WO2003045226A2 - Eb matrix production from animal tissue and its use for tissue repair - Google Patents
Eb matrix production from animal tissue and its use for tissue repair Download PDFInfo
- Publication number
- WO2003045226A2 WO2003045226A2 PCT/US2002/038189 US0238189W WO03045226A2 WO 2003045226 A2 WO2003045226 A2 WO 2003045226A2 US 0238189 W US0238189 W US 0238189W WO 03045226 A2 WO03045226 A2 WO 03045226A2
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- WIPO (PCT)
- Prior art keywords
- tissue
- scaffold material
- biopolymer scaffold
- blood vessel
- repair
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
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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
- A61L27/36—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
- A61L27/3604—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 human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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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
- A61L27/36—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
- A61L27/3604—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 human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3625—Vascular tissue, e.g. heart valves
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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
- A61L27/36—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
- A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
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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
- A61L27/36—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
- A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
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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
- A61L27/36—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
- A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3691—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
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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
- A61L27/36—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
- A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/90—Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2537/00—Supports and/or coatings for cell culture characterised by physical or chemical treatment
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2537/00—Supports and/or coatings for cell culture characterised by physical or chemical treatment
- C12N2537/10—Cross-linking
Definitions
- This invention relates to the field of tissue engineering, and in particular to animal-derived, bioremodelable, biopolymer scaffold materials used to repair animal tissue.
- bioremodelable or “bioremodelability” refers to a material that lends itself to the breakdown by cells that occupy it and use it as a template for creating a replacement made up mainly of newly synthesized components secreted by the cells.
- scaffolds made of naturally-occurring polymers (e.g. collagens), man-made polymers, (e.g. PTFE, Dacron, PET or polyethylene) or self-degrading, man-made polymers (e.g. PLA or PGA); 2) signaling molecules that give developmental instructions to cells; and 3) cells.
- naturally-occurring polymers e.g. collagens
- man-made polymers e.g. PTFE, Dacron, PET or polyethylene
- self-degrading, man-made polymers e.g. PLA or PGA
- Man-made implant materials such as synthetic polymers, plastics, and surface- coated metals may have different degrees of immunogenicity and suffer from significant limitations that prohibit their broad applications.
- a major limitation is that cells cannot remodel them after implantation. They are highly susceptible to microbial infection, and some undergo calcification. Synthetic vascular conduits have a high incidence of occlusion after peripheral vascular bypass procedures.
- aldehydic processing effectively destroys any biological activity, such as cell binding sites, associated with the original tissue and greatly reduces or eliminates the ability of cells to attach to it. It also eliminates binding sites for cell-synthesized products which attach to cells or to intermediates able to bind to cells and cell products that make up the extracellular matrix by cells.
- Collagen-based devices that are animal-derived and fixed with glutaraldehyde or a similar agent can not be remodeled since they are highly resistant to metalloproteinase enzymes.
- the methods suggested in U.S. Patent No. 4,801,299 and U.S. Patent No. 5,916,265 include the use of glutaraldehyde or a similar agent for the fixation of tissue derived from a post-natal animal source; the resulting products can not be faithfully remodeled.
- Glutaraldehyde-treated devices are known to undergo gradual calcification. Heart valves made from fixed animal tissues can require replacement in 5-7 years or sooner due to calcification.
- EBM is a bioremodelable, biopolymer scaffold material derived from fetal, neo- natal or post-natal animal tissue. EBM is processed in a way that preserves its tissue strength without reducing its intrinsic biological properties or compromising the ability of cells that occupy the tissue to remodel it.
- EBM Upon processing EBM, binding sites for cells and cell-secreted products that make up the extracellular matrix surrounding cells that occupy it are preserved.
- Undesirable tissue components of EBM e.g., DNA, RNA
- delipidyzing organic solvents are used to reduce the presence of cell and nuclear membranes.
- EBM does not calcify, making it safe for use in the human body for repair of soft tissues.
- EBM can be used as a scaffold for bone repair if treated with an appropriate growth factor(s), if seeded with bone precursor cells or if occupied by bone forming cells when implanted.
- EBM may be used as a tissue-building component with or without cells for creating human body replacements. It can be used after the addition of signaling molecules, which will further promote tissue repair. It can also be implanted after stem or differentiated cells are seeded into or onto it.
- a naturally occurring, biopolymer-based matrix is produced from animal tissue by a method comprising the following steps: (1) removing the tissue from its source; (2) optionally extracting growth and differentiation factors from the tissue; (3) inactivating infective agents of the tissue; (4) mechanically expressing undesirable components from the tissue; (5) washing the tissue for removal of chemical residues; (6) optionally drying; and (7) optionally cross-linking the tissue after chemical and mechanical treatment; and (8) optionally terminally sterilizing.
- inactivating refers to the reduction of the concentrations of infective agents (e.g., bacteria, molds, viruses and prions) by 4, 6 or 8 logs consistent with the requirements needed to insure against infectivity.
- mechanically expressing refers to mechanically applying the necessary pressure to express undesirable components from the tissue. With the aid of appropriate solvents, unwanted components from the product that are potentially antigenic (e.g., DNA, RNA) or other molecules released by reagents (e.g., NaOH) are removed.
- fetal or neo-natal animal tissue is used.
- One preferred source is fetal bovine tissue between 10 weeks of age and newborn age.
- fetal bovine skin is used.
- Other source material include blood vessels, other tubular structures, internal organs including the bladder, tendons, ligaments, cartilage, membranes such as the kidney capsule or diaphragm, or hard tissues such as cartilage or bone.
- EBM made from skin tissues can be used as a skin wound dressing or a skin replacement tissue. With or without the addition of signaling molecules and cells, EBM promotes wound healing. EBM is suitable for the treatment of chronic topical wounds such as burns, ulcers, and avulsion injuries. In grafts to host animals, such as rats, to replace full thickness skin wounds, acellular EBM is shown to remodel to replacement skin without scaring. However, secondary derivatives are absent. If seeded with dermal fibroblasts and keratinocytes, EMB can serve as a living skin replacement.
- EBM can be used as a repair or replacement device throughout the human body.
- EBM can be used as a urethral sling or laminectomy barrier because of its high physical strength, resistance to stretch, suturability, cell-compatibility and bioremodelability.
- EBM may be used for hernia repair, colon, rectal, vaginal and or urethral prolapse treatment; pelvic floor reconstruction; muscle flap reinforcement; lung tissue support; and soft tissue augmentation.
- EBM produced from fetal or neo-natal animal skins can be used for pericardial, periosteal, rotator cuff, or dura repair or replacement, or for hernia repair. It is drapable and has single suture-pullout strength of more than 20 Newtons.
- EBM used as a spinal fusion device can serve as a carrier of growth factors to generate bone.
- EBM derived from skin has been found to induce bone formation with the addition of rhBMP2 or bone signaling complexes. Meshed EBM enriched with rhBMP2 was implanted subcutaneously in rats. Freeze-dried EBM was soaked in a solution of rhBMP2 (0.1 mg/ml).
- Signaling complexes refer to tissue-specific compositions comprising a number of factors necessary to promote cell division, direct patterning, morphogenesis and differentiation of specific cells, tissues and organs. Methods of generating signaling complexes (Signal-plexTM) are described in U.S. Application No. 09/901,765, filed July 9, 2001, the entire contents of which are incorporated herein by reference.
- EBM can be used to repair the intervertebral disk after disketomy by acting as a barrier to cells surrounding the disk and promoting regeneration of cells within the disk.
- EBM can be used in periodontal repair by acting as a membrane barrier to specific cell populations and facilitating regeneration of soft tissue and bone.
- EBM can be homogenized for use in an injectable form or as a foam as a hemostat, dura replacement, and other similar areas of treatment.
- the same or similar processing described in the examples above can be applied to non-skin tissues of the body to provide scaffolds of replacement parts with or without the addition of cells, signaling complexes or drugs, with the expectation that if acellular or cellular they will be vascularized and populated with host cells.
- EBM may be derived from a wide variety of tissues and organs.
- the preferred protocol to prepare EBM derived. from a blood vessel is as follows. All of the following steps are performed in a laminar-flow hood using aseptic techniques and sterile solutions.
- a blood vessel is cut out from the body of an animal. Flesh is removed from the blood vessel, and the artery is placed on a 4mm mandrill. Flesh can be removed from the blood vessel using dissection tools, if done by hand; serrated tipped forceps are used to lift the flesh, and curved scissors are used to remove the flesh. Defleshing can also be performed by a defleshing machine. If carried out manually, the process should continue as follows.
- the blood vessel is placed in 20% bleach for 30 ⁇ 2 minutes on a rocking platform on ice.
- the temperature of the bleach is 4 ⁇ 2 °C.
- the volume of the bleach is 500+50 mis in a 1.0 liter square, wide-mouth bottle with a screw cap.
- the blood vessel is dipped into 1.0 liters of Milli-QTM water for approximately 5-10 seconds to wash off the bleach.
- the blood vessel is placed in a 5.2N solution of NaOH for 30+2 minutes on a rocking platform on ice.
- the temperature of the NaOH is 4+2 °C.
- the volume of the NaOH is 500 ⁇ 50 mis in a 1.0 liter square, wide-mouth bottle with a screw cap.
- the blood vessel is dipped 1.0 liters of 0.2 ⁇ m filtered Milli-QTM water for approximately 5- 10 seconds to wash off the NaOH.
- the concentration of NaOH and the time of exposure to the NaOH can be increased or decreased depending upon the thickness of the blood vessel. This is followed by three washes in 1.0 liter of 0.2 ⁇ m filtered Milli-QTM water for up to 20 minutes each.
- the blood vessel is transferred into a 1 :1 chloroform ethanol (95%) solution for 5 minutes on a rocking platform.
- the volume of the solution is 500+50 mis in a 1.0 liter square, wide-mouth bottle with a screw cap.
- a terminal sterilization step is optionally performed using either .5% hydrogen peroxide, ethylene oxide or gamma radiation.
- hydrogen peroxide as a sterlizing agent, it is necessary to aseptically package the product immediately afterwards.
- ethylene oxide or gamma radiation the product can be sterilized in a final package.
- the blood vessel is washed in 70% ethanol for approximately 10 minutes on a rocking platform.
- the volume is 1.0 liter in a 1.0 liter square, wide-mouth bottle with a screw cap.
- the blood vessel is washed i 1.0 liter of 0.2 ⁇ m filtered Milli-QTM water for approximately 5 minutes on a rocking platform, and then washed in 1.0 liter of 0.2 ⁇ m filtered Milli-QTM water for 10 minutes.
- the blood vessel is immersed in 1.0 liter of sterile PBS (phosphate buffered saline) for 20+4 hours on a rocking platform at a temperature of 4 ⁇ 2 °C.
- the blood vessel may be optionally freeze-dried.
- the EBM blood vessel can be enhanced by the addition to it of vascular signaling complexes designed to attract circulating EPS (endothelial precursor cells) — cells able to differentiate into both smooth muscle and endothelial cells. Additional Methods
- the tissue is preferably taken from a fetus that is at 10-30 weeks of gestation, preferably 15-25 weeks of gestation, or 10-20 weeks of gestation.
- the age of the piglet used as the tissue source is preferably birth-8 weeks, more preferably 5 days-4 weeks, most preferably 7 days-3 weeks.
- the tissue is not chemically cross-linked.
- hydrogen peroxide In the place of bleach, hydrogen peroxide can be used.
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002364511A AU2002364511A1 (en) | 2001-11-28 | 2002-11-27 | Eb matrix production from animal tissue and its use for tissue repair |
EP02799887A EP1460930A2 (en) | 2001-11-28 | 2002-11-27 | Eb matrix production from animal tissue and its use for tissue repair |
CA002468310A CA2468310A1 (en) | 2001-11-28 | 2002-11-27 | Eb matrix production from animal tissue and its use for tissue repair |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/996,640 | 2001-11-28 | ||
US09/996,640 US20020182261A1 (en) | 2001-05-31 | 2001-11-28 | EB matrix production from fetal tissues and its use for tissue repair |
Publications (2)
Publication Number | Publication Date |
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WO2003045226A2 true WO2003045226A2 (en) | 2003-06-05 |
WO2003045226A3 WO2003045226A3 (en) | 2004-02-12 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/US2002/038189 WO2003045226A2 (en) | 2001-11-28 | 2002-11-27 | Eb matrix production from animal tissue and its use for tissue repair |
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US (4) | US20020182261A1 (en) |
EP (1) | EP1460930A2 (en) |
AU (1) | AU2002364511A1 (en) |
CA (1) | CA2468310A1 (en) |
WO (1) | WO2003045226A2 (en) |
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US7740576B2 (en) | 2005-04-05 | 2010-06-22 | Ams Research Corporation | Articles, devices, and methods for pelvic surgery |
US8460929B2 (en) | 2007-06-04 | 2013-06-11 | The Regents Of The University Of California | Methods of tissue generation and tissue engineered compositions |
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CZ54899A3 (en) | 1996-08-23 | 1999-08-11 | Cook Biotech, Incorporated | Graft prosthesis, materials connected therewith and processes for producing thereof |
US20080268054A1 (en) * | 2000-12-04 | 2008-10-30 | Eugene Bell | Dermal derived human stem cells and compositions and methods thereof |
WO2003002165A1 (en) * | 2001-06-28 | 2003-01-09 | Cook Biotech Incorporated | Graft prosthesis devices containing renal capsule collagen |
US8697139B2 (en) | 2004-09-21 | 2014-04-15 | Frank M. Phillips | Method of intervertebral disc treatment using articular chondrocyte cells |
US20060148080A1 (en) * | 2004-12-30 | 2006-07-06 | Paul Diamond | Methods for supporting and producing human cells and tissues in non-human mammal hosts |
US20060147429A1 (en) * | 2004-12-30 | 2006-07-06 | Paul Diamond | Facilitated cellular reconstitution of organs and tissues |
WO2007016083A1 (en) | 2005-07-26 | 2007-02-08 | Ams Research Corporation | Methods and systems for treatment of prolapse |
US20070092494A1 (en) * | 2005-10-26 | 2007-04-26 | Biomet Manufacturing Corp. | Composition for wound healing using lyophilized skin or skin-derived collagen |
US20100104608A1 (en) * | 2008-09-26 | 2010-04-29 | Tyco Healthcare Group Lp | Reactive surgical implant |
US8241654B2 (en) * | 2008-09-26 | 2012-08-14 | Tyco Healthcare Group Lp | Reactive surgical implant |
US20100111919A1 (en) * | 2008-10-31 | 2010-05-06 | Tyco Healthcare Group Lp | Delayed gelation compositions and methods of use |
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US7740576B2 (en) | 2005-04-05 | 2010-06-22 | Ams Research Corporation | Articles, devices, and methods for pelvic surgery |
US7811223B2 (en) | 2005-04-05 | 2010-10-12 | Ams Research Corporation | Articles, devices, and methods for pelvic surgery |
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Also Published As
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US20020182261A1 (en) | 2002-12-05 |
US20150307836A1 (en) | 2015-10-29 |
US20050008708A1 (en) | 2005-01-13 |
US20090162452A1 (en) | 2009-06-25 |
US9011895B2 (en) | 2015-04-21 |
EP1460930A2 (en) | 2004-09-29 |
WO2003045226A3 (en) | 2004-02-12 |
AU2002364511A1 (en) | 2003-06-10 |
CA2468310A1 (en) | 2003-06-05 |
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