WO2001060424A2 - Implantable tissues infused with growth factors and other additives - Google Patents
Implantable tissues infused with growth factors and other additives Download PDFInfo
- Publication number
- WO2001060424A2 WO2001060424A2 PCT/US2001/005414 US0105414W WO0160424A2 WO 2001060424 A2 WO2001060424 A2 WO 2001060424A2 US 0105414 W US0105414 W US 0105414W WO 0160424 A2 WO0160424 A2 WO 0160424A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tissue
- biomedical implant
- implant
- biomedical
- growth factor
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
- A61L27/3843—Connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
- A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
Definitions
- the subject invention pertains to novel configurations of tissue which lend themselves to ready and simple use for various medical applications.
- the subject invention relates to tissue shaped into the form of tape.
- the tissue tape is provided as a spool, whereby sections or an amount of tissue tape can be easily peeled off as needed.
- the subject invention pertains to tissue configured as several separate sections or "patches", and preferably provided together in a container, whereby sections can easily be removed from the container and ready to use.
- the tissue patches or tissue tape have a bioadhesive disposed on at least one side.
- the subject tissue tape and patches may also have a medically useful additive infused therein.
- tissue refers to any animal tissue types including, but not limited to, bone, bone marrow, fibrous connective tissue, yellow elastic connective tissue, cartilage, muscle, vasculature, epidermis, and dermis.
- Tissue for use in accord with the principles of the subject invention can be human and/or nonhuman tissue.
- the tissue used for producing the subject tape is skin or fibrous or elastic connective tissue (e.g., fascia lata, tendons, peritoneum, dura mater, cartilage, pericardium or ligaments).
- the subject invention pertains to tissue that is processed and shaped, cut, and/or stretched into an elongated tape form and "rolled" into a spool.
- Processing can include sterilizing and/or decellularization of crude tissue.
- Cleaning and sterilization of tissue can be accomplished by techniques known in the art, such as accordingly to procedures taught in U.S. Patent Nos. 5,993,844; 5,820,581 ; 5,797,871; 5,556,379; 5,513,662; 5,333,626; and 5,095,925. See also U.S. patent Application Serial Nos. 09/191,232; 09/390,174; and 09/378,527.
- the subject tape can be peeled from the spool in the desired size and used in various medical applications, including, but not limited to, bone fracture fixation, guided tissue regeneration, and repair trauma injuries to soft tissue and organs.
- the subject tape can be infused with medically/surgically useful substances.
- medically/surgically useful substances Those skilled in the art will readily appreciate appropriate substances to infuse into the subject tape based on the intended medical application.
- infuse or "infused” are used herein in their broad sense and are intended to mean any association with the tape whereby a substance is allowed to effectuate its intended beneficial effect, whether it be released or whether contact with the tape is maintained.
- substances useful in accord with the subject invention include, e.g., collagen and insoluble collagen derivatives; gelatin; hydroxyapatite, etc., and soluble solids and/or liquids dissolved therein, e.g., antiviricides, particularly those effective against viruses such as HIV and hepatitis; antimicrobials and/or antibiotics such as erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracyclines, viomycin, chloromycetin and streptomycins, cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamycin, etc.; amino acids, ' magainins, peptides, vitamins, inorganic elements, co-factors for protein synthesis; hormones; endocrine tissue or tissue fragments; enzymes such as collagenase, peptidases, oxidases, etc.; polymer cell scaffolds with parenchymal or other cells; surface cell
- the tape of the subject invention is infused with one or more growth factors.
- growth factor refers to a polynucleotide molecule, polypeptide molecule, or other related chemical agent that is capable of effectuating differentiation of cells.
- growth factors include an epidermal growth factor (EGF), transforming growth factor-alpha (TGF.
- TGF-.beta transforming growth factor-beta
- ECGF human endothelial cell growth factor
- GM-CSF granulocyte macrophage colony stimulating factor
- BMP bone morphogenetic protein
- NGF nerve growth factor
- NEGF vascular endothelial growth factor
- FGF insulin-like growth factor
- CDMP cartilage derived morphogenetic protein
- PDGF platelet derived growth factor
- Growth factors for use in accord with the teachings herein can be extracted from allograft, xenograft and/or autograft tissue, or can be produced by recombinant/genetic means, or be encoded by nucleic acids associated with appropriate transcriptional and translational elements associated with the tape.
- An alternative embodiment of the subject invention is directed to a section of tissue, and method of using the same, wherein the section of tissue has infused therein growth factors having properties related to the regeneration of tissue.
- the section of tissue comprises dermal tissue, and more preferably is provided in patch form.
- the subject invention is directed to a method comprising obtaining a section of tissue and infusing it with growth factors that comprise the ability to stimulate generation of specific tissues; and implanting said section in an area of a patient in need of repair of such specific tissues, or further generation of such tissues.
- the method comprises obtaining a section of tissue and infusing it with growth factors that comprise the ability to stimulate the generation of vascular tissue, e.g., VEGF, ECGF, TGF, FGF, or combinations thereof, as well as later developed growth factors having similar activity.
- the section of tissue infused with such growth factors is then implanted into a patient in an area where vascular tissue is damaged and in need of repair, or where the generation of further vascular tissue would be beneficial.
- a section of the subject tape infused with vascular tissue generating growth factors is surgically joined to a damaged vein or artery, such as by suturing of the section to the vein or artery or other conventional methods used in the surgical arts.
- the damaged artery or vein is located on the heart.
- An alternative aspect of this embodiment pertains to a method comprising obtaining a section of tissue and infusing it with growth factors having the ability to stimulate generation of muscle or connective tissue; and implanting the section in a patient in need thereof.
- the subject tissue tape can have a bioadhesive disposed on at least one side to aid in the attachment to the desired area.
- a bioadhesive substance is broadly defined as a material that is " capable of being bound to a biological membrane, and retained on that membrane for an extended period of time.
- bioadhesion is the attachment of a material to a biological substrate such as a biological membrane.
- bioadhesives include but are not limited to, fibrinogen, fatty acid ester adhesives as disclosed in U.S. Pat. No. 5,955,502, gelatin/aldehyde adehesives as disclosed in U.S.
- the subject tissue tape can also comprise a backing layer, which will facilitate peeling the tissue tape from a spool.
- This backing layer is particularly helpful when the tissue tape comprises a bioadhesive disposed on its surface.
- the backing layer can be comprised of a non-stick substance such as TEFLON(registered trademark), or other commercially available plastic and/or polymeric materials. Suitable materials will readily be appreciated by those skilled in the art.
- the backing material may also be comprised of a natural substance, for example, processed tissue.
- graft tissues are treated with Platelet Rich Plasma (PRP), or growth factors isolated from PRP.
- PRP Platelet Rich Plasma
- PRP obtained from autograft blood has been shown to increase the rate of healing of autogenic grafts.
- Current methods of applying PRP to such grafts involves the removal of blood from a patient (plasmapheresis), centrifuging the blood, drawing off the PRP layer, and applying the PRP to the graft, which occurs just prior to surgery.
- a method of obtaining an allograft and/or xenograft source of PRP for use in graft implantation is provided.
- the PRP is obtained by procuring blood from a cadaveric donor (such as by conventional exsanguination techniques) or procuring blood (preferably expired blood as to avoid depletion of blood earmarked for other purposes) from blood banks, and centrifuging the obtained blood to separate the PRP from other blood components via conventional methods.
- PRP is obtained from a cadaveric donor.
- the isolation of PRP from sources other than autogenous (recipient) allows for the manipulation and use of the PRP well prior to surgery, whereby the inefficient removal and treatment of blood from the recipient is alleviated.
- PDGF platelet derived growth factor
- PDAF platelet derived angiogenic growth factor
- PEGF platelet derived epidermal growth factor
- TGF-beta transforming growth factor
- Allogenic and/or xenogenic blood provides a vast and untapped source for PRP and growth factors.
- platelets are isolated from allogenic and/or xenogenic sources as described above, and growth factors are partially purified or purified from these isolated platelets via conventional methods (see, e.g., U.S. Pat Nos. 4,479,896; 4, 861,757; or 4,975,526).
- Partially purified refers to a state of purification above that which is found in nature, or said differently, that is not achievable unless through manipulation by the hand of man.
- purified refers to a state of purification such that in a given sample comprising a given growth factor, the growth factor is 95% or greater, by weight, of the sample.
- Partially purified growth factors may also be obtained from PRP by the following method:
- the growth factors can be stored and/or distributed in a lyophilized or frozen form. Accordingly, the subject methods allow for the mass production of implants (autogenic, allogenic, and/or xenogenic) that have been treated with PRP, and/or growth factors isolated therefrom, that are readily usable in implantation surgeries, which also decreases the costs and inconvenience associated with conventional methods.
- growth factors obtained from blood are placed in an easy to use container such as a bottle, vial, bag, etc. made from glass or plastics, or other suitable materials.
- an easy to use container such as a bottle, vial, bag, etc. made from glass or plastics, or other suitable materials.
- Providing the subject growth factors as a composition in containers will facilitate the use of the growth factors, for example, for the infusion or other treatment of implants to be implanted into a patient, or for the direct administration of the growth factors into a patient.
- the choice of carrier material for the growth factor composition is based on biocompatibility, biodegradability, and interface properties.
- the growth factor composition can be infused into the implant in any suitable manner. For example, the growth factor composition may be injected into the implant.
- the composition is dripped onto the implant or the implant is soaked in a solution containing an effective amount of the composition to carry out its intended effect.
- the implant is exposed to the growth factor composition for a period of time sufficient to allow the liquid to thoroughly soak the implant.
- the growth factors may be provided in freeze-dried form and reconstituted in a pharmaceutically acceptable liquid or gel carrier such as sterile water, physiological saline or any other suitable carrier.
- the carrier may be any suitable medium capable of delivering the proteins to the implant.
- the medium is supplemented with a buffer solution as is known in the art.
- growth factors are suspended or admixed in a carrier, such as water, saline, liquid collagen or injectable bicalcium phosphate.
- a carrier such as water, saline, liquid collagen or injectable bicalcium phosphate.
- the growth factor solution can be dripped - into the implant or the implant can be immersed in a suitable quantity of the liquid.
- the growth factor composition is applied to the implant and then lypholized or freeze-dried. The implant/growth factor composition can then be frozen for storage and transport.
- the subject invention is directed to an osteogenic tape comprised of an osteogenic material.
- osteogenic material is used herein in its broad sense and refers to a material comprising an osteoinductive substance, osteoconductive substance, chondro genie substance, or a combination of one or more of the foregoing substances.
- osteoconductive materials suitable for use with the subject invention include, but are not limited to, hydroxapatite (HA), tricalcium phosphate (TCP), corticocancellous chips (CCC), bioactive glass, bioactive ceramics, and/or mixtures thereof.
- osteoinductive materials suitable for use with the subject invention include, but are not limited to, allograft or xenograft pastes (osteogenic or chondrogenic pastes), demineralized bone matrix (DBM), bone morphogenic protein (BMP), TGF-beta, PDGF, FGF, CDMP, and/or mixtures thereof.
- the osteogenic material is combined with a carrier.
- osteogenic materials for use with the teachings herein include, but are not limited to, carrier associated Growth Factors, carrier associated mineralized particles, morsellized skin or other tissue, Fibrin powder, Fibrin/plasminogen glue, biomedical plastics, Demineralized Bone Matrix (DBM)/glycerol, cortico cancellous chips (CCC), DBM/pleuronic F127, and DBM/CCC/F127, human tissue/polyesters or polyhydroxy compounds, or polyvinyl compounds or polyamino compounds or polycarbonate compounds or any other suitable viscous carrier.
- Suitable carriers include, but are not limited to, amylopectin, collagen, gelatin, dextran, agrarose, or combinations thereof.
- the subject osteogenic tape has disposed on at least one side an inert material, such as a resorbable polymer.
- inert material such as a resorbable polymer.
- inert material refers to the quality of being non-immunogenic or otherwise does not invoke an undesirable effect once in contact with a tissue.
- inert materials contemplated for use herein do not necessarily have osteoinductive or osteoconductive qualities. Examples of inert materials suitable for use with the teachings herein include, but are not limited to, polylactide, poly (alpha-hydroxycarboxylic acids (e.g. poly-D-(-)-3hydroxybutyric acid, poly(lactones), poly(acetals), poly(orthoesters) or poly(orthocarbonates).
- the osteogenic tape of the subject invention comprises two or more layers, wherein a first layer is covered with a second layer.
- the second layer (or "backing layer”) can comprise a film like material derived from tissue.
- tissue refers to any animal tissue (human or nonhuman; allograft, xenograft and or autograft) types including, but not limited to, bone, bone marrow, fibrous connective tissue, yellow elastic connective tissue, cartilage, muscle, vasculature, and skin.
- the tissue used for producing the second layer of the subject tape is skin or fibrous or yellow elastic connective tissue (e.g., fascia lata, tendons, peritoneum, dura mater, pericardium or ligaments).
- the tape of the subject iinvention is shaped, cut, and/or stretched into an elongated tape form and "rolled" into a spool.
- the subject tape can be peeled from the spool in the desired size and used in various medical applications, including, but not limited to, bone fracture fixation, filling of voids in bone, or filling of voids between prostheses and bone, enclosing and protecting an implant site, and repairing trauma injuries to soft tissue and organs.
- the tape of the subject invention would also be useful in sealing a graft implant site.
- an osteogenic tape having woven (or otherwise attached) interiorly or exteriorly a support structure such as a mesh, suture, and/or wire material, to help strengthen the tape or otherwise make the tape more suitable for unrolling and "taping."
- a support structure such as a mesh, suture, and/or wire material
- materials for use as the support structure include, but are not limited to, inert metals such as titanium; inert and/or bioresorbable polymers; bone, dimeralized bone, and or human or nonhuman tissue.
- the subject osteogenic tape can have a bioadhesive disposed on at least one side to aid in the attachment to the desired area.
- a bioadhesive substance is broadly defined as a material that is capable of being bound to a biological membrane or tissue surface, and retained on that membrane or tissue surface for an extended period of time.
- bioadhesion is the attachment of a material to a biological substrate such as a biological membrane. Examples of bioadhesives that can be used in accord with the teachings herein, include but are not limited to, fibrinogen, fatty acid ester adhesives as disclosed in U.S. Pat. No.
- the subject osteogenic tape is produced by a number of conventional techniques currently used in the art.
- the subject osteogenic tape can be prepared by casting the osteogenic material as a dispersion in a solvent onto the backing layer (as described above) and drying the composition to remove the solvent.
- the tape of the subject invention can be formed by pressing the osteogenic material, either in a mold, by extrusion, calendering, or combinations of pressing, extruding and/or calendering, to thereby form the appropriate shape either with or without a backing layer. See U.S. Patent Nos. 5,997,675; 5,817,395; and 5,810,756 for a discussion of conventional methods for producing films or tapes.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01912854A EP1286707A2 (en) | 2000-02-18 | 2001-02-20 | Implantable tissues infused with growth factors and other additives |
CA002399224A CA2399224A1 (en) | 2000-02-18 | 2001-02-20 | Implantable tissues infused with growth factors and other additives |
JP2001559519A JP2003535620A (en) | 2000-02-18 | 2001-02-20 | Transplant tissue implanted with growth factors and other additives |
AU2001241594A AU2001241594A1 (en) | 2000-02-18 | 2001-02-20 | Implantable tissues infused with growth factors and other additives |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
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US18346800P | 2000-02-18 | 2000-02-18 | |
US60/183,468 | 2000-02-18 | ||
US18420300P | 2000-02-22 | 2000-02-22 | |
US60/184,203 | 2000-02-22 | ||
US19747700P | 2000-04-17 | 2000-04-17 | |
US60/197,477 | 2000-04-17 |
Publications (2)
Publication Number | Publication Date |
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WO2001060424A2 true WO2001060424A2 (en) | 2001-08-23 |
WO2001060424A3 WO2001060424A3 (en) | 2002-12-27 |
Family
ID=27391680
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2001/005414 WO2001060424A2 (en) | 2000-02-18 | 2001-02-20 | Implantable tissues infused with growth factors and other additives |
Country Status (6)
Country | Link |
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US (1) | US20010038848A1 (en) |
EP (1) | EP1286707A2 (en) |
JP (1) | JP2003535620A (en) |
AU (1) | AU2001241594A1 (en) |
CA (1) | CA2399224A1 (en) |
WO (1) | WO2001060424A2 (en) |
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JP2004123576A (en) * | 2002-09-30 | 2004-04-22 | Medgel Corp | Sustained release preparation containing platelet-rich plasma |
JP2006514018A (en) * | 2002-06-27 | 2006-04-27 | ベレッタ ロベルト | Method and apparatus for separating liquid components |
JP2007527853A (en) * | 2003-05-01 | 2007-10-04 | メドジニックス・インコーポレイテッド | Dermal organelles and methods and instruments for making and using the same |
US7923244B2 (en) | 2005-08-02 | 2011-04-12 | Pg Research Co., Ltd. | Artificial cartilage tissue and production method thereof |
US8501396B2 (en) | 2001-11-05 | 2013-08-06 | Medgenics Medical Israel Ltd. | Dermal micro-organs, methods and apparatuses for producing and using the same |
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Also Published As
Publication number | Publication date |
---|---|
JP2003535620A (en) | 2003-12-02 |
AU2001241594A1 (en) | 2001-08-27 |
EP1286707A2 (en) | 2003-03-05 |
CA2399224A1 (en) | 2001-08-23 |
US20010038848A1 (en) | 2001-11-08 |
WO2001060424A3 (en) | 2002-12-27 |
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