WO2004108178A1 - Bone graft substitute composition - Google Patents
Bone graft substitute composition Download PDFInfo
- Publication number
- WO2004108178A1 WO2004108178A1 PCT/US2004/015957 US2004015957W WO2004108178A1 WO 2004108178 A1 WO2004108178 A1 WO 2004108178A1 US 2004015957 W US2004015957 W US 2004015957W WO 2004108178 A1 WO2004108178 A1 WO 2004108178A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- parts
- calcium sulfate
- mixture
- hernihydrate
- kit
- Prior art date
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Classifications
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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
-
- 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
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
-
- 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
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- 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
- A61L27/02—Inorganic materials
- A61L27/10—Ceramics or glasses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
-
- 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
- A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/3645—Connective tissue
- A61L27/365—Bones
-
- 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
- A61L27/3695—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 function or physical properties of the final product, where no specific conditions are defined to achieve this
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
-
- 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
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- the invention relates to bone graft substitute compositions.
- compositions containing calcium sulfate can be used as filler for voids and/or defects defined by bone, h some embodiments, the compositions can promote bone growth.
- the invention relates to bone graft substitute compositions.
- the invention features a method of making a composition. The method includes contacting a mixing solution with a first mixture having calcium sulfate hernihydrate and a plasticizing material to form a second mixture; and after waiting a predetermined time, contacting dernineralized bone with the second mixture to form the composition.
- the invention features a kit, including a first mixture having calcium sulfate hernihydrate and a plasticizing substance, a second mixture having dernineralized bone, the second mixture being unblended with the first mixture, and a mixing solution unblended with the first and second mixtures.
- the kit can include instructions for making a bone graft composition as described herein.
- the first mixture can further include a first material capable of accelerating formation of calcium sulfate dihydrate from the calcium sulfate hernihydrate, such as calcium sulfate dihydrate coated with sucrose.
- a first material capable of accelerating formation of calcium sulfate dihydrate from the calcium sulfate hernihydrate such as calcium sulfate dihydrate coated with sucrose.
- Other aspects, features, and advantages of the invention will be apparent from the description of the preferred embodiments thereof and from the claims.
- DETAILED DESCRIPTION Bone graft substitute compositions including surgical-grade calcium sulfate hernihydrate (CaSO 4 -1 2H 2 O); dernineralized bone matrix; a material that accelerates hardening of the composition ("an accelerant"); a plasticizing material; and a mixing solution are described in Applicants' co-pending US Serial Number 10/179,533.
- bone graft compositions including surgical-grade calcium sulfate hernihydrate (CaSO -1 /2H O); dernineralized bone matrix; a plasticizing material; and a mixing solution are also described in Applicants' co-pending US Serial Number 10/060,697 (and other members of that family). These compositions are prepared by mixing all the dry materials together simultaneously, and then combining the dry materials with the mixing solution.
- the order and timing involves first forming a first mixture including the calcium sulfate, the plasticizing material, and the optional accelerant in a container.
- the mixing solution is then added to the container.
- the first mixture and the solution are mixed until blended, e.g., for about thirty seconds, and allowed to sit, e.g., for about another thirty seconds.
- the blend of the first mixture and mixing solution can be mixed the entire time or only a portion of the time (e.g., mixing and sitting).
- the dernineralized bone is then added to the blend and mixed thoroughly to form the composition.
- the composition can be delivered to a target site (e.g., a void or a defect) by injecting the composition through a syringe, and/or by forming (e.g., molding) a paste or a putty of the composition and applying the composition by hand (e.g., using fingers).
- a target site e.g., a void or a defect
- the composition can harden ex vivo or in vivo, e.g., to a hardness sufficient to support orthopedic hardware.
- calcium sulfate hernihydrate is converted, e.g., changes crystalline form, into calcium sulfate dihydrate (CaSO 4 -2H 2 O), which hardens the composition.
- Calcium sulfate dihydrate is capable of being sorbed by the body.
- the method described above of making the composition allows the calcium sulfate hernihydrate to begin converting to calcium sulfate dihydrate before other ingredients of the composition, such as proteins from the dernineralized bone, interfere (e.g., stop) the conversion, hi any event, beneficial results have been found by waiting a predetermined period of time before adding the dernineralized bone to the second mixture.
- This method is different from, for example, U.S. Pat. No. 5,385,887 to Yim, in which calcium sulfate is added directly to a blood-BMP mixture.
- the composition includes 100 parts of calcium sulfate, e.g., calcium sulfate hernihydrate.
- calcium sulfate hernihydrate Methods of making a calcium sulfate hernihydrate are described in U.S. Patent Nos. 5,614,206, 5,807,567, and 6,030,636, each of which is hereby incorporated by reference in its entirety.
- the dernineralized bone matrix is believed to enhance bone growth.
- the dernineralized bone matrix is freeze-dried to less than about 6% moisture.
- the dernineralized bone matrix can have a particle size of about 125-850 microns, e.g., about 125-710 microns.
- the particle size can be greater than or equal to about 125, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, or 800 microns; and/or less than or equal to about 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, or 150 microns.
- the calcium content in the dernineralized bone matrix can be about less than eight (8) percent.
- Dernineralized bone matrix is available, e.g., from Allosource (Denver, CO) or DCI (Nashville, TN).
- the composition includes between about 10 and about 30 parts of dernineralized bone matrix, such as between about 15 and about 25 parts, or between about 19 and about 21 parts, or about 20 parts.
- the composition may include greater than or equal to about 10, 12, 14, 16, 18, 20, 22, 24, 26, or 28 parts of dernineralized bone matrix; and/or less than or equal to about 30, 28, 26, 24, 22, 20, 18, 16, 14, or 12 parts of dernineralized bone matrix.
- the accelerant is believed to enhance, e.g., accelerate, the conversion of calcium sulfate hernihydrate to calcium sulfate dihydrate.
- particles of the accelerant act as crystallization nucleation sites for the conversion of calcium sulfate hernihydrate to calcium sulfate dihydrate.
- accelerants include calcium sulfate dihydrate, potassium sulfate, or sodium sulfate.
- Other examples include ionic salts.
- a preferred accelerant is calcium sulfate dihydrate crystals (available from U.S. Gypsum) coated with sucrose (available from VWR Scientific Products). A process of stabilizing the dihydrate crystals by coating with sucrose is described in U.S. Patent No. 3,573, 947, hereby incorporated by reference in its entirety.
- the composition includes between about 0.5 and about 5 parts of the accelerant, such as about 4.8 parts, or between about 1 and about 4 parts, or between about 2.5 and about 3.5 parts, or about 3 parts.
- the composition may include greater than or equal to about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, or 4.5 parts of the accelerant; and/or less than or equal to about 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, or 1 parts of the accelerant. Mixtures of two or more accelerants can be used.
- the plasticizing material is believed to provide the bone graft substitute composition with a consistency that helps the composition to form into a paste or putty, or to flow, e.g., to be injectable.
- plasticizing materials include cellulose derivatives, such as sodium carboxymethylcellulose, methylcellulose (MC), hydroxymethylcellulose, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), ethylcellulose (EC), hydroxyethylcellulose or cellulose acetate butyrate.
- Other examples of plasticizing material include high molecular weight alcohols including glycerol and vinyl alcohols, stearic acid, and hyaluronic acid.
- the composition includes between about 0.5 and about 5 parts of the plasticizing material, such as between about 1 and about 3 parts, or between about 1.5 and about 2.5 parts, or about 2 parts.
- the composition may include greater than or equal to about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, or 4.5 parts of the plasticizing material; and/or less than or equal to about 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, or 1 parts of the plasticizing material.
- Mixtures of two or more plasticizing materials can be used.
- the mixing solution is generally selected to provide the composition with a desired consistency and hardening time.
- Examples of a mixing solution include water, e.g., sterile water, solutions containing inorganic salts, or cationic surface active agents including sodium chloride, saline, e.g., phosphate buffered saline, potassium chloride, sodium sulfate, potassium sulfate, EDTA, ammonium sulfate, ammonium acetate, and sodium acetate.
- a specific example of a mixing solution is 0.9% NaCl saline solution (available from Baxter).
- the concentration of mixing solution in the substitute composition varies and can be a function of, for example, the source (e.g., tissue bank) of the dernineralized bone matrix, and/or the desired consistency of the composition.
- the amount of mixing solution added to the mixture of powders can affect the time the composition takes to set, i.e., the set time. Increasing the amount of mixing solution can increase the set time, and decreasing the amount of mixing solution added to the mixture of powders can reduce the set time. For example, for a putty comprising HPMC, 2.6 grams of water provided a set time of about 10-15 minutes, while 4.0 grams of water provided a set time of about 60 minutes.
- the composition for 100 parts of calcium sulfate (e.g., (CaSOA J ⁇ O), the composition includes between about 40 and about 60 parts of the mixing solution, such as between about 45 and about 55 parts, or between about 49 and about 51 parts, or about 50 parts.
- the composition may include greater than or equal to about 40, 45, 50, or 55 parts of the mixing solution; and/or less than or equal to about 60, 55, 50, or 45 parts of the mixing solution. Mixtures of two or more mixing solutions can be used.
- the mixing solution can further include one or more additives such as, for example, bone marrow aspirate, platelet concentrate, blood, pharmaceutical additives in solution, or combinations of these materials.
- additives include medicaments or pesticides.
- medicaments are antibiotics, chemotherapeutic agents, growth factors, and analgesics.
- antibiotics are tetracycline hydrochlori.de, vancomycin, cephalosporins, and aminoglycocides such as tobramycin and gentamicin.
- chemotherapeutic agents are cis-platinum, ifosfamide, ethotrexate, and doxorubicin hydrochloride (Adriamycin®).
- growth factors are transforming growth factor beta (TGF-Beta), bone morphogenic protein (BMP), basic fibroblast growth factor, platelet-derived growth factor, and other polypeptide growth factors.
- analgesics are anesthetics such as lidocaine hydrochloride (Xylocaine ⁇ ), bipivacaine hydrochloride (Marcaine®), and non-steroidal anti-inflammatory drugs such as ketorolac tromethamine (Toradol®).
- Certain mixing solution and/or additives can affect, e.g., delay, the hardening properties of the composition.
- the additive(s) can be added to the composition after the dernineralized bone matrix has been added.
- the composition as formed can be a conforming material having a paste-like or putty-like consistency, e.g., like Plaster of Paris, which can be applied digitally.
- the composition can be injected into a target site, for example, to fill into cracks or voids, some embodiments, the composition is capable of setting to a hardness, e.g., about 4.3 MPa, in about 5-15 minutes, e.g., greater than 5, 7, 9, 11, or 13 minutes, and/or less than 15, 13, 11, 9, or 7 minutes.
- the hardened composition can be used for intra-operative support of hardware, such as orthopedic hardware, e.g., bone plates, distal radius hardware, and hardware used for tibial plateau fractures.
- hardware such as orthopedic hardware, e.g., bone plates, distal radius hardware, and hardware used for tibial plateau fractures.
- SGCSH surgical-grade calcium sulfate hernihydrate
- HPMC hydroxypropylmethylcellulose
- the composition further includes a bioactive agent.
- bioactive agents include growth factors, hyaluronic acid, bone morphogenic proteins, bone autograft, bone marrow, etc.
- the composition may include sodium bicarbonate.
- the composition may include 0.1-2% sodium bicarbonate by weight to provide a porous structure in the resultant composition.
- the bone graft substitute composition may include one or more additive such as an antiviral agent, an antimicrobial agent, an antibiotic agent, an amino acid, a peptide, a vitamin, an inorganic element, a protein synthesis co-factor, a hormone, an endocrine tissue, a synthesizer, an enzyme, a polymer cell scaffolding agent with parenchymal cells, an angiogenic drug, a collagen lattice, an antigenic agent, a cytoskeletal agent, mesenchymal stem cells, a bone digester, an antitumor agent, a cellular attractant, fibronectin, a growth hormone, a cellular attachment agent, an immunosuppressant, a nucleic acid, a surface active agent, synthetically derived or naturally derived chips of minerals such as calcium phosphate, e.g., hydroxyapatite or tricalcium phosphate, or calcium carbonate, a penetration enhancer, allografts, e.g.,
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US10/448,885 | 2003-05-30 | ||
US10/448,885 US7291179B2 (en) | 2002-06-24 | 2003-05-30 | Bone graft substitute composition |
Publications (1)
Publication Number | Publication Date |
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WO2004108178A1 true WO2004108178A1 (en) | 2004-12-16 |
Family
ID=33510337
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2004/015957 WO2004108178A1 (en) | 2003-05-30 | 2004-05-21 | Bone graft substitute composition |
Country Status (2)
Country | Link |
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US (2) | US7291179B2 (en) |
WO (1) | WO2004108178A1 (en) |
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US7067123B2 (en) | 2003-04-29 | 2006-06-27 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
US20050222687A1 (en) * | 2004-04-02 | 2005-10-06 | Gordana Vunjak-Novakovic | Cartilage implant assembly and method for implantation |
US20090291112A1 (en) * | 2003-05-16 | 2009-11-26 | Truncale Katherine G | Allograft osteochondral plug combined with cartilage particle mixture |
US7901457B2 (en) * | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
WO2005102281A2 (en) * | 2004-04-16 | 2005-11-03 | University Of Massachusetts | Porous calcium phosphate networks for synthetic bone material |
US20090319045A1 (en) * | 2004-10-12 | 2009-12-24 | Truncale Katherine G | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
US20080220044A1 (en) * | 2007-03-06 | 2008-09-11 | Semler Eric J | Cancellous construct with support ring for repair of osteochondral defects |
US7837740B2 (en) | 2007-01-24 | 2010-11-23 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
WO2007035778A2 (en) | 2005-09-19 | 2007-03-29 | Histogenics Corporation | Cell-support matrix and a method for preparation thereof |
US7838022B2 (en) * | 2006-05-01 | 2010-11-23 | Warsaw Orthopedic, Inc | Malleable implants containing demineralized bone matrix |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
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US20140322292A1 (en) | 2010-12-10 | 2014-10-30 | Rutgers, The State University Of New Jersey | Insulin-mimetics as therapeutic adjuncts for bone regeneration |
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US9931348B2 (en) | 2011-07-06 | 2018-04-03 | Rutgers, The State University Of New Jersey | Vanadium compounds as therapeutic adjuncts for cartilage injury and repair |
JP2015534850A (en) * | 2012-10-25 | 2015-12-07 | ラトガース,ザ ステート ユニバーシティ オブ ニュー ジャージー | Insulin-pseudotopical adjuvant to promote spinal fixation |
TWI651103B (en) | 2013-12-13 | 2019-02-21 | 萊特醫技股份有限公司 | Multiphase bone graft replacement material |
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US10531957B2 (en) | 2015-05-21 | 2020-01-14 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
TW201801709A (en) * | 2016-07-12 | 2018-01-16 | 三鼎生物科技股份有限公司 | Bone repairing material and method for producing thereof |
CN108187133B (en) * | 2018-01-09 | 2020-12-29 | 楼毅 | Preparation method of medical composite alpha-calcium sulfate hemihydrate artificial bone material |
KR102196235B1 (en) * | 2019-08-14 | 2020-12-29 | (주)메드파크 | Composition for bone defect and preparation method of the same and kit for the same |
KR102196242B1 (en) * | 2020-03-31 | 2020-12-30 | (주)메드파크 | Bone graft composition and manufacturing method thereof |
KR102196254B1 (en) * | 2020-03-31 | 2020-12-30 | (주)메드파크 | Bone graft composition and manufacturing method thereof |
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US7658768B2 (en) | 2010-02-09 |
US20030235621A1 (en) | 2003-12-25 |
US7291179B2 (en) | 2007-11-06 |
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