is typically accomplished using metal and/or polymeric implants and devices. Such devices are typically fixated into existing bone by means of bone plates, adhesives, screws, and the like. [0006]
  • The joints of the body can be classified as between those that provide immovable articulations (synarthroidal), mixed articulations (amphiarthroidal), and movable articulations (diarthroidal). The ability of amphiarthroidal and diarthroidal joints to provide effective and pain-free articulation, and/or to serve their weight-bearing function, is generally dependent on the presence of intact, healthy cartilage (e.g., fibrocartilage or hyaline cartilage) within the joint. [0007]
  • Total joint replacement is indicated under conditions in which the cartilage surface between the bones forming a joint has degenerated. Often it has degenerated to a point where there is significant pain during locomotion, as well as during translation and rotation of joint components. Such degenerative joint disease is commonly treated by a technique known as total joint replacement arthroplasty, which is typically an invasive procedure that involves replacement of the original surfaces with artificial weight bearing materials in the form of implants. [0008]
  • Hip replacement generally involves the implantation of a femoral component in the form of a ball mounted on a shaft, together with an acetabular component in the form of a socket into which the ball sits. [0009]
  • Total knee replacement is somewhat more difficult than hip replacement because of the complex loading pattern of the knee. The tibial component of a total knee replacement is fixed in the cancellous bone of the tibia. The femoral component is typically fixed to the cortical bone of the femoral shaft using a suitable cement. [0010]
  • The tibial portion of a knee prosthetic device generally involves the insertion of a broad plateau region covering the tibia, after bone of the subchondral plate is removed. In most designs, a composite material is provided, involving a metal support underlying a polymeric, or fiber-reinforced polymeric tray. [0011]
  • A wide array of materials have been described for use in the manufacture of medical implants. See generally, Chapter 1, in [0012] Biomaterials, Medical Devices and Tissue Engineering: An Integrated Approach, Frederick H. Silver, ed., Chapman and Hall, 1994. Such materials generally fall into the categories of metals, polymers, ceramics, and composite materials.
  • A recent article entitled “New Challenges in Biomaterials”, Science, 263:1715-1720 (1994), Peppas et al., provides a useful overview of the current state of the art in biomaterials. The article describes a number of materials currently used for orthopedic applications, including metals (iron, cobalt, and titanium), degradable polymers, self-reinforced compositions of polyglycolic acid, stronger polymers such as polydioxanone, and ceramic materials such as hydroxyapatite and certain glasses. [0013]
  • Elsewhere, for instance at page 1719, the Peppas et al. article refers to the potential usefulness of polymers that can be triggered to undergo a phase change. The article itself does not identify such polymers, but instead postulates that materials that are initially liquid might be administered through a minimally invasive surgical device and then triggered to solidify or gel in the presence of ultraviolet light, visible light, or ionic change in vivo. As an example of this approach the article cites an article of Hill-West, et al., Obstet. Gynecol. 83(1):59-64 (1994). [0014]
  • The Hill-West et al. article, in turn, describes the use of a conformable, resorbable hydrogel barrier for preventing postoperative adhesions in animals. The article describes the formation of the hydrogel barrier in situ by photopolymerizing a solution of a macromolecular prepolymer using UV light. The hydrogel barrier is not described as being useful in weight-bearing, orthopedic applications, and in fact, was completely resorbed within 7 days after application. [0015]
  • There are a number of drawbacks associated with the biomaterials and related methods presently employed for orthopedic applications, and in particular joint repair and replacement. One such drawback is that these methods generally involve invasive surgery, i.e., resecting tissue in order to gain access to the injury site. In turn, invasive surgery typically involves up to 7 to 10 days of hospitalization, with the costs associated therewith. [0016]
  • A related drawback of an arthrotomy involves the need to cut through skin, nerves, vessels, muscles, ligaments, tendons, and/or joint capsules. Certain procedures can also require the use of either general or spinal anesthesia. They may also require blood transfusions and significant recovery time accompanied by post-surgical pain and discomfort. Lastly, prolonged physical therapy is typically required to strengthen operative areas and prevent contractures. Such therapy can often last up to six weeks or more. [0017]
  • It would be particularly useful to be able to repair such injuries in a manner that avoided such invasive surgical procedures and the problems associated therewith. [0018]
  • A number of approaches, and in turn compositions, are currently employed for such purposes as preparing prosthetic implants and repairing damaged joints and joint cartilage. Such approaches include the widespread use of artificial prosthetic implants that can be formed of an array of materials such as metals, ceramics, and bioerodible or resorbable materials. Indeed, the manufacture and use of such implants has grown exponentially in recent decades. See, for instance, “New Challenges in Biomaterials”, Science, 263:1715-1720 (1994), Peppas et al. [0019]
  • Similarly, a number of references, and particularly those in the dental area, have described methods or apparatuses for the delivery and cure of materials within the oral cavity. Outside of the dental area, however, the number of such applications is far more limited, and includes such references as Perkins et al. (PAT 4,446,578) and Oechsle III (U.S. Pat. No. 4,570,270 polyurethanes as luting agents for filling cavities in bones). See also, Kuslich (U.S. Pat. No. 5,571,189 expandable fabric spine implant device in combination with a ‘graft medium’ to promote fibrous union of joints); Parsons et al. (U.S. Pat. No. 5,545,229 intervertebral disc spacer formed of an elastomeric [0020] 20 material in nucleus and annulus); Porter et al. (U.S. Pat. No. 5,591,199 curable fiber composite stent, fibrous material treated with curable material to form curable fiber composite); Glastra (U.S. Pat. No. 5,529,653 expandable double walled sleeve, space filled with curable material; and Cowan (U.S. Pat. No. 5,334,201 vascular reinforcing stent having tubular sleeve of a cross-linkable substance, the sleeve being encapsulated within a biocompatible film).
  • Even more recently, Applicant's U.S. Pat. No. 5,556,429 describes a joint resurfacing system which, in a preferred embodiment, involves the use of minimally invasive means to access and prepare a joint site, such as a knee, and to deliver a curable biomaterial to the prepared site and cure the biomaterial in apposition to the prepared site. The system includes the use of curable biomaterials such as silicone polymers and polyurethane polymers. [0021]
  • Polyurethanes themselves have been developed and used since at least the 1940's for the preparation of a variety of materials, including cast polyurethane rubbers and millable gums. Cast polyurethane rubbers can be subdivided into four general groups, including 1) unstable prepolymer systems, 2) stable prepolymer systems, 3) quasi-prepolymer systems, and 4) “oneshot” systems. See, for instance, “Polyurethanes and Polyisocanurates”, Chapter 27 in [0022] Plastics Materials, J. Brydson, ed., 6th ed.Butterworth Heeinemann (1995).
  • Generally, such compositions involve the reaction of a polyhydroxy material (polyol) with an isocyanate to provide a polyurethane material. A limited number of references describe the use of components such as hydroxyl-terminated butadiene in the context of a polyurethane. Khalil, et al. (U.S. Pat. No. 5,288,797), for instance, describe moisture curable polyurethane adhesive compositions in the form of a blend of polyurethane prepolymers, together with additives (such as carbon black) and a resin, which are used to improve mechanical properties such as sag resistance. The list of polyols described as being useful for forming the prepolymer is said to include polybutadiene having at least two terminal primary and/or secondary hydroxyl groups. [0023]
  • Similarly, Graham et al. (U.S. Pat. No. 4,098,626) describes a hydroxy terminated polybutadiene based polyurethane bound propellant grains, while Chapin et al. (U.S. Pat. No. 4,594,380) describe an elastomeric controlled release article having a matrix formed of a polyurethane that itself is the reaction product of an isocyanate and a polyol selected from a group that includes hydroxyl-terminated polybutadiene. [0024]
  • While materials such as those described above are useful for their intended purposes, and have created new opportunities in their respective fields, it would be desirable to further improve various properties associated with such materials. With regard to their use as in vivo curable biomaterials, for instance, certain polyurethane compositions have been found to produce undesirable bubbles when delivered and cured in the presence of moisture. Improvement of this and other properties would be highly desirable, provided such improvement can be accomplished without undue effect on other desired and necessary properties. It would be highly desirable to have a polyurethane composition that improves the moisture cure characteristics and other properties of such a material, without detrimental effect on other necessary and preferred properties. [0025]
  • The development of implantable medical devices has grown dramatically over past decades. Correspondingly, those developing new and useful biomaterials for use in fabricating such devices have attempted to keep pace. The implantable medical devices can themselves take a wide variety of forms and purposes. [0026]
  • Many prostheses are used to replace or repair orthopedic joints. The joints of the body can be classified as between those that provide immovable articulations (synarthroidal), mixed articulations (amphiarthroidal), and movable articulations (diarthroidal). The ability of amphiarthroidal and diarthroidal joints to provide effective and pain-free articulation, and/or to serve their weight-bearing function, is generally dependent on the presence of intact, healthy cartilage within the joint. [0027]
  • Conventional joint prostheses are generally fabricated by the manufacturer, often as component parts of varying sizes, and selected and implanted by the surgeon in the course of invasive surgery. The applicant of the present invention, however, has demonstrated the manner in which curable biomaterials can be used to repair or resurface a joint. See, for instance, U.S. Pat. No. 5,556,429. This patent describes, for instance, the use of minimally invasive means to deliver and cure a biomaterial at a prepared site such as the knee, as well as the optional use of holes drilled into the bone, e.g., subchondral bone, that can be filled with the biomaterial to provide anchor points once cured. [0028]
  • The delivery of such biomaterials can take the shape of the prepared site, or can further incorporate the use of a mold, e.g., in the manner described in Applicant's corresponding PCT Patent Application No. PCT/US97/00457. In one such embodiment, for instance, a mold is provided in the form of a balloon that can be delivered to the site of an intervertebral disc space, and there filled with biomaterial in order to serve as a replacement disc. [0029]
  • Other examples of implanted or implantable devices include Kuslich (U.S. Pat. No. 5,571,189); Kuslich (U.S. Pat. No. 5,549,679); Parsons et al. (U.S. Pat. No. 5,545,229); Oka (U.S. Pat. No. 5,458,643); Baumgartner (U.S. Pat. No. 5,171,280); Frey et al. (U.S. Pat. No. 4,932,969); Ray et al. (U.S. Pat. No. 4,904,260); Monson (U.S. Pat. No. 4,863,477); and Froning (U.S. Pat. No. 3,875,595). [0030]
  • Implantable medical prostheses can take other forms as well, including other traditional types that are fabricated and packaged prior to use, and implanted in either a transitory, temporary or permanent fashion within the body. Such prostheses can be used, for instance, as or in connection with passageways within the body such as catheters, such as stents and shunts. Other examples of devices implantable on at least a transitory basis include catheters such as balloon catheters. See, for example, the following U.S. patents to Walinsky (U.S. Pat. No. 5,470,314); Saab (U.S. Pat. No. 5,411,477); Shonk (U.S. Pat. No. 5,342,305); Trotta et al. (U.S. Pat. No. 5,290,306); Tower (U.S. Pat. No. 4,913,701); Oechsle III (U.S. Pat. No. 4,570,270); and Perkins et al. (U.S. Pat. No. 4,446,578). [0031]
  • The use of stents, in particular, has become accepted as a means for preventing abrupt vessel closure and restenosis following balloon angioplasty and over the past decade has grown dramatically as problems inherent in early designs have been overcome. Typically, stents are constructed from nonthrombogenic materials of sufficient flexibility (in their unexpanded state) to allow passage through guiding catheters and tortuous vessels. Such stents are typically radiopaque to allow fluoroscopic visualization. To date, most coronary stents have been constructed from either stainless steel or titanium, e.g., in the form of an expandable mesh, wire coil, slotted tube, or zigzag design. [0032]
  • Recent developments have included the use of balloon-expandable stents. Such stents are available in a number of configurations, such as the Gianturco-Roubin Flex-Stent (Cook, Inc.), the Palmax-Schatz Coronary Stent (Johnson & Johnson), Wiktor Stent (Medtronic, Inc.), Strecker Stent (Boston Scientific), ACS Multi Link Stent (Advanced Cardiovascular Systems, Inc.) the AVE Micro Stent (Applied Vascular Engineering) and Cordis Stent (Cordis Corp.). Even more recently, temporary stents (e.g., removable or biodegradable) have been developed, in an effort to achieve the structural support and lumen stabilizing benefits of permanent stenting without the problem of thrombosis. [0033]
  • Most stents, and certainly most, if not all, commercially available stents, are manufactured and sterilized by the manufacturer, and provided in an insertable form. Other approaches have been described, however, including modification of the stent material either pre- or post-delivery. See, e.g., Porter et al., U.S. Pat. No. 5,591,199 (for a “Curable Fiber Composite Stent and Delivery System”). In spite of recent accomplishments, many stents available today continue to encounter problems upon insertion (e.g., lack of flexibility) and/or over the course of their use (e.g., erosion, tissue incomparability). [0034]
  • In a similar manner, a variety of preformed catheters and shunts have been developed in the form of tubular instruments to allow passage of fluid from, into, or between body cavities. Relatively few of the many known catheters are formed or prepared in situ. Recent patents of Glastra (U.S. Pat. Nos. 5,344,444 and 5,529,653) describe, for instance, a method for the fabrication and use of an expandable hollow sleeve for local support or reinforcement of a body vessel. The hollow sleeve is described as having a curable material, such as an “acrylate”, contained within an absorbent material within the sleeve. In a different approach, Cowan (U.S. Pat. No. 5,334,201) describes a stent made of a crosslinkable material, by a method that involves encapsulating an uncured stent in a biologically compatible film, transluminally inserting the stent/film into position, and curing the stent. [0035]
  • Preformed catheters and grafts have also been used in the treatment of abdominal aortic aneurysms. The ultimate goal in the treatment of aortic aneurysms is to exclude the aneurysm from the aortic bloodstream without interfering with limb and organ perfusion. Direct surgical repair of such aneurysms is associated with high morbidity and mortality. The technique of placing a prosthetic graft into the opened aneurysm and suturing it to “normal” aorta above and below requires extensive intraabdominal or retroperitoneal dissection, as well as interruption of blood flow during completion of the anastomoses, under general anesthesia. [0036]
  • Methods and materials used to prepare implantable prostheses, as described above, can be contrasted to those used in the burgeoning dental field, in which polymers play an important role as ingredients of composite restorative materials, cements and adhesives, cavity liners and protective sealants. See, for instance, Brauer and Antonucci, “Dental Applications” pp 257-258 in [0037] Concise Encyclopedia of Polymer Science and Engineering.
  • At times, the preparation of such dental prostheses relies on the use of molds taken of parts of the body in order to then cast or otherwise form prosthetic replacement parts. See, for instance, Weissman, U.S. Pat. No. 4,368,040 for “Dental impression tray for forming a dental prosthesis in situ”. See also, “Process for making a prosthetic implant”, Kaye U.S. Pat. No. 5,156,777, which involves the use of three-dimensional data to prepare a life size model of an organ site, which in turn is used to cast a prosthetic implant. [0038]
  • Clearly the ability to mold body parts, such as teeth, in order to form prosthetic devices is considerably different than the preparation and delivery of preformed implants themselves, particularly for implants used in internal sites or tissues that are not as readily accessible as the oral cavity. Among the several distinctions between preformed implantable prostheses and those formed in situ are the fact that the latter are typically restricted to external or surgically accessible sites or tissues. In these situations, the ability to deliver a material used to form a prosthesis at an accessible site, although certainly demanding in many respects, has far fewer considerations than a material intended for delivery and use internally. [0039]
  • A number of problems that continue to affect the further development of some or all of the above-described implanted prostheses, include problems that affect the preparation of the prostheses themselves, their delivery to the site of use, and their interactions with the host or surrounding tissue in the course of their use. [0040]
  • For example, the physician cannot correct the size and shape of the prostheses once it has been introduced to the body; therefore, all measurements and adjustments of size must be made preoperatively. In the case of aortic grafts, the aorta may continue to enlarge and thus pull away from the fixation stent. Problems associated with the healing interface between the stent, the graft, and the aorta is not known, and the graft may dislodge and migrate, causing acute iliac occlusion. The aneurysm may continue to function despite an intact functioning endovascular graft. [0041]
  • It would clearly be desirable to have a system that permits prostheses to be prepared and used in a manner that overcomes some or all of these concerns. [0042]
  • SUMMARY OF THE INVENTION
  • The present invention overcomes the drawbacks associated with the prior art by providing a method, and related composition and apparatus for repairing or resurfacing the site of injured tissue by minimally-invasive means. [0043]
  • In one embodiment, the method of the present invention comprises the steps of: [0044]
  • (a) providing a curable biomaterial; and [0045]
  • (b) employing minimally invasive means to: [0046]
  • (i) prepare the tissue injury site for receipt of the biomaterial; [0047]
  • (ii) deliver a quantity of the curable biomaterial to the prepared tissue injury site; [0048]
  • (iii) cure the delivered biomaterial in such a manner that the cured biomaterial is permanently retained in apposition to the prepared site; and [0049]
  • (iv) contour the cured, retained biomaterial to achieve a desired conformation approximating that of natural tissue. [0050]
  • The method of the invention lends itself to a corresponding system that comprises curable biomaterial, in combination with minimally invasive means for preparing the tissue site; delivering the biomaterial to the prepared tissue site; curing the biomaterial in situ; and contouring the cured biomaterial. The individual components of such a system, and particularly means for delivering and curing biomaterial in a minimally invasive fashion are considered novel as well. [0051]
  • In a preferred embodiment, a system is provided that comprises: (a) an arthroscopic surgical instrument; and (b) a fluid delivery cannula capable of delivering a flowable, curable biomaterial under arthroscopic visualization, the biomaterial comprising a curable polymer and hydrogel. [0052]
  • The preferred system can be used to perform a method that comprises the steps of: [0053]
  • (a) providing a flowable, curable biomaterial comprising a curable biomaterial; [0054]
  • (b) preparing the tissue injury site by operation of the arthroscopic instrument, and under arthroscopic visualization; [0055]
  • © preparing a tissue access site to include anchor points in the subchondral bone and inserting and directing the delivery cannula through the tissue access site to the site of tissue injury; [0056]
  • (d) delivering a quantity of the curable biomaterial through the cannula to the prepared site; [0057]
  • (e) curing the delivered biomaterial by minimally invasive means and in a manner such that the cured biomaterial is retained in apposition to the prepared site; and [0058]
  • (f) contouring the cured biomaterial to achieve a desired conformation approximating that of natural tissue. [0059]
  • In an alternative embodiment, the cured, shaped biomaterial can be treated or modified in order to improve one or more desirable properties, for instance, it can be coated with a permanent interface material in order to improve the biocompatibility or coefficient of friction of the final implant. [0060]
  • In another aspect, the present invention provides a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, one or more catalysts, and optionally, other ingredients such as an antioxidant and dye. Upon mixing, the composition is sufficiently flowable to permit it to be delivered to the body by minimally invasive means, and there fully cured under physiologically acceptable conditions. Preferably, the component parts are themselves flowable, or can be rendered flowable, in order to facilitate their mixing and use. [0061]
  • Applicants have discovered, inter alia, that the presence of the reactive hydrophobic additive of the prepolymer provides several unexpected and desirable features, both in the formulation and use of the prepolymer itself, as well as in the mixed composition. These features include an improved combination of such properties as moisture cure characteristics, crosslinking, viscosity, compression fatigue, and stability. In particular, the use of the polymer significantly lessens, and can avoid altogether, the appearance of bubbles seen previously with polyurethane compositions cured in vivo in the presence of moisture. While not intending to be bound by theory, it appears that the presence of a sufficient amount of hydrophobic or nonpolar additive, and particularly one that is miscible with the polyether component, alters or affects the surface tension (e.g., as determined by the contact angle) of the resulting composition, and in turn, permits the composition to cure with a significant reduction in the appearance of bubbles. Surprisingly, this and other improved characteristics are not achieved at the sacrifice of other desirable properties. [0062]
  • In a preferred embodiment, within the prepolymer, the polyether component is present at a concentration of between about 2% and about 10%, and preferably between about 4% and about 8% by weight, based on the weight of the composition, and is selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polytetramethylene oxide (polyoxytetramethylene), and copolymers thereof. A particularly preferred polyol is polytetramethylene oxide, preferably of relatively low molecular weights in the range of 250 to 2900, and combinations thereof. [0063]
  • In a further preferred embodiment the isocyanate is present in excess in the prepolymer component, e.g., at a concentration of between about 30% and about 50%, and preferably between about 35% and about 45%, by weight. The isocyanate is preferably an aromatic (poly)isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate (MDI), and combinations thereof. [0064]
  • In such an embodiment, the reactive polymer additive itself is present at a concentration of between about 1% and about 50% by weight, and is selected from the group consisting of hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisoprene, polyisobutylene, silicones, polyethylenepropylenediene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures of the above. In a particularly preferred embodiment the additive comprises hydroxyl-terminated polybutadiene, present at a concentration of between about 5% and about 30%, by weight, and preferably between about 5% and about 20% by weight. [0065]
  • In a further preferred embodiment, the polyether polyol of the curative component is as described above with regard to the prepolymer and is present at a final concentration of between about 20% and 60%, and preferably between about 30% and about 45%, by weight. In such an embodiment, the chain extender comprises a combination of linear (e.g., cyclohexane dimethanol (“CHDM”)) and branched (e.g, trimethyloyl propane (“TMP”) chain extenders, with the former being present at a final concentration of between about 1% and 20% (and preferably between about 5% and about 15%), and the latter being present at a final concentration of between about 1 % and about 20%, and preferably between about 1% and about 10%, by weight of the final composition. [0066]
  • Surprisingly, the composition provides improved properties, including an improved combination of such properties as hardness, strength and/or cure characteristics (particularly in the presence of moisture), as compared to compositions previously known. More surprisingly, Applicants have discovered that such improvement can be achieved without detrimental effect on other desired properties, including those that arise (a) prior to delivery, (b) in the course of delivery (including whatever mixing, curing, and/or shaping that may occur), and finally, (c) following cure and in the course of extended use in the body. [0067]
  • In another aspect, the invention provides a cured composition, prepared as the reaction product of a plurality of parts as described herein. In yet another aspect, the invention provides a kit that can be used to prepare a composition and/or that itself includes a composition as a component part. A kit, for instance, may take the form of a composition (or its components) in combination with pre-formed device components or accessories, such as an implantable mold apparatus for shaping and restraining the composition. Optionally, a kit can also include a composition (or its components or parts) in combination with a delivery device adapted to deliver the composition to the site of tissue injury. Optionally, a kit may also take the form of a composition, either as its component parts and/or in combination with other ingredients or materials, such as a filler or hydrogel (used to form a matrix), or together with an implantable prosthetic device. In any such kit, it is envisioned that a kit may include one or more protocols or instructions for use. [0068]
  • In yet another aspect, the invention provides a method of preparing and a method of using such a composition. In a further aspect, the invention provides a cured composition (optionally within a mold apparatus), for use in apposition to a joint surface, as well as the combination of such a joint surface with a cured composition (optionally within a mold apparatus) in apposition thereto. [0069]
  • In yet another aspect, the present invention provides an apparatus and method for forming a prosthesis, in situ, the method, in a preferred embodiment, comprising the steps of: [0070]
  • a) providing an implantable mold apparatus comprising a cavity adapted to receive and contain a flowable biomaterial and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial, [0071]
  • b) inserting the mold, preferably by minimally invasive means, to a desired site within the body, [0072]
  • c) delivering biomaterial to the mold in order to fill the cavity to a desired extent, [0073]
  • d) permitting the biomaterial to cure to a desired extent, and [0074]
  • e) employing the molded biomaterial in situ as a prosthetic device. [0075]
  • The apparatus, in turn, provides an implantable mold apparatus comprising an expandable cavity adapted to receive and contain a flowable biomaterial in a geometry, configuration and/or position optimal for the intended purpose, and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial. The conduit is preferably removable from the filled cavity, e.g., by cutting it at or near the point where it joins the cavity. Optionally, and preferably, the apparatus further includes means for providing positive or negative air pressure within or to the biomaterial cavity, in order to facilitate the delivery of biomaterial and/or to affect the final shape of the cured mold. [0076]
  • The apparatus and method can be used for a variety of applications, including for instance, to provide a balloon-like mold for use preparing a solid or intact prosthesis, e.g., for use in articulating joint repair or replacement and intervertebral disc repair. Alternatively, the method can be used to provide a hollow mold, such as a sleeve-like tubular mold for use in preparing implanted passageways, e.g., in the form of catheters, such as stents, shunts, or grafts. [0077]
  • In yet another aspect, the invention provides a mold apparatus useful for performing a method of the invention, e.g., in the form of an inflatable balloon or tubular mold, preferably in combination with the conduit used to deliver biomaterial. Along these lines, the invention further provides a system useful at the time of surgery to prepare an implanted prosthesis in vivo, the system comprising a mold apparatus (e.g., cavity and conduit) in combination with a supply of curable biomaterial, and optionally, with a source of positive and/or negative air pressure. [0078]
  • In a further aspect, the invention provides a corresponding prosthesis formed by a method of the present invention, including for instance, an implanted knee prosthesis, intervertebral disc prosthesis, and a tubular prosthesis for use as a catheter, such as a stent, shunt, or graft (e.g., vascular graft). The present invention further provides surgical kits that include a mold apparatus as presently described, in combination with a corresponding drilling template, and a kit in which a mold apparatus is provided in combination with a supply (e.g., sufficient for a single use) of biomaterial itself.[0079]
  • BRIEF DESCRIPTION OF THE DRAWING
  • In the Drawing: [0080]
  • FIG. 1 shows a top plan view of a mold apparatus including a balloon cavity and biomaterial delivery conduit for use in intervertebral disc replacement. [0081]
  • FIG. 2 shows the apparatus of FIG. 1 with the balloon in its collapsed form contained within an outer sheath, suitable for insertion and positioning within the disc space. [0082]
  • FIG. 3 shows a mandrel used for forming the balloon of FIG. 1 by dip-coating the mandrel in a suitable solution of curable polymer. [0083]
  • FIG. 4 shows a balloon as formed upon the mandrel shown in FIG. 3 [0084]
  • FIG. 5 shows the balloon of FIG. 1 positioned within the disc space and in the course of filling with biomaterial. [0085]
  • FIG. 6 shows a preferred embodiment of a mold apparatus for use in the repair or replacement of knee cartilage. [0086]
  • FIG. 7 shows a drilling template for use in connection with the apparatus of FIG. 6. [0087]
  • FIG. 8 shows a preferred embodiment of a mold apparatus, in uninflated and unfilled form, in the form of a tubular system for preparing an implanted passageway in situ. [0088]
  • FIG. 9 shows the mold of FIG. 8 in a form wherein relevant portions have been filled with air and biomaterial. [0089]
  • FIG. 10 shows a cross section of the mold apparatus of FIG. 9, taken along lines [0090] 10-10.
  • DETAILED DESCRIPTION
  • The present invention provides a method and system for the repair of natural tissue that involve the delivery of a biomaterial composition using minimally invasive means, the composition being curable in situ in order to provide a permanent replacement for natural tissue. Optionally, and preferably, the biomaterial is delivered to a mold apparatus that is positioned by minimally invasive means and filled with biomaterial composition, which is then cured in order to retain the mold and cured composition in situ. [0091]
  • As used herein the following words and terms shall have the meanings ascribed below: [0092]
  • “repair” will refer to the use of a composition to augment, replace or provide some or all of the structure or function of natural tissue in vivo, for instance, to provide an implant such as a catheter, or to repair (e.g., reconstruct or replace) cartilage, such as fibrocartilage or hyaline cartilage present in a diarthroidal or amphiarthroidal joint. Repair can take any suitable form, e.g., from patching the tissue to replacing it in its entirety, preferably in a manner that reconstructs its natural or other desired dimensions; [0093]
  • “cure” and inflections thereof, will refer to any chemical, physical, and/or mechanical transformation that allows a composition to progress from a form (e.g., flowable form) that allows it to be delivered to the joint site, into a more permanent (e.g., cured) form for final use in vivo. When used with regard to the method of the invention, for instance, “curable” can refer to uncured composition, having the potential to be cured in vivo (as by catalysis or the application of a suitable energy source), as well as to a composition in the process of curing (e.g., a composition formed at the time of delivery by the concurrent mixing of a plurality of composition components). As further described herein, the cure of a composition can generally be considered to include three stages, including (a) the onset of gelation, (b) a period in which gelation occurs and the composition becomes sufficiently tack-free to permit shaping, and (c) complete cure to the point where the composition has been finally shaped for its intended use. [0094]
  • “minimally invasive means” refers to surgical means, such as microsurgical or endoscopic or arthroscopic surgical means, that can be accomplished with minimal disruption of the pertinent musculature, for instance, without the need for open access to the tissue injury site or through minimal incisions (e.g., incisions of less than about 4 cm and preferably less than about 2 cm). Such surgical means are typically accomplished by the use of visualization such as fiberoptic or microscopic visualization, and provide a post-operative recovery time that is substantially less than the recovery time that accompanies the corresponding open surgical approach; [0095]
  • “endoscopic/arthroscopic surgical instrument” refers to the controllers and associated hardware and software necessary for performing conventional endoscopic or arthroscopic surgery; and [0096]
  • “delivery cannula” shall mean a cannula or other delivery device capable of being operated in a minimally invasive fashion, e.g., under arthroscopic visualization, and optionally together with associated connective tubing and containers for the operable and fluid attachment of the cannula to a source of composition for the storage, delivery, and recovery of compositions of the present invention. [0097]
  • “mold” will refer to the portion or portions of an apparatus of the invention used to receive, constrain, shape and/or retain a flowable biomaterial in the course of delivering and curing the biomaterial in situ. A mold may include or rely upon natural tissues (such as the annular shell of an intervertebral disc) for at least a portion of its structure, conformation or function. The mold, in turn, is responsible, at least in part, for determining the position and final dimensions of the cured prosthetic implant. As such, its dimensions and other physical characteristics can be predetermined to provide an optimal combination of such properties as the ability to be delivered to a site using minimally invasive means, filled with biomaterial, and optionally, then remain in place as or at the interface between cured biomaterial and natural tissue. In a particularly preferred embodiment the mold material can itself become integral to the body of the cured biomaterial. [0098]
  • As described herein, a mold apparatus will generally include both a cavity for the receipt of biomaterial and a conduit for the delivery of biomaterial to that cavity. Some or all of the material used to form the cavity will generally be retained in situ, in combination with the cured biomaterial, while some or all of the conduit will generally be removed upon completion of the method. An implanted prosthesis, in turn, can be used to replace, provide, or supplement the structure or function of natural tissue in vivo. The prosthesis can take any suitable form, e.g., including patching, repairing or replacing tissue (such as knee or intervertebral disc), supporting existing tissue (as by a stent, for instance), or creating new material having a tissue like function (as by a shunt). [0099]
  • The word “biomaterial” will be used interchangeably with the word “composition”, when used in the context of the present invention, and will generally refer to a material that is capable of being introduced to the site of a joint and cured to provide desired physical-chemical properties in vivo. In a preferred embodiment the term will refer to a material that is capable of being introduced to an site within the body using minimally invasive means, and cured or otherwise modified in order to cause it to be retained in a desired position and configuration. Generally such biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 1 mm to about 6 mm inner diameter, and preferably of about 2 mm to about 3 mm inner diameter. Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration. [0100]
  • Method and System [0101]
  • In a preferred embodiment, the present invention provides a method and related materials and apparatus for repairing diarthroidal and amphiarthroidal joints by minimally invasive means. The method involves the use of minimally invasive means to prepare the site of injury, deliver a curable biomaterial to the joint site, and to cure the biomaterial in situ in order to repair hyaline cartilage and/or fibrocartilage. [0102]
  • According to a preferred embodiment, a liquid phase polymeric composite material (e.g., formed of a two-part polyurethane system) is applied through a cannula under arthroscopic visualization. The composite is cured and contoured in situ to effectively resurface a damaged joint. The cured polymer composite exhibits physical/chemical characteristics analogous to those of human cartilage, and demonstrates an optimal combination of such properties as load bearing, shear stress resistance, impact absorption, and wear characteristics. The surface of the cured composite can optionally be modified after curing and contouring, e.g., in order to reduce its coefficient of friction. [0103]
  • In a preferred embodiment, the method of the present invention comprises the step of providing a curable biomaterial comprising a curable polymer, optionally in combination with a hydrogel. Biomaterials suitable for use in the present invention include those materials that are capable of being delivered by means of a cannula, as described herein, and cured in situ in order to form a replacement material for bone or cartilage. [0104]
  • Natural cartilage is a non-vascular structure found in various parts of the body, and particularly articular cartilage, which exists as a glycosamine matrix with a fibrillar scaffold of Type II collagen. Chondrocytes are typically interspersed in the matrix. Its natural elasticity enables it to break the force of concussions, while its smoothness affords ease and freedom of movement. In terms of thickness, cartilage tends to take on the shape of the articular surface on which it lies. Where this is convex, the cartilage is thickest at the center, where the greatest pressure is received. The reverse is generally true in the case of concave articular surfaces. [0105]
  • Preferred biomaterials are intended to mimic many of the physical-chemical characteristics of natural cartilage. Preferred biomaterials are composites of two or more individual materials, and particularly those comprising two phase systems formed from a polymeric matrix and a hydrogel filler. Particularly preferred biomaterials are polyurethane systems of the type described herein. [0106]
  • The method of the invention can be used to repair a number of tissues, including a variety of joints, and is particularly useful for diarthroidal and amphiarthroidal joints. Examples of suitable amphiarthroidal joints include the synphysoidal joints, such as the joints between bodies of the vertebrae. Such joints provide surfaces connected by fibrocartilage, and have limited motion. Other examples include syndesmoidal joints, having surfaces united by an interosseous ligament, as in the inferior tibio-fibular joint. [0107]
  • Examples of suitable diarthroidal joints include the ginglymus (a hinge joint, as in the interphalangeal joints and the joint between the humerus and the ulna); throchoides (a pivot joint, as in superior radio-ulnar articulation and atlanto-axial joint); condyloid (ovoid head with elliptical cavity, as in the wrist joint); reciprocal reception (saddle joint formed of convex and concave surfaces, as in the carpo-metacarpal joint of the thumb); enarthrosis (ball and socket joint, as in the hip and shoulder joints) and arthrodia (gliding joint, as in the carpal and tarsal articulations). [0108]
  • In a particularly preferred embodiment, the method and system of the present invention are used to resurface a joint selected from the group consisting of enarthroidial (“ball and socket”) joints, and in particular the hip and shoulder joints, and ginglymo-arthroidal (“hinge”) joints, and in particular the temporo-mandibular joint. Such joints provide a particularly unique advantage in that one or more components of the natural joint can themselves be temporarily repositioned in order to contour the biomaterial as it cures. [0109]
  • A degenerative shoulder joint is repaired, for instance, by resurfacing either the humeral head, or preferably, the glenoid fossa. The glenoid fossa is arthroscopically exposed and the residual cartilage is removed by burrs and cutters. Optionally, and preferably, the humeral head is smoothed and all roughened cartilage surfaces removed. With the patient suitably positioned, a curable biomaterial is delivered allowed to flow smoothly into the glenoid fossa. With the polymer in a non-tacky, but moldable stage of cure the humeral head is repositioned into the glenoid for use in molding the polymer as it continues to cure. In an alternative to the use of minimally invasive means, the process can be performed using invasive surgical procedures, given the unique qualities of the biomaterial. [0110]
  • A degenerative hip joint is repaired in a similar manner, for instance, by resurfacing either the femoral head, or preferably, the acetabular cup. The cup is arthroscopically exposed and the residual cartilage is removed by burrs and cutters. Optionally, and preferably, the femoral head is smoothed and all roughened cartilage surfaces removed. With the patient suitably positioned, a curable biomaterial is delivered allowed to flow smoothly into the acetabular cup. With the polymer in a non-tacky, but moldable stage of cure the femoral head is repositioned into the acetabulum for use in molding the polymer as it continues to cure. In an alternative to the use of minimally invasive means, the process can be performed using invasive surgical procedures, given the unique qualities of the biomaterial. [0111]
  • A degenerative temporo-mandibular joint can be arthroscopically repaired using two small portals. Through one portal a needle arthroscope is placed for visualization of the temporomandibular joint. Through the second portal the surface of the maxillar portion is prepared and the mandible ramus surface is smoothed. Optionally, anchor points are cut in the maxilla. With the patient suitably positioned, a curable biomaterial is delivered and allowed to flow smoothly into the covered socket. With the polymer in a non-tacky, but moldable stage of cure the ramus of the mandible is repositioned and compressed into the socket for use in molding the polymer as it continues to cure. As an alternative to the use of minimally invasive means, each of these processes can be performed using invasive surgical procedures, given the unique qualities of the biomaterial. [0112]
  • Biomaterial Compositions [0113]
  • Applicants have discovered that one or all of the improved properties set forth above can be achieved without detrimental effect on other properties of the composition, either before, during or following delivery and cure. The term “detrimental effect”, as used herein, refers to an effect on one or more other properties that would render the composition unsuitable for its intended use. [0114]
  • The musculoskeletal system, and more often its articulating joints, are subject to injury caused by traumatic events or diseases such as osteoarthritis and rheumatoid arthritis. Inherent lubricity ofjoint's connective tissue, the cartilage, is affected. The non-functioning cartilage causes, in turn, abnormal wear and tear of both the connective tissue and bones. This process often results in progressive, crippling pain. With in vivo tissue repair via cell transplant and implantation in its infancy and total joint athroplasty not always a practical solution, the need for alternative treatment is quite obvious. [0115]
  • We have developed methodology which utilizes minimally invasive athroscopic surgery to remove damaged cartilage followed with application of liquid, in situ cured polymer to resurface the tibial plateau of the knee joint. Two component PTMO polyether-based polyurethane system has been chosen as the polymer of choice. The MDI quasi prepolymer approach was selected to liquefy the MDI isocyanate and controlled cross-linking in the hard segment was utilized to achieve needed biodurability. In order to manage “isothermal curing environment” of in vivo application, delayed action catalysis with Tin/amine synergism was used. The system was mixed and delivered to the athroscopically prepared site via delivery device with static mixer/cannula combination, then shaped and cured to its desired shape. [0116]
  • Physical-mechanical properties were determined according to ASTM Methods and in vitro biodurability via accelerated oxidative/hydrolytic degradation. In vivo function in the knee of ovine (sheep) model were determined at 3, 12, 26 and 52 weeks of implantation. [0117]
  • Physical-mechanical properties of the polyurethane system can be highlighted by Hardness of 70-75A Shore, Tensile Strength of 60-75 Mpa, Ultimate Elongation of 350-450% and Die “C” Tear of 28-44 kN/M. Compression Moduli were determined at 4.48 kN load and indicated deformation of 20-40%. Finally, compression fatigue, at 2.2 kN force indicated that 1.5×10[0118] 7 cycles, at 10 cycles/sec, did not alter compression moduli of the polymer.
  • The system does not generate cytotoxic by-products when cured in n-saline, at 23° C., between 10 seconds and 24 days testing period. Finally, necropsy at time of sacrifice of the animal models revealed essential integrity of the implant and no adverse tissue reaction was detected by histopathology. Encouragingly, signs of cartilage regeneration were detected at tissue/polyurethane interface. We can conclude that in situ cured polyurethanes, combined with minimally invasive athroscopic procedure represent novel, promising way to resurface damaged body joints. [0119]
  • Concepts governing in vivo resurfacing of damaged articular cartilage by in situ curable polymers are outlined above. Briefly reviewed, a pre-polymer is delivered to the “repair site” by athroscopic procedure, shaped and polymerized in situ to restore and augment cushioning and lubricating functions of the cartilage. Material selection, its mechanical properties, biodurability and in vivo performance are subject of this paper. [0120]
  • The polymer system one must have certain key characteristics: (1) it should be amenable to microphase separation and domain formation to mimic the cartilage; (2) the system must be liquid at delivery; (3) polymerization kinetics must be fast and fully controllable; (4) no toxic or otherwise harmful by-products can be released; (5) resultant polymer must have broad range of mechanical properties, excellent loan bearing, fatigue and wear resistance; (6) the system should be amenable to form microcellular structure; (7) lastly, the polymer must biodurable. Polyurethanes could be the chosen one. [0121]
  • Although aromatic polyurethanes based on polycarbonate polyols are considered most resistant to stress- and oxidation-driven Environmental Stress Cracking, we have selected PTMO-based polyols recognized for their superb hydrolytic resistance. A two component system with MDI-quasi-prepolymer component “A” and OH-terminated intermediates as component “B” was used. Blend of polyols was the choice to keep their melting temperature close to the ambient. The “delayed action” fast curing kinetics was achieved with Tin compound/tertiary amine based catalyst system. Gel times of 10-40 sec. With predominant cure of 2-5 min. are required to mix, deliver, cure and shape the polyurethane. Such short times are preferred to lower total curing exotherm but require chemical cross-linking to augment virtual ones formed by hard segment domains. This is accomplished, in such soft materials with target harness of 60-80 Shore A, by the blend of linear and polyfunctional chain extenders. This also generates unique tensile and compression behavior similar to those of x-linked rubber and highlighted by Tensile strength of 60-75 Mpa, elongation of more than 300% and Compression fatigue in excess of 20 million cycles at 2.2 kN force. Finally, two-plus years of in vivo biodurability is expected as determined by hydrogen peroxide/cobalt chloride testing. [0122]
  • To enhance cushioning function and to promote tissue integration, microcellular structure can be achieved by controlled nucleation of N[0123] 2 gas. We can conclude that polyurethanes are ideally suited for in vivo resurfacing of articular cartilage.
  • Natural cartilage is a non-vascular structure found in various parts of the body. Articular cartilage tends to exist as a fine granular matrix forming a thin incrustation on the surfaces of joints. The natural elasticity of articular cartilage enables it to break the force of concussions, while its smoothness affords ease and freedom of movement. In one embodiment a preferred composition is intended to mimic many of the physical, chemical and/or mechanical characteristics of natural cartilage. In an another preferred embodiment, a composition of this invention provides a useful implant in the form of a catheter, e.g., a stent, graft or shunt, by the use of a mold apparatus as described above. In such an embodiment the cured composition provides a number of characteristics, including _iocompatibility, strength, and the like. [0124]
  • Compositions can be provided as one component systems, or as two or more component systems that can be mixed (or partially mixed) prior to or during delivery, or at the site of repair. Generally such compositions are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter. Such compositions are also curable, to enable them to be polymerized or otherwise modified, in situ, during delivery and/or at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration. [0125]
  • When cured, suitable materials can be homogeneous, providing the same physico-chemical properties throughout, or they can be heterogeneous and exhibit varying features or properties. An example of a suitable homogeneous composition, as presently used for knee joint repair, is described below. An example of a heterogeneous composition, e.g., for use as an intervertebral disc replacement, is a composition that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and an more liquid interior core (akin to the nucleus). Such heterogeneous compositions can be prepared by the use of a single composition, e.g., by employing varying states of cure and/or by the use of a plurality of compositions, including varying compositions of the same ingredients used to form the composition. [0126]
  • Suitable compositions for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use. In the uncured state, such properties include processability, and the ability to be safely sterilized and stored. In the course of applying such compositions, suitable materials exhibit an optimal combination of such properties as flowability, moldability, and in vivo curability. In the cured state, suitable compositions exhibit an optimal combination of such properties as cured strength (e.g., tensile and compressive), softness/stiffness ratio, _iocompatibility and biostability. [0127]
  • When cured, the compositions demonstrate an optimal combination of properties, particularly in terms of their conformational stability and retention of physical shape, dissolution stability, _iocompatibility, and physical performance, as well as physical properties such as density and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, shear strength, shear fatigue, impact absorption, wear characteristics, and surface abrasion. Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of materials and polymers in general. In particular, a preferred composition, in its cured form, exhibits mechanical properties that approximate or exceed those of the natural tissue it is intended to provide or replace. [0128]
  • Preferred components of compositions, and compositions themselves, are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by chemical catalysis, by exposure to an energy source such as ultraviolet light, or by chemical reaction producing exotherm. Thereafter the cured composition is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of its use in the body the cured, contoured composition exhibits physiological, physical-chemical and mechanical properties suitable for use in extended in vivo applications. [0129]
  • Components [0130]
  • A “polymer system”, as used herein refers to the component or components used to prepare a polymeric composition of the present invention. In a preferred embodiment, a polymer system comprises the components necessary to form two parts: Part I being an isocyanate-functional polyurethane pre-polymer (optionally referred to as an “isocyanate quasi-polymer”). The quasi-polymer of Part I typically includes a polyol component in combination with a hydrophobic additive component and an excess of an isocyanate component. [0131] 5 Part II of the two component system can include one long-chain polyols, chain extenders and/or cross-linkers, together with other ingredients (e.g., catalysts, stabilizers, placticizers, antioxidants, dyes and the like). Such adjuvants or ingredients can be added to or combined with any other component thereof either prior to or at the time of mixing, delivery, and/or curing.
  • In a particularly preferred embodiment, a polymer system of this invention is provided as a plurality of component parts and employs one or more catalysts. The component parts, including catalyst, can be mixed to initiate cure, and then delivered, set and fully cured under conditions (e.g., time and exotherm) sufficient for its desired purpose. Upon the completion of cure, the resultant composition provides an optimal combination of properties for use in repairing or replacing injured or damaged tissue. In the course of curing, a suitable composition provides a bulk exotherm (within samples sizes suitable for in vivo use) of between about 100 degrees C. and about 140 degrees C., and preferably between about 110 degrees C. and about 130 degrees C., and a surface exotherm of between about 50 degrees C. and about 80 degrees C., and preferably between about 60 degrees C. and about 70 degrees C. [0132]
  • In order to obtain a cured composition having desired physical-chemical, mechanical and physiological properties, a significant factor in the choice of appropriate isocyanate, polyol and chain extender/cross linker are their chemical composition and molecular weight. A composition of this invention can be expressed in terms of both: (1) the free isocyanate number (“FNCO”) (also known as the isocyanate equivalent), which can be defined as the average molecular weight of the isocyanate divided by the number of isocyanate functional groups, and (2) the average hydroxyl number (also know as hydroxyl equivalent weight), which can be defined as the average molecular weight of the polyol(s) divided by the average number of reactive hydroxyl groups per mole of polyol(s). [0133]
  • The isocyanate component can be provided in any suitable form, examples of which include 2,4′-diphenylmethane diisocyanate, 4,4′-diphenylmethane diisocyanate, and mixtures or combinations of these isomers, optionally together with small quantities of 2,2′-diphenylmethane diisocyanate (typical of commercially available diphenylmethane diisocyanates). Other examples include aromatic polyisocyanates and their mixtures or combinations, such as are derived from phosgenation of the condensation product of aniline and formaldehyde. It is suitable to use an isocyanate that has low volatility, such as diphenylmethane diisocyanate, rather than more volatile materials such as toluene diisocyanate. An example of a particularly suitable isocyanate component is the 4,4′-diphenylmethane diisocyanate (“MDI”), preferably provided in liquid form as a combination of 2,2′-, 2,4′- and 4,4′-isomers of MDI. [0134]
  • For a suitable composition, the stoichiometery between Parts I (quasi prepolymer) and II (curative component), expressed in terms of the NCO:OH ratio of the isocyanate pre-polymer (Part I) and the polyol components (Part II) is preferably within the range of about 0.8 to 1 to about 1.2 to 1, and more preferably between about 0.9 to 1 to about 1.1 to 1. It has been found that NCO:OH ratios of less than about 0.8 to 1 tend to provide less than desired cure kinetics or physical-mechanical properties upon cure. Those ratios greater than about 1.1 to 1, in turn, tend to increase the potential for cytotoxicity or for adverse tissue reaction characterized by over crosslinking via internal allophanate or biuret links, generated by an excess of FNCO groups. [0135]
  • The polyol component can be provided in any suitable form as well. As used herein, the term “polyol” includes virtually any functional compound having active hydrogens in accordance with the well-known Zerevitinov test, as described for instance in Chemistry of Organic Compounds by Carl R. Noller, Chapter 6, pp. 121-122 (157), the disclosure of which is incorporated herein by reference. Thus, for example, amine terminated polyethers and polyolefins, thiols, polyimines, and polyamines can also be used as polyols in the present invention. In such instances, the NCO:active hydrogen ratio of the isocyanate to the active hydrogen compound will preferably fall within the same ranges as disclosed herein for the NCO:OH ratios. [0136]
  • Suitable polyols for use in preparing a composition of this invention include polyalkylene ethers derived from the condensation of alkylene oxides (e.g., ethylene oxide, propylene oxide, and blends thereof), as well as tetrahydrofuran based polytetramethylene ether glycols, polycaprolactone polyols, polycarbonate polyols and polyester polyols. Examples of suitable polyols include polytetrahydrofuran polyol (“PTHF”, also known as polytetramethylene oxide (“PTMO”) or polytetramethylene ether glycol (“PTMEG”). [0137]
  • Preferably, the polyol component can be provided in the form of a blend of two or more different molecular weights selected from the commercially available group consisting of 250, 650, 1000, 1400, 2000, and 2900. Materials having different molecular weights can be blended, e.g., using between 10:1 and 1:10 equivalent weights of a lower and higher molecular weight component (e.g., 250 and 1000 MW components), respectively, and preferably between about 2:1 and about 1:2 equivalent weights. The optimal combination of components, as well as the absolute and relative proportions thereof, are selected to provide a polymer system that, upon mixing an/or heating, is sufficiently “flowable” under ambient or other selected controlled conditions (e.g., temperature) to permit it to be sterilized, mixed, delivered, and cured, e.g., using minimally invasive means, to provide the properties desired for in vivo applications as described herein. [0138]
  • A preferred polymer system of this invention also includes the use of one or more chain extenders. Suitable chain extenders for use in the present invention provide an optimal combination of such properties as hard segment molecular weight and molecular weight distribution, phase separation and domain formation, virtual cross-linking by hard segment domains. In cases in which more than two functional extenders are used, their combination also provides an optimal or desire level of chemical crosslinking between both hard segment chains and hard and soft segment chains. [0139]
  • An example of a particularly preferred chain extender is a combination of a linear (e.g., two-functional) chain extender, such as 1,4-butanediol (“BDO”), together with a cross-linking (e.g., tri- or higher-functional) chain extender such as trimethylol propane (“TMP”). Such chain extenders can be prepared in any suitable combination to produce a unique degree of crosslinking, predominantly in the hard segment domains but also crossing the phase boundaries. [0140]
  • Additional cross-linking in the hard segment augments the virtual cross-links generated by the hard segment domains and provides higher cross-link density and efficiency, resulting in the reinforcement of non cross-linked segments. This can be particularly useful in relatively soft polyurethanes, such as those suitable for the repair of damaged cartilage. Reinforcement by virtual cross-links alone may not generate sufficient strength for in vivo performance in certain applications. Additional cross-linking from the soft segment, potentially generated by use of higher functional polyols can be used to provide stiffer and less elastomeric materials. In this manner a balancing of hard and soft segments, and their relative contributions to overall properties can be achieved. [0141]
  • Additionally, a polymer system of the present invention preferably contains one or more, and more preferably two or more, biocompatible catalysts that can assist in controlling the curing process, including the following periods: (1) the induction period, (2) the setting period, and finally, (3) the final cure of the biomaterial. Together these three periods, including their absolute and relative lengths, and the rate of acceleration or cure within each period, determine the cure kinetics or profile. [0142]
  • The word “induction”, and inflections thereof, when used in this respect refers to the time period between mixing or activation of one or more polymer components (under conditions suitable to begin the curing process), and the onset of gelation. In a method of the present invention, this period generally corresponds with the delivery of the biomaterial to the site of ultimate use. The induction period is characterized by infinitesimal or limited increase in viscosity of reacting mixture and relatively flat exotherm profile. Generally, a biomaterial of this invention is simultaneously mixed just prior to actual delivery into the joint site, providing the surgeon with sufficient time to add and position material (e.g., into anchor points) before gelation causes the material to become less easily workable. Thereafter, the surgeon can leave the material in place as it sets, e.g., for on the order of three to twenty minutes, before placing instruments back into the site to finish sculpting the implant, or performing other desired steps such as positioning the femoral condyles to shape the implant. [0143]
  • The term “set time” (or gel time), as used herein, is determined from the initial mixing of components, and refers to the time needed for a mixed and delivered system to set to the point where it can be shaped. This period is characterized by a rapid rise in the slope of the reaction exotherm at the end of the period. By the end of this period, the surface of the gelled biomaterial is preferably tack free and will allow shaping, e.g., by positioning of the condyles. The “cure time”, as used herein, is determined from the initial mixing, and refers to the total time needed to mix, shape and fully cure the biomaterial to the desired extent under the conditions used. Preferred polymer systems of this invention preferably provide an induction period that ends within about thirty seconds to two minutes following mixing of the components, followed by a set time of about 3 to about 15 minutes following mixing. [0144]
  • During the curing process (including both setting and completion of cure) the polymer system preferably exhibits an exotherm compatible for its intended use, e.g., preferably an exotherm of less than about 70 to about 90 C, and more preferably less than about 80 C. Given the present description, those skilled in the art will appreciate the manner in which the polymer system can be adjusted in a variety of ways to obtain suitable exotherm, during setting and cure, e.g., by the use of temperature dependent synergistic catalysis. Catalysts suitable for use in compositions of the present invention provide an optimal combination of such properties as set time, cure time, and in turn, viscosity (and flowability) of the curing polymer system. [0145]
  • In a particularly preferred embodiment, the selection of catalyst and other ingredients provides a cure profile that exhibits both synergistic and “delayed action” kinetics, in which induction of cure begins immediately upon mixing the polymer components, and is relatively “flat” during the induction period, without significant increase of viscosity of reaction mixture. This period permits delivery of the “flowable” polymer to the tissue injury site, and is followed by a setting period characterized by variable increase in slope (in a plot of temperature vs. time) that is designed to quickly drive the curing process to completion, and in turn, to quickly provide a set polymer that is sufficiently strong and tack-free to permit final shaping. [0146]
  • Examples of suitable catalyts include tin compounds (such as tin esters, tin alkylesters, and tin mercaptides), amines, such as tertiary amines and the like. An example of a suitable catalyst system is a combination of a tin catalyst (e.g., “Cotin 222”, available under the trademark “Cotin 222” from Cascam, Company, Bayonne N.J.) and a tertiary amine (e.g., DABCO(TEDA), a triethylene diamine catalyst available from Air Products, Allentown, Pa. These components can be used in any suitable ratio, e.g., between about 1:1 parts and about 1:5 parts of the tin catalyst and the diamine, respectively. [0147]
  • Other ingredients can be used as well, including different amine-based catalysts available to those in the art. Examples of optional ingredients include antioxidants, such as vitamin E, which can be used as a biocompatible antioxidant and mediator of macrophage attack designed to destroy the implant in vivo. [0148]
  • Other suitable ingredients include dyes, such as “Green GLS Dye” (available from Clarian Corp., Charlotte, N.C.) that can be added (e.g., at a concentration of about 0.01% to about 0.05%, by weight) to facilitate the ability to visualize the polymer in the course of delivery to the “repair” site. Preferred dyes are stable to change in the course of sterilization, e.g., by irradiation such as gamma or Electron-beam. [0149]
  • Optionally, inorganic fillers, such as calcium carbonate, titanium dioxide or barium sulfate can be added as well, in about 0.5 to about 20 percent (by weight) to affect the viscosity and thixotropic properties of the resultant mixture, to modify or increase the load bearing ability of the polymer and/or to render the implanted biomaterial radiopaque. [0150]
  • Preparation and Delivery [0151]
  • The composition of the present invention can be delivered and cured within the body, preferably by minimally invasive means. In one preferred embodiment, the composition is used to resurface or repair a joint, such as a knee or intervertebral disc. In another preferred embodiment, the composition is used to form an implant in situ, e.g., in the form of a catheter such as a stent, graft, or shunt. [0152]
  • Ingredients such as those provided herein can be combined in any suitable manner to provide a composition capable of being delivered to the injury site, preferably via minimally invasive means. In a preferred embodiment, the composition is provided as a system having a plurality of parts, e.g., a two-part system, wherein the two parts are capable of being separately prepared, sterilized, and packaged, such that the parts can be mixed in the operating room and at the time of use in order to initiate the curing process. [0153]
  • Compositions provided as a plurality of components, e.g., a two-part polyurethane system, can be mixed at the time of use using suitable mixing techniques, such as those commonly used for the delivery of two-part adhesive formulations. A suitable mixing device involves, for instance, a static mixer having a hollow tube having a segmented, helical vein running through its lumen. A two-part polyurethane system can be mixed by forcing the respective components through the lumen, under pressure. In addition, any mechanically driven mixing device or impingement mixing device are suitable to accomplish the mixing of a plurality of components. [0154]
  • In a further embodiment, the static mixer can be used in a system having an application cannula, an application tip, and a cartridge having two or more chambers, each containing a separate component of the composition system. A hand-powered, pneumatically, or electrically controlled extrusion gun can be used to extrude or eject the components through, for example, the static mixer, in order to completely mix them and thereby begin the process of curing. The composition system then flows through the cannula and to the joint site or surface through the application tip. The length, diameter, and vein design of the mixing element can be varied as necessary to achieve the desired mixing efficiency. [0155]
  • The composition of the present invention can be delivered to a site within the body, and there cured, preferably using minimally invasive means, in order to repair (e.g., reconstruct or resurface) tissue such as cartilage, and particularly cartilage associated with diarthroidal and amphiarthroidal joints. Optionally, the composition can be delivered and cured within an implanted mold device. Using minimally invasive means a composition can be delivered to a site within the body, e.g., to a mold or a site of damaged or diseased cartilage, to be cured in situ in order to provide an implant or repair the cartilage without undue surgical trauma. [0156]
  • In other aspects, the invention provides compositions, including polymer systems, useful for performing such a method, as well as methods of preparing and using such compositions. In yet further aspects, the invention provides a joint, e.g., a diarthroidal or amphiarthroidal joint, having interposed therein a composition that has been delivered and cured in situ. [0157]
  • Properties [0158]
  • Compositions of the present invention provide improvement in one or more of the following properties as compared to those previously known, without detrimental effect on other desirable properties described herein. [0159]
  • In a particularly preferred embodiment, Applicants have discovered a composition that provides significantly improved hardness and strength during stage © identified above, while also providing improved cure kinetics during stage (b), all without undue effect on other desirable properties. In its fully cured state, for instance, a suitable composition of the present invention provides a hardness of about 60 Shore to about 95 Shore, as determined by ASTM Test Method D2240 set forth herein. Optionally, and preferably in addition to such improved hardness, the fully cured composition provides improved tensile strength as well, as determined by ASTM Test Method D412 herein. For instance, a preferred composition of this invention provides a tensile strength (measured in the dry state) of about 6,000 psi to about 10,000 psi. The composition provides a “wet” tensile strength (e.g., as determined after soaking the sample in saline for one week) of about 3,000 psi to about 5,000 psi. As a further optional feature, a preferred composition of this invention provides a biphasic cure pattern, as depicted and described with respect to FIG. 1 herein. [0160]
  • Optionally, or preferably in addition to improved hardness, a preferred fully cured composition of this invention provides a tensile strength of about 6,000 psi to about 10,000 psi, as determined by ASTM Test Method D412 herein. [0161]
  • Accordingly, in a preferred embodiment, the present invention provides a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts. [0162]
  • More preferred is a composition as described above wherein the reactive hydrophobic additive comprises an hydroxyl- or amine-terminated polymer or copolymer selected from the group consisting of poybutadiene, polyisobutylene, silicone, polyisoprene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof, and particularly preferred is a composition wherein the additive comprises hydroxyl-terminated polybutadiene. Within such a composition, the hydroxyl-terminated polybutadiene can be present at a concentration of between about 5% and about 20%, by weight, based on the weight of the composition, and more preferably between about 8% and about 15% by weight. [0163]
  • Also preferred is a composition as described herein wherein the polyether component is l selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polyoxytetramethylene, and copolymers thereof, e.g., wherein the polyether component is present in the prepolymer component at a concentration of between about 2% and about 10% by weight, and is present in the curative component at a final concentration of between about 25% and 45%, based on the weight of the composition. An example of such a composition is one in which the polyether component comprises polytetramethylene oxide having a molecular weight in the range of 250 to 1000. [0164]
  • Further preferred is a composition which the isocyanate component comprises an aromatic isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate, and combinations thereof, preferably where the isocyanate is present in excess in the prepolymer component, at a concentration of between about 30% and about 50% by weight, based on the weight of the composition. [0165]
  • In another aspect, the invention provides a curable polyurethane composition comprising a plurality of parts capable of being sterilized, stably stored, and mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including: [0166]
  • (1) a quasi-prepolymer component comprising the reaction product of [0167]
  • (a) one or more polyether polyols selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polyoxytetramethylene, and copolymers thereof, [0168]
  • (b) one or more isocyanates selected from the group consisting of 2,2′-, [0169] 2,4-, and 4,4′-diphenylmethanediisocyanate (MDI), and combinations thereof, and
  • © one or more reactive hydrophobic additives comprising hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisobutylene, silicones, polyisoprene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof, and [0170]
  • (2) a curative component comprising [0171]
  • (a) one or more polyether polyols as defined in part (1)(a), [0172]
  • (b) a combination of linear and branched chain extenders, and [0173]
  • © one or more catalysts. [0174]
  • Preferably the catalysts, in combination with the remaining components, are sufficient to permit the composition to cure upon mixing at physiological temperature with a cure profile that comprises sequentially an onset period, a gelation period, and a complete cure period. [0175]
  • In yet another aspect, the invention provides a cured polyurethane implant suitable for extended use in vivo, the implant being formed as the reaction product of a composition that comprises: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts. Such an implant exhibits improved Shore Hardness and tensile strength, as compared to an implant prepared from a comparable composition lacking hydrophobic additives, e.g., a Shore hardness of between about 60 and about 95 Shore, as determined by ASTM Test Method D2240, and a dry tensile strength of between about 6000 psi and about 10,000 psi, as determined by ASTM Test Method D412. The invention also provides such an implant according positioned in permanent or temporary contact with a joint surface in vivo, and preferably positioned in permanent contact with the surface of subchrondral bone in the knee joint. [0176]
  • The invention also provides a kit comprising a plurality of sterile, flowable parts capable of being mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts including: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts. Preferably, the kit further comprises a delivery device for use in mixing the quasi-prepolymer component and curative component, and delivering the mixture to a tissue site using minimally invasive means. [0177]
  • Common polymeric materials for use in medical devices include, for example, polyvinyl chlorides, polyethylenes, stryrenic resins, polypropylene, thermoplastic polyesters, thermoplastic elastomers, polycarbonates, acrylonitrile-butadiene-styrene (“ABS”) resins, acrylics, polyurethanes, nylons, styrene acrylonitriles, and cellulosics. See, for example, “Guide to Medical Plastics”, pages 41-78 in [0178] Medical Device & Diagnostic Industry, April, 1994, the disclosure of which is incorporated herein by reference.
  • Suitable matrix materials (i.e., biomaterials) for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use. In the uncured state, such properties include processability and the ability to be stably sterilized and stored. In the course of applying such material, such properties include hydrogel compatibility and capacity, flowability, and in vivo curability. In the cured state, such properties include moldability, cured strength (e.g., tensile and compressive), elongation to break, and _iocompatibility. Examples of suitable matrix materials include, but are not limited to, silicone polymers and polyurethane polymers. [0179]
  • In a preferred embodiment, the biomaterial matrix is formed of a silicone polymer, i.e., polymer containing a repeating silicon-oxygen backbone together with organic R groups attached to a significant portion of the silicon atoms by silicon-carbon bonds. See generally, “Silicones”, pages 1048-1059 in [0180] Concise Encyclopedia of Polymer Science and Engineering, Eds. Mark et al., Wiley and Sons, 1990, the disclosure of which is incorporated herein by reference.
  • Silicone polymers are commercially available in at least three general classes, namely as homopolymers, silicone random polymers, and silicone-organic (block) copolymers. Homopolymers in the form of polydimethyl siloxanes are preferred, and constitute the largest volume of homopolymers produced today. [0181]
  • In an alternative preferred embodiment, the biomaterial matrix is formed of a polyurethane polymer. Polyurethanes, e.g, thermoplastic polyurethanes (“TPU”), are typically prepared using three reactants: an isocyanate, a long-chain macrodiol, and a short-chain diol extender. The isocyanate and long-chain diol form a “soft” segment, while the isocyanate and short-chain diol form a “hard” segment. It is the interaction of soft and hard segments that determines and provide the polymer with rubber-like properties. [0182]
  • During melt processing, the polyurethane chains are linear and assume the configuration into which they are formed, such as by injection molding, or in the case of the present invention, by arthroscopic application. On cooling, the hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber. [0183]
  • Those skilled in the art, in view of the present invention, will appreciate the manner in which the choice of isocyanate, macrodiol, and chain extender can be varied to achieve a wide diversity of properties. Preferred TPU's for medical use are presently based on the use of a diisocyanate such as diphenylmethane diisocyanate (“MDI”), a glycol such as polytetramethylene ether glycol, and a diol such as 1,4-butanediol. [0184]
  • Natural cartilage is a non-vascular structure found in various parts of the body. The natural elasticity of articular cartilage enables it to break the force of concussions, while its smoothness affords ease and freedom of movement. In terms of thickness, cartilage tends to take on the shape of the articular surface on which it lies. [0185]
  • Preferred biomaterials, therefore, are intended to mimic many of the physical-chemical characteristics of natural cartilage. Biomaterials can be provided as one component systems, or as two or more component systems that can be mixed prior to or during delivery, or at the site of repair. Generally such biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 1 mm to about 6 mm inner diameter, and preferably of about 2 mm to about 3 mm inner diameter. Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration. [0186]
  • When cured, preferred materials can be homogeneous (i.e., providing the same chemical-physical parameters throughout), or they can be heterogeneous. An example of a heterogeneous biomaterial for use as a disc replacement is a biomaterial that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and a more liquid (e.g, cushioning or softer) interior core (akin to the nucleus). In an alternative embodiment, biomaterials can be used that provide implants having varying regions of varying or different physical-chemical properties. With disc replacement, for instance, biomaterials can be used to provide a more rigid, annulus-like outer region, and a more fluid, nucleus-like core. Such di-or higher phasic cured materials can be prepared by the use of a single biomaterial, e.g., one that undergoes varying states of cure, or a plurality of biomaterials. [0187]
  • Common polymeric materials for use in medical devices include, for example, polyvinyl chlorides, polyethylenes, styrenic resins, polypropylene, thermoplastic polyesters, thermoplastic elastomers, polycarbonates, acrylonitrile-butadiene-styrene (“ABS”) resins, acrylics, polyurethanes, nylons, styrene acrylonitriles, and cellulosics. See, for example, “Guide to Medical Plastics”, pages 41-78 in [0188] Medical Device & Diagnostic Industry, April, 1994, the disclosure of which is incorporated herein by reference.
  • Suitable biomaterials for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use. In the uncured state, such properties include processability, and the ability to be stably sterilized and stored. In the course of applying such material, such properties as flowability, moldability, and in vivo curability. In the cured state, such properties include cured strength (e.g., tensile and compressive), stiffness, _iocompatibility and biostability. Examples of suitable biomaterials include, but are not limited to, polyurethane polymers. [0189]
  • In a preferred embodiment, the biomaterial comprises a polyurethane polymer. Polyurethanes, e.g, thermoplastic polyurethanes (“TPU”), are typically prepared using three reactants: an isocyanate, a long-chain macrodiol, and a short-chain diol extender. The isocyanate and long-chain diol form a “soft” segment, while the isocyanate and short-chain diol form a “hard” segment. The hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber. It is the interaction of soft and hard segments that determines and provides the polymer with rubber-like properties. [0190]
  • Those skilled in the art, in view of the present invention, will appreciate the manner in which the choice of isocyanate, macrodiol, and chain extender can be varied to achieve a wide array of properties. Preferred TPU's for medical use are presently based on the use of a diisocyanate such as diphenylmethane diisocyanate (“MDI”), a glycol such as polytetramethylene ether glycol, and a diol such as 1,4-butanediol. [0191]
  • Biomaterials of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose. [0192]
  • When cured, the biomaterials demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, dissolution stability, _iocompatibility, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, shear strength, fatigue, impact absorption, wear characteristics, and surface abrasion. Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of biomaterials. [0193]
  • In particular, preferred biomaterials, in the cured form, exhibit mechanical properties that approximate those of the natural tissue that they are intended to replace. For instance, for load bearing applications, preferred cured composites exhibit a load bearing strength of between about 50 and about 500 psi (pounds per square inch), preferably between about 100 and about 300 psi, and more preferably between about 100 and 200 psi. Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints. Such composites also exhibit a tensile strength of between about 3500 and about 6000 psi, and preferably between about 4000 and about 5000 psi, using test methods generally available to those skilled in the art, for instance using an “Instron” tensile tester. [0194]
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications. [0195]
  • In a preferred embodiment, the biomaterial is a polyurethane provided as a two-part prepolymer system comprising a diisocyanate, a polyalkylene oxide and low molecular diols as chain extenders. The final polymer having a hard segment content of about 25 to about 50% by weight, and preferably of about 30 to about 40% by weight, based on the weight of the diisocyanate and chain extender. Optionally, and preferably, one or more catalysts are incorporated into one or more components of the biomaterial, in order to cure the biomaterial in the physiological environment within a desired length of time. Preferably, biomaterials of the present invention are able to cure (i.e., to the point where distraction means can be removed and/or other biomaterial added), within on the order of 5 minutes or less, and more preferably within on the order of 3 minutes or less. [0196]
  • Preferably, means are employed to improve the biostability, i.e., the oxidative and/or hydrolytic stability, of the biomaterial in vivo, thereby extending the life of the implant. See, for instance, A. Takahara, et al., “Effect of Soft Segment Chemistry on the Biostability of Segmented Polyurethanes. I. In vitro Oxidation”, [0197] J. Biomedical Materials Research, 25:341-356 (1991) and A. Takahara, et al., “Effect of Soft Segment Chemistry on the Biostability of Segmented Polyurethanes. II. In vitro Hydrolytic Degradation and Lipid Sorption”, J. Biomedical Materials Research, 26:801-818 (1992), the disclosures of both of which are incorporated herein by reference.
  • Suitable means for improving biostability include the use of an aliphatic macrodiol such as hydrogenated polybutadiene (HPDI). By judicious choice of the corresponding diisocyanate (e.g., MDI) and chain extender (e.g., ethylenediamine), those skilled in the art will be able to achieve the desired packing density, or crystallinity, of the hard segments, thereby improving the hydrolytic stability of the cured polyurethane. [0198]
  • Biomaterials provided as a plurality of components, e.g., a two-part polyurethane system, can be mixed at the time of use using suitable mixing techniques, such as those commonly used for the delivery of two-part adhesive formulations. A suitable mixing device involves, for instance, a static mixer having a hollow tube having a segmented, helical vein running through its lumen. A two-part polyurethane system can be mixed by forcing the respective components through the lumen, under pressure. [0199]
  • In a further embodiment, the static mixer can be used in a system having an application cannula, an application tip, and a cartridge having two or more chambers, each containing a separate component of the biomaterial system. A hand-powered or electrically controlled extrusion gun can be used to extrude the components through the static mixer, in order to completely mix them and thereby begin the process of curing. The biomaterial system then flows through the cannula and to the joint site or surface through the application tip. The length, diameter, and vein design of the mixing element can be varied as necessary to achieve the desired mixing efficiency. [0200]
  • Hydrogels suitable for use in composites of the present invention are water-containing gels, i.e., polymers characterized by hydrophilicity and insolubility in water. See, for instance, “Hydrogels”, pages 458-459 in [0201] Concise Encyclopedia of Polymer Science and Engineering, Eds. Mark et al., Wiley and Sons, 1990, the disclosure of which is incorporated herein by reference. Although their use is optional in the present invention, the inclusion of hydrogels is highly preferred since they tend to contribute a number of desirable qualities. By virtue of their hydrophilic, water-containing nature, hydrogels assist the cured composite with load bearing capabilities of the cured composite. They also tend to decrease frictional forces on the composite and add thermal elasticity.
  • In a preferred embodiment, the hydrogel is a fine, powdery synthetic hydrogel. Suitable hydrogels exhibit an optimal combination of such properties as compatibility with the matrix polymer of choice, and _iocompatibility. [0202]
  • Suitable hydrogels swell to an equilibrium volume in water, but preserve their shape. Synthetic hydrogels suitable for use in forming a composite of the present invention include those based on methacrylic and acrylic esters, (meth)acrylamide hydrogels, and those based on N-vinyl-2-pyrrolidinone. [0203]
  • Preferred hydrogels include those formed from monomeric hydroxyalkyl acrylates and methacrylates, copolymerized with a suitable cross-linking agent, such as ethylene dimethacrylate (“EDMA”). [0204]
  • In a particularly preferred embodiment the matrix polymer is a siloxane (i.e., silicone polymer), and preferably one selected from the group consisting of alpha, omega-dihydroxypoly(dimethylsiloxane) and poly(dimethylsiloxane) with 0.2 mol % of vinylmethyl-siloxane units. Dispersed as the hydrogel component in the preferred polymer is 15% to 30% (by weight based on the weight of the uncured composite) of a lightly cross-linked hydrogel aggregate. A preferred hydrogel aggregate is formed by 2-hydroxyethyl methacrylate (HEMA) cross-linked by ethylene dimethacrylate (EDMA) at a concentration of 2%-5% by weight, based on the weight of the hydrogel. [0205]
  • Those skilled in the art will appreciate the manner in which hydrogel/matrix combinations and concentrations can be altered based on their intended application. For instance, a stiffer composite with a low hydrogel concentration, e.g., 10% based on the final weight of the composite, would be suitable for intervertebral disc replacement. [0206]
  • Depending, for instance, on their intended application, biomaterials will preferably contain a hydrogel phase at a concentration of between about 15 and 50 weight percent, and preferably between about 10 and about 50 weight percent, and preferably between about 15 and about 30 weight percent, based on the weight of the combination of matrix and hydrogel. [0207]
  • Composites of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose. [0208]
  • Cured polymer-hydrogel composites demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, dissolution stability, _iocompatibility, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, static shear strength, fatigue of the anchor points, impact absorption, wear characteristics, and surface abrasion. Such performance can be evaluated using procedures commonly accepted for the evaluation of natural tissue and joints, as well as the evaluation of biomaterials. [0209]
  • In particular, preferred composite materials, in the cured form, exhibit mechanical properties approximating those of the natural tissue that they are intended to replace. For instance, preferred cured composites exhibit a load bearing strength of between about 50 and about 200 psi (pounds per square inch), and preferably between about 100 and about 150 psi. Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints. [0210]
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery cannula to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications. [0211]
  • Suitable biomaterials for use in a method of this invention include, but are not limited to, those described in Applicant's co-pending PCT Application Nos. PCT/US97/00457. Biomaterials can be provided as one component systems, or as two or more component systems that can be mixed prior to or during delivery, or at the site of repair. Generally such biomaterials are flowable in their uncured form, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter. Such biomaterials are also curable, meaning that they can be cured or otherwise modified, in situ, at the tissue site, in order to undergo a phase or chemical change sufficient to retain a desired position and configuration. [0212]
  • Preferred biomaterials, therefore, are intended to mimic many of the physical-chemical characteristics of natural tissue. When cured, preferred materials can be homogeneous (i.e., providing the same chemical-physical parameters throughout), or they can be heterogeneous. An example of a heterogeneous biomaterial for use as a disc replacement is a biomaterial that mimics the natural disc by providing a more rigid outer envelope (akin to the annulus) and a more liquid (e.g., cushioning or softer) interior core (akin to the nucleus). [0213]
  • Suitable biomaterials for use in the present invention are those polymeric materials that provide an optimal combination of properties relating to their manufacture, application, and in vivo use. In the uncured state, such properties include processability, and the ability to be stably sterilized and stored. In the course of applying such material, such properties as flowability, moldability, and in vivo curability. In the cured state, such properties include cured strength (e.g., tensile and compressive), stiffness, _iocompatibility and biostability. Examples of suitable biomaterials include, but are not limited to, polyurethane polymers. [0214]
  • Biomaterials of the present invention can also include other optional adjuvants and additives, such as stabilizers, fillers, antioxidants, catalysts, plasticizers, pigments, and lubricants, to the extent such optional ingredients do not diminish the utility of the composition for its intended purpose. [0215]
  • In particular, preferred biomaterials, in the cured form, exhibit mechanical properties that approximate those of the natural tissue that they are intended to replace. For instance, for load bearing applications, preferred cured composites exhibit a load bearing strength of between about 50 and about 500 psi (pounds per square inch), and preferably between about 100 and about 200 psi. Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints. Such composites further exhibit a tensile strength of between about 4,000 psi and about 10,000 psi, and preferably between about 6,000 psi and about 8,000 psi. Cured biomaterials for use in non-orthopedic applications, e.g., as catheters, can generally exhibit strength and stress parameters that are appreciably lower than those used in more demanding applications. [0216]
  • Preferred biomaterials are also stable under conditions used for sterilization, and additionally are stable on storage and in the course of delivery. They are also capable of flowing through a delivery conduit to an in vivo location, and being cured in situ, as by exposure to an energy source such as ultraviolet light or by chemical reaction. Thereafter the cured biomaterial is suitably amenable to shaping and contouring, by the use of conventional or custom designed arthroscopic tools or instruments. Over the course of their use in the body the cured, contoured biomaterial exhibits physical-chemical properties suitable for use in extended in vivo applications. [0217]
  • As described above, a biomaterial composition of the present invention can be provided in a heterogeneous form, e.g., having two or more portions that independently provide one or more properties that differ between the portions. For example, the present teaching can be employed in the following manner to provide a joint resurfacing implant having improved anchoring and tear resistance. Reactive liquid polyurethanes, as described above, can be mixed during delivery and polymerized in situ and in vivo in order resurface or restore damaged body joint. Commonly, and as also described herein, such an implant can be immobilized in the joint by means of one or more anchoring holes drilled into the implant site. Biomaterials having a surface hardness of about 65 to about 85 Shore A, are relatively soft, and can be used to simulate the cushioning properties of articulating cartilage they target to replace. [0218]
  • In certain applications it will be particularly desirable that the implant be even more firmly and permanently immobilized within the joint, in order to resist a “carpeting effect” that can otherwise be caused by load forces as well as frictional and/or twisting movements typical in the joint. Such an effect can serve to create extensive wear on the implant, leading to premature failure of the implant and even dislodging of the implant itself or portions thereof. [0219]
  • Given the present description, those skilled in the art will be able to determine the best manner to avoid such displacement, on a joint by joint and case by case basis. Suitable approaches can include, for instance, adjusting the size, shape, number and/or position of anchor points to be drilled in order to ensure optimal performance. Similarly, given the present description those skilled in the art will be able to determine the optimal biomaterial composition for use in a particular application, e.g., one that is sufficiently hard to avoid being “pulled out” of the anchoring holes under the expected prolonged use in vivo. [0220]
  • Compositions described herein can be made with an optimal combination of hardness, stiffness and strength, in order to resist deformation. Such properties, in turn, will permit the anchor points to better resist deformation, or failure. In turn, such biomaterials can provide improved immobilization of the implant, patient healing, and joint acceptance and performance. Harder implants, however, tend to experience significantly greater wear when introduced between surfaces of communicating or articulating bones. [0221]
  • Optionally, and preferably therefore, in order to provide an optimal combination of both stability and cushioning, the implant can be provided in the form of a heterogeneous composition, including a harder portion for use as anchor points, and a softer portion for cushioning. In an alternative embodiment, a multiphasic bulk morphology of the implant can be produced using an Interpenetrating Polymer Network (IPN), by bringing together softer and harder polymer networks while being polymerized. [0222]
  • In an alternative, and preferred embodiment, the present invention therefore provides a in situ formed composite that provides an optimal combination of anchoring and cushioning properties considered valuable for implant performance. [0223]
  • The respective portions of such a composite can be provided in any suitable form, for instance in a sandwich form, such as in the following manner: [0224]
  • 1. A thin layer (e.g., about 0.01 mm to about 1.0 mm) of strong, stiff and tough polyurethane, having the surface hardness of 55-75 Shore D is deposited into the lesion, filling completely the anchoring holes. This layer is preferably either solid or microcellular, neat or enhanced with all potentially available biologicals to augment integration and immobilization into the surrounding environment; e.g. bone, cartilage, synovium, etc. Predominantly, however, the anchoring is improved by increased resistance to deformation and thus the “pullout”, stemming from the harder and stiffer material. Aspects of biodurability vs. biodegradation can be considered for this anchoring layer. Given the present teaching, those skilled in the art will be able to provide suitable formulations to fulfill these needs. [0225]
  • 2. Immediately after this first layer is deposited, the second layer, in the form of a softer, cartilage-like polyurethane, is delivered and formed over the anchoring layer to form the composite. This softer layer provides the functional requirements of the joint restoring implant. [0226]
  • The in vitro performance of such a combination has been evaluated in a wear simulator, using simulated body environment (lactated ringer solution/37 deg C.). Under a specified load and motion conditions, when immobilized in cross-linked polyurethane foam simulating the cancellous bone, the double-layered composite of harder/softer material failed to tear at 320,000-380,000 cycles. The single-layered sample of the current material and current approach has failed this test at approximately 20,000 cycles. These and other results and observations confirm that such an approach is capable of providing marked improvement. [0227]
  • In a related aspect, the system described herein can be used to provide a joint implant having a mushroom-like appearance, in which “head” represents the implant; the “stem” represents the anchoring system. Such an implant will flow with the force-field acting upon it to extend its durability in the joint, and is particularly useful for indications where the necessary lesion as taught in U.S. Pat. No. 5,556,429 is impractical or impossible. [0228]
  • Reactive liquid polyurethanes, mixed during delivery and polymerized in situ and in vivo are used to resurface or restore damaged body joint as described herein. The in situ polymerized implant, based on polyurethanes having the surface hardness between 60-95 Shore A, is immobilized in the joint, in the prepared lesion, via drilled anchoring holes in the selected implant site. Anchoring holes are drilled at the “periphery” of the lesion. At least three holes are drilled to anchor the implant. As described above, such biomaterials are relatively soft, and are designed to simulate the properties of articulating cartilage they target to replace. Furthermore, these materials provide cushioning effect between respective bones of the respective joint. [0229]
  • As described above, and in order to avoid the “carpeting effect”, it is often necessary that anchor holes be drilled, essentially conical in shape and placed in a staggered pattern, to be filled with curable biomaterial and become an integral part of the implant. It is difficult to drill the holes in “toe-nail” fashion with the bottom tip of the hole pointing toward the periphery of the lesion. This diminishes the “holding” power of the anchoring hole system. Similarly, increasing numbers of anchor holes can serve to weaken the bone surface plateau (e.g. tibial plateau of the knee joint) causing potential “cave in” of the tibial plateau under the load. Holes can also serve to retain whatever folds might be brought on in the course of a carpeting effect, thereby potentially accelerating implant failure. [0230]
  • In order to address such a situation, a preferred method includes the following steps: [0231]
  • 1. A single, conically-shaped and center-located anchoring hole is drilled or otherwise generated within the joint surface to be restored. [0232]
  • 2. A thin layer of 0.01 mm to 1.0 mm of strong, stiff and tough polyurethane, having the surface hardness of about 55 to about 75 Shore D is delivered to the plateau surface or the lesion, filling completely the anchoring hole, in order to generate the “stem” of the “mushroom”. This stem layer can be provided in any suitable form, e.g., solid, microcellular, neat or enhanced with one or more biologicals to augment integration and immobilization into the surrounding environment; e.g. bone, cartilage, synovium, etc. Predominantly, however, the anchoring will be improved by increased resistance to deformation and thus the “pullout”, stemming from the harder and stiffer material. [0233]
  • 3. During or after delivery of the first layer, a second layer is delivered, e.g., in the form of a softer, cartilage-like polyurethane, which forms over the anchoring layer to form the composite in the form of “the head” of the “mushroom”. Optionally, one or more layers can be delivered, in any suitable order and using any suitable materials, in order to provide a multi-layered stem and/or head. [0234]
  • 4. Preferably, both the head and stem, and each layer therein, are provided in the form of a single material (e.g., polyurethane) in a manner that permits delivered in a single or multi-layered fashion. [0235]
  • The improved performance of such a composition has been verified in vitro, in a wear simulator, utilizing simulated body environment (lactated ringer solution/37 deg C.). Under a specified load and motion conditions, when immobilized in cross-linked polyurethane foam simulating the cancellous bone, the double-layered composite of harder/softer materials failed to tear at 320,000-380,000 cycles. The single layered sample of the current material and current approach has failed this test at approximately 20,000 cycles. [0236]
  • Mold Apparatus [0237]
  • In a preferred embodiment, the method of the invention involves an initial step of providing an implantable mold apparatus comprising a cavity adapted to receive and contain a flowable biomaterial and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial, A cavity can take any suitable form, e.g., a unitary balloon-like cavity capable of being partially or completely filled with biomaterial in order to provide an intact prosthesis, or a shell-like or tubular cavity used to form a corresponding tubular prostheses. The mold can be of any suitable shape or dimension, and can itself include a plurality of cavities and/or other chambers or conduits, such as those suitable for the delivery of air or vacuum, as described herein. [0238]
  • The method can be used for a variety of applications, including for instance, for the preparation of an integral prostheses, e.g., for use in articulating joint repair or replacement and intervertebral disc repair. Alternatively, the method can be used to provide a hollow mold, such as a tubular mold for use in preparing implanted passageways, e.g., in the form of catheters, such as stents, shunts, or grafts. [0239]
  • In one preferred embodiment, the method of the invention is used in the course of intervertebral discectomy. In an amphiarthroidal joint such as the lumbar joint of the back, the vertebra are separated by an intervertebral disc formed of cartilage. Applicant's copending PCT Application No. PCT/US97/00457 (the entirety of which is incorporated herein by reference), inter alia, describes a method for repairing an intervertebral disc that comprises the steps of: [0240]
  • a) using microsurgical techniques to perform a discectomy while preserving an outer annular shell, [0241]
  • b) providing one or more curable biomaterials to the interior of the annular shell, and [0242]
  • c) curing the biomaterials in order to provide a replacement disc. [0243]
  • In a preferred embodiment, the distraction of the disc space is accomplished by the use of suitable distraction means, such as an inflatable balloon or bladder. The balloon can be delivered in deflated form to the interior of the annulus and there inflated, as by the delivery of biomaterial, in order to distract the disc space and retain the biomaterial. [0244]
  • An improved inflatable device for used in intervertebral disc repair will be described with reference to the Drawing, and in particular FIGS. 1 through 4. In FIG. 1, an apparatus ([0245] 10) is shown having balloon portion (12) and biomaterial conduit (14). The balloon is dimensioned to be positioned within the annular shell following discectomy, and there filled with biomaterial in order to provide a replacement disc.
  • As shown, in a preferred embodiment, conduit ([0246] 14) includes a venting system (16) that includes air passageway (18) passing from a distal point along the conduit, into and through its wall (20) in order to pass along the interior of the conduit. Air passageway (18) terminates at a point at or near the proximal end of balloon (12), where it can be used to provide gas under pressure (e.g., in order to position the balloon and/or distract the joint) and where it can optionally be used to vent gas (e.g., air) within the balloon as the balloon is filled with biomaterial. As shown, the air passageway (18) is preferably provided with one or more vent holes (22) at locations within the balloon, which serve to facilitate the delivery of biomaterial by improving venting of gas from within the balloon. Conduit (14), including the air passageway, can be severed from balloon portion at or near the point (24) where they attach to or pass through the wall of the balloon. In this manner the conduit can be removed from the balloon as or after the biomaterial cures.
  • As shown in FIG. 2, the balloon is preferably provided in a form collapsed or rolled within sheath ([0247] 26), which can be drawn back in situ in order to release the balloon. Sheath (26), conduit (14) and air passageway (18) can each prepared from materials commonly used for such purposes, such as polyurethane catheters, and suitably dimensioned to provide the respective functions. The conduit portion, for instance, will preferably be about 10 cm to about 30 cm in length, more preferably between about 15 cm to about 25 cm in length, and about 0.1 cm to about 10 cm, and more preferably about 0.3 cm to about 0.7 cm in outer diameter. The air passageway, in contrast, will typically be about 1 mm to about 3 mm in outer diameter, and of sufficient length to extend about 2 cm to about 4 cm beyond the proximal end of the conduit (and therefore into the balloon). The balloon, in turn, will typically be about 2 cm to about 3 cm in its longest dimension, about 1.5 cm to about 2.5 cm in width, and about 0.5 cm to about 1.5 cm in thickness, once filled with biomaterial. Both the biomaterial conduit (14) and air passageway (18) are preferably provided with controllable and adjustable valves (28) and (30), for use in adjusting the flow of biomaterial and gas, respectively, between the two.
  • Optionally, air passageway ([0248] 18) can be provided such that it terminates at point substantially at or near where it meets the balloon, i.e., such that it does not extend into the balloon itself. In this manner it has been found that the balloon can still be adequately evacuated, yet in a manner that avoids the need to keep the distal portion of the air passageway permanently encased in cured biomaterial within the implant.
  • In a related embodiment, the mold apparatus, or a kit that contains or is adapted for use with such a mold apparatus, can include means for positioning the balloon in situ, e.g., in the form of a vascular guide wire that can be placed through the delivery conduit itself, or preferably through an air passageway that terminates at or near the point of contact with the balloon. The guide wire can be designed to substantially assume the curved contour of the extended but unfilled balloon, and to provide a plane of orientation, in order to both facilitate placement of the balloon and provide an outline of the periphery of the balloon in position and prior to filling. Thereafter the guide wire can be removed from the site prior to delivery of the biomaterial and air evacuation. The use of a guide wire in this manner is particularly facilitated by the use of an air passageway that is unconnected to, and positioned outside of, the biomaterial conduit. [0249]
  • Optionally, and in order to facilitate the placement and storage of the collapsed balloon within a sheath, the invention further provides a rod, e.g., a plastic core material, dimensioned to be placed within the balloon, preferably by extending the rod through the conduit. Once in place, a vacuum can be drawn on the balloon through the air passageway in order to collapse the balloon around the rod. Simultaneously, the balloon can also be twisted or otherwise positioned into a desired conformation to facilitate a particular desired unfolding pattern when later inflated or filled with biomaterial. Provided the user has, or is provided with, a suitable vacuum source, the step of collapsing the balloon in this manner can be accomplished at any suitable time, including just prior to use. In certain embodiments it will be desirable to collapse the balloon just prior to its use, e.g., when using balloon materials that may tend to stick together or lose structural integrity over the course of extended storage in a collapsed form. Alternatively, such balloon materials can be provided with a suitable surface coating, e.g., a covalently bound polymeric coating, in order to improve the lubricity of the surface and thereby minimize the chance that contacting balloon surfaces will adhere to each other. [0250]
  • Mold cavities of the present invention, e.g., the balloon of FIG. 1, can be formed by any suitable means. In a preferred embodiment, the balloon is fabricated by dipcoating a suitably shaped mandrel into a curable polymer solution. Applicants have discovered that a mandrel ideally suited for this purpose can be prepared from a remoldable bismuth-based material. Examples of suitable materials include low melting point fusible materials, such as bismuth alloys that are commercially available from a number of sources (e.g., as Part nos. E-LMA-117, 158, 255 and 281 from Small Parts, Inc. Miami Lakes, Fla.). Such an alloy, for instance, begins to melt at about 117 degrees C., and solidifies at room temperature, expanding slightly in the process of cooling. The allow can be melted out in hot water and collected for re-use. [0251]
  • A preferred mandrel will be described with reference to FIGS. 3 and 4. FIG. 3 shows a mandrel ([0252] 32) covered with newly formed balloon (34) and held in chuck (36). The solid mandrel (32) is used to form a balloon by dipcoating it in a suitable solution (not shown) as described herein. Once cast, the mandrel can be melted in order to remove it from the balloon by dipping the combination in water at about 120 degrees C. for about 5 to 15 minutes. As the mandrel _iocompat it can be poured and/or squeezed out of the balloon and reformed for further use. FIG. 4 shows the resultant balloon (34), after removal of the mandrel, formed by this process. In the preferred embodiment shown, the balloon retains an integral stem portion (38) that provides an attachment site for the conduit shown in FIG. 1.
  • A preferred balloon provides an optimal combination of such properties as extendibility and strength. In this respect, a balloon that is substantially non-extendible, but strong, can be used to distract the disc space upon delivery of biomaterial, and by virtue of the biomaterial delivery pressure. Preferred materials for use in preparing balloons of the present invention include, for instance, block copolymers such as castable thermoplastic polyurethanes, for instance those available under the tradenames ESTANE (Goodrich), PELLETHANE (Dow), TEXIN (Bayer), Roylar (Uniroyal), and ELASTOTHANE (Thiocol), as well as castable linear polyurethane ureas, such as those available under the tradenames CHROMOFLEX AR (Cardiotech), BIONATE (Polymer Technology Group), and BIOMER (Thoratec). [0253]
  • Preferred elastomeric polymers provide an optimal combination of such properties as flexibility under static and dynamic conditions, strength, tensile strength, elongation, elastic modulus during cyclic deformation, ductility, stability and durability, compliance, porosity, and patency. See generally, M. Szycher, J. Biomater. Appl. “Biostability of polyurethane elastomers: a critical review”, 3(2):297-402 (1988); A. Coury, et al., “Factors and interactions affecting the performance of polyurethane elastomers in medical devices”, J. Biomater. Appl. 3(2):130-179 (1988); and Pavlova M, et al., “Biocompatible and biodegradable polyurethane polymers”, Biomaterials 14(13):1024-1029 (1993), the disclosures of which are incorporated herein by reference. [0254]
  • Given the present description those skilled in the art will be able to employ conventional methods, such as casting, for forming balloons and similar molds of this invention. See, for instance, “Casting”, pp. 109-110, in [0255] Concise Encyclopedia of Polymer Science and Engineering, Kroschwitz, ed., John Wiley & Sons (1990). In a preferred embodiment, a remoldable bismuth mandrel is formed having desired shape and dimensions. Balloons can be cast to achieve any desired final thickness, preferably on the order of 0.005 inches (0.01 cm) to about 0.015 (0.05 cm) inches thick, and preferably between about 0.008 inches (0.02 cm) to about 0.012 inches (0.03 cm). The balloon itself is preferably cleaned, e.g., by the use of suitable solvents.
  • Optionally, and preferably, reinforcing materials such as meshes formed of natural or synthetic materials can be incorporated into the balloon, e.g., by layering them onto various portions while still wet, and covering the mesh with subsequent dip coats. A mesh can be cut in a form sufficient to extend around the perimeter of the balloon, for instance, in order to provide added strength in the course of filling the balloon and distracting the space. Suitable materials for preparing meshes include polyamide (e.g., NYLON), polyester (e.g., tradenames DACRON and HYTREL), polyethylene, and polypropylene, as well as liquid crystal polymers available under the tradename VECTRA. [0256]
  • The various components of a mold apparatus can be prepared and assembled using techniques within the skill of those in the related art. For instance, a balloon, conduit and air passageway can be individually prepared and assembled by attaching the balloon to an end of the conduit, e.g., by gluing or sonic welding, and positioning the air passageway within or alongside the conduit and extending into the balloon. Thereafter the sheath can be applied to the conduit and slid over the balloon in its collapsed or rolled configuration. Other materials or means can be incorporated into the apparatus, such as radioopaque portions, to facilitate the surgeons ability to orient the balloon in situ. Also, various joints and junctures between the parts of the apparatus can be sealed by the use of suitable adhesives or other materials. [0257]
  • The use of a preferred mold apparatus will be described with reference to FIG. 5, which shows the balloon portion ([0258] 12) in place, with sheath (26) retracted, within a reamed annular shell (70). A curable biomaterial (72) is delivered into the balloon at the same time that air is withdrawn from the balloon through vent holes (22) of air passageway (18). In use, and with the balloon positioned within the sheath, the apparatus can be inserted into the body through minimally invasive means in order to position the proximal end at the site of intended use, e.g., within the disc space. Once positioned, the sheath can be withdrawn in order to release the balloon. Optionally, air or other suitable gas can be delivered to the balloon through the air passageway in order to position the balloon and/or distract the joint. Thereafter, the valve can be opened to begin the flow of curable biomaterial. As biomaterial enters the balloon, gas in the balloon can be vented through air passageway by drawing a slight vacuum on the distal end of the passageway, as by the use of a syringe or other suitable vacuum source. The biomaterial continues to fill the balloon, which in turn serves to distract (or assist in distracting) the space, until desired dimensions are obtained, whereupon the flow of biomaterial is stopped, the biomaterial is allowed to continue to fully cure (harden), and the balloon severed from the conduit.
  • The method and apparatus of the invention can also be used to repair other joints, including diarthroidal and amphiarthroidal joints. Examples of suitable diarthroidal joints include the ginglymus (a hinge joint, as in the interphalangeal joints and the joint between the humerus and the ulna); throchoides (a pivot joint, as in superior radio-ulnar articulation and atlanto-axial joint); condyloid (ovoid head with elliptical cavity, as in the wrist joint); reciprocal reception (saddle joint formed of convex and concave surfaces, as in the carpo-metacarpal joint of the thumb); enarthrosis (ball and socket joint, as in the hip and shoulder joints) and arthrodia (gliding joint, as in the carpal and tarsal articulations). [0259]
  • In a preferred embodiment, the method and apparatus are employed to repair the knee joint. FIGS. 6 and 7, for instance, show a preferred balloon for use in knee surgery. As seen in FIG. 6, the mold ([0260] 40) includes a generally ovoid inflatable portion (42), preferably having protruding foot portions (44) extending therefrom and flowably attached to biomaterial conduit (46). In use, the foot portions, or footpads, (44) can be implanted into corresponding anchor sites drilled into the bone, in order to provide improved attachment thereto.
  • As seen in FIG. 7, in a further preferred embodiment the present invention further provides a template ([0261] 50) for use in drilling the holes that will correspond with foot portions (44). As shown, template (50) includes both a substantially planar, disc-like, template portion (52) and an extendable delivery probe (54) useful for positioning the template by minimally invasive means. The disc portion, in turn, is provided with one or more, and preferably several apertures of predetermined spacing and diameter, to correspond with the foot portions of a corresponding inflatable portion. A template such as that shown is considered novel in its own right, and particularly in the context of a system in which a mold and template are packaged or paired together to facilitate the delivery and placement of the mold in situ.
  • One or more footpads are formed or formable in a manner integral with the balloon or are attached thereto in any suitable manner. The footpads can themselves be solid, or can be part of the cavity and filled with biomaterial. The footpads are dimensioned to be positioned into corresponding anchor points within the bone, to further secure the mold to the site of tissue injury. Optionally, or in addition to the use of footpads, the underside of the balloon may have multiple fenestrations (e.g., micro holes) sufficient to permit the biomaterial to traverse the barrier of the balloon in order to contact the subchondral bone and/or fill the anchor points. The apparatus can also be provided with means, such as a _iocompat air lumen or other means sufficient to evacuate the balloon in the course of biomaterial delivery, thereby facilitating the process further. [0262]
  • Optionally, and also preferably, the cavity provided by an apparatus of this invention can be in a form sufficient to provide a hollow, e.g., tubular biomaterial upon cure. As such, the apparatus can be used to form an internal passageway, for instance, to support (internally or externally) an existing passageway (such as a vessel), to provide a replacement for natural vessel, and/or to provide a new passageway such as a shunt, between areas not previously or naturally connected. [0263]
  • A tubular mold can be used to form a catheter, which in turn, can serve as a prosthethic device for a variety of applications. A catheter of the present invention can take a variety of forms, including, for instance, as an angiographic catheter, ureteral catheter, central venous catheter, _iocompati catheter, bladder catheter, intracardiac catheter, pacing catheter, and prostatic catheter. [0264]
  • A catheter of this invention can also serve as a shunt, to provide a diversion or bypass of accumulations of fluid to an absorbing or excreting system. Suitable applications include, for instance, the use of a catheter as an arteriovenous shunt, Blalock shunt (subclavian artery to pulmonary artery), cavopulmonary shunt, distal splenorenal shunt, jejunoileal shunt, “left-to-right” shunt (e.g., in the heart as through a septal defect, or from the systemic circulation to the pulmonary), mesocaval shunt, peritoneovenous shunt, portacaval shunt, portasystemic shunt, renal-splenic shunt, “right-to-left” shunt (e.g., in the heart as through a septal defect, or from the pulmonary artery into the aorta), Scribner shunt (artery, generally radial, to cephalic vein), splenorenal shunt (including a “Warren” distal splenorenal shunt), ventriculocisternal shunt, transjugular intrahepatic portosystemic shunt, and a Waterston shunt (ascending aorta and subjacent right pulmonary artery). [0265]
  • Similarly, the catheter can be used to form a graft for abdominal aortic aneurysms, and in micro form as a graft for cerebral aneurysms. [0266]
  • In yet a further preferred embodiment, a mold of this invention can be used to prepare a solid (e.g., curved and/or straight) rod, such as a medullary rod for internal fixation of various fractures. The balloon, and in turn rod, can also be placed by minimally invasive means. [0267]
  • For use as a stent-like prosthesis, a catheter of this invention can be used in a variety of applications. In yet another aspect the invention provides a stent formed by a method of the present invention. Stents of the present invention can be used in a variety of applications, including for peripheral vasculature, abdominal aortic aneurysms, and applications in connection with the prostate, esophagus, trachea, bile or biliary tract, and intestine. A stent of this invention can lay within the lumen of a tubular structure to provide support during or after anastomosis, or to assure patency of an intact but contracted lumen. [0268]
  • The construction and use of a tubular apparatus of the present invention will be further described with reference to the Drawing. A preferred embodiment is shown in FIGS. 8 and 9, wherein the former depicts the apparatus in its uninflated and unfilled form, and the latter depicts the apparatus of FIG. 8 in its inflated and filled condition. As seen in both Figures, apparatus ([0269] 60) comprises an inner fluid passageway (62), surrounded by a generally concentric and inflatable air chamber (64), the air chamber being surrounded by a generally concentric and sealed or sealable biomaterial cavity (66). The fluid passageway is adapted to permit the flow of a bodily fluid such as blood in the course of insertion and delivery of the apparatus. The air chamber is adapted for attachment to a source of positive or negative air pressure, and the biomaterial chamber is adapted to be attached to a source of flowable biomaterial which can be cured in situ to form a tubular prosthetic implant such as a catheter. Optionally, means can be provided to vent or evacuate the biomaterial chamber in the course of filling with biomaterial, e.g., by the application of slight vacuum using a separate and additional lumen (not shown).
  • As can be seen by reference to FIG. 10, the fluid passageway ([0270] 62) and air chamber (64) are separated by a first barrier (68), while air chamber (64) and biomaterial cavity (66) are separated by a second barrier (70). Outermost wall (72) provides the external surface of the biomaterial cavity and generally serves as an outer wall of the apparatus. Along its length, fluid passageway is sufficiently long to permit it to be delivered to a desired site within the body. The air chamber and biomaterial cavity, in turn, are provided along a portion of the fluid passageway, and generally need only be sufficiently long to serve their purpose in the preparation of a prosthetic implant.
  • In use, the air chamber can be inflated with air (or other suitable material) to a desired position and dimensions, whereupon the biomaterial can be delivered to fill the biomaterial cavity and cured in situ to form an implanted catheter. Optionally, the air chamber can be inflated before, during and/or after delivery and/or cure of the biomaterial. Thereafter the air chamber can be deflated and, together with the fluid passageway, removed from the body leaving the cured biomaterial in place as a catheter. [0271]
  • Optionally also, a mold apparatus of the type shown in FIG. 10 can be provided with means for venting the biomaterial chamber, e.g., in the course of filling that chamber with biomaterial. Venting means can be provided in a manner analogous to that described above with respect to the intervertebral disc balloon, that is, by the use of a separate air passageway operably attached to the biomaterial chamber on its proximal end, and attached or attachable to a vacuum source or source of pressurized air (or gas) on its opposite end. [0272]
  • The cross-sectional view provided in FIG. 10 demonstrates the manner in which fluid passageway ([0273] 62) serves to permit the continued flow of fluid within the body in the course of use. Adjacent or surrounding the passageway is one or more air passageways (64) that can be used to inflate biomaterial cavity (66) and establish it in a desired position with respect to the body and the passageway.
  • In another preferred embodiment, the present invention provides a method for forming a prosthesis in situ, the method comprising the steps of: [0274]
  • a) providing a mold apparatus comprising an inner fluid passageway, a portion of the passageway being surrounded by a circumferential inflatable air chamber, a portion of the air chamber being surrounded by a circumferential biomaterial cavity, the fluid passageway being adapted to permit the flow of a bodily fluid or substance in the course of insertion and delivery of the catheter, the air chamber being adapted for operable attachment to a source of positive or negative air pressure, and the biomaterial chamber being adapted for operable attachment to a source of flowable, curable biomaterial which can be cured in situ to form a catheter, wherein the air chamber, upon inflation serves to define the inner dimensions of the catheter, and upon deflation allows free separation and removal of the passageway and air chamber, leaving the newly formed biomaterial prosthesis in place, [0275]
  • b) inserting the apparatus to a desired point within the body, [0276]
  • c) applying positive air pressure to inflate the air chamber to a desired dimension, [0277]
  • d) filling the biomaterial cavity with biomaterial with the apparatus maintained in its inflated position, [0278]
  • d) curing the biomaterial, and [0279]
  • e) deflating and withdrawing the apparatus in a manner that leaves the cured biomaterial in situ, to serve as an implanted prosthesis. [0280]
  • In another embodiment, the invention provides a mold apparatus comprising a inner fluid passageway, a portion of which is surrounded by a circumferential, radially expansible, and inflatable air chamber, a portion of the air chamber being surrounded by a circumferential, radially expansible, biomaterial cavity, the fluid passageway being adapted to permit the flow of bodily fluid or substances in the course of insertion and delivery of the catheter, the air chamber being adapted for operable attachment to a source of positive or negative air pressure, and the biomaterial chamber being adapted to be flowably attached to a source of biomaterial which can be cured in situ to form an implanted prosthesis. [0281]
  • In an alternative embodiment, the biomaterial passageway can itself be contoured or shaped in any suitable manner, e.g., to provide a helical or spiral flow path along the length of the mold apparatus, e.g., in order to provide improved control over the flow of biomaterial and/or to provide improved dimensional stability to the cured implant. Similarly, the biomaterial passageway can be branched or segmented in any suitable fashion, e.g., to provide a “Y” shaped configuration to accommodate vascular branch points such as that of the aorta. [0282]
  • The fluid passageway of this embodiment can be provided by any material suitable to provide an optimal combination of such properties as nontoxicity, the ability to be bonded or otherwise attached to the material(s) used to form the air chamber and/or biomaterial cavity. An example of a suitable material for forming the fluid passageway is polyethylene. The air chamber and biomaterial can be formed from any suitable material, or combination of materials. Optionally, and preferably, the air chamber will be formed having, as its interior surface, the exterior surface of the fluid passageway. The remaining surface of the air chamber is preferably fabricated from a different, and expandable, material capable of being sealed to the passageway at its ends, and contacting and expanding the dimensions of the biomaterial cavity upon inflation. The outer wall of the fluid passageway, therefore, is preferably of sufficient strength to maintain its patency and integrity in order to withstand the pressure used to inflate the air chamber. [0283]
  • The biomaterial cavity, in turn, can similarly share a common wall (its interior) with the exterior wall of the air chamber, particularly if measures are taken to ensure that desired portions of the apparatus can be withdrawn from the cured biomaterial in a manner that permits the cured biomaterial to remain within the body. Optionally, and preferably, the barrier between the air chamber and biomaterial cavity is formed of two or more layers, one serving as the exterior, and expandable, wall of the air chamber, and the other laying substantially adjacent that wall and serving as the interior wall of the biomaterial cavity, and in turn, of the implanted prosthetic. In an alternative embodiment, the outer and inner walls of the biomaterial cavity can themselves be integrally attached (e.g., tacked) together in a spiral configuration in order to strengthen the cylindrical geometry and facilitate both the evacuation of air and biomaterial delivery. [0284]
  • The walls of the fluid passageway, air chamber and biomaterial cavity are each of suitable dimensions (e.g., thickness and length) for their intended purpose. Generally the walls of the fluid passageway will be on the order of 0.02 inches (about 0.05 cm) or less in thickness, with the outer walls of the chamber and cavity being appreciably thinner, e.g., on the order of 0.01 inches (about 0.02 cm) or less and 0.005 inches (about 0.01 cm) or less, respectively. In such an embodiment, it is the walls of the fluid passageway that provide with apparatus with much, if not all, of the necessary strength and rigidity for insertion and use. [0285]
  • The overall diameter of the fluid passageway can be adapted to its desired purpose, but is generally between about 0.1 cm and about 3 cm, and preferably between about 0.2 cm and about 2 cm. The diameters of the air chamber and biomaterial cavity, in turn, can also be adapted to their desired purpose, but will generally be between about 0.5 cm and about 5 cm (and preferably between about 1 cm and about 3 cm) for the overall diameter of the inflated air chamber and filled biomaterial cavity. In turn, the biomaterial cavity can be used to form an implanted catheter of any suitable inner and outer diameter, with a corresponding wall thickness of between about 0.1 mm and about 5 mm, and preferably between about 0.5 mm and about 2 mm. In its uninflated and unfilled condition the diameter of the entire assembly is generally less than that of the vessel into which it will be inserted. [0286]
  • Those skilled in the art, given the present description, will appreciate that the various materials and/or portions used to fabricate such an apparatus can be secured in any suitable fashion, e.g., by the use of appropriate medical-grade adhesives, by the use of multiple wraps of fine thread or suture, by heat sealing, sonic welding, and the like. Generally, the fluid passageway will be provided in the form of a cylindrical body, having the air chamber and biomaterial cavity similarly formed and positioned as cylindrical and concentric bodies, with the chamber configured to taper down at its ends for attachment to the outer surface of the fluid passageway, and the biomaterial cavity also tapered down at its ends for attachment to the outer surface of the air chamber. [0287]
  • In a particularly preferred embodiment, and as shown in FIGS. 8 and 9, at least two lumens are mounted as integral parts of the catheter body, including an air lumen ([0288] 74) and a biomaterial lumen (76). The air lumen is connected to an inflation port that passes through the outside wall and into the air chamber. The opposite end of the air lumen passes along the distal length of the catheter to be controllably connected to an air or vacuum source. The biomaterial lumen is flowably connected to an inflation port that passes through the outside wall and into the biomaterial cavity, with its opposite end passing along the distal length of the catheter to be controllably connected to a biomaterial source.
  • Preferably with the apparatus in its uninflated and unfilled condition, the apparatus is dimensioned to be delivered through minimally invasive means to a desired position within the body. The inflatable air chamber and fillable biomaterial cavity can both be stored and inserted in a collapsed condition adjacent the outside surface of the fluid passageway. Optionally, the apparatus can be covered by a removable sheath (not shown) or other means suitable to facilitate its delivery to the desired position. [0289]
  • In use, the apparatus can be inserted through minimally invasive means through an artery or other bodily vessel to a desired point within the body, for instance, to a stenosed region of a blood vessel. Once in place, positive air pressure is applied in order to inflate the air chamber to a desired dimension. In the course of inflating the air chamber the outer and surrounding biomaterial cavity is suitably positioned for the receipt of biomaterial. As biomaterial fills the cavity, the pressure in the air chamber can be reduced in order to accommodate the increasing pressure and volume of biomaterial. Once the biomaterial cavity is filled to the desired extent, the air pressure can be further reduced in the air chamber, to the point where a vacuum can be drawn if desired, and the delivery conduit (fluid passageway and deflated air chamber) can be removed from the site. Ideally, the outer wall of the air chamber is distinct from the inner wall of the biomaterial cavity, such that the air chamber can be readily separated from the filled cavity, and axially removed therefrom. [0290]
  • Suitable materials for preparing a mold apparatus of the present invention are those that are presently used for such purposes as balloon angioplasty. Suitable materials provide an optimal combination of such properties as compliance, biostability and _iocompatibility, and mechanical characteristics such as elasticity and strength. A mold apparatus can be provided in any suitable form, including having a plurality of layers and/or a plurality of compartments when expanded. A useful apparatus will include the balloon or other biomaterial cavity itself, together with a delivery catheter (optionally having a plurality of lumen extending longitudinally therewith), and fluid or gas pressure delivery means. [0291]
  • In each embodiment, it is possible to treat or otherwise adapt the outer, tissue contacting, surface of the mold in a manner that facilitates its use. For instance, mold material can be rendered porous or fenestrated in order to permit it to become saturated with the biomaterial and/or to permit tissue to growth into the material or attach itself thereto. Optionally, and also preferably, the mold material can be chemically or biochemically treated, e.g., coated, to enhance the function or prevent unwanted interactions with the surrounding biological environment. Suitable coatings can be used, for instance, to render the mold material lubricious, biocompatible. Such coatings can be attached in any suitable manner, e.g., covalently attached or passively adsorbed, and in a manner that is either permanent in nature or slowly releasable or replaceable over time. [0292]
  • Although the present invention has been described with reference to the structures disclosed herein, it is not confined to the details set forth and this application is intended to cover any and all modifications and changes as may come within the scope of the following claims. [0293]
  • As another step of the method of the invention, the tissue injury site is prepared for receipt of the biomaterial. Those skilled in the art will appreciate the manner in which computer analysis of subchondral bone mass can allow the operator to customize the mechanical properties of the polymer-hydrogel composite to match the adjacent subchondral bone. This can be accomplished by adjusting the size of the hydrogel aggregates and by changing the percentage of the hydrogel in the polymer composite. [0294]
  • In a preferred method, the patient is first prepped and draped as per routine arthroscopic procedure. The first area to by resurfaced is then positioned horizontally and facing upright. If the opposing bone requires resurfacing the joint can be repositioned after the initial application has cured. This will allow gravity to assist in filling the anchor points and distributing the liquid composite evenly over the surface to be covered. Based on the present description, all the necessary maneuvers will typically be carried out using only two or three access portals. [0295]
  • The surface to be bonded is first cleaned of inflammatory synovia and frayed or damaged cartilage using a laser knife and/or other instruments, such as an arthroscopic shaver. The surface is then be prepared in order to improve its ability to accept and retain biomaterial. For instance, the subchondral bone is roughened by a burr and any osteophytes removed, also by the use of a burr. The bone is then irrigated to remove debris and the site suctioned dry. The bone can also be abraded in order to roughen its surface, or it can be coated with a suitable cement or other interface material. [0296]
  • In a preferred embodiment, anchoring points are created in the supporting joint tissue. For instance, inverted pyramidal or inverted T-shaped (A) anchor points can be cut into the subchondral bone using specially designed arthroscopic drill bits or by laser means. [0297]
  • If only a small patch is needed only one or two anchor points may be sufficient, providing the number and arrangement of points is sufficient to prevent rotational or translational movement of the cured biomaterial. [0298]
  • If a larger area of cartilage is being replaced, then six to nine anchor points may be necessary. The number, size and location of sites can be determined on a case by case basis, by balancing the need to retain the cured biomaterial in permanent engagement with the natural tissue, with the need to avoid undue trauma or damage to the structural integrity of the natural tissue itself. Additional or other means, for instance the use of cements, can also be used to enhance the permanent engagement of the cured biomaterial with the natural joint tissue. [0299]
  • For instance, the prepared bone surface, including the anchor sites, can be treated with high molecular weight hyaluronic acid. This will improve adhesion of the polymer and act to inhibit inflammation and local osteoporosis. High molecular weight hyaluronic acid has also been shown to be an effective stimulator of osteophytes (i.e., bone-forming cells) as well as an inhibitor of Interleukin-1 (Il-1). As an IL-1 inhibitor, the acid will tend to decrease the inflammatory response in the area around the new insert. [0300]
  • As another step of the invention, a desired quantity of the curable biomaterial is delivered by minimally invasive means to the prepared site. Uncured biomaterial, either in bulk or in the form of separate reactive components, can be stored in suitable storage containers, e.g., sterile, _iocom-lined metal canisters. The biomaterial can be delivered, as with a pump, from a storage canister to the delivery cannula on demand. Biomaterial can be delivered in the form of a single composition, e.g., including both polymer matrix and hydrogel, or can be delivered in the form of a plurality of components or ingredients. For instance, polymer matrix and hydrogel can be separately stored and suitably mixed or combined either in the course of delivery or at the injury site itself. [0301]
  • An example of a delivery system that can serve as a model for the delivery of uncured biomaterials is one presently sold by Dyonics, Inc. as the “InteliJET Fluid Management System”. This system involves the a low pressure, high flow rate delivery of saline to a site, and combines delivery with suction that is automatically adjusted to specific blade styles. [0302]
  • In terms of its component parts, a preferred delivery system of the present invention will typically include a motor drive unit, with a remote controller, associated tube sets, a nonscope inflow delivery cannula, having independent fluid dynamics pressure and flow rate adjustments, an energy source for curing, attachments for the flush, vacuum, waste canister, overflow jars. [0303]
  • The application cannula will then be inserted into the joint and under visualization from the fiberoptic scope the polymer composite will be applied to the subchondral bone. The flow of the liquid phase polymer composite will be controlled by the operator via a foot pedal connected to the pumping mechanism on the polymer canister. The liquid phase polymer composite will flow from the tip of the application catheter to fill the anchor points and subsequently cover the subchondral bone. [0304]
  • As another step of the invention, the delivered biomaterial is cured by minimally invasive means and in such a manner that the cured biomaterial is retained in apposition to the prepared site. As described herein, the biomaterial can be cured by any suitable means, either in a single step or in stages as it is delivered. Preferred biomaterials are curable by the application of ultraviolet light, making them particularly amenable to a system that delivers such light by minimally invasive means. [0305]
  • When a sufficient amount of uncured biopolymer has been delivered, polymerization can be initiated by any suitable means, e.g., by the use of an ultraviolet light source at the tip of the application cannula. After the composite has cured (polymerized) the surface can be contoured as needed by other arthroscopic instruments. The joint will then be irrigated and the instruments removed from the portals. [0306]
  • Using the preferred composite materials described herein it is envisioned that there may be some natural migration of the hydrogel component to the composite surface in the course of curing. This migration will tend to produce a net positive charge across the surface of the composite. This positive charge, in turn, will tend to bind negatively charged hyaluronic acid, which is a compound that naturally occurs in the joint (produced by Type A synoviocytes). While not intending to be bound by theory, it would appear that the result of such binding will produce a lubricating effect to the surface of the composite. Since the hyaluronic acid is a normal product of the synovial lining cell it will be continuously replenished. A synthetic hydrophilic bilayer may alternatively be applied to reduce the coefficient of friction further. [0307]
  • The steps of preparing the joint surface and contouring the cured biomaterial, as described herein, can be accomplished using conventional arthroscopic instruments and tools. Stryker, Inc., Zimmer, Inc. and Dyonics, Inc. for instance, produce a wide array of arthroscopic surgical blades and instruments. Representative products are described in Dyonics' U.S. Pat. Nos. 4,274,414, 4,203,444, 4,705,038, 4,842,578, 4,834,729, and 4,983,179, the disclosure of each of which is incorporated herein by reference. [0308]
  • In yet another step of the present invention, the cured, retained biomaterial is contoured to achieve a desired conformation approximating that of natural tissue. [0309]
  • The preferred composite is heat moldable, allowing for sculpting with a probe that can be introduced through an arthroscopic portal. Such a probe will typically have a retractable, flat spatula-shaped end. The tip of the spatula can be heated to about 100 degrees centigrade, at which temperature the surface of the composite can be sculpted to the desired contour. As the composite cools, it will have sufficient memory to retain the shape it was given. [0310]
  • If unusual wear occurs in a given area, the implant can later be resculpted to cover the worn area without the need to repeat the entire process described above. Instead, the heat probe can simply be re-inserted under the arthroscopic visualization and the insert remolded to provide adequate size or properties in the needed area. [0311]
  • The steps described herein can be performed or combined in any suitable fashion. For instance, it is contemplated that the delivery, curing and contouring of biomaterial can be accomplished simultaneously and in a single step, for instance, by the use of a mold that retains a biomaterial in a desired shape as it is delivered and cured. [0312]
  • Optionally, and preferably, the final biomaterial can be subjected to further physical/chemical modifications, e.g., in order to enhance it performance, _iocompatibility, and the like. For instance, calcitonin and inflammatory inhibiting molecules such as Interleuken I inhibitors can be attached to the bone composite surface to prevent local osteoporosis and local inflammatory response which cause loosening. Similarly, the surface of the cured composite can optionally be modified in order to reduce the coefficient of friction. [0313]
  • In a preferred embodiment, a computer program can be used that is based on existing and ideal articulation angles. The program can assist the operator in producing a component having an optimal combination of physical characteristics, for instance contour and thickness, in order to provide optimal alignment of the involved joint. [0314]
  • Similarly, a holographic image can be generated through the arthroscope to aid the operator in producing the optimal thickness and contour of the polymer composite. Small joint applications, e.g., for wrists and ankles, as well as for metacarpal phalangeal joints, proximal interphalangeal joints, metatarsal phalangeal joints, and first carpalmetacarpal joints can also be developed. [0315]

Claims (45)

What is claimed is:
1. A method for repairing a tissue site, the method comprising the steps of:
(a) providing a curable polyurethane biomaterial composition comprising a plurality of parts adapted to be mixed at the time of use in order to provide a flowable composition and to initiate cure,
(b) mixing the composition parts in order to initiate cure and employing minimally invasive means to deliver a quantity of the curing composition to the tissue site, and
© completely curing the delivered composition to provide a permanent repair of the tissue site.
2. A method according to claim 1 wherein the composition parts comprise: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts,
wherein the composition is sufficiently flowable to permit it to be delivered to the tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.
3. A method according to claim 2 wherein the composition provides improved cure characteristics and cured properties as compared to a comparable composition lacking the reactive hydrophobic additive component.
4. A method according to claim 3 wherein the improved cure characteristics include a significant reduction in the appearance of bubbles when cured in the presence of moisture.
5. A method according to claim 1 wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.
6. A method according to claim 1 wherein the method is used to repair an orthopedic joint selected from the group consisting of diarthroidal and amphiarthroidal joints.
7. A method according to claim 6 wherein the amphiarthroidal joints are selected from the group consisting of synphysoidal joints and syndemoidal joints.
8. A method according to claim 7 wherein the synphysiodal joints are intervertebral joints.
9. A method according to claim 6 wherein the method is performed using endoscopic/arthroscopic surgical instrumentation and under fiberoptic visualization.
10. A method according to claim 9 wherein the instrumentation comprises a static mixer and delivery cannula to mix and deliver the composition.
11. A curable polyurethane composition comprising a plurality of parts capable of being mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts comprising: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts,
wherein the composition is sufficiently flowable to permit it to be delivered to a tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.
12. A composition according to claim 11 wherein the composition provides improved cure characteristics and cured properties as compared to a comparable composition lacking the reactive hydrophobic additive
13. A composition according to claim 12 wherein the hydrophobic polymer additive is present at a concentration of between about 1% and about 50% by weight, and is selected from the group consisting of hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisoprene, polyisobutylene, silicones, polyethylenepropylenediene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof.
14. A composition according to claim 12 wherein the improved cure characteristics include a significant reduction in the appearance of bubbles when cured in the presence of moisture.
15. A composition according to claim 11 wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.
16. A composition according to claim 12 wherein the improved cured properties include a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.
17. A composition according to claim 13 wherein, within the prepolymer, the polyether component is present at a concentration of between about 2% and about 10%, by weight, based on the weight of the composition, and is selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polytetramethylene oxide (polyoxytetramethylene), and copolymers thereof.
18. A composition according to claim 17 wherein the polyol comprises one or more polytetramethylene oxides having molecular weights in the range of 250 to 2900.
19. A composition according to claim 13 wherein the isocyanate is present in excess in the prepolymer component and comprises an aromatic (poly)isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate (MDI), and combinations thereof.
20. A kit comprising a plurality of compositions according to claim 11, the compositions providing different hardnesses in their cured form, for use in preparing a heterogeneous implant.
21. A method according to claim 1, wherein the method comprises the further steps of:
a) providing an implantable mold apparatus comprising an expandable cavity adapted to receive and contain the flowable biomaterial composition and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial composition,
b) inserting the mold apparatus to the tissue site,
c) mixing and delivering biomaterial composition to the mold in order to fill the cavity to a desired extent,
d) permitting the biomaterial composition to completely cure, and
e) employing the molded biomaterial in situ as a prosthesis at the tissue site.
22. A method according to claim 21 wherein the steps of inserting the mold apparatus, delivering the biomaterial composition, and curing the composition are each performed by minimally invasive means.
23. A method according to claim 21 wherein the cavity is provided in the form of an inflatable balloon and the method is used to prepare an intact prosthesis.
24. A method according to claim 23 wherein the method is used to repair an intervertebral disc.
25. A method according to claim 23 wherein the method is used to resurface a knee.
26. A method according to claim 21 wherein the cavity is provided in tubular form and the method is used to prepare a tubular implant.
27. A method according to claim 26 wherein the tubular implant is used to form an implant selected from the group consisting of stents, shunts and grafts.
28. A method according to claim 27 wherein the tubular implant comprises a prosthetic implant for repairing an abdominal aortic aneurysm.
29. A method according to claim 21 wherein the composition parts comprise: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, one or more catalysts, wherein the composition is sufficiently flowable to permit it to be delivered to the tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.
30. A method according to claim 29 wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.
31. A mold apparatus for forming a prosthesis in situ, the apparatus comprising an implantable, expandable cavity adapted to receive and contain a flowable, curable biomaterial, and a removable conduit adapted to connect the cavity to a source of flowable biomaterial.
32. An apparatus according to claim 31, wherein the apparatus is adapted for use by minimally invasive means and the cavity is a provided in the form of an inflatable balloon for use in preparing an intact prosthesis.
33. An apparatus according to claim 32 wherein the balloon is adapted for use in repairing an intervertebral disc.
34. An apparatus according to claim 33 wherein the apparatus further comprises an air passageway positioned to vent the balloon in the course of filling with biomaterial.
35. An apparatus according to claim 33 further comprising distal control valves for the biomaterial conduit and air passageway, respectively.
36. An apparatus according to claim 32 wherein the balloon provides a knee prosthesis and is adapted to be permanently positioned and filled in apposition to subchondral bone.
37. An apparatus according to claim 36 wherein the balloon comprises a surface for contact with subchondral bone, the surface being provided with one or more foot pads adapted to be implanted into corresponding anchor points drilled within subchondral bone.
38. An apparatus according to claim 36 wherein the balloon comprises a surface for contact with subchondral bone, the surface being fenestrated in order to permit the passage of biomaterial from the cavity to contact with the subchondral bone.
39. A surgical kit comprising an apparatus according to claim 37 in combination with a template for use in drilling anchor points in subchondral bone at positions corresponding to those of foot pads on the apparatus.
40. A surgical kit for use in preparing a prosthesis in vivo, the kit comprising (a) an implantable mold apparatus comprising an expandable cavity adapted to receive and contain a flowable, curable biomaterial, and a removable conduit adapted to connect the cavity to a source of curable, flowable biomaterial and (b) a supply of a curable, flowable polyurethane biomaterial composition.
41. A prosthesis for repairing an intervertebral disc, the prosthesis comprising an expanded mold cavity containing a cured, biocompatible, polyurethane biomaterial composition, the prosthesis providing a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.
42. A prosthesis for repairing the surface of a knee joint, the prosthesis comprising a cured, biocompatible, polyurethane biomaterial composition providing a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.
43. A prosthesis according to claim 42 wherein the prosthesis is heterogeneous, comprising a plurality of cured polyurethane compositions, in order to provide layers having one or more different properties.
44. A prosthesis according to claim 42 wherein the cured biomaterial is provided within a mold cavity and the prosthesis is adapted to be permanently positioned in apposition to subchondral bone.
45. A prosthesis according to claim 43 wherein the mold cavity is provided in the form of a balloon comprising a surface for contact with subchondral bone, the surface being provided with one or more foot pads adapted to be implanted into corresponding anchor points drilled within subchondral bone.
US10/167,372 1994-05-06 2002-06-11 Biomaterial system for in situ tissue repair Abandoned US20020156531A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
US10/167,372 US20020156531A1 (en) 1994-05-06 2002-06-11 Biomaterial system for in situ tissue repair
PCT/US2003/002142 WO2003061522A2 (en) 2002-01-22 2003-01-22 Interpositional arthroplasty system and method
CA002473858A CA2473858A1 (en) 2002-01-22 2003-01-22 Interpositional arthroplasty system and method
EP03703997A EP1474071B1 (en) 2002-01-22 2003-01-22 Interpositional arthroplasty system
US10/500,929 US20040247641A1 (en) 2002-01-22 2003-01-22 Interpositional arthroplasty system & method
JP2003561468A JP4324478B2 (en) 2002-01-22 2003-01-22 Interposition arthroplasty system
US10/935,041 US20050043808A1 (en) 1994-05-06 2004-09-07 Knee joint prosthesis
AU2010200382A AU2010200382A1 (en) 2002-01-22 2010-02-03 Interpositional Arthroplasty System and Method

Applications Claiming Priority (11)

Application Number Priority Date Filing Date Title
US08/239,248 US5556429A (en) 1994-05-06 1994-05-06 Joint resurfacing system
US47411395A 1995-06-07 1995-06-07
US08/590,293 US5888220A (en) 1994-05-06 1996-01-23 Articulating joint repair
US08/742,444 US5795353A (en) 1994-05-06 1996-11-02 Joint resurfacing system
US74942996A 1996-11-15 1996-11-15
US90345597A 1997-07-30 1997-07-30
US5662497P 1997-08-20 1997-08-20
PCT/US1997/020874 WO1998020939A2 (en) 1996-11-15 1997-11-14 Biomaterial system for in situ tissue repair
US08/993,468 US6306177B1 (en) 1994-05-06 1997-12-18 Biomaterial system for in situ tissue repair
US09/193,973 US6443988B2 (en) 1994-05-06 1998-11-18 Mold apparatus and kit for in situ tissue repair
US10/167,372 US20020156531A1 (en) 1994-05-06 2002-06-11 Biomaterial system for in situ tissue repair

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/193,973 Continuation US6443988B2 (en) 1994-05-06 1998-11-18 Mold apparatus and kit for in situ tissue repair

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/935,041 Continuation US20050043808A1 (en) 1994-05-06 2004-09-07 Knee joint prosthesis

Publications (1)

Publication Number Publication Date
US20020156531A1 true US20020156531A1 (en) 2002-10-24

Family

ID=27369064

Family Applications (7)

Application Number Title Priority Date Filing Date
US08/993,468 Expired - Fee Related US6306177B1 (en) 1994-05-06 1997-12-18 Biomaterial system for in situ tissue repair
US09/193,973 Expired - Fee Related US6443988B2 (en) 1994-05-06 1998-11-18 Mold apparatus and kit for in situ tissue repair
US10/167,372 Abandoned US20020156531A1 (en) 1994-05-06 2002-06-11 Biomaterial system for in situ tissue repair
US10/365,868 Expired - Fee Related US7001431B2 (en) 1994-05-06 2003-02-13 Intervertebral disc prosthesis
US10/365,842 Expired - Fee Related US7077865B2 (en) 1994-05-06 2003-02-13 Method of making an intervertebral disc prosthesis
US11/277,887 Expired - Fee Related US7713301B2 (en) 1994-05-06 2006-03-29 Intervertebral disc prosthesis
US11/428,120 Expired - Fee Related US7766965B2 (en) 1994-05-06 2006-06-30 Method of making an intervertebral disc prosthesis

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US08/993,468 Expired - Fee Related US6306177B1 (en) 1994-05-06 1997-12-18 Biomaterial system for in situ tissue repair
US09/193,973 Expired - Fee Related US6443988B2 (en) 1994-05-06 1998-11-18 Mold apparatus and kit for in situ tissue repair

Family Applications After (4)

Application Number Title Priority Date Filing Date
US10/365,868 Expired - Fee Related US7001431B2 (en) 1994-05-06 2003-02-13 Intervertebral disc prosthesis
US10/365,842 Expired - Fee Related US7077865B2 (en) 1994-05-06 2003-02-13 Method of making an intervertebral disc prosthesis
US11/277,887 Expired - Fee Related US7713301B2 (en) 1994-05-06 2006-03-29 Intervertebral disc prosthesis
US11/428,120 Expired - Fee Related US7766965B2 (en) 1994-05-06 2006-06-30 Method of making an intervertebral disc prosthesis

Country Status (5)

Country Link
US (7) US6306177B1 (en)
EP (2) EP0873145A2 (en)
JP (1) JP2002505592A (en)
AU (1) AU7178698A (en)
WO (1) WO1998020939A2 (en)

Cited By (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040073308A1 (en) * 2000-07-21 2004-04-15 Spineology, Inc. Expandable porous mesh bag device and methods of use for reduction, filling, fixation, and supporting of bone
US20040215344A1 (en) * 2000-02-28 2004-10-28 Stephen Hochschuler Method and apparatus for treating a vertebral body
US20050015140A1 (en) * 2003-07-14 2005-01-20 Debeer Nicholas Encapsulation device and methods of use
WO2005034781A1 (en) * 2003-09-29 2005-04-21 Promethean Surgical Devices Llc Devices and methods for spine repair
US20050113928A1 (en) * 2000-02-16 2005-05-26 Cragg Andrew H. Dual anchor prosthetic nucleus apparatus
WO2005065324A2 (en) * 2003-12-24 2005-07-21 Synecor, Llc Liquid perfluoropolymers and medical applications incorporating same
EP1599241A2 (en) * 2003-02-21 2005-11-30 Jeffrey S. Kadan Diagnostic needle arthroscopy and lavage system
US20050273146A1 (en) * 2003-12-24 2005-12-08 Synecor, Llc Liquid perfluoropolymers and medical applications incorporating same
US20050271794A1 (en) * 2003-12-24 2005-12-08 Synecor, Llc Liquid perfluoropolymers and medical and cosmetic applications incorporating same
US20060009779A1 (en) * 2004-06-29 2006-01-12 Keith Collins Devices for injecting a curable biomaterial into a intervertebral space
US20060195115A1 (en) * 2005-02-23 2006-08-31 Ferree Bret A Method and apparatus for kyphoplasty
US7184827B1 (en) * 2000-01-24 2007-02-27 Stuart D. Edwards Shrinkage of dilatations in the body
US20070067032A1 (en) * 2003-06-27 2007-03-22 Felt Jeffrey C Meniscus preserving implant method and apparatus
US20070093899A1 (en) * 2005-09-28 2007-04-26 Christof Dutoit Apparatus and methods for treating bone
US20070173943A1 (en) * 2003-01-17 2007-07-26 Dulak Gary R Artificial nucleus pulposus and method of injecting same
US20070208426A1 (en) * 2006-03-03 2007-09-06 Sdgi Holdings, Inc. Spinal implant with improved surface properties for delivery
US7329259B2 (en) 2000-02-16 2008-02-12 Transl Inc. Articulating spinal implant
US20080086133A1 (en) * 2003-05-16 2008-04-10 Spineology Expandable porous mesh bag device and methods of use for reduction, filling, fixation and supporting of bone
US20080195219A1 (en) * 2007-02-08 2008-08-14 Zimmer, Inc. Hydrogel proximal interphalangeal implant
US20080221700A1 (en) * 2005-08-31 2008-09-11 Zimmer, Gmbh Implant
US7481839B2 (en) * 2003-12-02 2009-01-27 Kyphon Sarl Bioresorbable interspinous process implant for use with intervertebral disk remediation or replacement implants and procedures
US20090036995A1 (en) * 2007-07-31 2009-02-05 Zimmer, Inc. Joint space interpositional prosthetic device with internal bearing surfaces
US20090048679A1 (en) * 2006-02-09 2009-02-19 Zimmer Gmbh Implant
US20090060974A1 (en) * 2007-08-27 2009-03-05 Reinhold Schmieding Methods of arthroscopic osteochondral resurfacing
US20090105792A1 (en) * 2007-10-19 2009-04-23 Kucklick Theodore R Method and Devices for Treating Damaged Articular Cartilage
US20090105772A1 (en) * 2005-11-09 2009-04-23 Zimmer Gmbh Implant
US20090130174A1 (en) * 2007-08-20 2009-05-21 Vanderbilt University Poly (ester urethane) urea foams with enhanced mechanical and biological properties
US20090187252A1 (en) * 2006-04-28 2009-07-23 Zimmer Gmbh Implant
US20090281250A1 (en) * 2004-02-13 2009-11-12 The University Of North Carolina At Chapel Hill Methods and materials for fabricating microfluidic devices
US7628859B1 (en) * 2002-12-27 2009-12-08 Advanced Cardiovascular Systems, Inc. Mounting assembly for a stent and a method of using the same to coat a stent
US20100049251A1 (en) * 2008-03-28 2010-02-25 Kuslich Stephen D Method and device for interspinous process fusion
US7727263B2 (en) 2000-02-16 2010-06-01 Trans1, Inc. Articulating spinal implant
US7740633B2 (en) 2003-10-23 2010-06-22 Trans1 Inc. Guide pin for guiding instrumentation along a soft tissue tract to a point on the spine
US7789912B2 (en) 2004-01-08 2010-09-07 Spine Wave, Inc. Apparatus and method for injecting fluent material at a distracted tissue site
US7799833B2 (en) 2001-11-01 2010-09-21 Spine Wave, Inc. System and method for the pretreatment of the endplates of an intervertebral disc
US7879103B2 (en) 2005-04-15 2011-02-01 Musculoskeletal Transplant Foundation Vertebral disc repair
US20110066244A1 (en) * 2009-09-11 2011-03-17 William Frasier Minimally Invasive Intervertebral Staple Distraction Devices
US20110066192A1 (en) * 2009-09-15 2011-03-17 William Frasier Expandable Ring Intervertebral Fusion Device
US7959683B2 (en) 2006-07-25 2011-06-14 Musculoskeletal Transplant Foundation Packed demineralized cancellous tissue forms for disc nucleus augmentation, restoration, or replacement and methods of implantation
US20110208308A1 (en) * 2006-11-28 2011-08-25 Columna Pty Ltd Tissue prosthesis insertion system and method
US20110224791A1 (en) * 2006-01-31 2011-09-15 Zimmer Technology, Inc. Orthopedic implant with bone interface anchoring
US8070818B2 (en) 2005-04-29 2011-12-06 Jmea Corporation Disc annulus repair system
US8197545B2 (en) 2005-10-27 2012-06-12 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
US8211126B2 (en) 2009-09-22 2012-07-03 Jmea Corporation Tissue repair system
US8556949B2 (en) 2007-11-14 2013-10-15 DePuy Synthes Products, LLC Hybrid bone fixation element and methods of using the same
US8668739B2 (en) 2010-08-20 2014-03-11 Zimmer, Inc. Unitary orthopedic implant
US20140074247A1 (en) * 2009-05-08 2014-03-13 Kevin L. Ohashi Joint reconstruction system and method
US8697139B2 (en) 2004-09-21 2014-04-15 Frank M. Phillips Method of intervertebral disc treatment using articular chondrocyte cells
US8702718B2 (en) 2005-04-29 2014-04-22 Jmea Corporation Implantation system for tissue repair
US8740846B2 (en) 1996-09-20 2014-06-03 Verathon, Inc. Treatment of tissue in sphincters, sinuses, and orifices
US8968284B2 (en) 2000-10-02 2015-03-03 Verathon Inc. Apparatus and methods for treating female urinary incontinence
US9023031B2 (en) 1997-08-13 2015-05-05 Verathon Inc. Noninvasive devices, methods, and systems for modifying tissues
US9155578B2 (en) 2012-02-28 2015-10-13 DePuy Synthes Products, Inc. Expandable fastener
US9204971B2 (en) 2003-06-27 2015-12-08 Memometal Technologies System and method for ankle arthroplasty
US9289240B2 (en) 2005-12-23 2016-03-22 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US9814598B2 (en) 2013-03-14 2017-11-14 Quandary Medical, Llc Spinal implants and implantation system

Families Citing this family (837)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5888220A (en) * 1994-05-06 1999-03-30 Advanced Bio Surfaces, Inc. Articulating joint repair
US6602248B1 (en) * 1995-06-07 2003-08-05 Arthro Care Corp. Methods for repairing damaged intervertebral discs
US20050004634A1 (en) * 1995-06-07 2005-01-06 Arthrocare Corporation Methods for electrosurgical treatment of spinal tissue
US6287322B1 (en) * 1995-12-07 2001-09-11 Loma Linda University Medical Center Tissue opening locator and everter and method
US7357798B2 (en) * 1996-07-16 2008-04-15 Arthrocare Corporation Systems and methods for electrosurgical prevention of disc herniations
US6726684B1 (en) * 1996-07-16 2004-04-27 Arthrocare Corporation Methods for electrosurgical spine surgery
AU7178698A (en) 1996-11-15 1998-06-03 Advanced Bio Surfaces, Inc. Biomaterial system for in situ tissue repair
US8771365B2 (en) 2009-02-25 2014-07-08 Conformis, Inc. Patient-adapted and improved orthopedic implants, designs, and related tools
US8234097B2 (en) 2001-05-25 2012-07-31 Conformis, Inc. Automated systems for manufacturing patient-specific orthopedic implants and instrumentation
US8545569B2 (en) 2001-05-25 2013-10-01 Conformis, Inc. Patient selectable knee arthroplasty devices
US8617242B2 (en) 2001-05-25 2013-12-31 Conformis, Inc. Implant device and method for manufacture
US8083745B2 (en) 2001-05-25 2011-12-27 Conformis, Inc. Surgical tools for arthroplasty
US7534263B2 (en) 2001-05-25 2009-05-19 Conformis, Inc. Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty
US9603711B2 (en) 2001-05-25 2017-03-28 Conformis, Inc. Patient-adapted and improved articular implants, designs and related guide tools
US10085839B2 (en) 2004-01-05 2018-10-02 Conformis, Inc. Patient-specific and patient-engineered orthopedic implants
US8556983B2 (en) 2001-05-25 2013-10-15 Conformis, Inc. Patient-adapted and improved orthopedic implants, designs and related tools
US8882847B2 (en) 2001-05-25 2014-11-11 Conformis, Inc. Patient selectable knee joint arthroplasty devices
US7618451B2 (en) * 2001-05-25 2009-11-17 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools facilitating increased accuracy, speed and simplicity in performing total and partial joint arthroplasty
US8735773B2 (en) 2007-02-14 2014-05-27 Conformis, Inc. Implant device and method for manufacture
US8480754B2 (en) 2001-05-25 2013-07-09 Conformis, Inc. Patient-adapted and improved articular implants, designs and related guide tools
US7468075B2 (en) 2001-05-25 2008-12-23 Conformis, Inc. Methods and compositions for articular repair
US5951160A (en) * 1997-11-20 1999-09-14 Biomet, Inc. Method and apparatus for packaging, mixing and delivering bone cement
DE69942858D1 (en) * 1998-06-01 2010-11-25 Kyphon S A R L DEFINABLE, PREFORMED STRUCTURES FOR ESTABLISHMENT IN REGIONS INSIDE THE BODY
US6477400B1 (en) 1998-08-20 2002-11-05 Sofamor Danek Holdings, Inc. Fluoroscopic image guided orthopaedic surgery system with intraoperative registration
US7239908B1 (en) 1998-09-14 2007-07-03 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and devising treatment
JP2002532126A (en) 1998-09-14 2002-10-02 スタンフォード ユニバーシティ Joint condition evaluation and damage prevention device
CA2591678C (en) * 1999-03-07 2008-05-20 Active Implants Corporation Method and apparatus for computerized surgery
US6146357A (en) * 1999-05-07 2000-11-14 Embol-X, Inc. Balloon occlusion diameter and pressure measuring devices and methods of use
AU4606700A (en) * 1999-05-07 2000-11-21 Salviac Limited A tissue engineering scaffold
US6245107B1 (en) * 1999-05-28 2001-06-12 Bret A. Ferree Methods and apparatus for treating disc herniation
US7273497B2 (en) 1999-05-28 2007-09-25 Anova Corp. Methods for treating a defect in the annulus fibrosis
US20070038231A1 (en) 1999-05-28 2007-02-15 Ferree Bret A Methods and apparatus for treating disc herniation and preventing the extrusion of interbody bone graft
US20060247665A1 (en) 1999-05-28 2006-11-02 Ferree Bret A Methods and apparatus for treating disc herniation and preventing the extrusion of interbody bone graft
US20020095157A1 (en) 1999-07-23 2002-07-18 Bowman Steven M. Graft fixation device combination
US6179840B1 (en) 1999-07-23 2001-01-30 Ethicon, Inc. Graft fixation device and method
US6719797B1 (en) * 1999-08-13 2004-04-13 Bret A. Ferree Nucleus augmentation with in situ formed hydrogels
US6685695B2 (en) * 1999-08-13 2004-02-03 Bret A. Ferree Method and apparatus for providing nutrition to intervertebral disc tissue
US7717961B2 (en) 1999-08-18 2010-05-18 Intrinsic Therapeutics, Inc. Apparatus delivery in an intervertebral disc
US8323341B2 (en) 2007-09-07 2012-12-04 Intrinsic Therapeutics, Inc. Impaction grafting for vertebral fusion
EP1328221B1 (en) 1999-08-18 2009-03-25 Intrinsic Therapeutics, Inc. Devices for nucleus pulposus augmentation and retention
US7998213B2 (en) 1999-08-18 2011-08-16 Intrinsic Therapeutics, Inc. Intervertebral disc herniation repair
US7553329B2 (en) 1999-08-18 2009-06-30 Intrinsic Therapeutics, Inc. Stabilized intervertebral disc barrier
WO2009033100A1 (en) 2007-09-07 2009-03-12 Intrinsic Therapeutics, Inc. Bone anchoring systems
US7972337B2 (en) * 2005-12-28 2011-07-05 Intrinsic Therapeutics, Inc. Devices and methods for bone anchoring
US7220281B2 (en) * 1999-08-18 2007-05-22 Intrinsic Therapeutics, Inc. Implant for reinforcing and annulus fibrosis
WO2004100841A1 (en) 1999-08-18 2004-11-25 Intrinsic Therapeutics, Inc. Devices and method for augmenting a vertebral disc nucleus
AU5812299A (en) 1999-09-07 2001-04-10 Microvena Corporation Retrievable septal defect closure device
US6371984B1 (en) * 1999-09-13 2002-04-16 Keraplast Technologies, Ltd. Implantable prosthetic or tissue expanding device
US7201774B2 (en) * 1999-10-08 2007-04-10 Ferree Bret A Artificial intervertebral disc replacements incorporating reinforced wall sections
US8128698B2 (en) 1999-10-20 2012-03-06 Anulex Technologies, Inc. Method and apparatus for the treatment of the intervertebral disc annulus
US20030153976A1 (en) 1999-10-20 2003-08-14 Cauthen Joseph C. Spinal disc annulus reconstruction method and spinal disc annulus stent
US7004970B2 (en) 1999-10-20 2006-02-28 Anulex Technologies, Inc. Methods and devices for spinal disc annulus reconstruction and repair
US7951201B2 (en) 1999-10-20 2011-05-31 Anulex Technologies, Inc. Method and apparatus for the treatment of the intervertebral disc annulus
US6592625B2 (en) 1999-10-20 2003-07-15 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and spinal disc annulus stent
US7935147B2 (en) 1999-10-20 2011-05-03 Anulex Technologies, Inc. Method and apparatus for enhanced delivery of treatment device to the intervertebral disc annulus
US7052516B2 (en) * 1999-10-20 2006-05-30 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and deformable spinal disc annulus stent
US7615076B2 (en) 1999-10-20 2009-11-10 Anulex Technologies, Inc. Method and apparatus for the treatment of the intervertebral disc annulus
US8632590B2 (en) 1999-10-20 2014-01-21 Anulex Technologies, Inc. Apparatus and methods for the treatment of the intervertebral disc
WO2001028469A2 (en) 1999-10-21 2001-04-26 Sdgi Holdings, Inc. Devices and techniques for a posterior lateral disc space approach
US7938836B2 (en) * 2003-10-23 2011-05-10 Trans1, Inc. Driver assembly for simultaneous axial delivery of spinal implants
US7776068B2 (en) * 2003-10-23 2010-08-17 Trans1 Inc. Spinal motion preservation assemblies
US7601171B2 (en) * 2003-10-23 2009-10-13 Trans1 Inc. Spinal motion preservation assemblies
AU2001243291A1 (en) * 2000-02-24 2001-09-03 Loma Linda University Medical Center Patch and glue delivery system for closing tissue openings during surgery
US6447514B1 (en) * 2000-03-07 2002-09-10 Zimmer Polymer filled hip fracture fixation device
US7488329B2 (en) 2000-03-07 2009-02-10 Zimmer Technology, Inc. Method and apparatus for reducing femoral fractures
US6332894B1 (en) * 2000-03-07 2001-12-25 Zimmer, Inc. Polymer filled spinal fusion cage
US7258692B2 (en) 2000-03-07 2007-08-21 Zimmer, Inc. Method and apparatus for reducing femoral fractures
US20030220644A1 (en) * 2002-05-23 2003-11-27 Thelen Sarah L. Method and apparatus for reducing femoral fractures
US7485119B2 (en) * 2000-03-07 2009-02-03 Zimmer Technology, Inc. Method and apparatus for reducing femoral fractures
US6626945B2 (en) * 2000-03-14 2003-09-30 Chondrosite, Llc Cartilage repair plug
US6805695B2 (en) 2000-04-04 2004-10-19 Spinalabs, Llc Devices and methods for annular repair of intervertebral discs
EP1272131B1 (en) * 2000-04-05 2006-03-01 Kyphon Inc. Devices for treating fractured and/or diseased bone
US6723335B1 (en) * 2000-04-07 2004-04-20 Jeffrey William Moehlenbruck Methods and compositions for treating intervertebral disc degeneration
US6875212B2 (en) 2000-06-23 2005-04-05 Vertelink Corporation Curable media for implantable medical device
CA2414168C (en) 2000-06-23 2010-02-09 University Of Southern California Percutaneous vertebral fusion system
US6964667B2 (en) 2000-06-23 2005-11-15 Sdgi Holdings, Inc. Formed in place fixation system with thermal acceleration
US6899713B2 (en) 2000-06-23 2005-05-31 Vertelink Corporation Formable orthopedic fixation system
US6749614B2 (en) 2000-06-23 2004-06-15 Vertelink Corporation Formable orthopedic fixation system with cross linking
FR2812185B1 (en) 2000-07-25 2003-02-28 Spine Next Sa SEMI-RIGID CONNECTION PIECE FOR RACHIS STABILIZATION
US6440152B1 (en) 2000-07-28 2002-08-27 Microvena Corporation Defect occluder release assembly and method
US7056321B2 (en) 2000-08-01 2006-06-06 Endius, Incorporated Method of securing vertebrae
US6890342B2 (en) * 2000-08-02 2005-05-10 Loma Linda University Method and apparatus for closing vascular puncture using hemostatic material
US8366787B2 (en) 2000-08-04 2013-02-05 Depuy Products, Inc. Hybrid biologic-synthetic bioabsorbable scaffolds
US6638312B2 (en) 2000-08-04 2003-10-28 Depuy Orthopaedics, Inc. Reinforced small intestinal submucosa (SIS)
JP2004521666A (en) 2000-08-28 2004-07-22 アドバンスト バイオ サーフェイシズ,インコーポレイティド Methods and systems for enhancing mammalian joints
CN1192750C (en) * 2000-08-28 2005-03-16 迪斯科动力学公司 Prosthesis of vertebral disc
US7503936B2 (en) * 2000-08-30 2009-03-17 Warsaw Orthopedic, Inc. Methods for forming and retaining intervertebral disc implants
US7204851B2 (en) * 2000-08-30 2007-04-17 Sdgi Holdings, Inc. Method and apparatus for delivering an intervertebral disc implant
US20020026244A1 (en) * 2000-08-30 2002-02-28 Trieu Hai H. Intervertebral disc nucleus implants and methods
US6620196B1 (en) * 2000-08-30 2003-09-16 Sdgi Holdings, Inc. Intervertebral disc nucleus implants and methods
WO2002022014A1 (en) 2000-09-14 2002-03-21 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and devising treatment
EP1322224B1 (en) 2000-09-14 2008-11-05 The Board Of Trustees Of The Leland Stanford Junior University Assessing condition of a joint and cartilage loss
US20030158545A1 (en) * 2000-09-28 2003-08-21 Arthrocare Corporation Methods and apparatus for treating back pain
US6953560B1 (en) 2000-09-28 2005-10-11 Advanced Cardiovascular Systems, Inc. Barriers for polymer-coated implantable medical devices and methods for making the same
US6716444B1 (en) 2000-09-28 2004-04-06 Advanced Cardiovascular Systems, Inc. Barriers for polymer-coated implantable medical devices and methods for making the same
WO2002043628A1 (en) * 2000-12-01 2002-06-06 Sabitzer Ronald J Method and device for expanding a body cavity
US8083768B2 (en) 2000-12-14 2011-12-27 Ensure Medical, Inc. Vascular plug having composite construction
US6896692B2 (en) 2000-12-14 2005-05-24 Ensure Medical, Inc. Plug with collet and apparatus and method for delivering such plugs
US6846319B2 (en) 2000-12-14 2005-01-25 Core Medical, Inc. Devices for sealing openings through tissue and apparatus and methods for delivering them
US20020127265A1 (en) * 2000-12-21 2002-09-12 Bowman Steven M. Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration
CA2365376C (en) 2000-12-21 2006-03-28 Ethicon, Inc. Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration
US6663662B2 (en) 2000-12-28 2003-12-16 Advanced Cardiovascular Systems, Inc. Diffusion barrier layer for implantable devices
EP1227094B1 (en) * 2001-01-30 2005-12-14 Nissan Chemical Industries Ltd. Isocyanurate compound and method for producing the same
US20020147496A1 (en) * 2001-04-06 2002-10-10 Integrated Vascular Systems, Inc. Apparatus for treating spinal discs
JP4499310B2 (en) * 2001-04-12 2010-07-07 経憲 武井 Surgical instruments
US20050209629A1 (en) * 2001-04-19 2005-09-22 Kerr Sean H Resorbable containment device and process for making and using same
US6632235B2 (en) 2001-04-19 2003-10-14 Synthes (U.S.A.) Inflatable device and method for reducing fractures in bone and in treating the spine
WO2002085262A1 (en) * 2001-04-24 2002-10-31 Galley Geoffrey H Surgical restoration of an intervertebral disc
US8439926B2 (en) 2001-05-25 2013-05-14 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US8951260B2 (en) 2001-05-25 2015-02-10 Conformis, Inc. Surgical cutting guide
AU2002310193B8 (en) 2001-05-25 2007-05-17 Conformis, Inc. Methods and compositions for articular resurfacing
US7308300B2 (en) * 2001-05-30 2007-12-11 Acist Medical Systems, Inc. Medical injection system
US6537300B2 (en) * 2001-05-30 2003-03-25 Scimed Life Systems, Inc. Implantable obstruction device for septal defects
US7156877B2 (en) * 2001-06-29 2007-01-02 The Regents Of The University Of California Biodegradable/bioactive nucleus pulposus implant and method for treating degenerated intervertebral discs
US20090234457A1 (en) * 2001-06-29 2009-09-17 The Regents Of The University Of California Systems, devices and methods for treatment of intervertebral disorders
WO2003007787A2 (en) 2001-07-16 2003-01-30 Depuy Products, Inc. Cartilage repair and regeneration device and method
US7914808B2 (en) 2001-07-16 2011-03-29 Depuy Products, Inc. Hybrid biologic/synthetic porous extracellular matrix scaffolds
AU2002322567B2 (en) 2001-07-16 2007-09-06 Depuy Products, Inc. Devices form naturally occurring biologically derived
US8025896B2 (en) 2001-07-16 2011-09-27 Depuy Products, Inc. Porous extracellular matrix scaffold and method
US7361195B2 (en) * 2001-07-16 2008-04-22 Depuy Products, Inc. Cartilage repair apparatus and method
US7819918B2 (en) 2001-07-16 2010-10-26 Depuy Products, Inc. Implantable tissue repair device
EP1416888A4 (en) 2001-07-16 2007-04-25 Depuy Products Inc Meniscus regeneration device and method
US7288105B2 (en) 2001-08-01 2007-10-30 Ev3 Endovascular, Inc. Tissue opening occluder
US6589286B1 (en) * 2001-09-12 2003-07-08 Jason Litner Eustachian tube stent
AU2002362310A1 (en) * 2001-09-14 2003-04-01 Arthrocare Corporation Methods and apparatus for treating intervertebral discs
JP3993855B2 (en) 2001-11-01 2007-10-17 スパイン・ウェイブ・インコーポレーテッド Device for spinal disc recovery
DE10154163A1 (en) 2001-11-03 2003-05-22 Advanced Med Tech Device for straightening and stabilizing the spine
US20030130738A1 (en) * 2001-11-08 2003-07-10 Arthrocare Corporation System and method for repairing a damaged intervertebral disc
DE50111393D1 (en) * 2001-12-05 2006-12-14 Synthes Gmbh BRAKE PURTHEES OR NUCLEUS PROSTHESIS
SE0104323D0 (en) * 2001-12-20 2001-12-20 Matts Andersson Method and arrangement of implants for preferably human intermediate disc and such implant
US6733534B2 (en) * 2002-01-29 2004-05-11 Sdgi Holdings, Inc. System and method for spine spacing
US6942475B2 (en) * 2002-03-13 2005-09-13 Ortho Development Corporation Disposable knee mold
US8529956B2 (en) 2002-03-18 2013-09-10 Carnell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US20040127563A1 (en) * 2002-03-22 2004-07-01 Deslauriers Richard J. Methods of performing medical procedures which promote bone growth, compositions which promote bone growth, and methods of making such compositions
US20030195630A1 (en) * 2002-04-10 2003-10-16 Ferree Bret A. Disc augmentation using materials that expand in situ
CN1306910C (en) * 2002-06-14 2007-03-28 洛马林达大学医学中心 Vascular wound closure device and method
US6793678B2 (en) 2002-06-27 2004-09-21 Depuy Acromed, Inc. Prosthetic intervertebral motion disc having dampening
WO2004006811A2 (en) * 2002-07-11 2004-01-22 Advanced Bio Surfaces, Inc. Method and kit for interpositional arthroplasty
FR2842724B1 (en) 2002-07-23 2005-05-27 Spine Next Sa VERTEBRAL FASTENING SYSTEM
US7485670B2 (en) 2002-08-02 2009-02-03 Cambridge Polymer Group, Inc. Systems and methods for controlling and forming polymer gels
US7745532B2 (en) * 2002-08-02 2010-06-29 Cambridge Polymer Group, Inc. Systems and methods for controlling and forming polymer gels
US7901407B2 (en) * 2002-08-02 2011-03-08 Boston Scientific Scimed, Inc. Media delivery device for bone structures
CA2495373C (en) * 2002-08-15 2012-07-24 David Gerber Controlled artificial intervertebral disc implant
DE60322066D1 (en) * 2002-08-15 2008-08-21 Hfsc Co BAND DISC IMPLANT
US20040054413A1 (en) * 2002-09-16 2004-03-18 Howmedica Osteonics Corp. Radiovisible hydrogel intervertebral disc nucleus
US7309359B2 (en) * 2003-08-21 2007-12-18 Warsaw Orthopedic, Inc. Allogenic/xenogenic implants and methods for augmenting or repairing intervertebral discs
US20040054414A1 (en) * 2002-09-18 2004-03-18 Trieu Hai H. Collagen-based materials and methods for augmenting intervertebral discs
US7744651B2 (en) 2002-09-18 2010-06-29 Warsaw Orthopedic, Inc Compositions and methods for treating intervertebral discs with collagen-based materials
CA2499116A1 (en) * 2002-09-18 2004-04-01 Sdgi Holdings, Inc. Natural tissue devices and methods of implantation
EP1542616B1 (en) 2002-09-20 2015-04-22 Endologix, Inc. Stent-graft with positioning anchor
CA2499035A1 (en) * 2002-09-24 2004-04-08 Bogomir Gorensek Stabilizing device for intervertebral disc, and methods thereof
US6932843B2 (en) 2002-09-25 2005-08-23 Medicinelodge, Inc. Apparatus and method for the in-situ formation of a structural prosthesis
US20110153021A1 (en) * 2002-10-01 2011-06-23 Spinecell Pty Ltd. Acn 114 462 725 Nucleus pulposus replacement device
ATE497740T1 (en) * 2002-10-07 2011-02-15 Conformis Inc MINIMALLY INVASIVE JOINT IMPLANT WITH A THREE-DIMENSIONAL GEOMETRY ADAPTED TO THE JOINT SURFACES
GB0223327D0 (en) * 2002-10-08 2002-11-13 Ranier Ltd Artificial spinal disc
US7320686B2 (en) * 2002-10-09 2008-01-22 Depuy Acromed, Inc. Device for distracting vertebrae and delivering a flowable material into a disc space
US20040078090A1 (en) 2002-10-18 2004-04-22 Francois Binette Biocompatible scaffolds with tissue fragments
US7824701B2 (en) 2002-10-18 2010-11-02 Ethicon, Inc. Biocompatible scaffold for ligament or tendon repair
US7549999B2 (en) 2003-05-22 2009-06-23 Kyphon Sarl Interspinous process distraction implant and method of implantation
US20080021468A1 (en) 2002-10-29 2008-01-24 Zucherman James F Interspinous process implants and methods of use
HUP0203719A2 (en) * 2002-10-31 2007-09-28 Stepan Dr Gudak Polyuretan composition for fillin blood vessels and method of aplication of it
WO2004041075A2 (en) * 2002-11-05 2004-05-21 Spineology, Inc. A semi-biological intervertebral disc replacement system
US7351430B2 (en) * 2002-11-06 2008-04-01 Uluru Inc. Shape-retentive hydrogel particle aggregates and their uses
US7811605B2 (en) * 2002-11-06 2010-10-12 Uluru Inc. Method of formation of shape-retentive aggregates of gel particles and their uses
EP3075356B1 (en) 2002-11-07 2023-07-05 ConforMIS, Inc. Method of selecting a meniscal implant
US7621903B2 (en) * 2002-11-12 2009-11-24 Delegge Rebecca Anchor for implanted devices and method of using same
CN100394989C (en) 2002-11-15 2008-06-18 华沙整形外科股份有限公司 Collagen-based materials and methods for augmenting intervertebral discs
JP2006507090A (en) * 2002-11-21 2006-03-02 エスディージーアイ・ホールディングス・インコーポレーテッド System for intravertebral reduction
WO2004047689A1 (en) * 2002-11-21 2004-06-10 Sdgi Holdings, Inc. Systems and techniques for intravertebral spinal stablization with expandable devices
US20040186471A1 (en) * 2002-12-07 2004-09-23 Sdgi Holdings, Inc. Method and apparatus for intervertebral disc expansion
US20040127893A1 (en) * 2002-12-13 2004-07-01 Arthrocare Corporation Methods for visualizing and treating intervertebral discs
EP2072064B1 (en) 2003-01-02 2019-04-24 de Vries, Alexander Cornelis Composition for in vivo vessel repair
EP1435248A1 (en) * 2003-01-02 2004-07-07 Vesalius N.V. Composition for in vivo vessel repair
WO2004065450A2 (en) * 2003-01-16 2004-08-05 Carnegie Mellon University Biodegradable polyurethanes and use thereof
WO2004069296A1 (en) * 2003-01-31 2004-08-19 Zimmer Orthobiologics Inc. Hydrogel compositions comprising nucleus pulposus tissue
GB2397766A (en) * 2003-02-03 2004-08-04 Univ London A Surgical Kit For Hemiarthroplasty Hip Replacement
WO2004069890A2 (en) 2003-02-04 2004-08-19 Osteotech, Inc. Polyurethanes for osteoimplants
EP1596723A2 (en) 2003-02-04 2005-11-23 ev3 Sunnyvale, Inc. Patent foramen ovale closure system
WO2004073563A2 (en) 2003-02-14 2004-09-02 Depuy Spine, Inc. In-situ formed intervertebral fusion device
US8197837B2 (en) 2003-03-07 2012-06-12 Depuy Mitek, Inc. Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof
US7771478B2 (en) * 2003-04-04 2010-08-10 Theken Spine, Llc Artificial disc prosthesis
KR101161784B1 (en) * 2003-04-11 2012-07-05 에텍스 코포레이션 Osteoinductive Bone Material
US7067123B2 (en) * 2003-04-29 2006-06-27 Musculoskeletal Transplant Foundation Glue for cartilage repair
US7794456B2 (en) 2003-05-13 2010-09-14 Arthrocare Corporation Systems and methods for electrosurgical intervertebral disc replacement
US7901457B2 (en) 2003-05-16 2011-03-08 Musculoskeletal Transplant Foundation Cartilage allograft plug
TWI235055B (en) * 2003-05-21 2005-07-01 Guan-Gu Lin Filling device capable of removing animal tissues
TW587932B (en) 2003-05-21 2004-05-21 Guan-Gu Lin Removable animal tissue filling device
US20040249459A1 (en) * 2003-06-02 2004-12-09 Ferree Bret A. Nucleus replacements with asymmetrical stiffness
US7632291B2 (en) 2003-06-13 2009-12-15 Trivascular2, Inc. Inflatable implant
DK1638485T3 (en) 2003-06-20 2011-05-02 Intrinsic Therapeutics Inc Device for delivery of an implant through an annular defect in an intervertebral disc
US20040267367A1 (en) 2003-06-30 2004-12-30 Depuy Acromed, Inc Intervertebral implant with conformable endplate
US8226715B2 (en) 2003-06-30 2012-07-24 Depuy Mitek, Inc. Scaffold for connective tissue repair
US7758647B2 (en) * 2003-07-25 2010-07-20 Impliant Ltd. Elastomeric spinal disc nucleus replacement
US7537788B2 (en) * 2003-07-25 2009-05-26 Rubicor Medical, Inc. Post-biopsy cavity treatment implants and methods
US6958077B2 (en) * 2003-07-29 2005-10-25 Loubert Suddaby Inflatable nuclear prosthesis
US10583220B2 (en) 2003-08-11 2020-03-10 DePuy Synthes Products, Inc. Method and apparatus for resurfacing an articular surface
WO2005016152A2 (en) 2003-08-14 2005-02-24 Loma Linda University Medical Center Vascular wound closure device
US20050131417A1 (en) * 2003-08-22 2005-06-16 Ahern James W. Kit for treating bony defects
DE10340150A1 (en) * 2003-08-26 2005-03-31 Aesculap Ag & Co. Kg Implant for closing an opening of the annulus fibrosus
US9326806B2 (en) * 2003-09-02 2016-05-03 Crosstrees Medical, Inc. Devices and methods for the treatment of bone fracture
US8187627B2 (en) * 2003-09-05 2012-05-29 Loma Linda University Medical Center Dressing delivery system for internal wounds
AU2004272602B2 (en) * 2003-09-12 2010-07-22 Lubrizol Advanced Materials, Inc. Improved agricultural soil heating processes using aromatic thermoplastic polyurethane films
EP1516636A3 (en) * 2003-09-19 2005-08-03 Broockeville Corporation N.V. Use of a curable elastomer-precursor for a medical treatment
TW200511970A (en) * 2003-09-29 2005-04-01 Kwan-Ku Lin A spine wrapping and filling apparatus
US7655012B2 (en) 2003-10-02 2010-02-02 Zimmer Spine, Inc. Methods and apparatuses for minimally invasive replacement of intervertebral discs
US20050090899A1 (en) * 2003-10-24 2005-04-28 Dipoto Gene Methods and apparatuses for treating the spine through an access device
US20050113923A1 (en) * 2003-10-03 2005-05-26 David Acker Prosthetic spinal disc nucleus
US8974528B2 (en) * 2003-10-08 2015-03-10 The University Of North Carolina At Chapel Hill Spine replacement system for the treatment of spine instability and degenerative disc disease
US8852229B2 (en) 2003-10-17 2014-10-07 Cordis Corporation Locator and closure device and method of use
US7708733B2 (en) 2003-10-20 2010-05-04 Arthrocare Corporation Electrosurgical method and apparatus for removing tissue within a bone body
US7004972B2 (en) * 2003-11-03 2006-02-28 Taek-Rim Yoon Two-incision minimally invasive total hip arthroplasty
US20050105384A1 (en) * 2003-11-18 2005-05-19 Scimed Life Systems, Inc. Apparatus for mixing and dispensing a multi-component bone cement
JP2007512874A (en) * 2003-11-18 2007-05-24 スパイナル・エレメンツ・インコーポレーテッド Osteoconductive integrated spinal cage and method of making same
US20050119752A1 (en) * 2003-11-19 2005-06-02 Synecor Llc Artificial intervertebral disc
US7316822B2 (en) 2003-11-26 2008-01-08 Ethicon, Inc. Conformable tissue repair implant capable of injection delivery
US7901461B2 (en) 2003-12-05 2011-03-08 Ethicon, Inc. Viable tissue repair implants and methods of use
US7553320B2 (en) * 2003-12-10 2009-06-30 Warsaw Orthopedic, Inc. Method and apparatus for replacing the function of facet joints
ATE515245T1 (en) 2003-12-11 2011-07-15 Isto Technologies Inc PARTICLE CARTILAGE SYSTEM
WO2005069957A2 (en) * 2004-01-20 2005-08-04 Alexander Michalow Unicondylar knee implant
US7842013B2 (en) * 2004-01-23 2010-11-30 Genico, Inc. Trocar and cannula assembly having conical valve and related methods
US11395865B2 (en) 2004-02-09 2022-07-26 DePuy Synthes Products, Inc. Scaffolds with viable tissue
US20050197711A1 (en) * 2004-03-03 2005-09-08 Cachia Victor V. Catheter deliverable foot implant and method of delivering the same
US20050229433A1 (en) 2004-03-03 2005-10-20 Cachia Victor V Catheter deliverable foot implant and method of delivering the same
US8945223B2 (en) 2004-03-12 2015-02-03 Warsaw Orthopedic, Inc. In-situ formable nucleus pulposus implant with water absorption and swelling capability
US20060135959A1 (en) * 2004-03-22 2006-06-22 Disc Dynamics, Inc. Nuclectomy method and apparatus
US20050209602A1 (en) 2004-03-22 2005-09-22 Disc Dynamics, Inc. Multi-stage biomaterial injection system for spinal implants
EP1789088A4 (en) 2004-03-24 2009-12-30 Doctor S Res Group Inc Methods of performing medical procedures that promote bone growth, methods of making compositions that promote bone growth, and apparatus for use in such methods
DE102004016397A1 (en) * 2004-03-26 2005-10-13 Ossacur Ag Application aid for the treatment of bone defects
US7896881B2 (en) * 2004-03-30 2011-03-01 Depuy Products, Inc. Acetabular instrument and associated method
JP2007533376A (en) * 2004-04-15 2007-11-22 エテックス コーポレーション Delayed solidification calcium phosphate paste
US7465318B2 (en) 2004-04-15 2008-12-16 Soteira, Inc. Cement-directing orthopedic implants
US7824390B2 (en) 2004-04-16 2010-11-02 Kyphon SÀRL Spinal diagnostic methods and apparatus
US7452351B2 (en) 2004-04-16 2008-11-18 Kyphon Sarl Spinal diagnostic methods and apparatus
US8137686B2 (en) 2004-04-20 2012-03-20 Depuy Mitek, Inc. Nonwoven tissue scaffold
US8221780B2 (en) 2004-04-20 2012-07-17 Depuy Mitek, Inc. Nonwoven tissue scaffold
US20050245938A1 (en) * 2004-04-28 2005-11-03 Kochan Jeffrey P Method and apparatus for minimally invasive repair of intervertebral discs and articular joints
BRPI0510550A (en) * 2004-05-03 2007-11-20 Ams Res Corp surgical implant, surgical kit, method for forming or assembling a surgical implant, insertion mold, apparatus, and method for producing a surgical implant
US7567834B2 (en) 2004-05-03 2009-07-28 Medtronic Navigation, Inc. Method and apparatus for implantation between two vertebral bodies
WO2005112833A1 (en) * 2004-05-20 2005-12-01 Pearsalls Limited Improvements in and relating to surgical implants
US8142462B2 (en) * 2004-05-28 2012-03-27 Cavitech, Llc Instruments and methods for reducing and stabilizing bone fractures
US20060095138A1 (en) 2004-06-09 2006-05-04 Csaba Truckai Composites and methods for treating bone
EP1763320B8 (en) 2004-06-23 2020-01-01 Bioprotect Ltd. Device for tissue displacement or separation
CA2572603C (en) * 2004-06-29 2013-01-15 Biocure, Inc. Spinal disc nucleus pulposus implant
US8206448B2 (en) 2004-10-29 2012-06-26 Spinal Restoration, Inc. Injection of fibrin sealant using reconstituted components in spinal applications
US7597687B2 (en) * 2004-10-29 2009-10-06 Spinal Restoration, Inc. Injection of fibrin sealant including an anesthetic in spinal applications
US8357147B2 (en) * 2005-08-17 2013-01-22 Spinal Restoration, Inc. Method for repairing intervertebral discs
US8048145B2 (en) 2004-07-22 2011-11-01 Endologix, Inc. Graft systems having filling structures supported by scaffolds and methods for their use
CA2576660A1 (en) * 2004-08-09 2006-02-23 Trans1, Inc. Prosthetic nucleus apparatus and methods
US8038682B2 (en) 2004-08-17 2011-10-18 Boston Scientific Scimed, Inc. Apparatus and methods for delivering compounds into vertebrae for vertebroplasty
JP2008511422A (en) * 2004-09-02 2008-04-17 クロストゥリーズ・メディカル・インコーポレーテッド Device and method for distraction of spinal disc space
US20060052870A1 (en) * 2004-09-09 2006-03-09 Ferree Bret A Methods and apparatus to prevent movement through artificial disc replacements
US7641688B2 (en) * 2004-09-16 2010-01-05 Evera Medical, Inc. Tissue augmentation device
AU2005292029A1 (en) * 2004-09-30 2006-04-13 Synecor, Llc Artificial intervertebral disc nucleus
US20090088846A1 (en) 2007-04-17 2009-04-02 David Myung Hydrogel arthroplasty device
US7235592B2 (en) 2004-10-12 2007-06-26 Zimmer Gmbh PVA hydrogel
US7837740B2 (en) 2007-01-24 2010-11-23 Musculoskeletal Transplant Foundation Two piece cancellous construct for cartilage repair
US20060085073A1 (en) * 2004-10-18 2006-04-20 Kamshad Raiszadeh Medical device systems for the spine
US8167944B2 (en) 2004-10-20 2012-05-01 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for posterior dynamic stabilization of the spine
US7763074B2 (en) 2004-10-20 2010-07-27 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for posterior dynamic stabilization of the spine
US8123807B2 (en) 2004-10-20 2012-02-28 Vertiflex, Inc. Systems and methods for posterior dynamic stabilization of the spine
US8864828B2 (en) 2004-10-20 2014-10-21 Vertiflex, Inc. Interspinous spacer
US8012207B2 (en) 2004-10-20 2011-09-06 Vertiflex, Inc. Systems and methods for posterior dynamic stabilization of the spine
US9023084B2 (en) 2004-10-20 2015-05-05 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for stabilizing the motion or adjusting the position of the spine
US8123782B2 (en) 2004-10-20 2012-02-28 Vertiflex, Inc. Interspinous spacer
US8945183B2 (en) 2004-10-20 2015-02-03 Vertiflex, Inc. Interspinous process spacer instrument system with deployment indicator
US9161783B2 (en) 2004-10-20 2015-10-20 Vertiflex, Inc. Interspinous spacer
US8128662B2 (en) 2004-10-20 2012-03-06 Vertiflex, Inc. Minimally invasive tooling for delivery of interspinous spacer
US8317864B2 (en) 2004-10-20 2012-11-27 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for posterior dynamic stabilization of the spine
WO2009009049A2 (en) 2004-10-20 2009-01-15 Vertiflex, Inc. Interspinous spacer
US9119680B2 (en) 2004-10-20 2015-09-01 Vertiflex, Inc. Interspinous spacer
US8152837B2 (en) 2004-10-20 2012-04-10 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for posterior dynamic stabilization of the spine
US8613747B2 (en) 2004-10-20 2013-12-24 Vertiflex, Inc. Spacer insertion instrument
US8277488B2 (en) 2004-10-20 2012-10-02 Vertiflex, Inc. Interspinous spacer
US8409282B2 (en) 2004-10-20 2013-04-02 Vertiflex, Inc. Systems and methods for posterior dynamic stabilization of the spine
US8425559B2 (en) 2004-10-20 2013-04-23 Vertiflex, Inc. Systems and methods for posterior dynamic stabilization of the spine
US20110213464A1 (en) * 2004-10-29 2011-09-01 Whitlock Steven I Injection of fibrin sealant in the absence of corticosteroids in spinal applications
US7559932B2 (en) 2004-12-06 2009-07-14 Dfine, Inc. Bone treatment systems and methods
US7678116B2 (en) * 2004-12-06 2010-03-16 Dfine, Inc. Bone treatment systems and methods
US8318820B2 (en) * 2004-11-05 2012-11-27 Carnegie Mellon University Degradable polyurethane foams
US7682378B2 (en) 2004-11-10 2010-03-23 Dfine, Inc. Bone treatment systems and methods for introducing an abrading structure to abrade bone
US7799078B2 (en) * 2004-11-12 2010-09-21 Warsaw Orthopedic, Inc. Implantable vertebral lift
US8562607B2 (en) * 2004-11-19 2013-10-22 Dfine, Inc. Bone treatment systems and methods
US20060122614A1 (en) * 2004-12-06 2006-06-08 Csaba Truckai Bone treatment systems and methods
AU2008343092B2 (en) 2004-12-06 2014-09-11 Vertiflex, Inc. Spacer insertion instrument
US7722620B2 (en) * 2004-12-06 2010-05-25 Dfine, Inc. Bone treatment systems and methods
US8070753B2 (en) 2004-12-06 2011-12-06 Dfine, Inc. Bone treatment systems and methods
US7717918B2 (en) 2004-12-06 2010-05-18 Dfine, Inc. Bone treatment systems and methods
US20090264939A9 (en) * 2004-12-16 2009-10-22 Martz Erik O Instrument set and method for performing spinal nuclectomy
US20060149372A1 (en) * 2004-12-17 2006-07-06 Paxson Robert D Artificial spinal disc
US20060282169A1 (en) * 2004-12-17 2006-12-14 Felt Jeffrey C System and method for upper extremity joint arthroplasty
CH697330B1 (en) 2004-12-28 2008-08-29 Synthes Gmbh Intervertebral prosthesis.
AR055833A1 (en) * 2005-01-07 2007-09-12 Celonova Biosciences Inc IMPLANTABLE THREE DIMENSIONAL BEAR SUPPORT
JP2008526373A (en) * 2005-01-08 2008-07-24 アルファスパイン インコーポレイテッド Modular disk device
US20060184192A1 (en) * 2005-02-11 2006-08-17 Markworth Aaron D Systems and methods for providing cavities in interior body regions
US8828080B2 (en) 2005-02-22 2014-09-09 Barry M. Fell Method and system for knee joint repair
JP2008531769A (en) 2005-02-23 2008-08-14 ズィマー・テクノロジー・インコーポレーテッド Blend hydrogel and method for producing the same
US20060200245A1 (en) * 2005-03-07 2006-09-07 Sdgi Holdings, Inc. Materials, devices, and methods for in-situ formation of composite intervertebral implants
US8696707B2 (en) * 2005-03-08 2014-04-15 Zyga Technology, Inc. Facet joint stabilization
US7267690B2 (en) 2005-03-09 2007-09-11 Vertebral Technologies, Inc. Interlocked modular disc nucleus prosthesis
US7857856B2 (en) * 2005-03-15 2010-12-28 Warsaw Ortho Pedic, Inc. Composite spinal nucleus implant with water absorption and swelling capabilities
AU2006226818B2 (en) * 2005-03-24 2011-05-12 Medtronic, Inc. Modification of thermoplastic polymers
DE102005054479A1 (en) * 2005-03-24 2006-09-28 Fehling Ag Method and device for producing spinal implants
US7931029B2 (en) * 2005-03-25 2011-04-26 Boston Scientific Scimed, Inc. Method and apparatus for uterus stabilization
JP2008534147A (en) 2005-03-29 2008-08-28 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Method and apparatus for implanting hydrogel prosthesis for nucleus pulposus
US20060224244A1 (en) * 2005-03-31 2006-10-05 Zimmer Technology, Inc. Hydrogel implant
US20060235542A1 (en) * 2005-04-15 2006-10-19 Zimmer Technology, Inc. Flexible segmented bearing implant
US20060241758A1 (en) * 2005-04-20 2006-10-26 Sdgi Holdings, Inc. Facet spacers
US20060241766A1 (en) * 2005-04-20 2006-10-26 Sdgi Holdings, Inc. Method and apparatus for preventing articulation in an artificial joint
US20060241759A1 (en) * 2005-04-25 2006-10-26 Sdgi Holdings, Inc. Oriented polymeric spinal implants
US8109866B2 (en) * 2005-04-26 2012-02-07 Ams Research Corporation Method and apparatus for prolapse repair
US20060247780A1 (en) * 2005-04-27 2006-11-02 Bert Jeffrey K Expandable artificial disc and associated methods and instrumentation
US7608108B2 (en) * 2005-04-29 2009-10-27 Jmea Corporation Tissue repair system
US20060247776A1 (en) 2005-05-02 2006-11-02 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for augmenting intervertebral discs
US20060253198A1 (en) * 2005-05-03 2006-11-09 Disc Dynamics, Inc. Multi-lumen mold for intervertebral prosthesis and method of using same
US20060265076A1 (en) * 2005-05-03 2006-11-23 Disc Dynamics, Inc. Catheter holder for spinal implant
US8926654B2 (en) 2005-05-04 2015-01-06 Cordis Corporation Locator and closure device and method of use
US20070049849A1 (en) * 2005-05-24 2007-03-01 Schwardt Jeffrey D Bone probe apparatus and method of use
KR101330340B1 (en) * 2005-05-24 2013-11-15 버터브럴 테크놀로지스, 인크. Rail-based modular disc nucleus prosthesis
US20070042326A1 (en) * 2005-06-01 2007-02-22 Osseous Technologies Of America Collagen antral membrane expander
WO2006133130A2 (en) * 2005-06-03 2006-12-14 Nuvasive, Inc. Fibrous spinal implant and method of implantation
US7628800B2 (en) * 2005-06-03 2009-12-08 Warsaw Orthopedic, Inc. Formed in place corpectomy device
US7547319B2 (en) * 2005-06-15 2009-06-16 Ouroboros Medical Mechanical apparatus and method for artificial disc replacement
US7988735B2 (en) * 2005-06-15 2011-08-02 Matthew Yurek Mechanical apparatus and method for delivering materials into the inter-vertebral body space for nucleus replacement
KR100948082B1 (en) * 2005-06-15 2010-04-01 베절릴 엘엘씨 Tool and Technique for Continually Delivering an Orthopaedic Paste
US20060293561A1 (en) * 2005-06-24 2006-12-28 Abay Eustaquio O Ii System and methods for intervertebral disc surgery
US20070010815A1 (en) * 2005-06-30 2007-01-11 Sdgi Holdings, Inc. Fixation systems with modulated stiffness
US7666220B2 (en) * 2005-07-07 2010-02-23 Nellix, Inc. System and methods for endovascular aneurysm treatment
CN101272742B (en) * 2005-07-07 2011-08-31 十字桅杆药品公司 Devices for the treatment of bone fracture
EP1909707A2 (en) * 2005-07-11 2008-04-16 Kyphon Inc. Systems and methods for providing prostheses
EP1909671B1 (en) * 2005-07-11 2012-01-18 Kyphon SÀRL System for inserting biocompatible filler materials in interior body regions
US7815926B2 (en) * 2005-07-11 2010-10-19 Musculoskeletal Transplant Foundation Implant for articular cartilage repair
CN101267783A (en) * 2005-07-19 2008-09-17 脊椎科技股份有限公司 Multi-composite disc prosthesis
US7611537B2 (en) * 2005-08-01 2009-11-03 Warsaw Orthopedic, Inc. System, device, and method for percutaneous interbody device and nucleus removal system
US7618457B2 (en) * 2005-08-10 2009-11-17 Zimmer Spine, Inc. Devices and methods for disc nucleus replacement
US7722674B1 (en) 2005-08-12 2010-05-25 Innvotec Surgical Inc. Linearly expanding spine cage for enhanced spinal fusion
WO2007019631A1 (en) 2005-08-15 2007-02-22 Columna Pty Ltd A tissue prosthesis and a method of, and equipment for, forming a tissue prosthesis
US8777479B2 (en) 2008-10-13 2014-07-15 Dfine, Inc. System for use in bone cement preparation and delivery
US8540723B2 (en) 2009-04-14 2013-09-24 Dfine, Inc. Medical system and method of use
US9066769B2 (en) 2005-08-22 2015-06-30 Dfine, Inc. Bone treatment systems and methods
WO2007025290A2 (en) 2005-08-26 2007-03-01 Isto Technologies, Inc. Implants and methods for repair, replacement and treatment of joint disease
US7731753B2 (en) * 2005-09-01 2010-06-08 Spinal Kinetics, Inc. Prosthetic intervertebral discs
EP1926459B1 (en) 2005-09-19 2015-01-07 Histogenics Corporation Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof
US20070067036A1 (en) * 2005-09-20 2007-03-22 Zimmer Spine, Inc. Hydrogel total disc prosthesis
FR2890851B1 (en) * 2005-09-21 2008-06-20 Abbott Spine Sa ANCILLARY TO TENSION A FLEXIBLE LINK.
US9028550B2 (en) 2005-09-26 2015-05-12 Coalign Innovations, Inc. Selectively expanding spine cage with enhanced bone graft infusion
US8070813B2 (en) 2005-09-26 2011-12-06 Coalign Innovations, Inc. Selectively expanding spine cage, hydraulically controllable in three dimensions for vertebral body replacement
US7985256B2 (en) 2005-09-26 2011-07-26 Coalign Innovations, Inc. Selectively expanding spine cage, hydraulically controllable in three dimensions for enhanced spinal fusion
US8088145B2 (en) * 2005-10-05 2012-01-03 Loma Linda University Medical Center Vascular wound closure device and method
US20070093906A1 (en) * 2005-10-26 2007-04-26 Zimmer Spine, Inc. Nucleus implant and method
US20070173935A1 (en) * 2005-10-28 2007-07-26 O'neil Michael J Nucleus pulposus augmentation pretreatment technique
US7927373B2 (en) * 2005-10-31 2011-04-19 Depuy Spine, Inc. Intervertebral disc prosthesis
US20070100449A1 (en) * 2005-10-31 2007-05-03 O'neil Michael Injectable soft tissue fixation technique
US8202320B2 (en) * 2005-10-31 2012-06-19 Depuy Spine, Inc. Intervertebral disc prosthesis
US8403985B2 (en) * 2005-11-02 2013-03-26 Zimmer, Inc. Joint spacer implant
US7744630B2 (en) * 2005-11-15 2010-06-29 Zimmer Spine, Inc. Facet repair and stabilization
US20070118218A1 (en) * 2005-11-22 2007-05-24 Hooper David M Facet joint implant and procedure
EP1957012A4 (en) * 2005-11-22 2012-05-02 Bonwrx Method and composition for repair and reconstruction of intervertebral discs and other reconstructive surgery
US8147860B2 (en) 2005-12-06 2012-04-03 Etex Corporation Porous calcium phosphate bone material
EP1957124A2 (en) 2005-12-07 2008-08-20 Zimmer Inc. Methods of bonding or modifying hydrogels using irradiation
US20070135921A1 (en) * 2005-12-09 2007-06-14 Park Kee B Surgical implant
US20070150059A1 (en) * 2005-12-22 2007-06-28 Depuy Spine, Inc. Methods and devices for intervertebral augmentation using injectable formulations and enclosures
US7699894B2 (en) * 2005-12-22 2010-04-20 Depuy Spine, Inc. Nucleus pulposus trial device and technique
JP2007177244A (en) 2005-12-22 2007-07-12 Zimmer Inc Perfluorocyclobutane crosslinked hydrogel
US20070150064A1 (en) * 2005-12-22 2007-06-28 Depuy Spine, Inc. Methods and devices for intervertebral augmentation
US20070150063A1 (en) * 2005-12-22 2007-06-28 Depuy Spine, Inc. Devices for intervertebral augmentation and methods of controlling their delivery
US8506633B2 (en) * 2005-12-27 2013-08-13 Warsaw Orthopedic, Inc. Rehydration and restoration of intervertebral discs with polyelectrolytes
US8801790B2 (en) * 2005-12-27 2014-08-12 Warsaw Orthopedic, Inc. Intervertebral disc augmentation and rehydration with superabsorbent polymers
US20070149641A1 (en) * 2005-12-28 2007-06-28 Goupil Dennis W Injectable bone cement
US20070161962A1 (en) * 2006-01-09 2007-07-12 Edie Jason A Device and method for moving fill material to an implant
CA2636957A1 (en) * 2006-01-12 2007-07-19 Histogenics Corporation Method for repair and reconstruction of ruptured ligaments or tendons and for treatment of ligament and tendon injuries
US7645301B2 (en) * 2006-01-13 2010-01-12 Zimmer Spine, Inc. Devices and methods for disc replacement
US20070168037A1 (en) * 2006-01-13 2007-07-19 Posnick Jeffrey C Orthopedic implant
US20070168039A1 (en) * 2006-01-13 2007-07-19 Sdgi Holdings, Inc. Materials, devices and methods for treating multiple spinal regions including vertebral body and endplate regions
US20070173821A1 (en) * 2006-01-13 2007-07-26 Sdgi Holdings, Inc. Materials, devices, and methods for treating multiple spinal regions including the posterior and spinous process regions
US20070168038A1 (en) * 2006-01-13 2007-07-19 Sdgi Holdings, Inc. Materials, devices and methods for treating multiple spinal regions including the interbody region
US20070173820A1 (en) * 2006-01-13 2007-07-26 Sdgi Holdings, Inc. Materials, devices, and methods for treating multiple spinal regions including the anterior region
US20070173855A1 (en) * 2006-01-17 2007-07-26 Sdgi Holdings, Inc. Devices and methods for spacing of vertebral members over multiple levels
US7662183B2 (en) 2006-01-24 2010-02-16 Timothy Haines Dynamic spinal implants incorporating cartilage bearing graft material
US20070179614A1 (en) * 2006-01-30 2007-08-02 Sdgi Holdings, Inc. Intervertebral prosthetic disc and method of installing same
US20070191861A1 (en) * 2006-01-30 2007-08-16 Sdgi Holdings, Inc. Instruments and methods for implanting nucleus replacement material in an intervertebral disc nucleus space
US20070191860A1 (en) * 2006-01-30 2007-08-16 Sdgi Holdings, Inc. Intervertebral prosthetic disc inserter
US8623026B2 (en) 2006-02-06 2014-01-07 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief
CN101420911B (en) 2006-02-06 2012-07-18 康复米斯公司 Patient selectable arthroplasty device and surjical tool
US20070213641A1 (en) * 2006-02-08 2007-09-13 Sdgi Holdings, Inc. Constrained balloon disc sizer
US20070213642A1 (en) * 2006-02-13 2007-09-13 Sdgi Holdings, Inc. Device and method for measuring parameters of intradiscal space
US7918889B2 (en) * 2006-02-27 2011-04-05 Warsaw Orthopedic, Inc. Expandable spinal prosthetic devices and associated methods
US7879034B2 (en) 2006-03-02 2011-02-01 Arthrocare Corporation Internally located return electrode electrosurgical apparatus, system and method
US7927358B2 (en) * 2006-03-07 2011-04-19 Zimmer Spine, Inc. Spinal stabilization device
US20070219585A1 (en) * 2006-03-14 2007-09-20 Cornet Douglas A System for administering reduced pressure treatment having a manifold with a primary flow passage and a blockage prevention member
US8110242B2 (en) 2006-03-24 2012-02-07 Zimmer, Inc. Methods of preparing hydrogel coatings
US20070225809A1 (en) * 2006-03-27 2007-09-27 Ray Charles D System and device for filling a human implantable container with a filler material
US7993404B2 (en) * 2006-03-29 2011-08-09 Warsaw Orthopedic, Inc. Transformable spinal implants and methods of use
US20070233245A1 (en) * 2006-03-31 2007-10-04 Sdgi Holdings, Inc. Methods and instruments for delivering intervertebral devices
US20070233268A1 (en) * 2006-03-31 2007-10-04 Depuy Products, Inc. Interpositional knee arthroplasty
US20070232905A1 (en) * 2006-04-04 2007-10-04 Francis Tom J Unconstrained Balloon Sizer
DE202006005868U1 (en) * 2006-04-06 2006-06-08 Aesculap Ag & Co. Kg Implant replacing intervertebral disk, comprising plates divided into movable segments lifted by expanding elements
US8118844B2 (en) * 2006-04-24 2012-02-21 Warsaw Orthopedic, Inc. Expandable device for insertion between anatomical structures and a procedure utilizing same
US7806900B2 (en) 2006-04-26 2010-10-05 Illuminoss Medical, Inc. Apparatus and methods for delivery of reinforcing materials to bone
WO2007127260A2 (en) * 2006-04-26 2007-11-08 Illuminoss Medical, Inc. Apparatus and methods for delivery of reinforcing materials to bone
AU2007243353B2 (en) 2006-04-26 2012-05-31 Illuminoss Medical, Inc. Apparatus and methods for reinforcing bone
US8133279B2 (en) 2006-04-27 2012-03-13 Warsaw Orthopedic, Inc. Methods for treating an annulus defect of an intervertebral disc
US20070255286A1 (en) * 2006-04-27 2007-11-01 Sdgi Holdings, Inc. Devices, apparatus, and methods for improved disc augmentation
US20070255406A1 (en) * 2006-04-27 2007-11-01 Sdgi Holdings, Inc. Devices, apparatus, and methods for bilateral approach to disc augmentation
US8348978B2 (en) 2006-04-28 2013-01-08 Warsaw Orthopedic, Inc. Interosteotic implant
US8105357B2 (en) 2006-04-28 2012-01-31 Warsaw Orthopedic, Inc. Interspinous process brace
US8048118B2 (en) 2006-04-28 2011-11-01 Warsaw Orthopedic, Inc. Adjustable interspinous process brace
US7846185B2 (en) * 2006-04-28 2010-12-07 Warsaw Orthopedic, Inc. Expandable interspinous process implant and method of installing same
US8252031B2 (en) 2006-04-28 2012-08-28 Warsaw Orthopedic, Inc. Molding device for an expandable interspinous process implant
US8062337B2 (en) * 2006-05-04 2011-11-22 Warsaw Orthopedic, Inc. Expandable device for insertion between anatomical structures and a procedure utilizing same
US20080071379A1 (en) * 2006-05-10 2008-03-20 Mark Rydell Intervertebral disc replacement
EP2015710A1 (en) 2006-05-11 2009-01-21 Columna Pty Ltd Implanting a tissue prosthesis
US20070265565A1 (en) * 2006-05-15 2007-11-15 Medtronic Vascular, Inc. Mesh-Reinforced Catheter Balloons and Methods for Making the Same
WO2007133214A1 (en) * 2006-05-17 2007-11-22 Massachusetts General Hospital Prosthetic disc nuclear replacement and soft-tissue reconstruction devices
US20090299476A1 (en) * 2006-05-19 2009-12-03 Ashish Diwan Tissue prosthesis
US8147517B2 (en) 2006-05-23 2012-04-03 Warsaw Orthopedic, Inc. Systems and methods for adjusting properties of a spinal implant
US20070276496A1 (en) 2006-05-23 2007-11-29 Sdgi Holdings, Inc. Surgical spacer with shape control
US8092536B2 (en) 2006-05-24 2012-01-10 Disc Dynamics, Inc. Retention structure for in situ formation of an intervertebral prosthesis
US20070276491A1 (en) * 2006-05-24 2007-11-29 Disc Dynamics, Inc. Mold assembly for intervertebral prosthesis
US20090131939A1 (en) * 2006-05-24 2009-05-21 Disc Dynamics, Inc. Inflatable mold for maintaining posterior spinal elements in a desired alignment
EP2020956A2 (en) * 2006-05-26 2009-02-11 Nanyang Technological University Implantable article, method of forming same and method for reducing thrombogenicity
US7872068B2 (en) 2006-05-30 2011-01-18 Incept Llc Materials formable in situ within a medical device
US8226722B2 (en) * 2006-06-08 2012-07-24 Francis Pflum Sac for use in spinal surgery
US10143560B2 (en) 2006-06-08 2018-12-04 Francis Pflum Sac for use in spinal surgery
US8834496B2 (en) 2006-06-13 2014-09-16 Bret A. Ferree Soft tissue repair methods and apparatus
US9232938B2 (en) 2006-06-13 2016-01-12 Anova Corp. Method and apparatus for closing fissures in the annulus fibrosus
WO2008002482A2 (en) * 2006-06-23 2008-01-03 Surmodics, Inc. Hydrogel-based joint repair system and method
US8399619B2 (en) 2006-06-30 2013-03-19 Warsaw Orthopedic, Inc. Injectable collagen material
US8118779B2 (en) 2006-06-30 2012-02-21 Warsaw Orthopedic, Inc. Collagen delivery device
US20080021457A1 (en) * 2006-07-05 2008-01-24 Warsaw Orthopedic Inc. Zygapophysial joint repair system
US20080009876A1 (en) * 2006-07-07 2008-01-10 Meera Sankaran Medical device with expansion mechanism
US8048119B2 (en) 2006-07-20 2011-11-01 Warsaw Orthopedic, Inc. Apparatus for insertion between anatomical structures and a procedure utilizing same
US20080058931A1 (en) * 2006-07-21 2008-03-06 John White Expandable vertebral implant and methods of use
US20080021556A1 (en) * 2006-07-21 2008-01-24 Edie Jason A Expandable vertebral implant and methods of use
US20080058932A1 (en) * 2006-07-26 2008-03-06 Warsaw Orthopedic Inc. Rigidization-on-command orthopedic devices and methods
US8034110B2 (en) 2006-07-31 2011-10-11 Depuy Spine, Inc. Spinal fusion implant
US20080031914A1 (en) * 2006-08-02 2008-02-07 Drapeau Susan J Flowable biomaterial composition
US7758649B2 (en) * 2006-08-04 2010-07-20 Integrity Intellect Inc. Reversibly deformable implant
US20080039942A1 (en) * 2006-08-11 2008-02-14 Bergeron Brian J Spinal implant
WO2008033501A2 (en) * 2006-09-14 2008-03-20 Spineology, Inc. Absorbent fabric implant
US9017388B2 (en) * 2006-09-14 2015-04-28 Warsaw Orthopedic, Inc. Methods for correcting spinal deformities
US20080172126A1 (en) * 2006-10-03 2008-07-17 Reynolds Martin A Nucleus pulposus injection devices and methods
US8066750B2 (en) 2006-10-06 2011-11-29 Warsaw Orthopedic, Inc Port structures for non-rigid bone plates
US7910135B2 (en) * 2006-10-13 2011-03-22 Uluru Inc. Hydrogel wound dressing and biomaterials formed in situ and their uses
US8529958B2 (en) 2006-10-17 2013-09-10 Carmell Therapeutics Corporation Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
US8845726B2 (en) 2006-10-18 2014-09-30 Vertiflex, Inc. Dilator
US20100145462A1 (en) * 2006-10-24 2010-06-10 Trans1 Inc. Preformed membranes for use in intervertebral disc spaces
US8088147B2 (en) * 2006-10-24 2012-01-03 Trans1 Inc. Multi-membrane prosthetic nucleus
US8840621B2 (en) 2006-11-03 2014-09-23 Innovative Spine, Inc. Spinal access systems and methods
US8057481B2 (en) * 2006-11-03 2011-11-15 Innovative Spine, Llc System and method for providing surgical access to a spine
US7879041B2 (en) 2006-11-10 2011-02-01 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
JP5442444B2 (en) 2006-11-10 2014-03-12 イルミンオス・メディカル・インコーポレイテッド System and method for internal bone fixation
US20080114402A1 (en) * 2006-11-10 2008-05-15 Warsaw Orthopedic, Inc. Devices and Methods for Correcting a Spinal Deformity
US8029569B2 (en) * 2006-11-20 2011-10-04 International Spinal Innovations, Llc Implantable spinal disk
US9737414B2 (en) 2006-11-21 2017-08-22 Vertebral Technologies, Inc. Methods and apparatus for minimally invasive modular interbody fusion devices
WO2008064397A1 (en) * 2006-11-28 2008-06-05 Columna Pty Ltd A prosthesis delivery system
US20080125782A1 (en) 2006-11-29 2008-05-29 Disc Dynamics, Inc. Method and apparatus for removing an extension from a prosthesis
WO2008070863A2 (en) 2006-12-07 2008-06-12 Interventional Spine, Inc. Intervertebral implant
US8696679B2 (en) 2006-12-08 2014-04-15 Dfine, Inc. Bone treatment systems and methods
US8979931B2 (en) 2006-12-08 2015-03-17 DePuy Synthes Products, LLC Nucleus replacement device and method
US7871440B2 (en) 2006-12-11 2011-01-18 Depuy Products, Inc. Unitary surgical device and method
US7875079B2 (en) 2006-12-14 2011-01-25 Warsaw Orthopedic, Inc. Vertebral implant containment device and methods of use
US8043308B2 (en) 2006-12-14 2011-10-25 Depuy Mitek, Inc. Bone suture
US9237916B2 (en) 2006-12-15 2016-01-19 Gmedeleware 2 Llc Devices and methods for vertebrostenting
US9192397B2 (en) 2006-12-15 2015-11-24 Gmedelaware 2 Llc Devices and methods for fracture reduction
US20080154233A1 (en) * 2006-12-20 2008-06-26 Zimmer Orthobiologics, Inc. Apparatus for delivering a biocompatible material to a surgical site and method of using same
US8163549B2 (en) 2006-12-20 2012-04-24 Zimmer Orthobiologics, Inc. Method of obtaining viable small tissue particles and use for tissue repair
US8663328B2 (en) 2006-12-21 2014-03-04 Warsaw Orthopedic, Inc. Methods for positioning a load-bearing component of an orthopedic implant device by inserting a malleable device that hardens in vivo
US8758407B2 (en) 2006-12-21 2014-06-24 Warsaw Orthopedic, Inc. Methods for positioning a load-bearing orthopedic implant device in vivo
US8480718B2 (en) 2006-12-21 2013-07-09 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to be hardened after placement in vivo
US20080177389A1 (en) * 2006-12-21 2008-07-24 Rob Gene Parrish Intervertebral disc spacer
US7771476B2 (en) 2006-12-21 2010-08-10 Warsaw Orthopedic Inc. Curable orthopedic implant devices configured to harden after placement in vivo by application of a cure-initiating energy before insertion
US7972382B2 (en) * 2006-12-26 2011-07-05 Warsaw Orthopedic, Inc. Minimally invasive spinal distraction devices and methods
US20080161929A1 (en) 2006-12-29 2008-07-03 Mccormack Bruce Cervical distraction device
WO2008086274A2 (en) * 2007-01-05 2008-07-17 University Of Virginia Patent Foundation Expandable intervertebral prosthesis device for posterior implantation and related method thereof
US8187328B2 (en) * 2007-01-08 2012-05-29 Warsaw Orthopedic, Inc. Expandable containment devices and methods
FR2911492A1 (en) * 2007-01-19 2008-07-25 Georges Pierre Gauthier Biological cement e.g. biocompatible cement, injecting assembly for e.g. acetabulum of human body, has pouch including wall defining biological cement extrusion orifices through which cement in pasty state, is ejected to exterior of pouch
US20080195221A1 (en) * 2007-01-22 2008-08-14 Zimmer Gmbh Implant and a method for partial replacement of joint surfaces
US7655004B2 (en) 2007-02-15 2010-02-02 Ethicon Endo-Surgery, Inc. Electroporation ablation apparatus, system, and method
US20080215151A1 (en) * 2007-03-02 2008-09-04 Andrew Kohm Bone barrier device, system, and method
US8435551B2 (en) 2007-03-06 2013-05-07 Musculoskeletal Transplant Foundation Cancellous construct with support ring for repair of osteochondral defects
US20080269754A1 (en) * 2007-03-06 2008-10-30 Orthobond, Inc. Preparation Tools and Methods of Using the Same
US20080228268A1 (en) * 2007-03-15 2008-09-18 Uluru, Inc. Method of Formation of Viscous, Shape Conforming Gels and Their Uses as Medical Prosthesis
DK3111869T3 (en) 2007-03-15 2017-11-20 Ortho-Space Ltd SYSTEM FOR SEALING AN INFLATABLE PROSTHESIS
EP2129299A4 (en) * 2007-03-15 2016-02-10 Bioprotect Ltd Soft tissue fixation devices
US8403937B2 (en) * 2007-03-30 2013-03-26 Kyphon Sarl Apparatus and method for medical procedures within a spine
WO2008120215A2 (en) * 2007-04-02 2008-10-09 Novocart Medical Solutions Ltd Intra-articular implant for treating irregularities in cartilage surfaces
ES2438999T3 (en) * 2007-04-03 2014-01-21 Dfine, Inc. Bone treatment systems
WO2008124748A1 (en) * 2007-04-09 2008-10-16 Adrian Edward Park Frame device
WO2008128075A1 (en) * 2007-04-12 2008-10-23 Isto Technologies, Inc. Compositions and methods for tissue repair
AU2008241447B2 (en) 2007-04-16 2014-03-27 Vertiflex, Inc. Interspinous spacer
US20080268056A1 (en) * 2007-04-26 2008-10-30 Abhijeet Joshi Injectable copolymer hydrogel useful for repairing vertebral compression fractures
US20080269897A1 (en) * 2007-04-26 2008-10-30 Abhijeet Joshi Implantable device and methods for repairing articulating joints for using the same
US8062364B1 (en) 2007-04-27 2011-11-22 Knee Creations, Llc Osteoarthritis treatment and device
WO2008137428A2 (en) 2007-04-30 2008-11-13 Dfine, Inc. Bone treatment systems and methods
US8840646B2 (en) 2007-05-10 2014-09-23 Warsaw Orthopedic, Inc. Spinous process implants and methods
CA2692002A1 (en) 2007-05-21 2008-11-27 Aoi Medical Inc. Articulating cavitation device
US7785314B2 (en) * 2007-06-15 2010-08-31 Kyphon SÀRL Systems and methods for needle access to an intervertebral disc
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
US20090005816A1 (en) * 2007-06-26 2009-01-01 Denardo Andrew J Spinal rod, insertion device, and method of using
US8900307B2 (en) 2007-06-26 2014-12-02 DePuy Synthes Products, LLC Highly lordosed fusion cage
US20090005734A1 (en) * 2007-06-27 2009-01-01 Tessaron Medical, Inc. Systems and methods for delivering particles into patient body
US9597118B2 (en) 2007-07-20 2017-03-21 Dfine, Inc. Bone anchor apparatus and method
US8182647B2 (en) 2007-07-23 2012-05-22 Cohera Medical, Inc. Hydrophilic biodegradable adhesives
BRPI0814102A2 (en) 2007-07-27 2015-02-03 Ams Res Corp PELVIC IMPLANT, AND, KIT.
US7731988B2 (en) 2007-08-03 2010-06-08 Zimmer, Inc. Multi-polymer hydrogels
US20090043344A1 (en) * 2007-08-06 2009-02-12 Zimmer, Inc. Methods for repairing defects in bone
EP2166990B1 (en) * 2007-08-13 2018-10-03 MicroAire Surgical Instruments, LLC Tissue positioning device
US8523901B2 (en) * 2007-08-14 2013-09-03 Illuminoss Medical, Inc. Apparatus and methods for attaching soft tissue to bone
US8262655B2 (en) 2007-11-21 2012-09-11 Ethicon Endo-Surgery, Inc. Bipolar forceps
US8568410B2 (en) 2007-08-31 2013-10-29 Ethicon Endo-Surgery, Inc. Electrical ablation surgical instruments
US8579897B2 (en) 2007-11-21 2013-11-12 Ethicon Endo-Surgery, Inc. Bipolar forceps
US8062739B2 (en) 2007-08-31 2011-11-22 Zimmer, Inc. Hydrogels with gradient
US8961553B2 (en) * 2007-09-14 2015-02-24 Crosstrees Medical, Inc. Material control device for inserting material into a targeted anatomical region
US8540772B2 (en) * 2007-09-20 2013-09-24 Said G. Osman Transpedicular, extrapedicular and transcorporeal partial disc replacement
US8343189B2 (en) 2007-09-25 2013-01-01 Zyga Technology, Inc. Method and apparatus for facet joint stabilization
US8066755B2 (en) 2007-09-26 2011-11-29 Trivascular, Inc. System and method of pivoted stent deployment
US8226701B2 (en) 2007-09-26 2012-07-24 Trivascular, Inc. Stent and delivery system for deployment thereof
US8663309B2 (en) 2007-09-26 2014-03-04 Trivascular, Inc. Asymmetric stent apparatus and method
US20090088789A1 (en) * 2007-09-28 2009-04-02 O'neil Michael J Balloon With Shape Control For Spinal Procedures
WO2009046372A2 (en) 2007-10-04 2009-04-09 Trivascular2, Inc. Modular vascular graft for low profile percutaneous delivery
US20090093819A1 (en) * 2007-10-05 2009-04-09 Abhijeet Joshi Anisotropic spinal stabilization rod
WO2009046399A1 (en) * 2007-10-05 2009-04-09 Hynes Richard A Spinal stabilization treatment methods for maintaining axial spine height and sagital plane spine balance
US20110230973A1 (en) * 2007-10-10 2011-09-22 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US8608049B2 (en) * 2007-10-10 2013-12-17 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20100292798A1 (en) * 2007-10-19 2010-11-18 Gianluca Maestretti Hemi-prosthesis
US20090112326A1 (en) * 2007-10-24 2009-04-30 Disc Dynamics, Inc. In situ adjustable dynamic intervertebral implant
US20090112221A1 (en) * 2007-10-25 2009-04-30 Disc Dynamics, Inc. System and method for measuring the shape of internal body cavities
US8043381B2 (en) * 2007-10-29 2011-10-25 Zimmer Spine, Inc. Minimally invasive interbody device and method
US8480657B2 (en) 2007-10-31 2013-07-09 Ethicon Endo-Surgery, Inc. Detachable distal overtube section and methods for forming a sealable opening in the wall of an organ
US20090112059A1 (en) 2007-10-31 2009-04-30 Nobis Rudolph H Apparatus and methods for closing a gastrotomy
US9427289B2 (en) 2007-10-31 2016-08-30 Illuminoss Medical, Inc. Light source
US20090149958A1 (en) * 2007-11-01 2009-06-11 Ann Prewett Structurally reinforced spinal nucleus implants
WO2009058397A1 (en) * 2007-11-01 2009-05-07 The University Of Akron Thermoplastic amphiphilic co-networks
US20090118833A1 (en) * 2007-11-05 2009-05-07 Zimmer Spine, Inc. In-situ curable interspinous process spacer
WO2009064847A2 (en) 2007-11-16 2009-05-22 Synthes (U.S.A.) Porous containment device and associated method for stabilization of vertebral compression fractures
US8083789B2 (en) 2007-11-16 2011-12-27 Trivascular, Inc. Securement assembly and method for expandable endovascular device
US7947784B2 (en) 2007-11-16 2011-05-24 Zimmer, Inc. Reactive compounding of hydrogels
US8328861B2 (en) 2007-11-16 2012-12-11 Trivascular, Inc. Delivery system and method for bifurcated graft
US7846199B2 (en) * 2007-11-19 2010-12-07 Cook Incorporated Remodelable prosthetic valve
US20100298630A1 (en) * 2007-12-07 2010-11-25 Shawn Michael Wignall Pelvic floor treatments and related tools and implants
US8403968B2 (en) 2007-12-26 2013-03-26 Illuminoss Medical, Inc. Apparatus and methods for repairing craniomaxillofacial bones using customized bone plates
US9043018B2 (en) * 2007-12-27 2015-05-26 Intuitive Surgical Operations, Inc. Medical device with orientable tip for robotically directed laser cutting and biomaterial application
US8034362B2 (en) 2008-01-04 2011-10-11 Zimmer, Inc. Chemical composition of hydrogels for use as articulating surfaces
US20090177206A1 (en) * 2008-01-08 2009-07-09 Zimmer Spine, Inc. Instruments, implants, and methods for fixation of vertebral compression fractures
WO2009089367A2 (en) 2008-01-09 2009-07-16 Providence Medical Technology, Inc. Methods and apparatus for accessing and treating the facet joint
AU2009205896A1 (en) 2008-01-17 2009-07-23 Synthes Gmbh An expandable intervertebral implant and associated method of manufacturing the same
US20090187256A1 (en) * 2008-01-21 2009-07-23 Zimmer, Inc. Method for forming an integral porous region in a cast implant
US9445854B2 (en) 2008-02-01 2016-09-20 Dfine, Inc. Bone treatment systems and methods
US20090198329A1 (en) 2008-02-01 2009-08-06 Kesten Randy J Breast implant with internal flow dampening
US8487021B2 (en) 2008-02-01 2013-07-16 Dfine, Inc. Bone treatment systems and methods
US20090198286A1 (en) * 2008-02-05 2009-08-06 Zimmer, Inc. Bone fracture fixation system
US8252029B2 (en) * 2008-02-21 2012-08-28 Zimmer Gmbh Expandable interspinous process spacer with lateral support and method for implantation
US8696751B2 (en) * 2008-12-10 2014-04-15 Coalign Innovations, Inc. Adjustable distraction cage with linked locking mechanisms
US8932355B2 (en) 2008-02-22 2015-01-13 Coalign Innovations, Inc. Spinal implant with expandable fixation
US8992620B2 (en) 2008-12-10 2015-03-31 Coalign Innovations, Inc. Adjustable distraction cage with linked locking mechanisms
US20100145455A1 (en) * 2008-12-10 2010-06-10 Innvotec Surgical, Inc. Lockable spinal implant
US20090222093A1 (en) * 2008-02-28 2009-09-03 Warsaw Orthopedic, Inc. Nucleus Implant and Method of Installing Same
US20090222097A1 (en) * 2008-02-28 2009-09-03 Warsaw Orthopedic, Inc. Nucleus implant and method of installing same
US20090222096A1 (en) * 2008-02-28 2009-09-03 Warsaw Orthopedic, Inc. Multi-compartment expandable devices and methods for intervertebral disc expansion and augmentation
WO2009111626A2 (en) 2008-03-05 2009-09-11 Conformis, Inc. Implants for altering wear patterns of articular surfaces
EP2265220A1 (en) * 2008-03-05 2010-12-29 Musculoskeletal Transplant Foundation Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
US8262680B2 (en) 2008-03-10 2012-09-11 Ethicon Endo-Surgery, Inc. Anastomotic device
US8915963B2 (en) * 2008-03-31 2014-12-23 Kamran Aflatoon Artificial disc prosthesis for replacing a damaged nucleus
US20090248077A1 (en) * 2008-03-31 2009-10-01 Derrick William Johns Hybrid dynamic stabilization
BRPI0910325A8 (en) 2008-04-05 2019-01-29 Synthes Gmbh expandable intervertebral implant
US9180416B2 (en) 2008-04-21 2015-11-10 Dfine, Inc. System for use in bone cement preparation and delivery
CN101902988A (en) 2008-04-25 2010-12-01 耐利克斯股份有限公司 The induction system of stent graft
US10716573B2 (en) 2008-05-01 2020-07-21 Aneuclose Janjua aneurysm net with a resilient neck-bridging portion for occluding a cerebral aneurysm
KR101464983B1 (en) 2008-05-01 2014-11-25 스파인셀 프러프라이어테리 리미티드 System methods and apparatuses for formation and insertion of tissue prothesis
US10028747B2 (en) 2008-05-01 2018-07-24 Aneuclose Llc Coils with a series of proximally-and-distally-connected loops for occluding a cerebral aneurysm
JP2011519713A (en) 2008-05-12 2011-07-14 コンフォーミス・インコーポレイテッド Devices and methods for treatment of facet joints and other joints
US20100068171A1 (en) * 2008-05-27 2010-03-18 Vanderbilt University Injectable bone/polymer composite bone void fillers
US20090297603A1 (en) * 2008-05-29 2009-12-03 Abhijeet Joshi Interspinous dynamic stabilization system with anisotropic hydrogels
US8771260B2 (en) 2008-05-30 2014-07-08 Ethicon Endo-Surgery, Inc. Actuating and articulating surgical device
US8679003B2 (en) 2008-05-30 2014-03-25 Ethicon Endo-Surgery, Inc. Surgical device and endoscope including same
US20090299478A1 (en) * 2008-06-03 2009-12-03 Warsaw Orthopedic, Inc. Lordotic Implant for Posterior Approach
US7976578B2 (en) * 2008-06-04 2011-07-12 James Marvel Buffer for a human joint and method of arthroscopically inserting
CA2726596A1 (en) 2008-06-04 2009-12-10 Nellix, Inc. Sealing apparatus and methods of use
US8403926B2 (en) 2008-06-05 2013-03-26 Ethicon Endo-Surgery, Inc. Manually articulating devices
US9381049B2 (en) 2008-06-06 2016-07-05 Providence Medical Technology, Inc. Composite spinal facet implant with textured surfaces
US8512347B2 (en) 2008-06-06 2013-08-20 Providence Medical Technology, Inc. Cervical distraction/implant delivery device
US8361152B2 (en) 2008-06-06 2013-01-29 Providence Medical Technology, Inc. Facet joint implants and delivery tools
US8267966B2 (en) 2008-06-06 2012-09-18 Providence Medical Technology, Inc. Facet joint implants and delivery tools
EP3412231A1 (en) 2008-06-06 2018-12-12 Providence Medical Technology, Inc. Facet joint implants and delivery tools
US11224521B2 (en) 2008-06-06 2022-01-18 Providence Medical Technology, Inc. Cervical distraction/implant delivery device
US9333086B2 (en) 2008-06-06 2016-05-10 Providence Medical Technology, Inc. Spinal facet cage implant
US20090312841A1 (en) * 2008-06-13 2009-12-17 Zimmer, Inc. Bone void filler
US8206636B2 (en) * 2008-06-20 2012-06-26 Amaranth Medical Pte. Stent fabrication via tubular casting processes
US8206635B2 (en) * 2008-06-20 2012-06-26 Amaranth Medical Pte. Stent fabrication via tubular casting processes
US20090326657A1 (en) * 2008-06-25 2009-12-31 Alexander Grinberg Pliable Artificial Disc Endplate
US8361112B2 (en) 2008-06-27 2013-01-29 Ethicon Endo-Surgery, Inc. Surgical suture arrangement
US20100004745A1 (en) * 2008-07-01 2010-01-07 Doctors Research Group, Inc. Fusing Bone
US20120209396A1 (en) 2008-07-07 2012-08-16 David Myung Orthopedic implants having gradient polymer alloys
US8262563B2 (en) 2008-07-14 2012-09-11 Ethicon Endo-Surgery, Inc. Endoscopic translumenal articulatable steerable overtube
US8888792B2 (en) 2008-07-14 2014-11-18 Ethicon Endo-Surgery, Inc. Tissue apposition clip application devices and methods
KR101614561B1 (en) 2008-07-23 2016-04-21 마르크 아이. 말베르크 Modular nucleus pulposus prosthesis
US9364338B2 (en) 2008-07-23 2016-06-14 Resspond Spinal Systems Modular nucleus pulposus prosthesis
US9808345B2 (en) * 2008-07-24 2017-11-07 Iorthopedics, Inc. Resilient arthroplasty device
GB0813659D0 (en) 2008-07-25 2008-09-03 Smith & Nephew Fracture putty
US8497023B2 (en) 2008-08-05 2013-07-30 Biomimedica, Inc. Polyurethane-grafted hydrogels
US8211125B2 (en) 2008-08-15 2012-07-03 Ethicon Endo-Surgery, Inc. Sterile appliance delivery device for endoscopic procedures
US8529563B2 (en) 2008-08-25 2013-09-10 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8241204B2 (en) 2008-08-29 2012-08-14 Ethicon Endo-Surgery, Inc. Articulating end cap
US8480689B2 (en) * 2008-09-02 2013-07-09 Ethicon Endo-Surgery, Inc. Suturing device
US8409200B2 (en) 2008-09-03 2013-04-02 Ethicon Endo-Surgery, Inc. Surgical grasping device
US8187333B2 (en) * 2008-09-18 2012-05-29 Mayer Peter L Intervertebral disc prosthesis and method for implanting and explanting
US8814937B2 (en) 2008-09-18 2014-08-26 Peter L. Mayer Intervertebral disc prosthesis, method for assembling, method for implanting prosthesis, and method for explanting
US8337394B2 (en) 2008-10-01 2012-12-25 Ethicon Endo-Surgery, Inc. Overtube with expandable tip
US8163022B2 (en) 2008-10-14 2012-04-24 Anulex Technologies, Inc. Method and apparatus for the treatment of the intervertebral disc annulus
JP5804325B2 (en) * 2008-10-30 2015-11-04 デピュイ・シンセス・プロダクツ・インコーポレイテッド System and method for delivering bone cement to a bone anchor
WO2012134540A2 (en) 2010-10-22 2012-10-04 Vanderbilt University Injectable synthetic pur composite
EP2358408A2 (en) * 2008-10-30 2011-08-24 Osteotech, Inc., Bone/polyurethane composites and methods thereof
US20100114067A1 (en) * 2008-10-31 2010-05-06 Warsaw Orthopedic, Inc. Multi-Chamber Mixing System
US20100121239A1 (en) * 2008-11-10 2010-05-13 Linares Medical Devices, Llc Support including stabilizing brace and inserts for use with any number of spinal vertebrae such as upper thoracic vertebrae
US8128591B2 (en) * 2008-11-10 2012-03-06 Warsaw Orthopedic, Inc. Multiple component mixing and delivery system
US8157834B2 (en) 2008-11-25 2012-04-17 Ethicon Endo-Surgery, Inc. Rotational coupling device for surgical instrument with flexible actuators
US8361066B2 (en) 2009-01-12 2013-01-29 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8252057B2 (en) * 2009-01-30 2012-08-28 Ethicon Endo-Surgery, Inc. Surgical access device
US9226772B2 (en) * 2009-01-30 2016-01-05 Ethicon Endo-Surgery, Inc. Surgical device
US20110295379A1 (en) * 2009-02-06 2011-12-01 Ortho-Space Ltd. Expandable joint implant
US9011537B2 (en) * 2009-02-12 2015-04-21 Warsaw Orthopedic, Inc. Delivery system cartridge
WO2010094032A2 (en) 2009-02-16 2010-08-19 Aoi Medical Inc. Trauma nail accumulator
US8808303B2 (en) 2009-02-24 2014-08-19 Microport Orthopedics Holdings Inc. Orthopedic surgical guide
US9017334B2 (en) 2009-02-24 2015-04-28 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
US8808297B2 (en) 2009-02-24 2014-08-19 Microport Orthopedics Holdings Inc. Orthopedic surgical guide
WO2010099463A2 (en) * 2009-02-27 2010-09-02 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Joint bioscaffolds
WO2010100287A1 (en) * 2009-03-06 2010-09-10 Somatex Medical Technologies Gmbh Barrier for implantation into bone, in particular for vertebroplasty
US8155759B2 (en) * 2009-03-20 2012-04-10 Innovia, Llc Pacemaker lead and method of making same
WO2010111246A1 (en) 2009-03-23 2010-09-30 Soteira, Inc. Devices and methods for vertebrostenting
US9526620B2 (en) 2009-03-30 2016-12-27 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US9344902B2 (en) * 2009-04-03 2016-05-17 Broadcom Corporation Method and system for evaluating deployment of femtocells as part of a cellular network
US8210729B2 (en) 2009-04-06 2012-07-03 Illuminoss Medical, Inc. Attachment system for light-conducting fibers
US8636803B2 (en) 2009-04-07 2014-01-28 Spinal Stabilization Technologies, Llc Percutaneous implantable nuclear prosthesis
US8512338B2 (en) 2009-04-07 2013-08-20 Illuminoss Medical, Inc. Photodynamic bone stabilization systems and methods for reinforcing bone
JP5662999B2 (en) 2009-04-09 2015-02-04 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Minimally invasive spinal reinforcement and stabilization system and method
JP2012523897A (en) 2009-04-16 2012-10-11 コンフォーミス・インコーポレイテッド Patient-specific joint replacement device for ligament repair
US8123808B2 (en) * 2009-04-16 2012-02-28 Warsaw Orthopedic, Inc. Vertebral endplate connection implant and method
US9216023B2 (en) 2009-05-08 2015-12-22 DePuy Synthes Products, Inc. Expandable bone implant
JP5283227B2 (en) * 2009-06-05 2013-09-04 学校法人日本大学 Intervertebral disk hardness measurement device
US20100318091A1 (en) * 2009-06-10 2010-12-16 Linares Medical Devices, Llc Plasticized material, delivery device and method for filling a bone cavity and including both foam plastic spray and injected liquid pellets and for promoting bone growth and adhesion
WO2010145036A1 (en) * 2009-06-18 2010-12-23 The Royal Institution For The Advancement Of Learning/Mcgill University Hollow highly-expandable prosthetic vertebral body
WO2011005199A1 (en) * 2009-07-10 2011-01-13 Milux Holding S.A. Apparatus and methods for treatment of arthrosis or osteoarthritis in a joint of a mammal or human patient
US8394125B2 (en) 2009-07-24 2013-03-12 Zyga Technology, Inc. Systems and methods for facet joint treatment
CN102548511B (en) * 2009-08-19 2015-07-15 斯恩蒂斯有限公司 Method and apparatus for augmenting bone
BR112012003783A2 (en) 2009-08-19 2016-04-19 Illuminoss Medical Inc devices and methods for bone alignment, stabilization and distraction
US9173817B2 (en) 2009-08-24 2015-11-03 Arsenal Medical, Inc. In situ forming hemostatic foam implants
JP2013504389A (en) 2009-09-11 2013-02-07 アーティキュリンクス, インコーポレイテッド Disc-shaped orthopedic device
US8454563B2 (en) 2009-10-09 2013-06-04 Rogelio A. Insignares Trocar and cannula assembly having improved conical valve, and methods related thereto
US20110098704A1 (en) 2009-10-28 2011-04-28 Ethicon Endo-Surgery, Inc. Electrical ablation devices
US8608652B2 (en) 2009-11-05 2013-12-17 Ethicon Endo-Surgery, Inc. Vaginal entry surgical devices, kit, system, and method
US9155571B2 (en) 2009-11-06 2015-10-13 DePuy Synthes Products, Inc. Minimally invasive interspinous process spacer implants and methods
WO2011060062A1 (en) * 2009-11-10 2011-05-19 Illuminoss Medical, Inc. Intramedullary implants having variable fastener placement
US9358140B1 (en) 2009-11-18 2016-06-07 Aneuclose Llc Stent with outer member to embolize an aneurysm
US8951261B2 (en) 2009-11-20 2015-02-10 Zimmer Knee Creations, Inc. Subchondral treatment of joint pain
WO2011063250A1 (en) * 2009-11-20 2011-05-26 Knee Creations, Llc Implantable devices for subchondral treatment of joint pain
US8906032B2 (en) * 2009-11-20 2014-12-09 Zimmer Knee Creations, Inc. Instruments for a variable angle approach to a joint
WO2011063260A1 (en) 2009-11-20 2011-05-26 Knee Creations, Llc Bone-derived implantable devices for subchondral treatment of joint pain
US8821504B2 (en) * 2009-11-20 2014-09-02 Zimmer Knee Creations, Inc. Method for treating joint pain and associated instruments
US8608802B2 (en) 2009-11-20 2013-12-17 Zimmer Knee Creations, Inc. Implantable devices for subchondral treatment of joint pain
US9259257B2 (en) * 2009-11-20 2016-02-16 Zimmer Knee Creations, Inc. Instruments for targeting a joint defect
JP2013511358A (en) * 2009-11-20 2013-04-04 ニー・クリエイションズ・リミテッド・ライアビリティ・カンパニー Navigation and positioning equipment for joint repair
CN102770067A (en) * 2009-11-20 2012-11-07 膝部创造物有限责任公司 Coordinate mapping system for joint treatment
US9168138B2 (en) 2009-12-09 2015-10-27 DePuy Synthes Products, Inc. Aspirating implants and method of bony regeneration
US9393129B2 (en) 2009-12-10 2016-07-19 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US8740948B2 (en) 2009-12-15 2014-06-03 Vertiflex, Inc. Spinal spacer for cervical and other vertebra, and associated systems and methods
US8496574B2 (en) 2009-12-17 2013-07-30 Ethicon Endo-Surgery, Inc. Selectively positionable camera for surgical guide tube assembly
US8353487B2 (en) 2009-12-17 2013-01-15 Ethicon Endo-Surgery, Inc. User interface support devices for endoscopic surgical instruments
US8506564B2 (en) 2009-12-18 2013-08-13 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US9028483B2 (en) 2009-12-18 2015-05-12 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US20110276078A1 (en) 2009-12-30 2011-11-10 Nellix, Inc. Filling structure for a graft system and methods of use
US8652153B2 (en) 2010-01-11 2014-02-18 Anulex Technologies, Inc. Intervertebral disc annulus repair system and bone anchor delivery tool
WO2013033447A2 (en) 2011-09-01 2013-03-07 Grotz R Thomas Resilient interpositional arthroplasty device
WO2011091005A2 (en) 2010-01-22 2011-07-28 Grotz R Thomas Resilient knee implant and methods
US10307257B2 (en) 2010-01-22 2019-06-04 Iorthopedics, Inc. Resilient knee implant and methods
US9005198B2 (en) 2010-01-29 2015-04-14 Ethicon Endo-Surgery, Inc. Surgical instrument comprising an electrode
US20110196464A1 (en) * 2010-02-09 2011-08-11 Leonard Pinchuk Pacemaker Lead and Method of Making Same
US8147526B2 (en) 2010-02-26 2012-04-03 Kyphon Sarl Interspinous process spacer diagnostic parallel balloon catheter and methods of use
JP5812613B2 (en) * 2010-03-09 2015-11-17 キヤノン株式会社 Photoacoustic matching material and human tissue simulation material
US9039769B2 (en) * 2010-03-17 2015-05-26 Globus Medical, Inc. Intervertebral nucleus and annulus implants and method of use thereof
US8409287B2 (en) * 2010-05-21 2013-04-02 Warsaw Orthopedic, Inc. Intervertebral prosthetic systems, devices, and associated methods
US8979838B2 (en) 2010-05-24 2015-03-17 Arthrocare Corporation Symmetric switching electrode method and related system
US20110295370A1 (en) * 2010-06-01 2011-12-01 Sean Suh Spinal Implants and Methods of Use Thereof
US8663293B2 (en) 2010-06-15 2014-03-04 Zyga Technology, Inc. Systems and methods for facet joint treatment
US9233006B2 (en) 2010-06-15 2016-01-12 Zyga Technology, Inc. Systems and methods for facet joint treatment
US8684965B2 (en) 2010-06-21 2014-04-01 Illuminoss Medical, Inc. Photodynamic bone stabilization and drug delivery systems
US9592063B2 (en) 2010-06-24 2017-03-14 DePuy Synthes Products, Inc. Universal trial for lateral cages
US8979860B2 (en) 2010-06-24 2015-03-17 DePuy Synthes Products. LLC Enhanced cage insertion device
AU2011271465B2 (en) 2010-06-29 2015-03-19 Synthes Gmbh Distractible intervertebral implant
US8486080B2 (en) 2010-07-23 2013-07-16 Warsaw Orthopedic, Inc. Bone replacement material delivery devices and methods of monitoring bone replacement material
WO2012017438A1 (en) 2010-08-04 2012-02-09 Ortho-Space Ltd. Shoulder implant
GB2482921A (en) * 2010-08-19 2012-02-22 Illuminoss Medical Inc Devices and methods for bone alignment, stabilization and distraction
CA2808528A1 (en) 2010-08-27 2012-03-01 Biomimedica, Inc. Hydrophobic and hydrophilic interpenetrating polymer networks derived from hydrophobic polymers and methods of preparing the same
US9402732B2 (en) 2010-10-11 2016-08-02 DePuy Synthes Products, Inc. Expandable interspinous process spacer implant
US9433455B2 (en) 2010-12-16 2016-09-06 DePuy Synthes Products, Inc. Fracture fragment mobility testing for vertebral body procedures
EP2654584A1 (en) 2010-12-22 2013-10-30 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
USD833613S1 (en) 2011-01-19 2018-11-13 Iorthopedics, Inc. Resilient knee implant
US8801768B2 (en) 2011-01-21 2014-08-12 Endologix, Inc. Graft systems having semi-permeable filling structures and methods for their use
US10092291B2 (en) 2011-01-25 2018-10-09 Ethicon Endo-Surgery, Inc. Surgical instrument with selectively rigidizable features
EP2754419B1 (en) 2011-02-15 2024-02-07 ConforMIS, Inc. Patient-adapted and improved orthopedic implants
CN103945780B (en) 2011-02-22 2016-12-07 齐默尔膝部创造物公司 Navigation and alignment system and for the guide instrument of joint repair
US9233241B2 (en) 2011-02-28 2016-01-12 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
US9254169B2 (en) 2011-02-28 2016-02-09 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
US9314620B2 (en) 2011-02-28 2016-04-19 Ethicon Endo-Surgery, Inc. Electrical ablation devices and methods
WO2012125785A1 (en) 2011-03-17 2012-09-20 Ethicon Endo-Surgery, Inc. Hand held surgical device for manipulating an internal magnet assembly within a patient
WO2012139054A1 (en) 2011-04-06 2012-10-11 Endologix, Inc. Method and system for endovascular aneurysm treatment
GB201108185D0 (en) * 2011-05-17 2011-06-29 Depuy Spine Sarl Medical implant, method for manufacturing a medical implant and curable mixture
WO2012170805A2 (en) 2011-06-09 2012-12-13 Knee Creations, Llc Instruments and devices for subchondral joint repair
US20120316571A1 (en) 2011-06-10 2012-12-13 Knee Creations, Llc Subchondral treatment of osteoarthritis in joints
CA2841795C (en) 2011-07-05 2020-09-15 The Research Foundation For The State University Of New York Compositions and methods for spinal disc repair and other surgical and non-surgical indications
BR112014001078A2 (en) 2011-07-19 2017-02-21 Illuminoss Medical Inc bone restructuring and stabilization devices and methods
US9138187B2 (en) 2011-08-07 2015-09-22 Zimmer Knee Creations, Inc. Treatment of subchondral bone by biochemical diagnosis to prevent the progression of osteoarthritis of the joint
US8623089B2 (en) 2011-08-07 2014-01-07 Zimmer Knee Creations, Inc. Subchondral treatment of joint pain of the spine
US9119646B2 (en) 2011-08-07 2015-09-01 Zimmer Knee Creations, Inc. Subchondral treatment to prevent the progression of osteoarthritis of the joint
US9155580B2 (en) 2011-08-25 2015-10-13 Medos International Sarl Multi-threaded cannulated bone anchors
EP2753371B1 (en) 2011-09-09 2021-08-04 Abyrx, Inc. Absorbable multi-putty bone cements and hemostatic compositions and methods of use
WO2013052105A2 (en) 2011-10-03 2013-04-11 Biomimedica, Inc. Polymeric adhesive for anchoring compliant materials to another surface
AU2012322814A1 (en) 2011-10-11 2014-05-29 Zimmer Knee Creations, Inc. Methods and instruments for subchondral treatment of osteoarthritis in a small joint
US9289307B2 (en) 2011-10-18 2016-03-22 Ortho-Space Ltd. Prosthetic devices and methods for using same
WO2013059609A1 (en) 2011-10-19 2013-04-25 Illuminoss Medical, Inc. Systems and methods for joint stabilization
US9814592B2 (en) * 2011-10-20 2017-11-14 Clariance Silicone nucleus implants
KR20140113655A (en) 2011-11-21 2014-09-24 바이오미메디카, 인코포레이티드 Systems, devices, and methods for anchoring orthopaedic implants to bone
WO2013082497A1 (en) * 2011-11-30 2013-06-06 Beth Israel Deaconess Medical Center Systems and methods for endoscopic vertebral fusion
EP2601995B1 (en) 2011-12-07 2022-08-17 CAR Holding B.V. An arrangement for implementing kissing balloons for simulating a bifurcated vessel, a kit, a method of manufacturing the arrangement and a catheter provided with a buffer volume.
US8986199B2 (en) 2012-02-17 2015-03-24 Ethicon Endo-Surgery, Inc. Apparatus and methods for cleaning the lens of an endoscope
US9510953B2 (en) 2012-03-16 2016-12-06 Vertebral Technologies, Inc. Modular segmented disc nucleus implant
US9949755B2 (en) 2012-03-30 2018-04-24 Zimmer Knee Creations, Inc. Surgical access systems, instruments and accessories
US8992595B2 (en) 2012-04-04 2015-03-31 Trivascular, Inc. Durable stent graft with tapered struts and stable delivery methods and devices
US9498363B2 (en) 2012-04-06 2016-11-22 Trivascular, Inc. Delivery catheter for endovascular device
US20150057756A1 (en) 2012-04-13 2015-02-26 Conformis, Inc. Patient Adapted Joint Arthroplasty Systems, Devices, Surgical Tools and Methods of Use
US9486226B2 (en) 2012-04-18 2016-11-08 Conformis, Inc. Tibial guides, tools, and techniques for resecting the tibial plateau
US9393126B2 (en) 2012-04-20 2016-07-19 Peter L. Mayer Bilaterally placed disc prosthesis for spinal implant and method of bilateral placement
US9364339B2 (en) 2012-04-30 2016-06-14 Peter L. Mayer Unilaterally placed expansile spinal prosthesis
US9095443B2 (en) 2012-05-08 2015-08-04 Eric R. VonGunten Nucleus pulposus spinal implant and method of using the same
US9427255B2 (en) 2012-05-14 2016-08-30 Ethicon Endo-Surgery, Inc. Apparatus for introducing a steerable camera assembly into a patient
NL2008861C2 (en) * 2012-05-23 2013-11-26 Urogyn B V Composition for soft tissue treatment.
WO2013185104A1 (en) * 2012-06-08 2013-12-12 Poly-Med, Inc. Polyether urethane and polyether urea based copolymers and methods related thereto
US9675471B2 (en) 2012-06-11 2017-06-13 Conformis, Inc. Devices, techniques and methods for assessing joint spacing, balancing soft tissues and obtaining desired kinematics for joint implant components
US9078662B2 (en) 2012-07-03 2015-07-14 Ethicon Endo-Surgery, Inc. Endoscopic cap electrode and method for using the same
US8939977B2 (en) 2012-07-10 2015-01-27 Illuminoss Medical, Inc. Systems and methods for separating bone fixation devices from introducer
US9510934B2 (en) 2012-07-20 2016-12-06 Cook Medical Technologies Llc Implantable medical device having a sleeve
US20140031894A1 (en) * 2012-07-23 2014-01-30 Eugene G. Lipov Method and device for post-operative application of pulsed radiofrequency for prevention of pain and cartilage loss
US9545290B2 (en) 2012-07-30 2017-01-17 Ethicon Endo-Surgery, Inc. Needle probe guide
US10314649B2 (en) 2012-08-02 2019-06-11 Ethicon Endo-Surgery, Inc. Flexible expandable electrode and method of intraluminal delivery of pulsed power
US9572623B2 (en) 2012-08-02 2017-02-21 Ethicon Endo-Surgery, Inc. Reusable electrode and disposable sheath
US9277957B2 (en) 2012-08-15 2016-03-08 Ethicon Endo-Surgery, Inc. Electrosurgical devices and methods
EP2892458B1 (en) 2012-09-07 2019-08-14 Zimmer Knee Creations, Inc. Instruments for controlled delivery of injectable materials into bone
AU2013326219B2 (en) 2012-09-07 2018-02-15 Zimmer Knee Creations, Inc. Navigation instruments for subchondral bone treatment
US9034044B2 (en) 2012-09-13 2015-05-19 H & M Innovations, Llc Bone infusion apparatus and methods for interbody grafts
USD732667S1 (en) 2012-10-23 2015-06-23 Providence Medical Technology, Inc. Cage spinal implant
USD745156S1 (en) 2012-10-23 2015-12-08 Providence Medical Technology, Inc. Spinal implant
KR20150087273A (en) 2012-11-15 2015-07-29 지가 테크놀로지 인코포레이티드 Systems and methods for facet joint treatment
US9687281B2 (en) 2012-12-20 2017-06-27 Illuminoss Medical, Inc. Distal tip for bone fixation devices
US20140178343A1 (en) 2012-12-21 2014-06-26 Jian Q. Yao Supports and methods for promoting integration of cartilage tissue explants
US10285818B2 (en) 2012-12-26 2019-05-14 Symbiomedik, Llc Apparatus, kit, and method for percutaneous intervertebral disc restoration
EP2948068A4 (en) 2013-01-28 2016-09-28 Cartiva Inc Systems and methods for orthopedic repair
US9737294B2 (en) 2013-01-28 2017-08-22 Cartiva, Inc. Method and system for orthopedic repair
US9408711B2 (en) * 2013-03-14 2016-08-09 Brian D. Burkinshaw Unitary spinal disc implant
US10098527B2 (en) 2013-02-27 2018-10-16 Ethidcon Endo-Surgery, Inc. System for performing a minimally invasive surgical procedure
US9522070B2 (en) 2013-03-07 2016-12-20 Interventional Spine, Inc. Intervertebral implant
US9345577B2 (en) * 2013-03-14 2016-05-24 Microaire Surgical Instruments Llc Balloon implant device
EP2968692B8 (en) 2013-03-14 2021-02-24 Endologix LLC Method for forming materials in situ within a medical device
US9295479B2 (en) 2013-03-14 2016-03-29 Spinal Stabilization Technologies, Llc Surgical device
US20140277467A1 (en) 2013-03-14 2014-09-18 Spinal Stabilization Technologies, Llc Prosthetic Spinal Disk Nucleus
US9675303B2 (en) 2013-03-15 2017-06-13 Vertiflex, Inc. Visualization systems, instruments and methods of using the same in spinal decompression procedures
WO2014152742A2 (en) * 2013-03-15 2014-09-25 Arsenal Medical, Inc. Delivery system for in situ forming foams and methods of using the same
JPWO2014162499A1 (en) 2013-04-02 2017-02-16 テルモ株式会社 Implant assembly
US9539041B2 (en) 2013-09-12 2017-01-10 DePuy Synthes Products, Inc. Minimally invasive biomaterial injection system
WO2015038200A1 (en) 2013-09-16 2015-03-19 Neuraxis, Llc Implantable devices for thermal therapy and related methods
WO2015039104A2 (en) 2013-09-16 2015-03-19 Neuraxis, Llc Methods and devices for applying localized thermal therapy
DE102013016899A1 (en) * 2013-10-11 2015-05-21 Josef Jansen Gelenkspacer
US9827349B1 (en) 2013-11-26 2017-11-28 Abyrx Inc. Settable surgical implants and their packaging
AU2014354694B2 (en) 2013-11-27 2019-07-04 Howmedica Osteonics Corp., Structurally supporting insert for spinal fusion cage
EP3113722A4 (en) 2014-03-07 2017-12-06 Endologix, Inc. Forming hydrogels and materials therefor
US10524772B2 (en) 2014-05-07 2020-01-07 Vertiflex, Inc. Spinal nerve decompression systems, dilation systems, and methods of using the same
AU2015267061B9 (en) 2014-05-28 2020-08-13 Providence Medical Technology, Inc. Lateral mass fixation system
US9782270B2 (en) * 2014-08-08 2017-10-10 Warsaw Orthopedic, Inc. Spinal implant system and method
FR3024834B1 (en) 2014-08-13 2021-10-29 In2Bones CANNULA SURGICAL TOOL, SURGICAL KIT, MANUFACTURING PROCESS AND MACHINE FOR MANUFACTURING SUCH A TOOL
EP3215069B1 (en) 2014-11-04 2023-03-08 Spinal Stabilization Technologies LLC Percutaneous implantable nuclear prosthesis
PL3215067T3 (en) 2014-11-04 2020-11-02 Spinal Stabilization Technologies Llc Percutaneous implantable nuclear prosthesis
US10077420B2 (en) 2014-12-02 2018-09-18 Histogenics Corporation Cell and tissue culture container
JP2018500395A (en) * 2014-12-15 2018-01-11 ノースイースタン・ユニバーシティ Collagen tissue treatment device
US11426290B2 (en) 2015-03-06 2022-08-30 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US9968388B2 (en) * 2015-03-24 2018-05-15 Warsaw Orthopedic, Inc. Surgical injection system and method
US10449055B2 (en) 2015-04-23 2019-10-22 Disc Fix L.L.C. Systems and methods for treatment of intervertebral disc derangements
US11077228B2 (en) 2015-08-10 2021-08-03 Hyalex Orthopaedics, Inc. Interpenetrating polymer networks
KR102607758B1 (en) 2015-09-01 2023-11-29 스파이널 스태빌라이제이션 테크놀로지스, 엘엘씨 Implantable nuclear prosthesis
US10959761B2 (en) 2015-09-18 2021-03-30 Ortho-Space Ltd. Intramedullary fixated subacromial spacers
CN108289689A (en) 2015-10-13 2018-07-17 普罗维登斯医疗技术公司 Joint of vertebral column implantation material conveying device and system
USD841165S1 (en) 2015-10-13 2019-02-19 Providence Medical Technology, Inc. Cervical cage
WO2017176973A1 (en) * 2016-04-07 2017-10-12 Rowan University Methods and compositions for inducing multi-targeted healing of intervertebral disc defects
AU2017202311B2 (en) 2016-04-07 2022-03-03 Howmedica Osteonics Corp. Expandable interbody implant
EP3245982B1 (en) 2016-05-20 2023-11-01 Howmedica Osteonics Corp. Expandable interbody implant with lordosis correction
CN109312049A (en) * 2016-05-26 2019-02-05 康宁光电通信有限责任公司 For coating the material prescription of molding covering fiber optic cables
EP4233801A3 (en) 2016-06-28 2023-09-06 Eit Emerging Implant Technologies GmbH Expandable, angularly adjustable intervertebral cages
EP3474782A2 (en) 2016-06-28 2019-05-01 Eit Emerging Implant Technologies GmbH Expandable and angularly adjustable articulating intervertebral cages
US11065039B2 (en) 2016-06-28 2021-07-20 Providence Medical Technology, Inc. Spinal implant and methods of using the same
USD887552S1 (en) 2016-07-01 2020-06-16 Providence Medical Technology, Inc. Cervical cage
AU2017204355B2 (en) 2016-07-08 2021-09-09 Mako Surgical Corp. Scaffold for alloprosthetic composite implant
EP3292841B8 (en) 2016-09-12 2023-05-31 Howmedica Osteonics Corp. Interbody implant with independent control of expansion at multiple locations
AU2017251734B2 (en) 2016-10-26 2022-10-20 Howmedica Osteonics Corp. Expandable interbody implant with lateral articulation
US20220160519A1 (en) * 2016-12-13 2022-05-26 Aurora Spine, Inc. Bone density scan result-matched orthopedic implants and methods of use
US10888433B2 (en) 2016-12-14 2021-01-12 DePuy Synthes Products, Inc. Intervertebral implant inserter and related methods
US11045981B2 (en) 2017-01-30 2021-06-29 Ortho-Space Ltd. Processing machine and methods for processing dip-molded articles
US10398563B2 (en) 2017-05-08 2019-09-03 Medos International Sarl Expandable cage
EP3624708A1 (en) 2017-05-19 2020-03-25 Providence Medical Technology, Inc. Spinal fixation access and delivery system
WO2018222743A1 (en) 2017-05-30 2018-12-06 Abyrx, Inc. Therapeutic putties containing additives including processed human blood plasma
US11344424B2 (en) 2017-06-14 2022-05-31 Medos International Sarl Expandable intervertebral implant and related methods
US10940016B2 (en) 2017-07-05 2021-03-09 Medos International Sarl Expandable intervertebral fusion cage
EP3456294A1 (en) 2017-09-15 2019-03-20 Stryker European Holdings I, LLC Intervertebral body fusion device expanded with hardening material
CA3081827A1 (en) 2017-11-07 2019-05-16 Abyrx, Inc. Intraoperative uses of settable surgical compositions
US10806828B2 (en) * 2017-11-15 2020-10-20 De Novo Orthopedics Inc. Methods for reattaching detached tissue to hard tissue using bioinductive patch
US11648128B2 (en) 2018-01-04 2023-05-16 Providence Medical Technology, Inc. Facet screw and delivery device
US11419733B2 (en) 2018-01-12 2022-08-23 Percheron Spine, Llc Spinal disc implant and device and method for percutaneous delivery of the spinal disc implant
WO2019152917A1 (en) 2018-02-02 2019-08-08 Galen Therapeutics Llc Apparatus and method for protecting neurons and reducing inflammation and scarring
CN112203614A (en) * 2018-05-23 2021-01-08 帕多瓦大学 Fenestrated endoprosthesis for correction of aortic aneurysms
EP3813696A4 (en) 2018-06-27 2022-04-13 IlluminOss Medical, Inc. Systems and methods for bone stabilization and fixation
US10869950B2 (en) 2018-07-17 2020-12-22 Hyalex Orthopaedics, Inc. Ionic polymer compositions
AU2019384660A1 (en) 2018-09-04 2021-03-25 Spinal Stabilization Technologies, Llc Implantable nuclear prosthesis, kits, and related methods
NL2021601B1 (en) 2018-09-11 2020-05-01 Car Holding B V Kissing balloons and method for implementing the same
US11446156B2 (en) 2018-10-25 2022-09-20 Medos International Sarl Expandable intervertebral implant, inserter instrument, and related methods
WO2020181103A1 (en) * 2019-03-06 2020-09-10 Fp Medtech, Inc. Devices and methods to optimize the form and function of a pessary
CN109770994B (en) * 2019-03-12 2021-04-13 杭州华移技术有限公司 Full-automatic orthopedics bores bone, water injection, integrative device that draws water
US11129727B2 (en) 2019-03-29 2021-09-28 Medos International Sari Inflatable non-distracting intervertebral implants and related methods
USD933230S1 (en) 2019-04-15 2021-10-12 Providence Medical Technology, Inc. Cervical cage
DE102019115933A1 (en) * 2019-06-12 2020-12-17 Heraeus Medical Gmbh Medical implant for gas exchange
DE102019115932A1 (en) * 2019-06-12 2020-12-17 Heraeus Medical Gmbh Medically applicable placeholder
USD911525S1 (en) 2019-06-21 2021-02-23 Providence Medical Technology, Inc. Spinal cage
USD945621S1 (en) 2020-02-27 2022-03-08 Providence Medical Technology, Inc. Spinal cage
US11426286B2 (en) 2020-03-06 2022-08-30 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
DE102020111377B4 (en) 2020-04-27 2023-04-27 Carl Zeiss Meditec Ag system in the field of brachytherapy
US20220241457A1 (en) 2021-01-29 2022-08-04 Abyrx, Inc. Multi-putty bone hemostatic and adhesive compositions for use in methods of installing and securing surgical hardware in bones
US11850160B2 (en) 2021-03-26 2023-12-26 Medos International Sarl Expandable lordotic intervertebral fusion cage
US11752009B2 (en) 2021-04-06 2023-09-12 Medos International Sarl Expandable intervertebral fusion cage
CN113171164B (en) * 2021-04-13 2023-02-17 清华大学 Device for repairing premature rupture of fetal membrane for in-vivo in-situ biological manufacturing
US11801143B2 (en) * 2021-07-01 2023-10-31 Hyalex Orthopaedics, Inc. Multi-layered biomimetic osteochondral implants and methods of using thereof
CA3227376A1 (en) 2021-08-04 2023-02-09 Abyrx, Inc. Nonabsorbable settable multi-putty bone cements, hemostatic compositions and methods of use

Family Cites Families (281)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US34553A (en) * 1862-02-25 Improvement in shifting hinge-joints or coupling-shafts of wagons
US47207A (en) * 1865-04-11 Instrument for lighting gas
US29345A (en) * 1860-07-24 Martin shirk
US22843A (en) * 1859-02-08 peters
US4683A (en) * 1846-08-08 waring and richard e
US16583A (en) * 1857-02-10 godfrey
US11174A (en) * 1854-06-27 Improved charger for fire-arsvis
US41896A (en) * 1864-03-08 Improvement in gear wheels and pulleys
US47208A (en) * 1865-04-11 John johnston
US10511A (en) * 1854-02-07 Joseph w
US37479A (en) * 1863-01-20 Improvement in axles
US16595A (en) * 1857-02-10 Improved sash-fastener
US3030951A (en) 1959-04-10 1962-04-24 Michael P Mandarino Methods and materials for orthopedic surgery
US3223083A (en) 1960-09-09 1965-12-14 President And Directors Of Geo Method for adhesively securing together skin and other soft tissue and bone
US3320131A (en) 1964-10-23 1967-05-16 Baxter Laboratories Inc Method for the treatment of herniation of intervertebral discs
US3879767A (en) 1972-01-26 1975-04-29 Cutter Lab Prosthesis for articulating body structures
US3805767A (en) 1973-02-26 1974-04-23 Erb Rene Method and apparatus for non-surgical, reversible sterilization of females
USRE29345E (en) 1973-02-26 1977-08-09 The Franklin Institute Method and apparatus for non-surgical, reversible sterilization of females
US3875595A (en) 1974-04-15 1975-04-08 Edward C Froning Intervertebral disc prosthesis and instruments for locating same
US4085466A (en) 1974-11-18 1978-04-25 National Research Development Corporation Prosthetic joint device
US4052753A (en) 1976-08-02 1977-10-11 Dedo Richard G Knee spacer and method of reforming sliding body surfaces
US4098626A (en) 1976-11-15 1978-07-04 Thiokol Corporation Hydroxy terminated polybutadiene based polyurethane bound propellant grains
US4203444A (en) 1977-11-07 1980-05-20 Dyonics, Inc. Surgical instrument suitable for closed surgery such as of the knee
US4245623A (en) 1978-06-06 1981-01-20 Erb Robert A Method and apparatus for the hysteroscopic non-surgical sterilization of females
US4274414A (en) 1979-02-21 1981-06-23 Dyonics, Inc. Surgical instrument
ATE4440T1 (en) 1980-02-21 1983-08-15 J. & P. Coats, Limited DEVICE FOR TREATMENT OF DAMAGED SURFACES OF HUMAN JOINTS.
US4292972A (en) 1980-07-09 1981-10-06 E. R. Squibb & Sons, Inc. Lyophilized hydrocolloio foam
US4368040A (en) 1981-06-01 1983-01-11 Ipco Corporation Dental impression tray for forming a dental prosthesis in situ
US4734097A (en) 1981-09-25 1988-03-29 Nippon Oil Company, Ltd. Medical material of polyvinyl alcohol and process of making
US4463141A (en) 1981-11-30 1984-07-31 E. I. Du Pont De Nemours And Company Polyether carbonate diols and polyurethanes prepared therefrom
US4476293A (en) 1981-11-30 1984-10-09 E. I. Du Pont De Nemours And Company Polymeric carbonate diols of copolyether glycols and polyurethanes prepared therefrom
US4446578A (en) 1982-03-08 1984-05-08 Perkins Ezra C Joint treatment
US4456745A (en) 1982-05-24 1984-06-26 Ethyl Corporation Polyurethanes prepared from polycarbonates
US4545374A (en) 1982-09-03 1985-10-08 Jacobson Robert E Method and instruments for performing a percutaneous lumbar diskectomy
US4477604A (en) 1982-09-20 1984-10-16 Oechsle Iii Sixtus J Polyurethane compositions and their use as luting agents
US4570270A (en) * 1982-09-20 1986-02-18 Oechsle Iii Sixtus J Polyurethane compositions and their use as luting agents
DE3318730A1 (en) 1983-05-21 1984-11-22 Akzo Gmbh, 5600 Wuppertal Biocompatible polyurethanes
US4722948A (en) 1984-03-16 1988-02-02 Dynatech Corporation Bone replacement and repair putty material from unsaturated polyester resin and vinyl pyrrolidone
EP0176728B1 (en) 1984-09-04 1989-07-26 Humboldt-Universität zu Berlin Intervertebral-disc prosthesis
US4705038A (en) 1985-01-23 1987-11-10 Dyonics, Inc. Surgical system for powered instruments
US4594380A (en) 1985-05-01 1986-06-10 At&T Bell Laboratories Elastomeric controlled release formulation and article comprising same
US4647643A (en) 1985-11-08 1987-03-03 Becton, Dickinson And Company Soft non-blocking polyurethanes
US4651736A (en) 1986-02-01 1987-03-24 Bruce Sanders Methods for temporomandibular joint small incision surgery
US4842578A (en) 1986-03-12 1989-06-27 Dyonics, Inc. Surgical abrading instrument
US4834729A (en) 1986-12-30 1989-05-30 Dyonics, Inc. Arthroscopic surgical instrument
US4983179A (en) 1986-12-30 1991-01-08 Smith & Nephew Dyonics Inc. Arthroscopic surgical instrument
CH671691A5 (en) 1987-01-08 1989-09-29 Sulzer Ag
US4834757A (en) 1987-01-22 1989-05-30 Brantigan John W Prosthetic implant
US4743632A (en) 1987-02-25 1988-05-10 Pfizer Hospital Products Group, Inc. Polyetherurethane urea polymers as space filling tissue adhesives
US4863477A (en) 1987-05-12 1989-09-05 Monson Gary L Synthetic intervertebral disc prosthesis
DE3717060A1 (en) 1987-05-21 1988-12-01 Bayer Ag POLYETHER-POLYCARBONATE-DIOLE, THEIR PRODUCTION AND USE AS STARTING PRODUCTS FOR POLYURETHANE PLASTICS
US5306311A (en) 1987-07-20 1994-04-26 Regen Corporation Prosthetic articular cartilage
US4772287A (en) 1987-08-20 1988-09-20 Cedar Surgical, Inc. Prosthetic disc and method of implanting
US5064426A (en) 1987-12-11 1991-11-12 Huebsch Donald L Apparatus for removal of bone cement
AU618772B2 (en) 1987-12-30 1992-01-09 Minnesota Mining And Manufacturing Company Photocurable ionomer cement systems
US5834011A (en) 1988-02-19 1998-11-10 The Regents Of The University Of California Method for aiding in the reduction of incidence of tobacco smoking
US4880610A (en) 1988-04-20 1989-11-14 Norian Corporation In situ calcium phosphate minerals--method and composition
DE8807485U1 (en) 1988-06-06 1989-08-10 Mecron Medizinische Produkte Gmbh, 1000 Berlin, De
US6770074B2 (en) 1988-06-13 2004-08-03 Gary Karlin Michelson Apparatus for use in inserting spinal implants
US5484437A (en) 1988-06-13 1996-01-16 Michelson; Gary K. Apparatus and method of inserting spinal implants
EP0703757B1 (en) 1988-06-13 2003-08-27 Karlin Technology, Inc. Apparatus for inserting spinal implants
US5545229A (en) 1988-08-18 1996-08-13 University Of Medicine And Dentistry Of Nj Functional and biocompatible intervertebral disc spacer containing elastomeric material of varying hardness
AU624627B2 (en) 1988-08-18 1992-06-18 Johnson & Johnson Orthopaedics, Inc. Functional and biocompatible intervertebral disc spacer containing elastomeric material of varying hardness
US4873308A (en) 1988-09-30 1989-10-10 Medtronic, Inc. Biostable, segmented aliphatic polyurethanes and process therefor
US4938763B1 (en) 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US4913701A (en) 1988-10-06 1990-04-03 Numed, Inc. Balloon catheter and method of manufacturing the same
FR2639823A1 (en) * 1988-12-06 1990-06-08 Garcia Alain Replacement of the nucleus of the intervertebral disc by a polyurethane polymerised in situ
US5258028A (en) 1988-12-12 1993-11-02 Ersek Robert A Textured micro implants
US4969888A (en) * 1989-02-09 1990-11-13 Arie Scholten Surgical protocol for fixation of osteoporotic bone using inflatable device
CA1318469C (en) 1989-02-15 1993-06-01 Acromed Corporation Artificial disc
US5356436A (en) 1989-06-06 1994-10-18 Tdk Corporation Materials for living hard tissue replacements
US5007940A (en) 1989-06-09 1991-04-16 American Medical Systems, Inc. Injectable polymeric bodies
US5895427A (en) * 1989-07-06 1999-04-20 Sulzer Spine-Tech Inc. Method for spinal fixation
US5458638A (en) 1989-07-06 1995-10-17 Spine-Tech, Inc. Non-threaded spinal implant
DE4029969A1 (en) 1989-09-21 1991-04-04 Asahi Optical Co Ltd METHOD FOR PRODUCING BONE PROSTHESES
US5059193A (en) 1989-11-20 1991-10-22 Spine-Tech, Inc. Expandable spinal implant and surgical method
US5478320A (en) * 1989-11-29 1995-12-26 Cordis Corporation Puncture resistant balloon catheter and method of manufacturing
US5290306A (en) 1989-11-29 1994-03-01 Cordis Corporation Puncture resistant balloon catheter
US5067964A (en) 1989-12-13 1991-11-26 Stryker Corporation Articular surface repair
US5171244A (en) 1990-01-08 1992-12-15 Caspari Richard B Methods and apparatus for arthroscopic prosthetic knee replacement
US5954739A (en) 1990-03-02 1999-09-21 General Surgical Innovations, Inc. Method of dissecting tissue layers
US5331975A (en) * 1990-03-02 1994-07-26 Bonutti Peter M Fluid operated retractors
US6277136B1 (en) 1990-03-02 2001-08-21 General Surgical Innovations, Inc. Method for developing an anatomic space
US5163949A (en) 1990-03-02 1992-11-17 Bonutti Peter M Fluid operated retractors
US5295994A (en) 1991-11-15 1994-03-22 Bonutti Peter M Active cannulas
US5514153A (en) 1990-03-02 1996-05-07 General Surgical Innovations, Inc. Method of dissecting tissue layers
FR2659226B1 (en) 1990-03-07 1992-05-29 Jbs Sa PROSTHESIS FOR INTERVERTEBRAL DISCS AND ITS IMPLEMENTATION INSTRUMENTS.
EP0453393B1 (en) 1990-04-20 1993-10-06 SULZER Medizinaltechnik AG Implant, particularly intervertebral prosthesis
US5078720A (en) 1990-05-02 1992-01-07 American Medical Systems, Inc. Stent placement instrument and method
CA2082805A1 (en) 1990-05-11 1991-11-12 Mark A. Saab High-strength, thin-walled single piece catheters
US5254662A (en) 1990-09-12 1993-10-19 Polymedia Industries, Inc. Biostable polyurethane products
US5047055A (en) 1990-12-21 1991-09-10 Pfizer Hospital Products Group, Inc. Hydrogel intervertebral disc nucleus
US5192326A (en) 1990-12-21 1993-03-09 Pfizer Hospital Products Group, Inc. Hydrogel bead intervertebral disc nucleus
JP2766082B2 (en) * 1991-02-15 1998-06-18 シャープ株式会社 Semiconductor storage device
US5156777A (en) 1991-03-21 1992-10-20 Kaye Alan H Process for making a prosthetic implant
JP3007903B2 (en) 1991-03-29 2000-02-14 京セラ株式会社 Artificial disc
CA2041532C (en) * 1991-04-30 2002-01-01 Hamdy Khalil Urethane sealant having improved sag properties
NL9101159A (en) 1991-07-03 1993-02-01 Industrial Res Bv FORMATTABLE EXPANDABLE RING, CYLINDER OR SLEEVE.
US5269797A (en) 1991-09-12 1993-12-14 Meditron Devices, Inc. Cervical discectomy instruments
US5285795A (en) * 1991-09-12 1994-02-15 Surgical Dynamics, Inc. Percutaneous discectomy system having a bendable discectomy probe and a steerable cannula
US5143942A (en) 1991-10-28 1992-09-01 Ethyl Corporation Polyurethanes
US5166115A (en) 1991-10-28 1992-11-24 Brown William R Polyurethanes
US5762629A (en) 1991-10-30 1998-06-09 Smith & Nephew, Inc. Oval cannula assembly and method of use
US5395317A (en) * 1991-10-30 1995-03-07 Smith & Nephew Dyonics, Inc. Unilateral biportal percutaneous surgical procedure
US5344459A (en) 1991-12-03 1994-09-06 Swartz Stephen J Arthroscopically implantable prosthesis
DE9202745U1 (en) * 1992-03-02 1992-04-30 Howmedica Gmbh, 2314 Schoenkirchen, De
JPH05298662A (en) 1992-04-14 1993-11-12 Fuji Photo Film Co Ltd Binder for magnetic recording medium and magnetic recording medium
US5589563A (en) 1992-04-24 1996-12-31 The Polymer Technology Group Surface-modifying endgroups for biomedical polymers
US5385469A (en) 1992-06-12 1995-01-31 Weissman; Bernard Method for forming a coronal replacement for a tooth and product for casting the crown
US5447497A (en) 1992-08-06 1995-09-05 Scimed Life Systems, Inc Balloon catheter having nonlinear compliance curve and method of using
US5342305A (en) 1992-08-13 1994-08-30 Cordis Corporation Variable distention angioplasty balloon assembly
US5320611A (en) 1993-02-04 1994-06-14 Peter M. Bonutti Expandable cannula having longitudinal wire and method of use
US5334201A (en) 1993-03-12 1994-08-02 Cowan Kevin P Permanent stent made of a cross linkable material
NL9300500A (en) 1993-03-22 1994-10-17 Industrial Res Bv Expandable hollow sleeve for locally supporting and / or strengthening a body vessel, as well as a method for manufacturing it.
US5534028A (en) 1993-04-20 1996-07-09 Howmedica, Inc. Hydrogel intervertebral disc nucleus with diminished lateral bulging
FR2705351B1 (en) * 1993-05-18 1995-06-23 Garcia Alain Method of manufacturing and preserving a polymerizable mixture leading to a polyurethane intended to fill biological cavities.
ATE263511T1 (en) * 1993-06-10 2004-04-15 Karlin Technology Inc PROTECTIVE DEVICE WITH TWO PASSAGES FOR SURGERY OF THE INTERVERBEL SPACE
FR2706309B1 (en) 1993-06-17 1995-10-06 Sofamor Instrument for surgical treatment of an intervertebral disc by the anterior route.
US5314432A (en) 1993-08-05 1994-05-24 Paul Kamaljit S Lumbar spinal disc trocar placement device
US5830125A (en) 1993-08-12 1998-11-03 Scribner-Browne Medical Design Incorporated Catheter introducer with suture capability
US5425772A (en) 1993-09-20 1995-06-20 Brantigan; John W. Prosthetic implant for intervertebral spinal fusion
WO1995009667A1 (en) 1993-10-01 1995-04-13 Boston Scientific Corporation Medical device balloons containing thermoplastic elastomers
EP0650738B1 (en) 1993-10-28 2003-05-02 Medrad, Inc. Multi-patient fluid dispensing
US5376064A (en) 1993-11-24 1994-12-27 Bard International, Inc. Inflatable prosthesis
US5458642A (en) 1994-01-18 1995-10-17 Beer; John C. Synthetic intervertebral disc
US7044954B2 (en) 1994-01-26 2006-05-16 Kyphon Inc. Method for treating a vertebral body
US6248110B1 (en) * 1994-01-26 2001-06-19 Kyphon, Inc. Systems and methods for treating fractured or diseased bone using expandable bodies
EP0741547B1 (en) * 1994-01-26 2005-04-20 Kyphon Inc. Improved inflatable device for use in surgical protocol relating to fixation of bone
ATE293395T1 (en) 1994-01-26 2005-05-15 Kyphon Inc IMPROVED INFLATABLE DEVICE FOR USE IN SURGICAL PROTOCOLS RELATING TO BONE FIXATION
US6241734B1 (en) * 1998-08-14 2001-06-05 Kyphon, Inc. Systems and methods for placing materials into bone
US5620458A (en) * 1994-03-16 1997-04-15 United States Surgical Corporation Surgical instruments useful for endoscopic spinal procedures
CA2144211C (en) 1994-03-16 2005-05-24 David T. Green Surgical instruments useful for endoscopic spinal procedures
CA2551185C (en) * 1994-03-28 2007-10-30 Sdgi Holdings, Inc. Apparatus and method for anterior spinal stabilization
US5556429A (en) 1994-05-06 1996-09-17 Advanced Bio Surfaces, Inc. Joint resurfacing system
US6248131B1 (en) * 1994-05-06 2001-06-19 Advanced Bio Surfaces, Inc. Articulating joint repair
US5888220A (en) * 1994-05-06 1999-03-30 Advanced Bio Surfaces, Inc. Articulating joint repair
US6140452A (en) 1994-05-06 2000-10-31 Advanced Bio Surfaces, Inc. Biomaterial for in situ tissue repair
US5571189A (en) 1994-05-20 1996-11-05 Kuslich; Stephen D. Expandable fabric implant for stabilizing the spinal motion segment
AU2621295A (en) * 1994-05-24 1995-12-18 Smith & Nephew Plc Intervertebral disc implant
US5470314A (en) 1994-07-22 1995-11-28 Walinsky; Paul Perfusion balloon catheter with differential compliance
US5587125A (en) 1994-08-15 1996-12-24 Schneider (Usa) Inc. Non-coextrusion method of making multi-layer angioplasty balloons
DE69522060T2 (en) 1994-09-08 2002-05-29 Stryker Technologies Corp Intervertebral disc core made of hydrogel
US5632275A (en) * 1994-09-16 1997-05-27 Scribner-Browne Medical Design Incorporated Catheter lab table pad and method for using the same
CA2159685C (en) 1994-10-07 2007-07-31 Scott W. Larsen Endoscopic surgical instruments useful for spinal procedures
EP0786963B1 (en) 1994-10-17 2004-04-07 RayMedica, Inc. Prosthetic spinal disc nucleus
US5824093A (en) 1994-10-17 1998-10-20 Raymedica, Inc. Prosthetic spinal disc nucleus
US5562736A (en) 1994-10-17 1996-10-08 Raymedica, Inc. Method for surgical implantation of a prosthetic spinal disc nucleus
US5674296A (en) 1994-11-14 1997-10-07 Spinal Dynamics Corporation Human spinal disc prosthesis
US5591235A (en) * 1995-03-15 1997-01-07 Kuslich; Stephen D. Spinal fixation device
US5584855A (en) 1995-04-27 1996-12-17 Onik; Gary M. Safety surgical grasping forceps
US5683391A (en) 1995-06-07 1997-11-04 Danek Medical, Inc. Anterior spinal instrumentation and method for implantation and revision
US5591199A (en) 1995-06-07 1997-01-07 Porter; Christopher H. Curable fiber composite stent and delivery system
US6095149A (en) 1996-08-13 2000-08-01 Oratec Interventions, Inc. Method for treating intervertebral disc degeneration
EP2111876B1 (en) * 1995-12-18 2011-09-07 AngioDevice International GmbH Crosslinked polymer compositions and methods for their use
US6458889B1 (en) 1995-12-18 2002-10-01 Cohesion Technologies, Inc. Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use
US5645597A (en) * 1995-12-29 1997-07-08 Krapiva; Pavel I. Disc replacement method and apparatus
DE29600879U1 (en) * 1996-01-19 1996-03-28 Howmedica Gmbh Spinal implant
US5797679A (en) 1996-02-09 1998-08-25 Stryker Corporation Surgical cement mixer apparatus
US5792044A (en) * 1996-03-22 1998-08-11 Danek Medical, Inc. Devices and methods for percutaneous surgery
EP1466564B1 (en) 1996-03-22 2010-10-20 Warsaw Orthopedic, Inc. Devices for percutaneous surgery related applications
US6053904A (en) * 1996-04-05 2000-04-25 Robert M. Scribner Thin wall catheter introducer system
US5788625A (en) 1996-04-05 1998-08-04 Depuy Orthopaedics, Inc. Method of making reconstructive SIS structure for cartilaginous elements in situ
US5785647A (en) 1996-07-31 1998-07-28 United States Surgical Corporation Surgical instruments useful for spinal surgery
US6126682A (en) 1996-08-13 2000-10-03 Oratec Interventions, Inc. Method for treating annular fissures in intervertebral discs
DE29616778U1 (en) * 1996-09-26 1998-01-29 Howmedica Gmbh Vertebral body placeholder
TW375522B (en) 1996-10-24 1999-12-01 Danek Medical Inc Devices for percutaneous surgery under direct visualization and through an elongated cannula
US5895428A (en) * 1996-11-01 1999-04-20 Berry; Don Load bearing spinal joint implant
AU7178698A (en) * 1996-11-15 1998-06-03 Advanced Bio Surfaces, Inc. Biomaterial system for in situ tissue repair
US5897428A (en) * 1997-02-04 1999-04-27 Sakcriska; Glenn Device for contouring and sharpening ice skate blades
WO1998034556A1 (en) 1997-02-11 1998-08-13 Michelson Gary K Skeletal plating system
ES2268267T3 (en) * 1997-02-11 2007-03-16 Warsaw Orthopedic, Inc. PREVIOUS CERVICAL PLATE FOR UNIQUE TYPE LOCK DEVICE.
US5769817A (en) * 1997-02-28 1998-06-23 Schneider (Usa) Inc. Coextruded balloon and method of making same
JP2001527437A (en) 1997-03-07 2001-12-25 ベイヤー、モルデキイ System for percutaneous bone and spine stabilization, fixation and repair
US6306170B2 (en) 1997-04-25 2001-10-23 Tegementa, L.L.C. Threaded fusion cage anchoring device and method
US5800549A (en) 1997-04-30 1998-09-01 Howmedica Inc. Method and apparatus for injecting an elastic spinal implant
US6033438A (en) * 1997-06-03 2000-03-07 Sdgi Holdings, Inc. Open intervertebral spacer
US6022376A (en) * 1997-06-06 2000-02-08 Raymedica, Inc. Percutaneous prosthetic spinal disc nucleus and method of manufacture
US5972015A (en) 1997-08-15 1999-10-26 Kyphon Inc. Expandable, asymetric structures for deployment in interior body regions
DE29710484U1 (en) * 1997-06-16 1998-10-15 Howmedica Gmbh Receiving part for a holding component of a spinal implant
GB9714580D0 (en) 1997-07-10 1997-09-17 Wardlaw Douglas Prosthetic intervertebral disc nucleus
US6042262A (en) * 1997-07-29 2000-03-28 Stryker Technologies Corportion Apparatus for storing, mixing, and dispensing two-component bone cement
US6048346A (en) * 1997-08-13 2000-04-11 Kyphon Inc. Systems and methods for injecting flowable materials into bones
EP1018944A4 (en) * 1997-09-26 2001-08-22 Cryolife Inc Sutureless anastomotic technique using a bioadhesive and device therefor
DE19746492A1 (en) * 1997-10-22 1999-04-29 Bosch Gmbh Robert Dual fluid injection system for IC engine
US6146420A (en) 1997-12-10 2000-11-14 Sdgi Holdings, Inc. Osteogenic fusion device
US6079868A (en) 1997-12-18 2000-06-27 Advanced Bio Surfaces, Inc. Static mixer
WO1999043271A1 (en) * 1998-02-27 1999-09-02 Bioelastics Research, Ltd. Injectable implants for tissue augmentation and restoration
DE19817698A1 (en) * 1998-04-22 1999-10-28 Jan Zoellner Composition used for flat disk implant, especially nucleus pulposus implant
DE29808593U1 (en) 1998-05-13 1999-09-23 Howmedica Gmbh Device for connecting two spaced longitudinal rods of a spinal implant
US6224630B1 (en) * 1998-05-29 2001-05-01 Advanced Bio Surfaces, Inc. Implantable tissue repair device
US6132465A (en) 1998-06-04 2000-10-17 Raymedica, Inc. Tapered prosthetic spinal disc nucleus
DE29813139U1 (en) 1998-07-23 1998-12-03 Howmedica Gmbh Vertebral body reconstruction system
WO2000025707A1 (en) 1998-10-30 2000-05-11 Michelson Gary K Self-broaching, rotatable, push-in interbody fusion implant and method for deployment thereof
US5989256A (en) 1999-01-19 1999-11-23 Spineology, Inc. Bone fixation cable ferrule
US6086589A (en) * 1999-02-02 2000-07-11 Spineology, Inc. Method and device for fixing spondylolisthesis posteriorly
US6648895B2 (en) 2000-02-04 2003-11-18 Sdgi Holdings, Inc. Methods and instrumentation for vertebral interbody fusion
US6183518B1 (en) * 1999-02-22 2001-02-06 Anthony C. Ross Method of replacing nucleus pulposus and repairing the intervertebral disk
US6241770B1 (en) * 1999-03-05 2001-06-05 Gary K. Michelson Interbody spinal fusion implant having an anatomically conformed trailing end
US6056749A (en) * 1999-03-15 2000-05-02 Spineology, Inc. Method and device for fixing and correcting spondylolisthesis anteriorly
US6113639A (en) 1999-03-23 2000-09-05 Raymedica, Inc. Trial implant and trial implant kit for evaluating an intradiscal space
US6110210A (en) 1999-04-08 2000-08-29 Raymedica, Inc. Prosthetic spinal disc nucleus having selectively coupled bodies
US6428576B1 (en) 1999-04-16 2002-08-06 Endospine, Ltd. System for repairing inter-vertebral discs
AU4810800A (en) 1999-04-26 2000-11-10 Li Medical Technologies, Inc. Prosthetic apparatus and method
US6533799B1 (en) * 1999-04-27 2003-03-18 Ams Research Corporation Cavity measurement device and method of assembly
US7094239B1 (en) * 1999-05-05 2006-08-22 Sdgi Holdings, Inc. Screws of cortical bone and method of manufacture thereof
US6224599B1 (en) 1999-05-19 2001-05-01 Matthew G. Baynham Viewable wedge distractor device
US6491724B1 (en) 1999-08-13 2002-12-10 Bret Ferree Spinal fusion cage with lordosis correction
US6371990B1 (en) * 1999-10-08 2002-04-16 Bret A. Ferree Annulus fibrosis augmentation methods and apparatus
US6969404B2 (en) 1999-10-08 2005-11-29 Ferree Bret A Annulus fibrosis augmentation methods and apparatus
US6245107B1 (en) * 1999-05-28 2001-06-12 Bret A. Ferree Methods and apparatus for treating disc herniation
US6419704B1 (en) 1999-10-08 2002-07-16 Bret Ferree Artificial intervertebral disc replacement methods and apparatus
US6283966B1 (en) 1999-07-07 2001-09-04 Sulzer Spine-Tech Inc. Spinal surgery tools and positioning method
NL1012719C1 (en) 1999-07-28 2001-01-30 Veldhuizen Dr Ag Spine prosthesis.
US6685695B2 (en) * 1999-08-13 2004-02-03 Bret A. Ferree Method and apparatus for providing nutrition to intervertebral disc tissue
US6793677B2 (en) 1999-08-13 2004-09-21 Bret A. Ferree Method of providing cells and other biologic materials for transplantation
US6719797B1 (en) * 1999-08-13 2004-04-13 Bret A. Ferree Nucleus augmentation with in situ formed hydrogels
US7220281B2 (en) 1999-08-18 2007-05-22 Intrinsic Therapeutics, Inc. Implant for reinforcing and annulus fibrosis
US6508839B1 (en) * 1999-08-18 2003-01-21 Intrinsic Orthopedics, Inc. Devices and methods of vertebral disc augmentation
US6425919B1 (en) 1999-08-18 2002-07-30 Intrinsic Orthopedics, Inc. Devices and methods of vertebral disc augmentation
US6264695B1 (en) * 1999-09-30 2001-07-24 Replication Medical, Inc. Spinal nucleus implant
US6436119B1 (en) 1999-09-30 2002-08-20 Raymedica, Inc. Adjustable surgical dilator
US6432107B1 (en) 2000-01-15 2002-08-13 Bret A. Ferree Enhanced surface area spinal fusion devices
US6592625B2 (en) 1999-10-20 2003-07-15 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and spinal disc annulus stent
US7052516B2 (en) 1999-10-20 2006-05-30 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and deformable spinal disc annulus stent
US6830570B1 (en) 1999-10-21 2004-12-14 Sdgi Holdings, Inc. Devices and techniques for a posterior lateral disc space approach
WO2001028469A2 (en) 1999-10-21 2001-04-26 Sdgi Holdings, Inc. Devices and techniques for a posterior lateral disc space approach
US6395034B1 (en) * 1999-11-24 2002-05-28 Loubert Suddaby Intervertebral disc prosthesis
US6827740B1 (en) 1999-12-08 2004-12-07 Gary K. Michelson Spinal implant surface configuration
US6709458B2 (en) 2000-02-04 2004-03-23 Gary Karlin Michelson Expandable push-in arcuate interbody spinal fusion implant with tapered configuration during insertion
US7014633B2 (en) * 2000-02-16 2006-03-21 Trans1, Inc. Methods of performing procedures in the spine
US6558386B1 (en) 2000-02-16 2003-05-06 Trans1 Inc. Axial spinal implant and method and apparatus for implanting an axial spinal implant within the vertebrae of the spine
US6558390B2 (en) 2000-02-16 2003-05-06 Axiamed, Inc. Methods and apparatus for performing therapeutic procedures in the spine
US6899716B2 (en) 2000-02-16 2005-05-31 Trans1, Inc. Method and apparatus for spinal augmentation
US6332894B1 (en) 2000-03-07 2001-12-25 Zimmer, Inc. Polymer filled spinal fusion cage
US6689125B1 (en) * 2000-04-04 2004-02-10 Spinalabs, Llc Devices and methods for the treatment of spinal disorders
US6402750B1 (en) 2000-04-04 2002-06-11 Spinlabs, Llc Devices and methods for the treatment of spinal disorders
US6579291B1 (en) 2000-10-10 2003-06-17 Spinalabs, Llc Devices and methods for the treatment of spinal disorders
KR100882365B1 (en) * 2000-04-07 2009-02-05 키폰 에스에이알엘 Insertion devices and method of use
US6350283B1 (en) * 2000-04-19 2002-02-26 Gary K. Michelson Bone hemi-lumbar interbody spinal implant having an asymmetrical leading end and method of installation thereof
US6851430B2 (en) * 2000-05-01 2005-02-08 Paul M. Tsou Method and apparatus for endoscopic spinal surgery
US7008427B2 (en) 2000-05-25 2006-03-07 Orthoplex, Llc Inter-vertebral disc prosthesis for rachis through anterior surgery thereof
US6533817B1 (en) 2000-06-05 2003-03-18 Raymedica, Inc. Packaged, partially hydrated prosthetic disc nucleus
US6579318B2 (en) * 2000-06-12 2003-06-17 Ortho Development Corporation Intervertebral spacer
WO2001095837A1 (en) 2000-06-13 2001-12-20 Michelson Gary K Manufactured major long bone ring implant shaped to conform to a prepared intervertebral implantation space
US6921532B1 (en) 2000-06-22 2005-07-26 Spinal Restoration, Inc. Biological Bioadhesive composition and methods of preparation and use
US6500132B1 (en) * 2000-06-30 2002-12-31 Sdgi Holdings, Inc. Device and method for determining parameters of blind voids
US6808537B2 (en) * 2000-07-07 2004-10-26 Gary Karlin Michelson Expandable implant with interlocking walls
WO2002003885A2 (en) * 2000-07-10 2002-01-17 Michelson Gary K Flanged interbody spinal fusion implants
WO2002013731A1 (en) 2000-08-15 2002-02-21 Thalgott John S Improved disc prosthesis
CN1192750C (en) 2000-08-28 2005-03-16 迪斯科动力学公司 Prosthesis of vertebral disc
US6824565B2 (en) 2000-09-08 2004-11-30 Nabil L. Muhanna System and methods for inserting a vertebral spacer
ATE390899T1 (en) 2000-08-30 2008-04-15 Warsaw Orthopedic Inc DISC IMPLANTS
US6599291B1 (en) 2000-10-20 2003-07-29 Sdgi Holdings, Inc. Methods and instruments for interbody surgical techniques
ES2358498T3 (en) 2000-10-24 2011-05-11 Cryolife, Inc. BIOPROSTÉTICO FILLING AND METHODS, PARTICULARLY FOR THE IN SITU TRAINING OF BIOPRÓTESIS OF INTERVERTEBRAL DISCS.
AU4327002A (en) 2000-10-25 2002-06-24 Sdgi Holdings Inc Vertically expanding intervertebral body fusion device
US6692501B2 (en) * 2000-12-14 2004-02-17 Gary K. Michelson Spinal interspace shaper
HUP0302127A2 (en) * 2000-12-15 2005-12-28 Spineology, Inc. Annulus-reinforcing band
US6936070B1 (en) 2001-01-17 2005-08-30 Nabil L. Muhanna Intervertebral disc prosthesis and methods of implantation
US6986772B2 (en) * 2001-03-01 2006-01-17 Michelson Gary K Dynamic lordotic guard with movable extensions for creating an implantation space posteriorly in the lumbar spine
US7156877B2 (en) * 2001-06-29 2007-01-02 The Regents Of The University Of California Biodegradable/bioactive nucleus pulposus implant and method for treating degenerated intervertebral discs
US6607558B2 (en) 2001-07-03 2003-08-19 Axiomed Spine Corporation Artificial disc
US6805715B2 (en) * 2001-10-09 2004-10-19 Pmt Corporation Method and device for treating intervertebral disc herniations
JP3993855B2 (en) 2001-11-01 2007-10-17 スパイン・ウェイブ・インコーポレーテッド Device for spinal disc recovery
US7048963B2 (en) 2001-11-30 2006-05-23 Cambridge Polymers Group, Inc. Layered aligned polymer structures and methods of making same
US6733534B2 (en) 2002-01-29 2004-05-11 Sdgi Holdings, Inc. System and method for spine spacing
US6736835B2 (en) 2002-03-21 2004-05-18 Depuy Acromed, Inc. Early intervention spinal treatment methods and devices for use therein
US6726720B2 (en) * 2002-03-27 2004-04-27 Depuy Spine, Inc. Modular disc prosthesis
US7128746B2 (en) 2002-05-16 2006-10-31 Pmt Corporation Device for treating intervertebral disc herniations
AU2002950340A0 (en) 2002-07-23 2002-09-12 Commonwealth Scientific And Industrial Research Organisation Biodegradable polyurethane/urea compositions
US6932843B2 (en) 2002-09-25 2005-08-23 Medicinelodge, Inc. Apparatus and method for the in-situ formation of a structural prosthesis
US7004971B2 (en) * 2002-12-31 2006-02-28 Depuy Acromed, Inc. Annular nucleus pulposus replacement
US7060097B2 (en) 2003-03-31 2006-06-13 Depuy Spine, Inc. Method and apparatus for implant stability
US6969405B2 (en) 2003-04-23 2005-11-29 Loubert Suddaby Inflatable intervertebral disc replacement prosthesis
US6958077B2 (en) 2003-07-29 2005-10-25 Loubert Suddaby Inflatable nuclear prosthesis
JP2007526942A (en) 2004-03-03 2007-09-20 コモンウエルス サイエンティフィック アンド インダストリアル リサーチ オーガナイゼーション Biocompatible polymer composition for two-stage or multi-stage curing
JP5496457B2 (en) * 2004-03-24 2014-05-21 ポリィノボ バイオマテリアルズ ピーティワイ リミテッド Biodegradable polyurethane and polyurethaneurea
US20050278023A1 (en) 2004-06-10 2005-12-15 Zwirkoski Paul A Method and apparatus for filling a cavity
EP1778134A1 (en) 2004-07-27 2007-05-02 Synthes USA Supplementation or replacement of a nucleus pulposus, of an intervertebral disc
US20060095045A1 (en) 2004-11-01 2006-05-04 Sdgi Holdings, Inc. Methods for explantation of intervertebral disc implants
US20060149380A1 (en) 2004-12-01 2006-07-06 Lotz Jeffrey C Systems, devices and methods for treatment of intervertebral disorders
US20060265077A1 (en) 2005-02-23 2006-11-23 Zwirkoski Paul A Spinal repair

Cited By (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8740846B2 (en) 1996-09-20 2014-06-03 Verathon, Inc. Treatment of tissue in sphincters, sinuses, and orifices
US9023031B2 (en) 1997-08-13 2015-05-05 Verathon Inc. Noninvasive devices, methods, and systems for modifying tissues
US7184827B1 (en) * 2000-01-24 2007-02-27 Stuart D. Edwards Shrinkage of dilatations in the body
US7491236B2 (en) 2000-02-16 2009-02-17 Trans1, Inc. Dual anchor prosthetic nucleus apparatus
US7727263B2 (en) 2000-02-16 2010-06-01 Trans1, Inc. Articulating spinal implant
US20050113929A1 (en) * 2000-02-16 2005-05-26 Cragg Andrew H. Spinal mobility preservation apparatus
US20050149191A1 (en) * 2000-02-16 2005-07-07 Cragg Andrew H. Spinal mobility preservation apparatus having an expandable membrane
US7547324B2 (en) 2000-02-16 2009-06-16 Trans1, Inc. Spinal mobility preservation apparatus having an expandable membrane
US7905908B2 (en) 2000-02-16 2011-03-15 Trans1, Inc. Spinal mobility preservation method
US7905905B2 (en) 2000-02-16 2011-03-15 Trans1, Inc. Spinal mobility preservation apparatus
US7329259B2 (en) 2000-02-16 2008-02-12 Transl Inc. Articulating spinal implant
US7744599B2 (en) 2000-02-16 2010-06-29 Trans1 Inc. Articulating spinal implant
US20050113928A1 (en) * 2000-02-16 2005-05-26 Cragg Andrew H. Dual anchor prosthetic nucleus apparatus
US7662173B2 (en) 2000-02-16 2010-02-16 Transl, Inc. Spinal mobility preservation apparatus
US7717958B2 (en) 2000-02-16 2010-05-18 Trans1, Inc. Prosthetic nucleus apparatus
US20040215344A1 (en) * 2000-02-28 2004-10-28 Stephen Hochschuler Method and apparatus for treating a vertebral body
US7931689B2 (en) 2000-02-28 2011-04-26 Spineology Inc. Method and apparatus for treating a vertebral body
US20040073308A1 (en) * 2000-07-21 2004-04-15 Spineology, Inc. Expandable porous mesh bag device and methods of use for reduction, filling, fixation, and supporting of bone
US7226481B2 (en) 2000-07-21 2007-06-05 Spineology, Inc. Expandable porous mesh bag device and methods of use for reduction, filling, fixation, and supporting of bone
US8968284B2 (en) 2000-10-02 2015-03-03 Verathon Inc. Apparatus and methods for treating female urinary incontinence
US7799833B2 (en) 2001-11-01 2010-09-21 Spine Wave, Inc. System and method for the pretreatment of the endplates of an intervertebral disc
US8450288B2 (en) 2001-11-01 2013-05-28 Spine Wave, Inc. System and method for the pretreatment of the endplates of an intervertebral disc
US20100098834A1 (en) * 2002-12-27 2010-04-22 Advanced Cardiovascular Systems, Inc. Mounting assembly for a stent and a method of using the same to coat a stent
US7628859B1 (en) * 2002-12-27 2009-12-08 Advanced Cardiovascular Systems, Inc. Mounting assembly for a stent and a method of using the same to coat a stent
US8051798B2 (en) 2002-12-27 2011-11-08 Advanced Cardiovascular Systems, Inc. Mounting assembly for a stent and a method of using the same to coat a stent
US8007856B2 (en) 2002-12-27 2011-08-30 Advanced Cardiovascular Systems, Inc. Mounting assembly for a stent and a method of using the same to coat a stent
US20100126414A1 (en) * 2002-12-27 2010-05-27 Abbott Cardiovascular Systems, Inc. Mounting Assembly For A Stent And A Method Of Using The Same To Coat A Stent
US20070173943A1 (en) * 2003-01-17 2007-07-26 Dulak Gary R Artificial nucleus pulposus and method of injecting same
EP1599241A2 (en) * 2003-02-21 2005-11-30 Jeffrey S. Kadan Diagnostic needle arthroscopy and lavage system
EP1599241A4 (en) * 2003-02-21 2007-06-20 Jeffrey S Kadan Diagnostic needle arthroscopy and lavage system
US20080086133A1 (en) * 2003-05-16 2008-04-10 Spineology Expandable porous mesh bag device and methods of use for reduction, filling, fixation and supporting of bone
US20070067032A1 (en) * 2003-06-27 2007-03-22 Felt Jeffrey C Meniscus preserving implant method and apparatus
US9204971B2 (en) 2003-06-27 2015-12-08 Memometal Technologies System and method for ankle arthroplasty
US20050015140A1 (en) * 2003-07-14 2005-01-20 Debeer Nicholas Encapsulation device and methods of use
WO2005034781A1 (en) * 2003-09-29 2005-04-21 Promethean Surgical Devices Llc Devices and methods for spine repair
US8052613B2 (en) 2003-10-23 2011-11-08 Trans1 Inc. Spinal nucleus extraction tool
US7740633B2 (en) 2003-10-23 2010-06-22 Trans1 Inc. Guide pin for guiding instrumentation along a soft tissue tract to a point on the spine
US7799032B2 (en) 2003-10-23 2010-09-21 Trans1 Inc. Guide pin introducer for guiding instrumentation through soft tissue to a point on the spine
US7763025B2 (en) 2003-10-23 2010-07-27 Trans1 Inc. Spinal fusion kit for guiding instrumentation through soft tissue to a point on the spine
US7799033B2 (en) 2003-10-23 2010-09-21 Trans1 Inc. Access kits for enabling axial access and procedures in the spine
US7914535B2 (en) 2003-10-23 2011-03-29 Trans1 Inc. Method and apparatus for manipulating material in the spine
US7481839B2 (en) * 2003-12-02 2009-01-27 Kyphon Sarl Bioresorbable interspinous process implant for use with intervertebral disk remediation or replacement implants and procedures
US20050273146A1 (en) * 2003-12-24 2005-12-08 Synecor, Llc Liquid perfluoropolymers and medical applications incorporating same
WO2005065324A3 (en) * 2003-12-24 2009-04-09 Synecor Llc Liquid perfluoropolymers and medical applications incorporating same
WO2005065324A2 (en) * 2003-12-24 2005-07-21 Synecor, Llc Liquid perfluoropolymers and medical applications incorporating same
US20050271794A1 (en) * 2003-12-24 2005-12-08 Synecor, Llc Liquid perfluoropolymers and medical and cosmetic applications incorporating same
US8197544B1 (en) 2004-01-08 2012-06-12 Spine Wave, Inc. Method for distracting opposing vertebral bodies of a spine
US8246630B2 (en) 2004-01-08 2012-08-21 Spine Wave, Inc. Apparatus and method for injecting fluent material at a distracted tissue site
US7789912B2 (en) 2004-01-08 2010-09-07 Spine Wave, Inc. Apparatus and method for injecting fluent material at a distracted tissue site
US20110004217A1 (en) * 2004-01-08 2011-01-06 Spine Wave, Inc. Apparatus and Method for Injecting Fluent Material at a Distracted Tissue Site
US8317802B1 (en) 2004-01-08 2012-11-27 Spine Wave, Inc. System for distracting opposing vertebral bodies of a spine
US8158728B2 (en) 2004-02-13 2012-04-17 The University Of North Carolina At Chapel Hill Methods and materials for fabricating microfluidic devices
US8444899B2 (en) 2004-02-13 2013-05-21 The University Of North Carolina At Chapel Hill Methods and materials for fabricating microfluidic devices
US20090281250A1 (en) * 2004-02-13 2009-11-12 The University Of North Carolina At Chapel Hill Methods and materials for fabricating microfluidic devices
US7722579B2 (en) 2004-06-29 2010-05-25 Spine Wave, Inc. Devices for injecting a curable biomaterial into a intervertebral space
US20060009779A1 (en) * 2004-06-29 2006-01-12 Keith Collins Devices for injecting a curable biomaterial into a intervertebral space
US7837733B2 (en) 2004-06-29 2010-11-23 Spine Wave, Inc. Percutaneous methods for injecting a curable biomaterial into an intervertebral space
US8697139B2 (en) 2004-09-21 2014-04-15 Frank M. Phillips Method of intervertebral disc treatment using articular chondrocyte cells
US20060195115A1 (en) * 2005-02-23 2006-08-31 Ferree Bret A Method and apparatus for kyphoplasty
US7879103B2 (en) 2005-04-15 2011-02-01 Musculoskeletal Transplant Foundation Vertebral disc repair
US8317868B2 (en) 2005-04-29 2012-11-27 Jmea Corporation Disc repair system
US8177847B2 (en) 2005-04-29 2012-05-15 Jmea Corporation Disc repair system
US8961530B2 (en) 2005-04-29 2015-02-24 Jmea Corporation Implantation system for tissue repair
US8702718B2 (en) 2005-04-29 2014-04-22 Jmea Corporation Implantation system for tissue repair
US8070818B2 (en) 2005-04-29 2011-12-06 Jmea Corporation Disc annulus repair system
US20080221700A1 (en) * 2005-08-31 2008-09-11 Zimmer, Gmbh Implant
US20100312353A1 (en) * 2005-08-31 2010-12-09 Zimmer, Gmbh Implant
US7799087B2 (en) 2005-08-31 2010-09-21 Zimmer Gmbh Implant
US8394149B2 (en) 2005-08-31 2013-03-12 Zimmer, Gmbh Method for implantation of a femoral implant
US20070093899A1 (en) * 2005-09-28 2007-04-26 Christof Dutoit Apparatus and methods for treating bone
US8197545B2 (en) 2005-10-27 2012-06-12 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
US8357199B2 (en) 2005-10-27 2013-01-22 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
US9162041B2 (en) 2005-10-27 2015-10-20 DePuy Synthes Products, Inc. Nucleus augmentation delivery device and technique
US8308807B2 (en) 2005-11-09 2012-11-13 Zimmer, Gmbh Implant with differential anchoring
US20090105772A1 (en) * 2005-11-09 2009-04-23 Zimmer Gmbh Implant
US9956085B2 (en) 2005-12-23 2018-05-01 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US11701233B2 (en) 2005-12-23 2023-07-18 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US9289240B2 (en) 2005-12-23 2016-03-22 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US11406508B2 (en) 2005-12-23 2022-08-09 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US10881520B2 (en) 2005-12-23 2021-01-05 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US8999000B2 (en) 2006-01-31 2015-04-07 Zimmer Technology, Inc. Orthopedic implant with bone interface anchoring
US20110224791A1 (en) * 2006-01-31 2011-09-15 Zimmer Technology, Inc. Orthopedic implant with bone interface anchoring
US20090048679A1 (en) * 2006-02-09 2009-02-19 Zimmer Gmbh Implant
US20070208426A1 (en) * 2006-03-03 2007-09-06 Sdgi Holdings, Inc. Spinal implant with improved surface properties for delivery
US8632601B2 (en) 2006-04-28 2014-01-21 Zimmer, Gmbh Implant
US20090187252A1 (en) * 2006-04-28 2009-07-23 Zimmer Gmbh Implant
US7959683B2 (en) 2006-07-25 2011-06-14 Musculoskeletal Transplant Foundation Packed demineralized cancellous tissue forms for disc nucleus augmentation, restoration, or replacement and methods of implantation
US9662227B2 (en) 2006-11-28 2017-05-30 Kunovus Party Ltd Tissue prosthesis insertion system and method
US20110208308A1 (en) * 2006-11-28 2011-08-25 Columna Pty Ltd Tissue prosthesis insertion system and method
US8728161B2 (en) * 2006-11-28 2014-05-20 Spinecell Private Ltd Tissue prosthesis insertion system and method
US20080195219A1 (en) * 2007-02-08 2008-08-14 Zimmer, Inc. Hydrogel proximal interphalangeal implant
US8852284B2 (en) 2007-02-08 2014-10-07 Zimmer, Inc. Hydrogel proximal interphalangeal implant
US20090036995A1 (en) * 2007-07-31 2009-02-05 Zimmer, Inc. Joint space interpositional prosthetic device with internal bearing surfaces
US8979935B2 (en) 2007-07-31 2015-03-17 Zimmer, Inc. Joint space interpositional prosthetic device with internal bearing surfaces
US20090130174A1 (en) * 2007-08-20 2009-05-21 Vanderbilt University Poly (ester urethane) urea foams with enhanced mechanical and biological properties
US20090060974A1 (en) * 2007-08-27 2009-03-05 Reinhold Schmieding Methods of arthroscopic osteochondral resurfacing
US8535703B2 (en) * 2007-08-27 2013-09-17 Arthrex, Inc. Methods of arthroscopic osteochondral resurfacing
US20090105792A1 (en) * 2007-10-19 2009-04-23 Kucklick Theodore R Method and Devices for Treating Damaged Articular Cartilage
US9510877B2 (en) 2007-11-14 2016-12-06 DePuy Synthes Products, Inc. Hybrid bone fixation element and methods of using the same
US8556949B2 (en) 2007-11-14 2013-10-15 DePuy Synthes Products, LLC Hybrid bone fixation element and methods of using the same
US20100049251A1 (en) * 2008-03-28 2010-02-25 Kuslich Stephen D Method and device for interspinous process fusion
US20140074247A1 (en) * 2009-05-08 2014-03-13 Kevin L. Ohashi Joint reconstruction system and method
US8403988B2 (en) 2009-09-11 2013-03-26 Depuy Spine, Inc. Minimally invasive intervertebral staple distraction devices
US20110066244A1 (en) * 2009-09-11 2011-03-17 William Frasier Minimally Invasive Intervertebral Staple Distraction Devices
US9216093B2 (en) 2009-09-11 2015-12-22 DePuy Synthes Products, Inc. Minimally invasive intervertebral staple distraction devices
US8685097B2 (en) 2009-09-11 2014-04-01 DePuy Sunthes Products, LLC. Minimally invasive intervertebral staple distraction devices
US9744054B2 (en) 2009-09-11 2017-08-29 DePuy Synthes Products, Inc. Minimally invasive intervertebral staple distraction devices
US20110066192A1 (en) * 2009-09-15 2011-03-17 William Frasier Expandable Ring Intervertebral Fusion Device
US9615933B2 (en) 2009-09-15 2017-04-11 DePuy Synthes Products, Inc. Expandable ring intervertebral fusion device
US8211126B2 (en) 2009-09-22 2012-07-03 Jmea Corporation Tissue repair system
US8603118B2 (en) 2009-09-22 2013-12-10 Jmea Corporation Tissue repair system
US8668739B2 (en) 2010-08-20 2014-03-11 Zimmer, Inc. Unitary orthopedic implant
US9155578B2 (en) 2012-02-28 2015-10-13 DePuy Synthes Products, Inc. Expandable fastener
US9814598B2 (en) 2013-03-14 2017-11-14 Quandary Medical, Llc Spinal implants and implantation system
US9913728B2 (en) 2013-03-14 2018-03-13 Quandary Medical, Llc Spinal implants and implantation system

Also Published As

Publication number Publication date
US6443988B2 (en) 2002-09-03
US20070038300A1 (en) 2007-02-15
US7077865B2 (en) 2006-07-18
WO1998020939A2 (en) 1998-05-22
US20010004710A1 (en) 2001-06-21
WO1998020939A3 (en) 1998-09-03
US20030220649A1 (en) 2003-11-27
EP0873145A2 (en) 1998-10-28
US20060253200A1 (en) 2006-11-09
EP1230902A1 (en) 2002-08-14
JP2002505592A (en) 2002-02-19
US20030195628A1 (en) 2003-10-16
US6306177B1 (en) 2001-10-23
US7766965B2 (en) 2010-08-03
US7001431B2 (en) 2006-02-21
US7713301B2 (en) 2010-05-11
AU7178698A (en) 1998-06-03

Similar Documents

Publication Publication Date Title
US6306177B1 (en) Biomaterial system for in situ tissue repair
US6140452A (en) Biomaterial for in situ tissue repair
US20050043808A1 (en) Knee joint prosthesis
JP4374188B2 (en) Artificial intervertebral disc
JP3769022B2 (en) Joint joint repair
EP0830114B1 (en) Joint resurfacing system
JP4324478B2 (en) Interposition arthroplasty system
US6652587B2 (en) Method and system for mammalian joint resurfacing
WO1999056800A1 (en) Porous composite biomaterial and biopolymer system
CA2243154A1 (en) Biomaterial system for in situ tissue repair
MXPA04007061A (en) Interpositional arthroplasty system and method

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION