US20080233203A1 - Porous orthapedic materials coated with demineralized bone matrix - Google Patents

Porous orthapedic materials coated with demineralized bone matrix Download PDF

Info

Publication number
US20080233203A1
US20080233203A1 US11688912 US68891207A US2008233203A1 US 20080233203 A1 US20080233203 A1 US 20080233203A1 US 11688912 US11688912 US 11688912 US 68891207 A US68891207 A US 68891207A US 2008233203 A1 US2008233203 A1 US 2008233203A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
demineralized bone
coating
biomaterial
extract
pores
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US11688912
Inventor
Jennifer Woodell-May
Karen Troxel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biomet Manufacturing LLC
Original Assignee
Biomet Manufacturing LLC
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

Links

Images

Classifications

    • 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
    • A61L27/3608Bone, e.g. demineralised bone matrix [DBM], bone powder
    • 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
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/042Iron or iron alloys
    • 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
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/045Cobalt or cobalt alloys
    • 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
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/047Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
    • 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
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/06Titanium or titanium alloys
    • 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
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • 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
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/005Ingredients of undetermined constitution or reaction products thereof
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/121Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L31/124Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L31/122 or A61L31/123
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/146Porous materials, e.g. foams or sponges
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • A61L2300/414Growth factors
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/02Methods for coating medical devices
    • 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/06Coatings containing a mixture of two or more compounds
    • 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
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Abstract

A biomaterial comprising a porous biocompatible structure and a demineralized bone extract coated onto into the pores of the biocompatible structure are provided. The biomaterial may also comprise a demineralized bone gelatin where the gelatin may be coated over the extract coating or mixed with the extract coating before being applied to the biocompatible structure. Methods for making the biomaterial are also provided.

Description

    BACKGROUND OF THE INVENTION
  • This invention relates generally to coated porous orthopedic materials and more specifically to porous orthopedic materials coated with demineralized bone matrix extracts comprising growth factors.
  • Prosthetic devices and bone implants can either be made of resorbable or non-resorbable materials. In particular, current bone graft materials include autografts (bone material obtained from the patient), allografts (cadaver bone and bone material typically obtained from tissue banks); xenografts (bone materials from animals), and a variety of artificial or synthetic bone substitute materials. Such bone substitute materials include materials that are biocompatible with existing bone, tendon, cartilage and ligaments, and may comprise metals, ceramics, or composite materials. Although synthetic materials can be designed to have porous structures that can accommodate de-novo bone in-growth, they are generally considered inadequate as being non-osteoinductive.
  • The prior art has extracted growth factors from demineralized bone matrix (DBM) to be used as a surface coating or a putty to induce bone growth into implant materials. Demineralized bone matrix (DBM) is a well characterized osteoinductive resorbable material containing growth factors, osteogenic proteins and collagen, which has also been extracted from DBM to be used as a gel coating for implant materials. U.S. Patent Application No. 2003/0044445 discloses a DBM soluble extract of proteins that is dried, reconstituted and then mixed with demineralized bone particles to provide a bone filling material. However, there is no teaching of applying a DBM soluble extract to a porous synthetic implant material where the extract coats within the pores.
  • Alternatively, U.S. Pat. No. 6,576,249 discloses a method for preparing a bone gel and bone putty by dissolving DBM in water, allowing it to form a gel and mixing it with non-demineralized bone particles to form putty. The '249 patent does not disclose using this material as a coating. The presence of the bone particles in the material would prohibit it from coating the pores of a porous implant material.
  • U.S. Pat. No. 6,376,573 discloses a porous ceramic implant material of coralline hydroxyapatite having a coating within the pores of the material. The coating however, is used to reinforce the implant material and not to promote bone growth. The coating therefore cannot fill the pores, but must only be on the walls of the pores. This is accomplished by adding the coating as a liquid and then catalyzing the conversion to a polymeric material in situ.
  • As can be seen, there is a need for a coating material for porous implants that promotes bone growth, allowing the integration of the implant within the patient. It would be desirable for the coating to comprise growth factors, including osteoinductive proteins to promote the bone growth.
  • SUMMARY OF THE INVENTION
  • In one aspect of the present invention there is provided a biomaterial comprising a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and may be interconnected by passageways, an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, a demineralized bone gelatin coating comprising a demineralized bone matrix gelatin, and wherein the demineralized bone extract coating and the demineralized bone gelatin coating may cover the interior walls and passageways. The demineralized bone extract coating and the demineralized bone gelatin coating may be combined into a single coating before being applied to the porous biocompatible substrate. Alternatively, the demineralized bone extract coating may be applied to the porous biocompatible substrate and then the demineralized bone gelatin coating may be applied over the demineralized bone extract coating.
  • In another aspect of the present invention, there is provided a biomaterial comprising a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways and an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways.
  • In a further aspect of the present invention, there is provided an orthopedic implant comprising a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways and wherein the pores have an average diameter of from about 200 microns to about 500 microns and an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways, wherein the bone extract coating is dried on the interior walls and passageways.
  • In yet another aspect of the present invention there is provided a method of preparing a biomaterial comprising mixing demineralized bone with an aqueous solution, the aqueous solution comprising a weak acid or guanidine hydrochloride, and wherein the mixing proceeds with constant agitation at a temperature of no greater than 50° C. for a time period of from about 8 hours to about 96 hours to prepare a demineralized bone extract; separating the demineralized bone extract from any remaining solids; diluting, removing or neutralizing the weak acid or guanidine hydrochloride in the demineralized bone extract; coating a porous biocompatible structure with the demineralized bone extract, wherein the porous biocompatible structure has a porosity comprising interconnected pores, the pores comprising interior walls and interconnected by passageways, and wherein the demineralized bone extract infiltrates the pores and coats the interior walls and passageways; and drying the applied demineralized bone extract onto the porous biocompatible structure. The method may further comprise the steps of mixing the solids separated from the extract with an aqueous saline solution to form a suspension; heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin; and mixing the demineralized bone gelatin with the demineralized bone extract before coating the biocompatible structure. Alternatively, the method may further comprise the steps of mixing the solids separated from the extract with an aqueous saline solution to form a suspension; heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin solution; applying the demineralized bone gelatin solution over the dried demineralized bone extract on the biocompatible structure, wherein the demineralized bone gelatin solution infiltrates the pores and coats the internal walls and passageways; allowing the applied demineralized bone gelatin solution to gel; and lyophilizing the biocompatible structure and the applied demineralized bone gelatin solution.
  • These and other features, aspects and advantages of the present invention will become better understood with reference to the following drawings, description and claims.
  • DETAILED DESCRIPTION OF THE INVENTION
  • The following detailed description is of the best currently contemplated modes of carrying out the invention. The description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the invention is best defined by the appended claims.
  • Broadly, the present invention provides a biomaterial comprising a porous biocompatible structure that may be coated with a demineralized bone (DBM) extract comprising growth factors that increase de novo bone growth into the porous composite material. Methods are also provided for making the biomaterial of the present invention. The biomaterial may further comprise a demineralized bone gelatin coating over the extract coating or the demineralized bone extract may be combined with the gelatin coating. The biomaterial is coated such that the pores and any connecting passageways are coated to support, but not block, bone growth into the biomaterial. The biomaterial may be in a form such as, but not limited to, granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices.
  • The biomaterial of the present invention may comprise a porous biocompatible structure where the porous biocompatible structure comprises pores interconnected by passageways. The porous biocompatible structure may be coated with an osteoinductive coating such that the coating is not only on the surface but may also coat the pores and passageways. It has been discovered that by coating the pores and the passageways, bone growth into the porous material may be scattered throughout most of the implant compared to the porous biomaterial alone or the porous biomaterial with just a gelatin coating. In contrast to the present invention, coatings of the prior art coat the outer surface of a biomaterial with a gelatin coating and are not designed to be used solely on a porous substrate. Many of the coatings of the prior art comprise demineralized bone powder which, although finely milled, prohibits the coating from completely coating the pores and passageways of a porous biomaterial and may even clog the pores. Other coatings of the prior art have been designed to strengthen porous biomaterials and are not osteoinductive.
  • In one embodiment, the biomaterial of the present invention may comprise a porous biocompatible structure which may comprise interconnected pores. The pores may comprise interior walls and may be connected by passageways. In one illustrative embodiment, the pores may have an average size from about 5 microns to 1000 microns or from about 200 microns to about 500 microns. In another illustrative embodiment, the porous biocompatible structure may be resorbable as new bone is formed or may be non-resorbable. The resorbable biocompatible structure may be, but not limited to, hydroxyapatite. The hydroxyapatite may be tricalcium phosphate such as, but not limited to, Calcigen® PSI. Alternatively, the hydroxyapatite may be a coralline hydroxyapatite such as, but not limited to, the coralline hydroxyapatite described in U.S. Pat. No. 4,976,736 (herein incorporated by reference), known under the trade name Pro Osteon™. By way of non-limiting example, the coralline hydroxyapatite may be Pro Osteon™ 200 or Pro Osteon™ 500 which may have an average pore size of 200 microns and 500 microns, respectively. In an alternate illustrative embodiment, the resorbable biocompatible structure may be, but not limited to, xenograft demineralized cancellous bone. The demineralized cancellous bone may be formed from cancellous bone from an animal such as, but not limited to, pig, cow or horse. The cancellous bone may be cleaned to remove all blood and marrow from the pores. The bone is then demineralized in hydrochloric acid or any other procedure known in the art. Following the demineralization, the bone may be washed and extracted guanidine hydrochloride. The remaining porous collagen structure that may have the architecture of cancellous bone may then be used in the present invention. In a further illustrative embodiment the porous biocompatible structure may be non-resorbable. By way of a non-limiting example, the non-resorbable biocompatible structure may comprise porous metal where the metal may be stainless steel, titanium, titanium alloy, tantalum or cobalt-chromium alloy. Examples of porous metal for use as implant material may be found in U.S. Pat. No. 6,206,924 and Publish Application Nos. 2006/0241776 and 2006/0241781, all of which are incorporated herein by reference. The porous biocompatible structure may have a form such as, but not limited to, granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices
  • The biomaterial may further comprise an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof. It will be appreciated that many growth factors may be proteins and the two categories are not mutually exclusive, one is not a subset of the other. The growth factors or proteins may be osteoinductive, helping to promote de novo growth of new bone. Non-limiting examples of growth factors may be bone morphogenic proteins, particularly BMP-2 and BMP-7, TGF-β, IGF-1, VEGF, PDGF, FGF, EGF or mixtures thereof. The aqueous demineralized bone extract coating may also comprise biologic solutions such as, but not limited to, blood, platelet rich plasma, platelet poor plasma concentrated plasma, bone marrow aspirate, concentrated bone marrow aspirate or combinations thereof.
  • In one illustrative embodiment, the aqueous demineralized bone extract may be an acid soluble demineralized bone extract. The acid soluble extract may be produced by mixing demineralized bone matrix (DBM) with a weak acid such as, but not limited to citric acid, acetic acid, lactic acid, malic acid or mixtures thereof. The mixture may be stirred or agitated from about 8 hours to about 96 hours at a temperature not greater than 50° C. At temperatures greater than 50° C. there may be inactivation of the growth factors and/or proteins. The extract may then be filtered to remove any remaining solids, the acid neutralized or removed and used to coat the porous biocompatible structure.
  • In another illustrative embodiment, the aqueous demineralized bone extract may be a guanidine hydrochloride demineralized bone extract. The guanidine hydrochloride demineralized bone extract may be produced by mixing DBM with a solution of guanidine hydrochloride where the guanidine hydrochloride may be from about 3M to about 6M. The mixture may be stirred or agitated from about 8 hours to about 96 hours at a temperature not greater than 50° C. The extract may then be filtered to remove any remaining solids, the guanidine hydrochloride neutralized or removed and used to coat the porous biocompatible structure. Although not wishing to be bound by theory, the guanidine hydrochloride demineralized bone extract may have a higher protein content than the acid soluble demineralized bone extract as it may be more likely to dissolve some of the DBM.
  • The aqueous demineralized bone extract coating may be applied to the porous biocompatible structure in a manner that allows for the coating to be delivered to the pores and passageways. For example, the coating may be applied under vacuum.
  • Alternatively, the coating may be applied by placing the material in the extract and allowing the extract to enter the pores and passageways by capillary action. Once the coating is applied to the biocompatible structure it may be dried onto the structure.
  • In another embodiment the biomaterial of the present invention may further comprise a demineralized bone gelatin coating. The demineralized bone gelatin coating may be formed from the remaining solids after the extract is filtered or it may be formed from a different demineralized bone sample. Alternatively, it may be formed from partially purified or isolated collagen. The demineralized bone or collagen may be mixed with a saline solution, water or any other biocompatible solution and heated under pressure to dissolve the demineralized bone matrix or collagen to form the demineralized bone gelatin coating. The coating may then be coated over the demineralized bone extract coating or it may be mixed with the demineralized bone extract coating and the mixture of the extract and gelatin coatings may then be applied to the biocompatible structure to give only a single coating. The demineralized gelatin coating is applied such that it coats the pores and the passageways. As with the demineralized bone extract coating, the gelatin coating, either alone or combined with the extract coating, may be applied under vacuum or it may coat the pores through capillary action. After application to the biocompatible structure, the demineralized bone gelatin coating may be dried. The demineralized bone gelatin coating may be less viscous at higher temperatures making it easier to apply to the biocompatible structure. However, care should be taken so that the demineralized bone gelatin coating is not at a temperature high enough to inactivate the growth factors and/or proteins of the demineralized bone extract coating.
  • It will be appreciated that although the embodiments describe a single coating, more than one coating of either the extract and/or the gelatin may be applied. If more than one coat is applied, the individual coats may be dried before the next coat is applied.
  • In one embodiment, the present invention provides a method of preparing a biomaterial comprising mixing DBM with an aqueous solution of a weak acid or guanidine hydrochloride with constant agitation for a set amount of time to produce an aqueous demineralized bone extract, filtering the extract solution to remove any remaining solids, neutralizing or removing the weak acid or guanidine hydrochloride and coating the porous biocompatible structure with the extract. The amount of DBM may be from about 2 g to about 10 g per 100 g of solution. The DBM may be in any form, including, but not limited to, powder, granules, fragments, slices, pellets, slices or shavings. It will be appreciated that the concentration of growth factors and/or proteins in the extract may be related to both the amount of DBM used and the form, as well as the strength of aqueous solution. The aqueous solution may comprise any biologically compatible aqueous solution, particularly those in which growth factors and proteins may be stable in. Examples of such solutions may be, but not limited to, Tris buffer, Tris buffered saline, phosphate buffer and phosphate buffered saline. In one illustrative embodiment, the solution may be a weak acid solution where the weak acid may be, but not limited to, citric acid, lactic acid, malic acid, ascorbic acid or combinations thereof. Any weak acid known in the art may be used. The concentration of the weak acid solution may be from about 2 M to about 3 M. In a second illustrative embodiment, the solution is a guanidine hydrochloride solution where the concentration of the guanidine hydrochloride solution may be from about 3 M to about 6 M.
  • The DBM may be mixed with the aqueous solution for a set amount of time with constant agitation at a temperature not greater than 50° C. The amount of time that the DBM and aqueous solution may be mixed may be from about 8 hours to about 96 hours. In one illustrative embodiment, the DBM and aqueous solution may be mixed together from about 24 hours to about 96 hours. The DBM and aqueous solution may be mixed together with constant agitation during that time. Constant agitation may be obtained by, but not limited to, stirring, shaking, ultrasound or any combination thereof as well as any other methods of agitating a mixture. The mixing may be carried out at a temperature that may be conducive to extracting growth factors and/or proteins from the DBM, but where growth factors and/or proteins may be stable. In an illustrative embodiment, the temperature may be no greater than 50° C. In another illustrative embodiment, the temperature may be room temperature.
  • After mixing for the appropriate amount of time, the resulting demineralized bone extract may be separated from any insoluble DBM remaining. This separation may occur by any number of processes such as, but not limited to, decanting, filtering or centrifuging. In one illustrative embodiment, the solution may be filtered to remove any soluble DBM remaining. The size of the sieve or filter will depend on the size of the DBM particles remaining, which may further depend on the initial form of DBM. In one illustrative embodiment, the filter may be from about 50 microns to about 300 microns. The filter may be a sieve, paper, scintered glass, woven or non-woven fabric, or any other means of filtering that is known in the art.
  • The demineralized bone extract may be diluted, neutralized or the weak acid or guanidine hydrochloride removed. Methods for doing this may be, but not limited to, titration, dialysis, liquid-liquid extraction, hollow fiber filtration, ultrafiltration, crossflow filtration or precipitation. In one illustrative embodiment aqueous solution may be neutralized to a pH of from about 6.5 to about 7.5 by titration with an appropriate counterion. Such methods are well known in the art. In another illustrative embodiment, the weak acid or guanidine hydrochloride may be removed by dialysis, hollow fiber filtration, ultrafiltration or crossflow filtration against a biologically compatible buffer, such as, but not limited to, Tris, TBS, phosphate, PBS or water, where the pH of the buffer may be from about 6.5 to about 7.5. The molecular weight cutoff of the dialysis membrane will depend on the size of the proteins and/or growth factors desired in the solution. The dialysis, hollow fiber filtration, ultrafiltration or crossflow filtration membrane may have, for example, a molecular weight cut off less than or equal to 12 Kd or from about 10 Kd to about 12 Kd. It is well known in the art how to select the molecular weight cut off of dialysis tubing to retain the desired molecules within the sample.
  • Once neutralized, a porous biocompatible structure may be coated with the demineralized bone extract. The demineralized bone extract may be applied to the biocompatible structure such that the demineralized bone extract infiltrates the pores and passageways of the biocompatible structure. In one illustrative embodiment, the demineralized bone extract may be applied to the biocompatible structure under vacuum. In another illustrative embodiment the demineralized bone extract may be applied to the biocompatible structure by dipping the structure into the extract and allowing it to infiltrate the pores and passageways by capillary action. After the demineralized bone extract has been applied to the biocompatible structure, it may be dried onto the biocompatible structure. The demineralized bone extract may be dried onto the structure by lyophilization, vacuum, heating at a temperature not greater than 50° C. or a combination thereof.
  • In another embodiment, the method of the present invention may further comprise making a demineralized bone gelatin. The demineralized bone gelatin may be coated over the demineralized bone extract or it may be mixed with the extract before coating to form a single coating. The demineralized bone gelatin may be formed by mixing DBM with an aqueous saline solution such as, but not limited to PBS, TBS or a sodium chloride solution, to form a suspension. The suspension may be treated to increased temperature and pressure such as, but not limited to, autoclaved. In one illustrative embodiment, the solution may be heated to a temperature of from about 85° C. to about 130° C. at a pressure of at least about 15 psig. The DBM may be dissolved to produce a demineralized bone gelatin. Methods for forming a demineralized bone gelatin are known in the art. The DBM may be the solids removed during the filtering step while forming the demineralized bone extract or it may be fresh DBM. Alternatively, it will be appreciated that since the demineralized bone gelatin comprises mainly collagen, collagen of any purity may be substituted for the DBM.
  • The demineralized bone gelatin may be coated over the dried demineralized bone extract coating on the biocompatible structure such that the gelatin coats the pores and passageways. Alternatively, the demineralized bone gelatin may be mixed with the demineralized bone extract prior to the extract being coated onto the biocompatible structure to form a single coating. The single coating comprising the demineralized bone extract and gelatin may then be applied to the biocompatible structure such that the pores and passageways are coated. It will be appreciated that the demineralized bone gelatin may be less viscous at higher temperatures, making it easier to apply to the biocompatible structure. If the demineralized bone gelatin is applied to the biocompatible structure in a less viscous form such as a solution, it should be allowed to gel before any other steps are performed. Care should be taken so that the demineralized bone gelatin coating is not at a temperature high enough to inactivate the growth factors and/or proteins of the demineralized bone extract coating.
  • Once applied, the demineralized bone gelatin, either alone or mixed with the demineralized bone extract, may be dried onto the biocompatible structure. The demineralized bone gelatin may be dried onto the structure by lyophilization, vacuum, heating at a temperature not greater than 50° C. or a combination thereof.
  • It should be understood, of course, that the foregoing relates to exemplary embodiments of the invention and that modifications may be made without departing from the spirit and scope of the invention as set forth in the following claims.

Claims (50)

  1. 1. A biomaterial comprising:
    a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways;
    an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof;
    a demineralized bone gelatin coating comprising a demineralized bone matrix gelatin; and
    wherein the demineralized bone extract coating and the demineralized bone gelatin coating cover the interior walls and passageways.
  2. 2. The biomaterial of claim 1 wherein the demineralized bone extract coating and the demineralized bone gelatin matrix coating are combined into a single coating material which covers the interior walls and passageways.
  3. 3. The biomaterial of claim 1 wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the demineralized bone extract coating.
  4. 4. The biomaterial of claim 1 wherein the demineralized bone extract coating and the demineralized bone gelatin coating are dried on interior walls and passageways.
  5. 5. The biomaterial of claim 1 wherein the demineralized bone extract coating is an acid soluble demineralized bone coating.
  6. 6. The biomaterial of claim 1 wherein the demineralized bone extract coating is a guanidine hydrochloride extract.
  7. 7. The biomaterial of claim 1 wherein the porous biocompatible structure comprises a porous metal, hydroxyapatite or xenograft demineralized cancellous bone.
  8. 8. The biomaterial of claim 7 wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy.
  9. 9. The biomaterial of claim 7 wherein the hydroxyapatite comprises tricalcium phosphate.
  10. 10. The biomaterial of claim 7 wherein the hydroxyapatite comprises a coralline hydroxyapatite.
  11. 11. The biomaterial of claim 1 wherein the pores have a size of from about 5 microns to about 1000 microns.
  12. 12. The biomaterial of claim 1 wherein the pores have an average diameter of from about 200 microns to about 500 microns.
  13. 13. The biomaterial of claim 1 wherein the biomaterial has a form of granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices.
  14. 14. The biomaterial of claim 1 wherein the biomaterial is used as an orthopedic implant.
  15. 15. A biomaterial comprising:
    a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways; and
    an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways.
  16. 16. The biomaterial of claim 15 wherein the demineralized bone extract coating is an acid soluble demineralized bone extract coating.
  17. 17. The biomaterial of claim 15 wherein the demineralized bone extract coating is a guanidine hydrochloride demineralized bone extract coating.
  18. 18. The biomaterial of claim 15 wherein the demineralized bone extract coating comprises a growth factor.
  19. 19. The biomaterial of claim 18 wherein the growth factor is a bone morphogenic protein, TGF-β, IGF-1, VEGF, PDGF, FGF, EGF or mixtures thereof.
  20. 20. The biomaterial of claim 15 wherein the porous biocompatible structure is metal, wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy.
  21. 21. The biomaterial of claim 15 wherein the porous biocompatible structure is xenograft demineralized cancellous bone.
  22. 22. The biomaterial of claim 15 wherein the porous biocompatible structure is hydroxyapatite, the hydroxyapatite comprising tricalcium phosphate or a coralline hydroxyapatite.
  23. 23. The biomaterial of claim 15 wherein the pores have an average diameter of from about 200 microns to about 500 microns.
  24. 24. The biomaterial of claim 15 further comprising a demineralized bone gelatin coating.
  25. 25. The biomaterial of claim 24 wherein the demineralized bone gelatin coating and the demineralized bone extract are combined into a single coating material which covers the interior walls and passageways.
  26. 26. The biomaterial of claim 24 wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the acid soluble demineralized bone coating.
  27. 27. The biomaterial of claim 15 wherein the biomaterial has a form of granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices
  28. 28. An orthopedic implant comprising:
    a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways and wherein the pores have an average diameter of from about 200 microns to about 500 microns; and
    an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways, wherein the bone extract coating is dried on the interior walls and passageways.
  29. 29. The orthopedic implant of claim 28 wherein the porous biocompatible structure is coralline hydroxyapatite.
  30. 30. The orthopedic implant of claim 28 wherein the demineralized bone extract is an acid soluble extract.
  31. 31. The orthopedic implant of claim 28 wherein the demineralized bone extract is a guanidine hydrochloride extract.
  32. 32. The biomaterial of claim 28 further comprising a demineralized bone gelatin coating, wherein the demineralized bone gelatin coating and the demineralized bone extract are combined into a single coating material which covers the interior walls and passageways.
  33. 33. The biomaterial of claim 28 further comprising a demineralized bone gelatin coating, wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the acid soluble demineralized bone coating.
  34. 34. A method of preparing a biomaterial comprising:
    a. mixing demineralized bone with an aqueous solution, the aqueous solution comprising a weak acid or guanidine hydrochloride, and wherein the mixing proceeds with constant agitation at a temperature of no greater than 50° C. for a time period of from about 8 hours to about 96 hours to prepare a demineralized bone extract;
    b. separating the demineralized bone extract from any remaining solids;
    c. diluting, removing or neutralizing the weak acid or guanidine hydrochloride in the demineralized bone extract;
    d. coating a porous biocompatible structure with the demineralized bone extract, wherein the porous biocompatible structure has a porosity comprising interconnected pores, the pores comprising interior walls and interconnected by passageways, and wherein the demineralized bone extract infiltrates the pores and coats the interior walls and passageways; and
    e. drying the applied demineralized bone extract onto the porous biocompatible structure.
  35. 35. The method of claim 34 wherein the aqueous solution comprises a weak acid, wherein the weak acid is citric acid, lactic acid, malic acid, acetic acid or a combination thereof.
  36. 36. The method of claim 34 wherein the aqueous solution comprises a weak acid, the weak acid having a concentration of from about 2 M to about 3 M.
  37. 37. The method of claim 34 wherein the weak acid or the guanidine hydrochloride is neutralized by adjusting the pH to from about 6.5 to about 7.5 by titrating with a counterion.
  38. 38. The method of claim 34 wherein the aqueous solution comprises guanidine hydrochloride, the guanidine hydrochloride having a concentration of from about 3 M to about 6 M.
  39. 39. The method of claim 34 wherein the weak acid or the guanidine hydrochloride is removed from the demineralized bone extract by dialysis, ultrafiltration, hollow fiber filtration or crossflow filtration.
  40. 40. The method of claim 34 wherein an amount of demineralized bone mixed with the aqueous solution is from about 4 grams to about 7 grams of demineralized bone per about 100 grams of aqueous solution.
  41. 42. The method of claim 34 wherein the mixing proceeds for a time period of from about 24 hrs to about 96 hrs.
  42. 43. The method of claim 34 wherein the demineralized bone extract infiltrates the pores under vacuum.
  43. 44. The method of claim 34 wherein the demineralized bone extract infiltrates the pores by capillary action.
  44. 45. The method of claim 34 wherein the porous biocompatible material comprises a metal, hydroxyapatite or xenograft demineralized cancellous bone.
  45. 46. The method of claim 45 wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy.
  46. 47. The method of claim 45 wherein the hydroxyapatite is a coralline hydroxyapatite.
  47. 48. The method of claim 34 wherein the pores have an average diameter of from about 200 microns to about 500 microns.
  48. 49. The method of claim 34 wherein the demineralized bone extract is mixed with a collagen gel before coating the porous biocompatible material and wherein the porous biocompatible material is coated with the combined demineralized bone extract and collagen gel.
  49. 50. The method of claim 34 further comprising:
    f. mixing the solids separated out in step b with an aqueous saline solution to form a suspension;
    g. heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin; and
    h. mixing the demineralized bone gelatin with the demineralized bone extract before coating the biocompatible structure.
  50. 51. The method of claim 34 further comprising the steps of:
    f. mixing the solids separated out in step b with an aqueous saline solution to form a suspension;
    g. heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin solution;
    h. applying the demineralized bone gelatin solution over the dried demineralized bone extract on the biocompatible structure, wherein the demineralized bone gelatin solution infiltrates the pores and coats the interior walls and passageways;
    i. allowing the applied demineralized bone gelatin solution to gel; and
    j. lyophilizing the biocompatible structure and the applied demineralized bone gelatin solution.
US11688912 2007-03-21 2007-03-21 Porous orthapedic materials coated with demineralized bone matrix Abandoned US20080233203A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11688912 US20080233203A1 (en) 2007-03-21 2007-03-21 Porous orthapedic materials coated with demineralized bone matrix

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US11688912 US20080233203A1 (en) 2007-03-21 2007-03-21 Porous orthapedic materials coated with demineralized bone matrix
PCT/US2008/057707 WO2008116096A3 (en) 2007-03-21 2008-03-20 Porous orthapedic materials coated with demineralized bone matrix
EP20080732598 EP2139536A2 (en) 2007-03-21 2008-03-20 Porous orthapedic materials coated with demineralized bone matrix
US14636487 US9849214B2 (en) 2007-03-21 2015-03-03 Porous orthopedic materials coated with demineralized bone matrix
US15841685 US20180104382A1 (en) 2007-03-21 2017-12-14 Porous orthopedic materials coated with demineralized bone matrix

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14636487 Continuation US9849214B2 (en) 2007-03-21 2015-03-03 Porous orthopedic materials coated with demineralized bone matrix

Publications (1)

Publication Number Publication Date
US20080233203A1 true true US20080233203A1 (en) 2008-09-25

Family

ID=39523709

Family Applications (3)

Application Number Title Priority Date Filing Date
US11688912 Abandoned US20080233203A1 (en) 2007-03-21 2007-03-21 Porous orthapedic materials coated with demineralized bone matrix
US14636487 Active 2027-05-09 US9849214B2 (en) 2007-03-21 2015-03-03 Porous orthopedic materials coated with demineralized bone matrix
US15841685 Pending US20180104382A1 (en) 2007-03-21 2017-12-14 Porous orthopedic materials coated with demineralized bone matrix

Family Applications After (2)

Application Number Title Priority Date Filing Date
US14636487 Active 2027-05-09 US9849214B2 (en) 2007-03-21 2015-03-03 Porous orthopedic materials coated with demineralized bone matrix
US15841685 Pending US20180104382A1 (en) 2007-03-21 2017-12-14 Porous orthopedic materials coated with demineralized bone matrix

Country Status (3)

Country Link
US (3) US20080233203A1 (en)
EP (1) EP2139536A2 (en)
WO (1) WO2008116096A3 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090227704A1 (en) * 2008-03-05 2009-09-10 Karen Troxel Cohesive and compression resistant demineralized bone carrier matrix
US8497236B2 (en) 1998-02-13 2013-07-30 Zimmer Orthobiologics, Inc. Implantable putty material
US8613938B2 (en) 2010-11-15 2013-12-24 Zimmer Orthobiologics, Inc. Bone void fillers
US8690874B2 (en) 2000-12-22 2014-04-08 Zimmer Orthobiologics, Inc. Composition and process for bone growth and repair
US8742072B2 (en) 2006-12-21 2014-06-03 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US20150005815A1 (en) * 2009-11-24 2015-01-01 Covidien Lp Wound plugs
US10130736B1 (en) 2010-05-14 2018-11-20 Musculoskeletal Transplant Foundation Tissue-derived tissuegenic implants, and methods of fabricating and using same

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2349365A4 (en) * 2008-11-04 2013-01-23 Perth Bone & Tissue Bank Carrier material for bone forming cells
US9192695B2 (en) 2008-11-20 2015-11-24 Allosource Allografts combined with tissue derived stem cells for bone healing
US8920511B2 (en) 2011-11-17 2014-12-30 Allosource Multi-piece machine graft systems and methods
WO2014138612A1 (en) 2013-03-07 2014-09-12 Allosource Consistent calcium content bone allograft systems and methods
KR20150132152A (en) 2013-03-15 2015-11-25 알로소스 Perforated osteochondral allograft compositions
WO2015175983A1 (en) 2014-05-16 2015-11-19 Allosource Composite bone constructs and methods

Citations (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294753A (en) * 1980-08-04 1981-10-13 The Regents Of The University Of California Bone morphogenetic protein process
US4976736A (en) * 1989-04-28 1990-12-11 Interpore International Coated biomaterials and methods for making same
US5073373A (en) * 1989-09-21 1991-12-17 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5284655A (en) * 1989-09-21 1994-02-08 Osteotech, Inc. Swollen demineralized bone particles, flowable osteogenic composition containing same and use of the composition in the repair of osseous defects
US6118043A (en) * 1991-06-26 2000-09-12 Merck Patent Gesellschaft Mit Beschrankter Haftung Bone replacement material with FGF
US6206924B1 (en) * 1999-10-20 2001-03-27 Interpore Cross Internat Three-dimensional geometric bio-compatible porous engineered structure for use as a bone mass replacement or fusion augmentation device
US6261586B1 (en) * 1997-06-11 2001-07-17 Sdgi Holdings, Inc. Bone graft composites and spacers
US6376573B1 (en) * 1994-12-21 2002-04-23 Interpore International Porous biomaterials and methods for their manufacture
US6451059B1 (en) * 1999-11-12 2002-09-17 Ethicon, Inc. Viscous suspension spinning process for producing resorbable ceramic fibers and scaffolds
US20030009235A1 (en) * 2000-07-19 2003-01-09 Albert Manrique Osteoimplant and method of making same
US6527810B2 (en) * 1997-10-01 2003-03-04 Wright Medical Technology, Inc. Bone substitutes
US20030044445A1 (en) * 2001-08-30 2003-03-06 Kay John F. Tissue repair compositions and methods for their manufacture and use
US6551995B1 (en) * 1988-04-08 2003-04-22 Stryker Corporation Osteogenic devices
US6565884B2 (en) * 2001-09-10 2003-05-20 Interpore Cross International Bone graft material incorporating demineralized bone matrix and lipids
US6576089B1 (en) * 1999-03-26 2003-06-10 Kao Corporation Paper making mold for pulp mold molding production and method and device for producing pulp mold molding
US6576249B1 (en) * 2000-11-13 2003-06-10 El Gendler Bone putty and method
US6613089B1 (en) * 2000-10-25 2003-09-02 Sdgi Holdings, Inc. Laterally expanding intervertebral fusion device
US6692790B2 (en) * 2000-02-04 2004-02-17 Chienna B.V. Proteinaceous coating
US20040265385A1 (en) * 2001-04-12 2004-12-30 Therics, Inc. Porous biostructure partially occupied by interpenetrant and method for making same
US20050142164A1 (en) * 1996-02-29 2005-06-30 Bioactive Bone Substitutes Oy, Ab Osteogenic device and a method for preparing the device
US20050175657A1 (en) * 2003-11-10 2005-08-11 Angiotech International Ag Medical implants and fibrosis-inducing agents
US20050201987A1 (en) * 2004-03-09 2005-09-15 Inion Ltd. Bone grafting material, method and implant
US6989033B1 (en) * 1992-09-17 2006-01-24 Karlheinz Schmidt Implant for recreating verterbrae and tubular bones
US20060241781A1 (en) * 2005-04-21 2006-10-26 Biomet Manufacturing Corp. Method and apparatus for use of porous implants
US20060241776A1 (en) * 2005-04-21 2006-10-26 Biomet Manufacturing Corp. Method and apparatus for use of porous implants
US20060271201A1 (en) * 2005-05-25 2006-11-30 Biomet Manufacturing Corp. Porous ceramic structure containing biologics

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7045141B2 (en) * 1998-02-27 2006-05-16 Musculoskeletal Transplant Foundation Allograft bone composition having a gelatin binder

Patent Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4294753A (en) * 1980-08-04 1981-10-13 The Regents Of The University Of California Bone morphogenetic protein process
US6551995B1 (en) * 1988-04-08 2003-04-22 Stryker Corporation Osteogenic devices
US4976736A (en) * 1989-04-28 1990-12-11 Interpore International Coated biomaterials and methods for making same
US5284655A (en) * 1989-09-21 1994-02-08 Osteotech, Inc. Swollen demineralized bone particles, flowable osteogenic composition containing same and use of the composition in the repair of osseous defects
US5290558A (en) * 1989-09-21 1994-03-01 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5073373A (en) * 1989-09-21 1991-12-17 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US6118043A (en) * 1991-06-26 2000-09-12 Merck Patent Gesellschaft Mit Beschrankter Haftung Bone replacement material with FGF
US6989033B1 (en) * 1992-09-17 2006-01-24 Karlheinz Schmidt Implant for recreating verterbrae and tubular bones
US6376573B1 (en) * 1994-12-21 2002-04-23 Interpore International Porous biomaterials and methods for their manufacture
US20050142164A1 (en) * 1996-02-29 2005-06-30 Bioactive Bone Substitutes Oy, Ab Osteogenic device and a method for preparing the device
US6261586B1 (en) * 1997-06-11 2001-07-17 Sdgi Holdings, Inc. Bone graft composites and spacers
US6527810B2 (en) * 1997-10-01 2003-03-04 Wright Medical Technology, Inc. Bone substitutes
US6576089B1 (en) * 1999-03-26 2003-06-10 Kao Corporation Paper making mold for pulp mold molding production and method and device for producing pulp mold molding
US6206924B1 (en) * 1999-10-20 2001-03-27 Interpore Cross Internat Three-dimensional geometric bio-compatible porous engineered structure for use as a bone mass replacement or fusion augmentation device
US6451059B1 (en) * 1999-11-12 2002-09-17 Ethicon, Inc. Viscous suspension spinning process for producing resorbable ceramic fibers and scaffolds
US6692790B2 (en) * 2000-02-04 2004-02-17 Chienna B.V. Proteinaceous coating
US20030009235A1 (en) * 2000-07-19 2003-01-09 Albert Manrique Osteoimplant and method of making same
US6613089B1 (en) * 2000-10-25 2003-09-02 Sdgi Holdings, Inc. Laterally expanding intervertebral fusion device
US6576249B1 (en) * 2000-11-13 2003-06-10 El Gendler Bone putty and method
US20040265385A1 (en) * 2001-04-12 2004-12-30 Therics, Inc. Porous biostructure partially occupied by interpenetrant and method for making same
US20030044445A1 (en) * 2001-08-30 2003-03-06 Kay John F. Tissue repair compositions and methods for their manufacture and use
US6565884B2 (en) * 2001-09-10 2003-05-20 Interpore Cross International Bone graft material incorporating demineralized bone matrix and lipids
US20050175657A1 (en) * 2003-11-10 2005-08-11 Angiotech International Ag Medical implants and fibrosis-inducing agents
US20050201987A1 (en) * 2004-03-09 2005-09-15 Inion Ltd. Bone grafting material, method and implant
US20060241781A1 (en) * 2005-04-21 2006-10-26 Biomet Manufacturing Corp. Method and apparatus for use of porous implants
US20060241776A1 (en) * 2005-04-21 2006-10-26 Biomet Manufacturing Corp. Method and apparatus for use of porous implants
US20060271201A1 (en) * 2005-05-25 2006-11-30 Biomet Manufacturing Corp. Porous ceramic structure containing biologics

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8497236B2 (en) 1998-02-13 2013-07-30 Zimmer Orthobiologics, Inc. Implantable putty material
US8690874B2 (en) 2000-12-22 2014-04-08 Zimmer Orthobiologics, Inc. Composition and process for bone growth and repair
US8742072B2 (en) 2006-12-21 2014-06-03 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US8293813B2 (en) * 2008-03-05 2012-10-23 Biomet Manufacturing Corporation Cohesive and compression resistant demineralized bone carrier matrix
US20090227704A1 (en) * 2008-03-05 2009-09-10 Karen Troxel Cohesive and compression resistant demineralized bone carrier matrix
US20150005815A1 (en) * 2009-11-24 2015-01-01 Covidien Lp Wound plugs
US9439636B2 (en) * 2009-11-24 2016-09-13 Covidien Lp Wound plugs
US10130736B1 (en) 2010-05-14 2018-11-20 Musculoskeletal Transplant Foundation Tissue-derived tissuegenic implants, and methods of fabricating and using same
US8613938B2 (en) 2010-11-15 2013-12-24 Zimmer Orthobiologics, Inc. Bone void fillers
WO2014024171A1 (en) 2012-08-10 2014-02-13 Akimedix S.R.L. Process for preparation of a biocompatible coating for bone grafts as well as coating and implant obtained therewith

Also Published As

Publication number Publication date Type
US20180104382A1 (en) 2018-04-19 application
WO2008116096A3 (en) 2009-11-26 application
US9849214B2 (en) 2017-12-26 grant
EP2139536A2 (en) 2010-01-06 application
WO2008116096A2 (en) 2008-09-25 application
US20150174295A1 (en) 2015-06-25 application

Similar Documents

Publication Publication Date Title
Hofmann et al. Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds
Gleeson et al. Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration
US7189263B2 (en) Biocompatible bone graft material
Rocha et al. Biocompatibility of anionic collagen matrix as scaffold for bone healing
US6723131B2 (en) Composite bone marrow graft material with method and kit
Mizuno et al. The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma
US6478825B1 (en) Implant, method of making same and use of the implant for the treatment of bone defects
US5162114A (en) Bone collagen matrix for xenogenic implants
US20080044449A1 (en) Medical implant sheets useful for tissue regeneration
US5405390A (en) Osteogenic composition and implant containing same
US4430760A (en) Nonstress-bearing implantable bone prosthesis
US4975526A (en) Bone collagen matrix for zenogenic implants
US20020082697A1 (en) Implantable osteogenic material
Dai et al. Repairing of goat tibial bone defects with BMP-2 gene–modified tissue-engineered bone
US6432436B1 (en) Partially demineralized cortical bone constructs
Oest et al. Quantitative assessment of scaffold and growth factor‐mediated repair of critically sized bone defects
US20070166348A1 (en) Keratin bioceramic compositions
US6294041B1 (en) Method for an osteoimplant manufacture
US20030065392A1 (en) Methods for purifying insoluble bone gelatin
Wang et al. Characterization of matrix-induced osteogenesis in rat calvarial bone defects: II. Origins of bone-forming cells
US20030036800A1 (en) Composite bone material implant and method
Fleming et al. Bone cells and matrices in orthopedic tissue engineering
US8202539B2 (en) Demineralized bone matrix compositions and methods
US20070142916A1 (en) Bone graft composition, method and implant
den Boer et al. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow

Legal Events

Date Code Title Description
AS Assignment

Owner name: BIOMET MANUFACTURING CORPORATION, INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WOODELL-MAY, JENNIFER;TROXEL, KAREN;REEL/FRAME:019310/0163

Effective date: 20070316

AS Assignment

Owner name: BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT FOR

Free format text: SECURITY AGREEMENT;ASSIGNORS:LVB ACQUISITION, INC.;BIOMET, INC.;REEL/FRAME:020362/0001

Effective date: 20070925

AS Assignment

Owner name: BIOMET MANUFACTURING, LLC, INDIANA

Free format text: CHANGE OF NAME;ASSIGNOR:BIOMET MANUFACTURING CORPORATION;REEL/FRAME:030837/0737

Effective date: 20130603

AS Assignment

Owner name: BIOMET, INC., INDIANA

Free format text: RELEASE OF SECURITY INTEREST IN PATENTS RECORDED AT REEL 020362/ FRAME 0001;ASSIGNOR:BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT;REEL/FRAME:037155/0133

Effective date: 20150624

Owner name: LVB ACQUISITION, INC., INDIANA

Free format text: RELEASE OF SECURITY INTEREST IN PATENTS RECORDED AT REEL 020362/ FRAME 0001;ASSIGNOR:BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT;REEL/FRAME:037155/0133

Effective date: 20150624