US20160022867A1 - Template for bacterial cellulose implant processed within bioreactor - Google Patents
Template for bacterial cellulose implant processed within bioreactor Download PDFInfo
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- US20160022867A1 US20160022867A1 US14/806,015 US201514806015A US2016022867A1 US 20160022867 A1 US20160022867 A1 US 20160022867A1 US 201514806015 A US201514806015 A US 201514806015A US 2016022867 A1 US2016022867 A1 US 2016022867A1
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- Prior art keywords
- implant
- bacterial cellulose
- sheet
- oxidized
- cellulose
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- Abandoned
Links
- 239000007943 implant Substances 0.000 title claims abstract description 42
- 229920002749 Bacterial cellulose Polymers 0.000 title claims abstract description 40
- 239000005016 bacterial cellulose Substances 0.000 title claims abstract description 40
- 229920002678 cellulose Polymers 0.000 claims description 19
- 239000001913 cellulose Substances 0.000 claims description 19
- 239000011148 porous material Substances 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 235000002837 Acetobacter xylinum Nutrition 0.000 claims description 5
- 241001136169 Komagataeibacter xylinus Species 0.000 claims description 5
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 4
- 230000010354 integration Effects 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 206010060932 Postoperative adhesion Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 241000894006 Bacteria Species 0.000 description 14
- 239000000463 material Substances 0.000 description 6
- -1 poly(lactic acid) Polymers 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
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- 229920001780 ECTFE Polymers 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
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- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
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- 238000007906 compression Methods 0.000 description 2
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- 238000011082 depyrogenation Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 150000003891 oxalate salts Chemical class 0.000 description 2
- 229920001281 polyalkylene Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000589220 Acetobacter Species 0.000 description 1
- 241000589158 Agrobacterium Species 0.000 description 1
- 0 CC(C1)C2C1(C)C1=*C2CC1 Chemical compound CC(C1)C2C1(C)C1=*C2CC1 0.000 description 1
- 241000819038 Chichester Species 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920002201 Oxidized cellulose Polymers 0.000 description 1
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- 238000013019 agitation Methods 0.000 description 1
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
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- 210000000988 bone and bone Anatomy 0.000 description 1
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- 238000007385 chemical modification Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- 230000003628 erosive effect Effects 0.000 description 1
- QHSJIZLJUFMIFP-UHFFFAOYSA-N ethene;1,1,2,2-tetrafluoroethene Chemical compound C=C.FC(F)=C(F)F QHSJIZLJUFMIFP-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
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- 230000002068 genetic effect Effects 0.000 description 1
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- 229920001519 homopolymer Polymers 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- IFVGFQAONSKBCR-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]pyrimidin-2-amine Chemical compound C1CN1P(N1CC1)(=O)NC1=NC=CC=N1 IFVGFQAONSKBCR-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229940107304 oxidized cellulose Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000003903 pelvic floor Anatomy 0.000 description 1
- 239000008104 plant cellulose Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
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- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Classifications
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- A—HUMAN NECESSITIES
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- 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
- A61L27/20—Polysaccharides
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- A61F13/01012—
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- 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
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- 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
- A61L27/56—Porous materials, e.g. foams or sponges
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- 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
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00059—Accessories for dressings provided with visual effects, e.g. printed or colored
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- A61F13/01021—
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- 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
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00089—Wound bandages
- A61F2013/00153—Wound bandages coloured or with decoration pattern or printing
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- 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
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00089—Wound bandages
- A61F2013/00246—Wound bandages in a special way pervious to air or vapours
- A61F2013/00255—Wound bandages in a special way pervious to air or vapours with pores
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- 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
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00089—Wound bandages
- A61F2013/00314—Wound bandages with surface treatments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- Y—GENERAL 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
- Y10T428/24479—Structurally defined web or sheet [e.g., overall dimension, etc.] including variation in thickness
Definitions
- the implants described herein include a sheet of bacterial cellulose having a macro-pattern positioned on at least one side of the sheet.
- Methods for producing such implants include culturing bacteria capable of producing a bacterial cellulose in a bioreactor in the presence of a template having a macro-patterned surface.
- An aspect of the present invention is an implant comprising:
- a sheet of bacterial cellulose having a macro-pattern positioned on at least a portion thereof.
- the bacterial cellulose may derived from Acetobacter xylinum.
- the bacterial cellulose may be oxidized.
- Another aspect of the present invention is a method of making an implant comprising:
- the bacteria may be Acetobacter xylinum.
- Another aspect of the present invention is a method of treating a wound comprising contacting a wound with an implant as described above.
- FIG. 1 is a schematic perspective view of a template having a three-dimensional macro-pattern according to an embodiment described in the present disclosure.
- FIG. 2 is schematic, cross-sectional view of a bioreactor including a template and a porous sheet of bacterial cellulose according to an embodiment described in the present disclosure.
- FIG. 3 is a schematic perspective view of a porous sheet of bacterial cellulose according to an embodiment described in the present disclosure.
- the term “implant” is intended to mean a biocompatible or bioresorbable medical device, at least a portion of which can be implanted in the human or animal body.
- bioresorbable is intended to mean the characteristic according to which an implant and/or a material is degraded by the biological tissues and the surrounding fluids, in vivo after a given period of time, that may vary, for example, from one day to several months, depending on the chemical nature of the implant and/or of the material.
- bioreactor is intended to include any device or system capable of supporting a biologically active environment for growing or culturing materials.
- the bioreactors may also include the ability to provide agitation, pressure changes, temperature controls, humidity controls, media exchange, and ventilation.
- sheet is intended to include generally planar-shaped formats, such as films, foams, pellicles, layers and combinations thereof.
- the sheet of bacterial cellulose may be produced from bacteria that synthesize cellulose.
- Cellulose is synthesized by bacteria belonging to the genera Acetobacter, Rhizobium, Agrobacterium, and Sarcina .
- Cellulose can be produced by certain bacteria from glucose in the presence of oxygen, (such as, for example, Acetobacter xylinum, referenced hereinafter as the “bacteria”), in static conditions or in a bioreactor (see, e.g. U.S. Pat. Nos. 4,912,049 and 5,955,326, the entire disclosures of which are incorporated herein by this reference).
- Cellulose suitable for use in the present implants can be obtained by the fermentation of the bacteria.
- a derivative of the cellulose is employed, such as oxidized cellulose resulting from the oxidation of the cellulose by periodic acid or nitrogen dioxide.
- Bacterial cellulose possesses inherent characteristics which allow effective promotion of wound healing (see, e.g. U.S. Pat. No. 7,390,492, the entire disclosures of which are incorporated herein by this reference).
- bacterial cellulose displays properties (such as unique multi-layer three dimensional laminar structures) that distinguish it from plant cellulose and other natural polymeric materials.
- Bacterial cellulose shows excellent wet strength, does not easily breakdown under compression and demonstrates high moisture handling ability.
- the sheet of bacterial cellulose is porous and includes a macro-pattern thereon.
- the porous sheet 100 is formed on or around a template 10 having a three dimensional (“3D”) macro-pattern positioned within the bioreactor 50 . (See FIG. 2 .)
- the template is positioned on or near the bottom of the bioreactor. It should be understood that instead of a separate structure positioned within the bioreactor, the template may be formed directly into a surface of the bioreactor, such as, for example, formed into the bottom surface of the bioreactor.
- the porosity of the cellulose sheet is created during the fermentation process when the cellulose is synthesized by the bacteria in a bioreactor which includes culture media.
- the cellulose synthesis on and around the template having the 3D macro-pattern formed on at least a portion of the bioreactor can lead to the sheet having a well-defined porosity. Because the sheet is formed in the presence of the template, the macro-pattern is imparted to the sheet during formation without the use of additional processing.
- the materials used to form the 3D macro-pattern on a template of the bioreactor are compatible with the culture media, the culture conditions and any other contents in the bioreactor which allows for growth of the bacteria on the predetermined 3D macro-pattern portion of the bioreactor.
- the template may be made from but not limited to poly(lactic acid), poly (glycolic acid), poly (hydroxybutyrate), poly (phosphazine), polyesters, polyethylene glycols, polyethylene oxides, polyacrylamides, polyhydroxyethylmethylacrylate, polyvinylpyrrolidone, polyvinyl alcohols, polyacrylic acid, polyacetate, polycaprolactone, polypropylene, aliphatic polyesters, glycerols, poly(amino acids), copoly (ether-esters), polyalkylene oxalates, polyamides, poly (iminocarbonates), polyalkylene oxalates, polyoxaesters, polyorthoesters, polyphosphazenes and copolymers, block copolymers, homopolymers, blends and combinations thereof, polychloride vinyle (PVC), polycarbonate, polysulfone, fluorocarbones (eg.
- PVC polychloride vinyle
- PVC
- 3D macro-pattern on the template can be designed having any form, geometry or topography which allows for removal of the implant from the bioreactor surface following the biosynthesis of the bacterial cellulose.
- the materials used to design the 3D macro-pattern such as peaks, tubes, rods, and spikes, have the ability to withstand the growth of the bacterial cellulose thereby creating a macro-pattern, while retaining a softness and flexibility in order to allow the bacterial cellulose to be withdrawn from the bioreactor without damaging the macro-pattern.
- 3D macro-pattern 10 includes a series of regularly spaced rods 15 .
- the macro-pattern may create pores, openings or perforations in the sheet having any geometric shape or dimension.
- the pores may be circular, conical, rectangular, square, oval, elliptical, polygonal and the like.
- the macro-pattern on the bacterial cellulose sheet improves the implants ability to integrate tissue.
- sheet 100 includes regularly distributed circular openings 120 resulting from culturing bacteria in the presence of the 3D macro-pattern shown in FIG. 1 .
- the size of the pores may be from about 0.5 mm to 5 mm, in embodiments from about 1 mm to 3 mm.
- the macro-pattern needs not pass completely through the sheet (e.g., holes), but rather may be indententions resulting from the sheet being formed around and over at least a portion of the macro-pattern template.
- the sheet may have a continuous, not indentented surface for the prevention of post-operative tissular adhesions.
- the macropattern may pass completely through the sheet (e.g., full thickness holes).
- the implants described herein are useful for implantation where soft tissues are in need of repair, reinforcement, replacement or augmentation.
- the implants may be useful near the abdominal wall, vascular tissue or the pelvic floor.
- the implants may be easily fixed for surgeries, by any known techniques, among them suturing, stitching, stapling and tacking.
- the bacterial cellulose is harvested at the end of the fermentation of the bacteria.
- the harvested cellulose is subjected to purification and depyrogenation processes.
- the bacterial cellulose may be oxidized by periodic acid or by nitrogen dioxide before, after, or during the purification and depyrogenation process.
- the bacterial cellulose may be oxidized when the cellulose is at least partly purified and depyrogenated.
- the final level of oxidation can be controlled in such a way to produce a resorption time of from several days to several months.
- the degree of oxidation can be from about 0.1 to about 0.9, in embodiments from about 0.2 to about 0.65.
- bacterial cellulose for the generation of cellulose derivatives
- Cellulose belong to the family of biodegradable, renewable polymers that provides a broad range of important functional properties, and are thus widely used in industry today.
- native cellulose are commonly modified by physical, chemical, enzymatic or genetic means in order to obtain specific functional properties (Richardson, et al., Analytica Chimica Acta, 2003; Kennedy, et al., Cellulose and its Derivatives: Chemistry, Biochemistry and Applications, Ellis Horwood, Chichester, 1985; Guilbot, et al., The Polysaccharides, G.
- Native cellulose has an intrinsic lack of solubility in water and most organic solvent systems which constitutes a major obstacle for utilizing cellulose in many industrial applications. It may be a goal to chemically derivatize the bacterial cellulose in such a way to obtain derivatives soluble in organic solvents, for an easier remodeling of the bacterial cellulose, for example.
- the present implants which include a bacterial cellulose sheet having a 3D macro-pattern may advantageously maintain one or more of the original properties of bacterial cellulose sheets (such as, for example, high biocompatibility, extreme hydrophilicity, unique multi-layered three dimensional laminar structures which provide its moisture handling properties, excellent wet strength, high resistance to breakdown under compression, conformability, absence of generation of harmful particles of the cellulose mesh after rubbing against surrounding tissues or erosion at sharp edges of tissues—e.g., sharp edges of bone and cartilage tissues) while inducing controlled porosity directly during the biosynthesis within the sheets for better tissue integration and cell colonization when implanted.
- Bacterial cellulose sheets can have superior mechanical properties compared to other bioresorbable implants.
- Medical implants in accordance with this disclosure may be produced at a predetermined size or produced in large sheets which may be cut to sizes appropriate for the envisaged application.
- the medical implants may be packaged in single or dual pouches and sterilized using conventional techniques, such as, but not limited to, irradiation with beta (electronic irradiation) or gamma (irradiation using radioactive cobalt) rays at about 25 KGy to about 35 KGy, and/or sterilized by ethylene oxide.
Abstract
The present invention relates to an implant comprising: a sheet of bacterial cellulose having a macro-pattern positioned on at least a portion thereof. The invention also relates to a method for making such an implant.
Description
- This application is a continuation of U.S. patent application Ser. No. 13/125,607 filed Jul. 11, 2011, now U.S. Pat. No. 9,107,978, which is a National Stage Application of PCT/1809/007661 filed Nov. 6, 2009, which claims benefit of U.S. Provisional Application No. 61/112,298 filed Nov. 7, 2008, and the disclosures of each of the above-identified applications are hereby incorporated by reference in their entirety.
- The implants described herein include a sheet of bacterial cellulose having a macro-pattern positioned on at least one side of the sheet.
- Methods for producing such implants include culturing bacteria capable of producing a bacterial cellulose in a bioreactor in the presence of a template having a macro-patterned surface.
- An aspect of the present invention is an implant comprising:
- a sheet of bacterial cellulose having a macro-pattern positioned on at least a portion thereof.
- The bacterial cellulose may derived from Acetobacter xylinum. The bacterial cellulose may be oxidized.
- Another aspect of the present invention is a method of making an implant comprising:
- providing a bioreactor having a macro-patterned surface; and
- culturing a bacteria on the macro-patterned surface, wherein the bacteria is capable of producing a sheet of bacterial cellulose.
- The bacteria may be Acetobacter xylinum.
- Another aspect of the present invention is a method of treating a wound comprising contacting a wound with an implant as described above.
-
FIG. 1 is a schematic perspective view of a template having a three-dimensional macro-pattern according to an embodiment described in the present disclosure. -
FIG. 2 is schematic, cross-sectional view of a bioreactor including a template and a porous sheet of bacterial cellulose according to an embodiment described in the present disclosure. -
FIG. 3 is a schematic perspective view of a porous sheet of bacterial cellulose according to an embodiment described in the present disclosure. - In the present disclosure, the term “implant” is intended to mean a biocompatible or bioresorbable medical device, at least a portion of which can be implanted in the human or animal body.
- In the present disclosure, the term “bioresorbable” is intended to mean the characteristic according to which an implant and/or a material is degraded by the biological tissues and the surrounding fluids, in vivo after a given period of time, that may vary, for example, from one day to several months, depending on the chemical nature of the implant and/or of the material.
- In the present disclosure, the term “bioreactor” is intended to include any device or system capable of supporting a biologically active environment for growing or culturing materials. In addition to containers or vessels capable of seeding or growing bacteria, the bioreactors may also include the ability to provide agitation, pressure changes, temperature controls, humidity controls, media exchange, and ventilation.
- In the present disclosure, the term “sheet” is intended to include generally planar-shaped formats, such as films, foams, pellicles, layers and combinations thereof.
- In the present disclosure, the sheet of bacterial cellulose may be produced from bacteria that synthesize cellulose. Cellulose is synthesized by bacteria belonging to the genera Acetobacter, Rhizobium, Agrobacterium, and Sarcina. Cellulose can be produced by certain bacteria from glucose in the presence of oxygen, (such as, for example, Acetobacter xylinum, referenced hereinafter as the “bacteria”), in static conditions or in a bioreactor (see, e.g. U.S. Pat. Nos. 4,912,049 and 5,955,326, the entire disclosures of which are incorporated herein by this reference). Cellulose suitable for use in the present implants can be obtained by the fermentation of the bacteria. In embodiments, a derivative of the cellulose is employed, such as oxidized cellulose resulting from the oxidation of the cellulose by periodic acid or nitrogen dioxide.
- Bacterial cellulose possesses inherent characteristics which allow effective promotion of wound healing (see, e.g. U.S. Pat. No. 7,390,492, the entire disclosures of which are incorporated herein by this reference). In this regard, bacterial cellulose displays properties (such as unique multi-layer three dimensional laminar structures) that distinguish it from plant cellulose and other natural polymeric materials. Bacterial cellulose shows excellent wet strength, does not easily breakdown under compression and demonstrates high moisture handling ability.
- In the present disclosure, at least a portion of the sheet of bacterial cellulose is porous and includes a macro-pattern thereon. The
porous sheet 100 is formed on or around atemplate 10 having a three dimensional (“3D”) macro-pattern positioned within thebioreactor 50. (SeeFIG. 2 .) In embodiments, the template is positioned on or near the bottom of the bioreactor. It should be understood that instead of a separate structure positioned within the bioreactor, the template may be formed directly into a surface of the bioreactor, such as, for example, formed into the bottom surface of the bioreactor. The porosity of the cellulose sheet is created during the fermentation process when the cellulose is synthesized by the bacteria in a bioreactor which includes culture media. The cellulose synthesis on and around the template having the 3D macro-pattern formed on at least a portion of the bioreactor can lead to the sheet having a well-defined porosity. Because the sheet is formed in the presence of the template, the macro-pattern is imparted to the sheet during formation without the use of additional processing. - The materials used to form the 3D macro-pattern on a template of the bioreactor are compatible with the culture media, the culture conditions and any other contents in the bioreactor which allows for growth of the bacteria on the predetermined 3D macro-pattern portion of the bioreactor. For example, the template may be made from but not limited to poly(lactic acid), poly (glycolic acid), poly (hydroxybutyrate), poly (phosphazine), polyesters, polyethylene glycols, polyethylene oxides, polyacrylamides, polyhydroxyethylmethylacrylate, polyvinylpyrrolidone, polyvinyl alcohols, polyacrylic acid, polyacetate, polycaprolactone, polypropylene, aliphatic polyesters, glycerols, poly(amino acids), copoly (ether-esters), polyalkylene oxalates, polyamides, poly (iminocarbonates), polyalkylene oxalates, polyoxaesters, polyorthoesters, polyphosphazenes and copolymers, block copolymers, homopolymers, blends and combinations thereof, polychloride vinyle (PVC), polycarbonate, polysulfone, fluorocarbones (eg. Teflon® and derivatives, Halar ECTFE [ethylenechlorortrifluoroethylene copolymers)], Tefzel EFTE [ethylene tetrafluorethylene], polyfluoride vinyle [PVDF], stainless steel. The 3D macro-pattern on the template can be designed having any form, geometry or topography which allows for removal of the implant from the bioreactor surface following the biosynthesis of the bacterial cellulose. The materials used to design the 3D macro-pattern, such as peaks, tubes, rods, and spikes, have the ability to withstand the growth of the bacterial cellulose thereby creating a macro-pattern, while retaining a softness and flexibility in order to allow the bacterial cellulose to be withdrawn from the bioreactor without damaging the macro-pattern. For example, as seen in
FIG. 1 ,3D macro-pattern 10 includes a series of regularly spacedrods 15. - The macro-pattern may create pores, openings or perforations in the sheet having any geometric shape or dimension. For example, the pores may be circular, conical, rectangular, square, oval, elliptical, polygonal and the like. The macro-pattern on the bacterial cellulose sheet improves the implants ability to integrate tissue. As seen in
FIG. 3 ,sheet 100 includes regularly distributedcircular openings 120 resulting from culturing bacteria in the presence of the 3D macro-pattern shown inFIG. 1 . - The size of the pores may be from about 0.5 mm to 5 mm, in embodiments from about 1 mm to 3 mm.
- It should be understood that the macro-pattern needs not pass completely through the sheet (e.g., holes), but rather may be indententions resulting from the sheet being formed around and over at least a portion of the macro-pattern template. In such embodiments, the sheet may have a continuous, not indentented surface for the prevention of post-operative tissular adhesions.
- In other embodiments, it should be understood that the macropattern may pass completely through the sheet (e.g., full thickness holes).
- The implants described herein are useful for implantation where soft tissues are in need of repair, reinforcement, replacement or augmentation. For instance, the implants may be useful near the abdominal wall, vascular tissue or the pelvic floor. The implants may be easily fixed for surgeries, by any known techniques, among them suturing, stitching, stapling and tacking.
- In embodiments, the bacterial cellulose is harvested at the end of the fermentation of the bacteria. The harvested cellulose is subjected to purification and depyrogenation processes. The bacterial cellulose may be oxidized by periodic acid or by nitrogen dioxide before, after, or during the purification and depyrogenation process. In embodiments, the bacterial cellulose may be oxidized when the cellulose is at least partly purified and depyrogenated. The final level of oxidation can be controlled in such a way to produce a resorption time of from several days to several months. The degree of oxidation can be from about 0.1 to about 0.9, in embodiments from about 0.2 to about 0.65.
- Other chemical modifications of the bacterial cellulose for the generation of cellulose derivatives are also within the scope of the present disclosure. Cellulose belong to the family of biodegradable, renewable polymers that provides a broad range of important functional properties, and are thus widely used in industry today. However, some of the inherent properties of these polysaccharides limit their utility in certain applications. Therefore, native cellulose are commonly modified by physical, chemical, enzymatic or genetic means in order to obtain specific functional properties (Richardson, et al., Analytica Chimica Acta, 2003; Kennedy, et al., Cellulose and its Derivatives: Chemistry, Biochemistry and Applications, Ellis Horwood, Chichester, 1985; Guilbot, et al., The Polysaccharides, G. Aspinall (Ed.), Academic Press, New York, 1985). Native cellulose has an intrinsic lack of solubility in water and most organic solvent systems which constitutes a major obstacle for utilizing cellulose in many industrial applications. It may be a goal to chemically derivatize the bacterial cellulose in such a way to obtain derivatives soluble in organic solvents, for an easier remodeling of the bacterial cellulose, for example.
- The present implants which include a bacterial cellulose sheet having a 3D macro-pattern may advantageously maintain one or more of the original properties of bacterial cellulose sheets (such as, for example, high biocompatibility, extreme hydrophilicity, unique multi-layered three dimensional laminar structures which provide its moisture handling properties, excellent wet strength, high resistance to breakdown under compression, conformability, absence of generation of harmful particles of the cellulose mesh after rubbing against surrounding tissues or erosion at sharp edges of tissues—e.g., sharp edges of bone and cartilage tissues) while inducing controlled porosity directly during the biosynthesis within the sheets for better tissue integration and cell colonization when implanted. Bacterial cellulose sheets can have superior mechanical properties compared to other bioresorbable implants.
- Medical implants in accordance with this disclosure may be produced at a predetermined size or produced in large sheets which may be cut to sizes appropriate for the envisaged application. The medical implants may be packaged in single or dual pouches and sterilized using conventional techniques, such as, but not limited to, irradiation with beta (electronic irradiation) or gamma (irradiation using radioactive cobalt) rays at about 25 KGy to about 35 KGy, and/or sterilized by ethylene oxide.
- It will be understood that various modifications may be made to the embodiments disclosed herein. Thus, those skilled in the art will envision other modifications within the scope and spirit of the disclosure.
Claims (21)
1-5. (canceled)
6. An implant comprising:
a sheet of bacterial cellulose having a macro-pattern positioned on at least a portion thereof, wherein the sheet includes pores of a size from about 0.5 to 5 mm and which do not pass completely through the sheet.
7. The implant of claim 6 , wherein the pores are from about 0.1 mm to 3 mm in size.
8. The implant of claim 6 , wherein the bacterial cellulose is derived from Acetobacter xylinum.
9. The implant of claim 6 , wherein the bacterial cellulose is oxidized.
10. The implant of claim 9 , wherein the bacterial cellulose is oxidized with a degree of oxidation from 0.1 to 0.9.
11. The implant of claim 9 , wherein the bacterial cellulose is oxidized with a degree of oxidation from 0.2 to 0.65.
12. The implant of claim 9 , wherein the bacterial cellulose is oxidized by periodic acid or nitrogen dioxide.
13. The implant of claim 12 , wherein the bacterial cellulose is oxidized when the cellulose is at least partially purified and depyrogenated.
14. The implant of claim 6 , wherein the sheet is a generally planar film.
15. The implant of claim 6 , wherein the implant is bioresorbable.
16. The implant of claim 6 , wherein the pores comprise a shape selected from the group consisting of circular, conical, rectangular, square, oval, and, elliptical.
17. The implant of claim 6 , wherein the pores are regularly distributed circular openings.
18. The implant of claim 6 , wherein the sheet is sterilized.
19. A bioresorbable implant comprising:
a sheet of bacterial cellulose which includes a first surface which allows tissue integration and includes a macro-pattern positioned on at least a portion thereof which includes pores which do not pass completely through the sheet, and a second continuous, not indented surface for the prevention of post-operative adhesions.
20. The bioresorbable implant of claim 19 , wherein the pores are from about 0.5 mm to 5 mm in size.
21. The bioresorbable implant of claim 19 , wherein the pores are from about 0.1 mm to 3 mm in size.
22. The bioresorbable implant of claim 19 , wherein the bacterial cellulose is derived from Acetobacter xylinum.
23. The bioresorbable implant of claim 19 , wherein the bacterial cellulose is oxidized.
24. The bioresorbable implant of claim 23 , wherein the bacterial cellulose is oxidized with a degree of oxidation from 0.1 to 0.9.
25. The bioresorbable implant of claim 23 , wherein the bacterial cellulose is oxidized by periodic acid or nitrogen dioxide.
Priority Applications (1)
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US14/806,015 US20160022867A1 (en) | 2008-11-07 | 2015-07-22 | Template for bacterial cellulose implant processed within bioreactor |
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US11229808P | 2008-11-07 | 2008-11-07 | |
PCT/IB2009/007661 WO2010052583A2 (en) | 2008-11-07 | 2009-11-06 | Template for bacterial cellulose implant processed within bioreactor |
US201113125607A | 2011-07-11 | 2011-07-11 | |
US14/806,015 US20160022867A1 (en) | 2008-11-07 | 2015-07-22 | Template for bacterial cellulose implant processed within bioreactor |
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US13/125,607 Continuation US9107978B2 (en) | 2008-11-07 | 2009-11-06 | Template for bacterial cellulose implant processed within bioreactor |
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US14/806,015 Abandoned US20160022867A1 (en) | 2008-11-07 | 2015-07-22 | Template for bacterial cellulose implant processed within bioreactor |
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KR20140129234A (en) | 2012-02-22 | 2014-11-06 | 신세스 게엠바하 | Resorbable cellulose based biomaterial and implant |
US9499636B2 (en) * | 2012-06-28 | 2016-11-22 | Covidien Lp | Dissolution of oxidized cellulose and particle preparation by cross-linking with multivalent cations |
FI126854B (en) * | 2013-12-30 | 2017-06-30 | Upm Kymmene Corp | A membrane, its use and a process for the preparation of the membranes |
US10774227B2 (en) * | 2017-04-25 | 2020-09-15 | Cellheal As | Preparation and applications of biocompatible conductive inks based on cellulose nanofibrils for 3D printing of conductive biomedical devices and for use as models for study of neurodegenerative disorders and connection between brain/neurons and communication or other electronic devices |
Citations (3)
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US4588400A (en) * | 1982-12-16 | 1986-05-13 | Johnson & Johnson Products, Inc. | Liquid loaded pad for medical applications |
US4803032A (en) * | 1983-05-17 | 1989-02-07 | James River-Norwalk, Inc. | Method of spot embossing a fibrous sheet |
US20040028722A1 (en) * | 2002-04-26 | 2004-02-12 | Xylos Corporation | Microbial cellulose wound dressing for treating chronic wounds |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
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US3364200A (en) * | 1960-03-28 | 1968-01-16 | Johnson & Johnson | Oxidized cellulose product and method for preparing the same |
BR8404937A (en) | 1984-10-01 | 1986-05-06 | Bio Fill Ind E Comercio De Pro | PROCESS FOR PREPARING CELLULOSE FILM, CELLULOSE FILM OBTAINED BY THE SAME, ARTIFICIAL SKIN IMPLANT, INJURY TREATMENT PROCESS USING THE REFERRED CELLULOSE FILM AND USE |
EP0396344A3 (en) | 1989-04-28 | 1991-04-03 | Ajinomoto Co., Inc. | Hollow microbial cellulose, process for preparation thereof, and artificial blood vessel formed of said cellulose |
US5955326A (en) * | 1995-08-01 | 1999-09-21 | Rensselaer Polytechnic Institute | Production of microbial cellulose using a rotating disk film bioreactor |
WO2001015708A1 (en) | 1999-09-02 | 2001-03-08 | Michigan State University | Vaccine to control equine protozoal myeloencephalitis in horses |
US6777227B2 (en) * | 2002-01-09 | 2004-08-17 | John L. Ricci | Bio-reactor and cell culture surface with microgeometric surfaces |
US6926950B2 (en) * | 2002-12-20 | 2005-08-09 | Sca Hygiene Products Ab | Production of a dyed patterned web |
US7884258B2 (en) * | 2004-04-13 | 2011-02-08 | Boehringer Technologies, L.P. | Wound contact device |
WO2006042287A2 (en) * | 2004-10-12 | 2006-04-20 | Trustees Of Tufts College | Method for producing biomaterial scaffolds |
US7709631B2 (en) * | 2006-03-13 | 2010-05-04 | Xylos Corporation | Oxidized microbial cellulose and use thereof |
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2009
- 2009-11-06 US US13/125,607 patent/US9107978B2/en not_active Expired - Fee Related
- 2009-11-06 EP EP09775280A patent/EP2365832A2/en not_active Withdrawn
- 2009-11-06 WO PCT/IB2009/007661 patent/WO2010052583A2/en active Application Filing
- 2009-11-06 CA CA2741516A patent/CA2741516A1/en not_active Abandoned
- 2009-11-06 AU AU2009312478A patent/AU2009312478A1/en not_active Abandoned
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2015
- 2015-07-22 US US14/806,015 patent/US20160022867A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4588400A (en) * | 1982-12-16 | 1986-05-13 | Johnson & Johnson Products, Inc. | Liquid loaded pad for medical applications |
US4803032A (en) * | 1983-05-17 | 1989-02-07 | James River-Norwalk, Inc. | Method of spot embossing a fibrous sheet |
US20040028722A1 (en) * | 2002-04-26 | 2004-02-12 | Xylos Corporation | Microbial cellulose wound dressing for treating chronic wounds |
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US20110262706A1 (en) | 2011-10-27 |
AU2009312478A1 (en) | 2010-05-14 |
US9107978B2 (en) | 2015-08-18 |
WO2010052583A2 (en) | 2010-05-14 |
WO2010052583A3 (en) | 2010-11-04 |
CA2741516A1 (en) | 2010-05-14 |
EP2365832A2 (en) | 2011-09-21 |
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