WO2012141454A2 - Matériaux de greffe obtenus à partir de cartilage de mammifère - Google Patents

Matériaux de greffe obtenus à partir de cartilage de mammifère Download PDF

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Publication number
WO2012141454A2
WO2012141454A2 PCT/KR2012/002616 KR2012002616W WO2012141454A2 WO 2012141454 A2 WO2012141454 A2 WO 2012141454A2 KR 2012002616 W KR2012002616 W KR 2012002616W WO 2012141454 A2 WO2012141454 A2 WO 2012141454A2
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WO
WIPO (PCT)
Prior art keywords
cartilage
solution
graft
preparing
immersing
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Application number
PCT/KR2012/002616
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English (en)
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WO2012141454A3 (fr
Inventor
Ho Chan Hwang
Ke Won Kang
Jin Young Kim
Jae Hyoung Ahn
Da Mi Choi
Original Assignee
Hans Biomed. Cor.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020110107351A external-priority patent/KR101269618B1/ko
Application filed by Hans Biomed. Cor. filed Critical Hans Biomed. Cor.
Priority to JP2013554409A priority Critical patent/JP5763790B2/ja
Priority to CN201280017628.1A priority patent/CN103491988B/zh
Publication of WO2012141454A2 publication Critical patent/WO2012141454A2/fr
Publication of WO2012141454A3 publication Critical patent/WO2012141454A3/fr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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
    • A61L27/3612Cartilage, synovial fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/32Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3641Materials 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
    • A61L27/3645Connective tissue
    • A61L27/3654Cartilage, e.g. meniscus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3683Materials 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
    • A61L27/3687Materials 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2835Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2835Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
    • A61F2002/2839Bone plugs or bone graft dowels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/06Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus

Definitions

  • the present invention relates to a graft material derived from mammalian cartilage.
  • a method for supplying cartilage from allograft or xenograft is provided.
  • viruses can be transferred with graft and such problems can be solved by processing the selected and non-infected tissues after determining whether a donor has virus infection in the world tissue bank. Since 1972, these kinds of allogeneic cartilage grafts have been used in orthopedic surgery, plastic surgery, ophthalmology, gynecology and urology surgery and do not require additional collection of autologous cartilage for the nasal tip plasty unlike alloplastic graft.
  • the inventors of the present invention has completed the invention by developing graft materials which not only have significantly low side effects during transplanting but also are easy to prepared in low cost.
  • An aspect of the present invention is to provide a method for preparing a graft material derived from mammalian.
  • Another aspect of the present invention is to provide a graft material prepared by the method according to the present invention.
  • a method for preparing cartilage graft comprising: preparing mammalian cartilage; treating the prepared cartilage with a sodium chloride hypertonic solution; treating the hypertonic solution-treated cartilage with a virus inactivation solution; treating the virus inactivation solution-treated cartilage with an alkali solution; dewatering treating or freezing treating the alkali solution-treated cartilage; and gamma irradiating the dewatering-treated or freezing-treated cartilage.
  • the mammalian may be at least one selected from the group consisting of pig, human, horse, cow, dog, and mouse.
  • the cartilage may be at least one selected from the group consisting of hyaline cartilage, elastic cartilage and fibrocartilage.
  • the step of preparing mammalian cartilage may further comprise immersing the cartilage in a solution of (acetone or methyl alcohol) : chloroform mixed in a ratio of 1 : 1 (v/v) for 24-72 hours and defatting the result.
  • the mammalian cartilage may be pig cartilage.
  • the pig cartilage may be elastic ear cartilage or rip cartilage.
  • the step of treating with a hypertonic solution may be immersing the cartilage in a 6-12% sodium chloride solution for 4-6 hours while applying ultrasonic wave to the cartilage.
  • the step of treating with a virus inactivation solution may be immersing in a virus inactivation solution comprising 0.5-1.5% of hydrogen peroxide, 0.1-1.0% of peracetic acid, 70-99% of alcohol, and 0.001-3% of sodium hypochlorite(NaOCl) for 1/2 to 1 hour.
  • the step of treating with an alkali solution may be immersing in a 0.25-0.75M sodium hydroxide(NaOH) for 15-45 minutes.
  • the dewatering treatment may be conducted by at least one method selected from the group consisting of immersing sequentially in 50%, 80% and 100% of acetone; immersing in absolute alcohol; immersing sequentially in 50% and 80% of acetone and then absolute alcohol; and immersing first in a solution comprising 0.1-1% of antibiotic and 90-99.9% of glycerol and then in 100% glycerol solution.
  • the freezing treatment may be conducted by freezing the alkali solution-treated cartilage at -70°C for 1-2 hours and freeze drying for 48-72 hours.
  • cartilage graft prepared by the above-described method.
  • the graft material according to the present invention can be prepared through multiple steps by eliminating antigenicity, pathogen and cytotoxicity without affecting biomechanics and tissue reconstruction abilities, in which all kinds of pathogens are inactivated. Since it does not use human cartilage but mammalian cartilage, there are advantages in smooth accepting and supplying and low cost of a graft material.
  • FIG. 1 is photographs of the cut section of fresh pig ear cartilages stained with various stains prior to treatments according to the present invention, observed through a microscope.
  • FIG. 2 is photographs of the cut section of fresh pig rip cartilages stained with various stains prior to treatments according to the present invention, observed through a microscope.
  • FIG. 3 is photographs of cut section of final pig ear cartilages stained with various stains after treatments according to the present invention, observed through a microscope.
  • FIG. 4 is photographs of cut section of final pig rip cartilages stained with various stains after treatments according to the present invention, observed through a microscope.
  • FIG. 5 is photographs illustrating collagen(A, C), karatan sulfate(B, D) present in fresh(A, B) and final(C, D) pig ear cartilages prior to and after treatments according to the present invention, respectively.
  • FIG. 6 is photographs illustrating fibronectin(A, C), chondroitin sulfate(B, D) present in fresh(A, B) and final(C, D) pig ear cartilages prior to and after treatments according to the present invention, respectively.
  • FIG. 7 is SEM of fresh and final pig ear cartilages prior to and after treatments according to the present invention, respectively.
  • A fresh cartilage
  • B Final product(EEC)
  • FIG. 8 is a graph of HPLC results illustrating chemical structures of fresh and final pig ear cartilages prior to and after treatments according to the present invention, respectively. (A:before treatment, B: during treatment, C: after treatment)
  • FIG. 9 illustrates comparison in the thermal property with acetone and glycerol treatment according to the present invention.
  • -glycerol sample dewatered by immersing in 100% of glycerol (including an antibiotic) after processing.
  • FIG. 10 illustrates difference in cytotoxicity according to acetone dewatering compared to glycerol dewatering and difference in cytotoxicity of final cartilage graft.
  • FIG. 11 illustrates transplanting process through animal experiment in order to evaluate biological stability of the cartilage graft prepared according to the method of the present invention.
  • FIG. 12 illustrates the result of the tissue obtained after performing transplantation test through an animal experiment in order to determine the biological stability of the cartilage graft prepared by the method of the present invention.
  • a method for preparing cartilage graft comprising: preparing mammalian cartilage; treating the prepared cartilage with a sodium chloride hypertonic solution; treating the hypertonic solution-treated cartilage with a virus inactivation solution; treating the virus inactivation solution-treated cartilage with an alkali solution; dewatering treating or freezing treating the alkali solution-treated cartilage; and gamma irradiating the dewatering-treated or freezing-treated cartilage.
  • the mammalian cartilage may be hyaline cartilage, elastic cartilage, or fibrocartilage of mammalian including pig, human, horse, cow, dog, and mouse, preferably pig cartilage. More preferably, it may be elastic ear cartilage or rip cartilage of pig.
  • the step of preparing mammalian cartilage may further comprise immersing the cartilage in a solution of (acetone or methyl alcohol) : chloroform mixed in a ratio of 1 : 1 (v/v) for 24-72 hours, preferably 48 hours and defatting the result.
  • the amount of the crude fat of the pig rip cartilage is determined as follows.
  • the step of treating with a sodium chloride hypertonic solution may be performed by immersing the cartilage in a 6-12% sodium chloride solution for 4-6 hours while applying ultrasonic wave to the cartilage.
  • concentration of sodium chloride is less than 6%
  • the osmotic destruction effect may be week because the osmosis action in the cartilage cells becomes little, while when it is more than 12%, un-dissolved salt may be participated in the cartilage or container.
  • the ultrasonic wave treatment helps the solution penetrating inside the cartilage and enhance osmotic destruction of cells.
  • the step of treating with a virus inactivation solution may be performed by immersing in a virus inactivation solution comprising 0.5-1.5% of hydrogen peroxide, 0.1-1.0% of peracetic acid, 70-99% of alcohol, and 0.001-3% of sodium hypochlorite(NaOCl) for 1/2 to 1 hour. All pathogens of virus particles and prion particles, etc. may be inactivated through the virus inactivation solution treatment. 0.1-0.5% of peracetic acid is preferable and 0.15-0.25% of peracetic acid is the most preferable.
  • concentration of hydrogen peroxide in the virus inactivation solution is less than 0.5%, inactivation of the pathogens may not be performed sufficiently, while when it is more than 1.5%, it may damage the cartilage.
  • concentration of alcohol is from more than 95.5% to close to 100%, it may result in undesirable side effects such as degeneration and dehydration of the cartilage.
  • the alkali solution treatment may be performed by immersing in a 0.25-0.75M sodium hydroxide(NaOH) for 15-45 minutes.
  • the viruses that are present in the cartilage or can be added during the process may be inactivated through the alkali solution treatment. It also allows eliminating cartilage cells in the cartilage tissue.
  • chemical reactions to inactivate such viruses and eliminate cells may not occur sufficiently, while when it is treated with more than 0.75M of sodium hydroxide, it may damage the cartilage.
  • the dewatering treatment after performing the alkali solution treatment may be conducted by at least one method selected from the group consisting of immersing the cartilage sequentially in 50%, 80% and 100% of acetone; immersing in absolute alcohol; immersing sequentially in 50% and 80% of acetone and then absolute alcohol; and immersing first in a solution comprising 0.1-1% of antibiotic and 90-99.9% of glycerol and then in 100% glycerol solution.
  • glycerol When water inside the cells of the cartilage graft is substituted with glycerol, since it improves conservative property, 2 or more of the above methods may be combined.
  • the alkali solution-treated cartilage may be stored, after washing step, at -20°C or lower, without the dewatering treatment.
  • the freezing treatment is performed by freezing the alkali solution-treated cartilage at -70°C for 1-2 hours and then freeze drying may be performed for 48-72 hours.
  • the final cartilage after the treatments may be individually packaged and disinfected with ethylene oxide(EO) gas.
  • the final cartilage after the treatments may be gamma irradiated with 10-60kGy, preferably 10-30kGy to sterilize the cartilage graft.
  • the cartilage graft may be prepared by performing only gamma sterilization process by immersing the cartilage graft in a sterilized isotonic solution.
  • Fresh cartilage extracted from a pig ear was immersed in a 9% NaCl solution for 5 hours and irradiated with ultrasonic wave. Cartilage cells were removed through this treatment. Then it was immersed in 1% of hydrogen peroxide as a virus inactivation solution for 45 minutes and stirred. Viruses and other pathogens were inactivated through this treatment. And then, it was immersed in 0.5M sodium hydroxide(NaOH) as an alkali solution for 30 minutes. Before each treatment, the pre-treated solution was completely washed out with a washing solution.
  • Dewatering treatment was performed by immersing sequentially in 50%, 80% and 100% acetone in order to minimize damages of the cartilage tissue, then sealed into a container and gamma-irradiated.
  • the cartilage graft prepared through the above process was gamma-irradiated with a 5kGy unit within a range of 5-30kGy in order to determine optimal dose of gamma rays.
  • Optimal dose of gamma rays is determined by digitizing degree of active cartilage cells depending on the gamma irradiation and amount of other materials forming the cartilage and the result is shown in Table 1.
  • the cartilage cells After the gamma-irradiation, the cartilage cells remained as the activated state were observed and compared through the H&E stain. Since alive cartilage cells may act as an antigen after implantation, it is the most important to inactivate them. Each sample depending on the amount of irradiation was tested to determine the degree of the maintained shape of the cartilage cells. When the shape of the cartilage cells was maintained the most, it was scored as 5 and degree of the maintained shape of the cartilage cells were scored. As a result, the cartilage cells maintaining the original shape were not observed in 25kGy and 30kGy conditions.
  • FIG. 5 and FIG. 6 illustrate the result when the amount of gamma rays was 25kGy.
  • the prepared cartilage was dewatered by using acetone or glycerol treatment.
  • the glycerol treatment was performed by immersing the tissue in glycerol including about 0.11% of antibiotic and then in more than 99.9% of glycerol to substitute water in the tissue with glycerol.
  • FIG. 9 after dewatering by using glycerol, thermal properties of the final products were compared.
  • FIG. 9 illustrating the thermal property depending on dewatering
  • the glass transition temperature of acetone was about 99° and that of glycerol was about 96°. Accordingly, it is noted that there was no significant difference and the thermal property of acetone and glycerol did not affect the shape of the samples.
  • FIG. 10 illustrating cytotoxicity depending on dewatering, it is also noted that there is no cytotoxicity with the dewatering using acetone or glycerol.
  • the cartilage graft according to the present invention can be dewatered by acetone or glycerol treatment and stored.
  • karatan sulfate As shown in FIG. 5 and FIG. 6, amount of karatan sulfate, collagen II, fibronectin, and chondroitin sulfate from fresh pig ear cartilage and final cartilage graft was determined.
  • Karatan sulfate was observed throughout the matrix, while chondroitin sulfate was observed mainly near the cartilage membrane, and particularly, chondroitin sulfate was concentrated on one side of the cartilage membrane. It is noted that the amount of karatan sulfate, collagen II, fibronectin, and chondroitin sulfate was decreased slightly in the final product but still maintained and maintained.
  • the final cartilage graft prepared by performing the above-described treatments was performed for biopsy with the staining agent selective to each factor to determine whether the cartilage cells causing antigenicity to the final cartilage graft existed, and how much other extracellular matrix were maintained.
  • any alive cartilage cell was not observed in the final cartilage graft and all cartilage cells in the matrix were inactivated when it was determined using a hematoxylin & eosin(H&E) stain. This was distinct from the result shown in FIG. 1 and FIG. 2 illustrating observation of the live cartilage cells.
  • MT Masson's Trichrome
  • VVG Veryhoeff-Van Gieson
  • the cartilage graft of the present invention was prepared by eliminating antigenicity, pathogen and cytotoxicity through multi-step processing treatments and inactivating all kinds of pathogens without affecting biomechanics and tissue reconstruction performance. It allows smooth accepting and supplying and low manufacturing cost because of use of mammalian cartilage not human’s.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
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  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Developmental Biology & Embryology (AREA)
  • Cell Biology (AREA)
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  • Orthopedic Medicine & Surgery (AREA)
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  • Urology & Nephrology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

La présente invention porte sur un matériau de greffe obtenu à partir de cartilage de mammifère. Le matériau de greffe selon la présente invention présente un risque significativement réduit par élimination de l'antigénicité, du caractère pathogène et de la cytotoxicité par l'intermédiaire de traitements multi-étapes et inactivation de tous les types d'agents pathogènes sans affecter la biomécanique et les performances de reconstruction tissulaire. Il permet une acceptation et une fourniture aisées et une fabrication à bas coûts en raison de l'utilisation de cartilage de mammifère ne provenant pas d'être humain.
PCT/KR2012/002616 2011-04-12 2012-04-06 Matériaux de greffe obtenus à partir de cartilage de mammifère WO2012141454A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2013554409A JP5763790B2 (ja) 2011-04-12 2012-04-06 哺乳類の軟骨組織由来の生体移植材
CN201280017628.1A CN103491988B (zh) 2011-04-12 2012-04-06 源自哺乳动物软骨的移植材料

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2011-0033653 2011-04-12
KR20110033653 2011-04-12
KR10-2011-0107351 2011-10-20
KR1020110107351A KR101269618B1 (ko) 2011-04-12 2011-10-20 포유류의 연골조직에서 유래한 생체이식재

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WO2012141454A2 true WO2012141454A2 (fr) 2012-10-18
WO2012141454A3 WO2012141454A3 (fr) 2012-12-13

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015128097A1 (fr) * 2014-02-26 2015-09-03 Tutogen Medical Gmbh Procédé pour conserver du tissu cartilagineux, et en particulier du tissu cartilagineux porcin
WO2017025053A1 (fr) * 2015-08-11 2017-02-16 Dar-Jen Hsieh Préparation de greffon de cartilage acellulaire et utilisations de celui-ci
CN106492282A (zh) * 2016-12-08 2017-03-15 大连裕辰科技发展有限公司 一种用于鼻部整形填充同种异体脱钙骨的材料及其制备方法
US11026980B1 (en) 2018-02-26 2021-06-08 Triad Life Sciences, Inc. Flowable birth tissue composition and related methods
CN113577389A (zh) * 2021-08-06 2021-11-02 中国医学科学院整形外科医院 一种来自猪耳软骨的脱细胞软骨材料及制备方法和应用
CN113599577A (zh) * 2021-08-06 2021-11-05 中国医学科学院整形外科医院 一种来自猪肋软骨的脱细胞软骨材料及制备方法和应用
US11602548B1 (en) 2018-02-26 2023-03-14 Convatec, Inc Fibrous birth tissue composition and method of use

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WO1984001894A1 (fr) * 1982-11-12 1984-05-24 American Hospital Supply Corp Sterilisation chimique de tissu biologique implantable
US5746775A (en) * 1988-04-01 1998-05-05 The Board Of Regent6S Of The University Of Michigan Method of making calcification-resistant bioprosthetic tissue
KR20050047109A (ko) * 2002-09-10 2005-05-19 코쿠리츠쥰칸키뵤우센타 소우쵸우가다이효우스루 니혼코쿠 초고정수압 인가에 의한 이식용 생체 조직의 처리방법
KR20070106696A (ko) * 2004-12-24 2007-11-05 셀스셀 피티와이 엘티디 이식가능한 바이오물질 및 그 제조 방법
KR20090088054A (ko) * 2008-02-14 2009-08-19 주식회사 바이오랜드 생체조직 이식재 및 그의 제조 방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1984001894A1 (fr) * 1982-11-12 1984-05-24 American Hospital Supply Corp Sterilisation chimique de tissu biologique implantable
US5746775A (en) * 1988-04-01 1998-05-05 The Board Of Regent6S Of The University Of Michigan Method of making calcification-resistant bioprosthetic tissue
KR20050047109A (ko) * 2002-09-10 2005-05-19 코쿠리츠쥰칸키뵤우센타 소우쵸우가다이효우스루 니혼코쿠 초고정수압 인가에 의한 이식용 생체 조직의 처리방법
KR20070106696A (ko) * 2004-12-24 2007-11-05 셀스셀 피티와이 엘티디 이식가능한 바이오물질 및 그 제조 방법
KR20090088054A (ko) * 2008-02-14 2009-08-19 주식회사 바이오랜드 생체조직 이식재 및 그의 제조 방법

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015128097A1 (fr) * 2014-02-26 2015-09-03 Tutogen Medical Gmbh Procédé pour conserver du tissu cartilagineux, et en particulier du tissu cartilagineux porcin
WO2017025053A1 (fr) * 2015-08-11 2017-02-16 Dar-Jen Hsieh Préparation de greffon de cartilage acellulaire et utilisations de celui-ci
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