WO2002047732A2 - Method of making demineralized bone particles - Google Patents
Method of making demineralized bone particles Download PDFInfo
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- WO2002047732A2 WO2002047732A2 PCT/US2001/048384 US0148384W WO0247732A2 WO 2002047732 A2 WO2002047732 A2 WO 2002047732A2 US 0148384 W US0148384 W US 0148384W WO 0247732 A2 WO0247732 A2 WO 0247732A2
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- demineralized
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- demineralized bone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
- A61L27/3843—Connective tissue
- A61L27/3847—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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
Definitions
- This invention relates to a method of making demineralized bone particles useful in, or as, implants having a variety of orthopedic applications. More particularly, this invention relates to a method of making particles from demineralized bone that results in a greater yield of demineralized bone particles than that provided by prior art methods of producing such particles.
- the manufacture of demineralized bone particles and compositions, materials and devices containing demineralized bone particles and their use in the repair of bone defects and for other orthopedic applications are known.
- the microstructure of cortical bone consists of bundles, or fibers, of mineralized collagen that are oriented parallel to the long axis of the known methods for making demineralized bone particles involve subdividing sections of whole, i.e., mineralized, bone, e.g., by such mechanical operations as shredding, milling, shaving, machining, etc., to provide particles which are then demineralized, e.g., by treatment with acid.
- the resulting demineralized bone particles exliibit osteoinductive properties that make them useful as, or in, implants intended for use in bone repair and other orthopedic applications.
- demineralized bone particles One drawback of known methods of making demineralized bone particles is that only a portion of the bone stock, e.g., 45 - 65 % by weight, will yield demineralized bone particles.
- a portion of the bone stock e.g., 45 - 65 % by weight
- demineralized bone particles Because of the mechanical limitations of the bone milling machinery, e.g., the need to grip the bone stock in the jaws of the machine, only donor bone of a fairly substantial size, e.g., intact cortical shafts, can be used as to the source of the demineralized bone particles.
- demineralized bone particles which comprises demineralizing whole bone and thereafter subdividing the demineralized bone into demineralized bone particles.
- the yield of demineralized bone particles obtained by the method of this invention is significantly greater, e.g., from about 5 to about 20 wt.% greater, than that obtained by first subdividing the whole bone into mineralized bone particles and only thereafter demineralizing the mineralized bone particles to provide demineralized bone particles.
- particles as utilized herein is intended to include relatively small bone pieces such as fibers, bundles of loosely connected fibers, threads, narrow strips, thin sheets, chips, shards, powders, etc., that possess regular, irregular or random geometries and which may, or may not be, completely separated from each other.
- whole bone refers to bone that contains its full naturally occurring mineral content and includes anatomically complete bones and sections thereof.
- demineralized refers to bone containing less than about
- osteogenesis as used herein shall be understood to refer to the ability of a material or substance to induce new bone formation via the participation of living cells from within the substance and "osteogenesis” as the mechanism or result.
- osteoinductive as used herein shall be understood to refer to the ability of a material or substance to recruit cells from the host which have osteogenic potential and the ability to form ectopic bone and "osteoinduction” as the mechanism or result.
- osteoconductive as used herein shall be understood to refer to the ability of a material or substance or material to provide surfaces that are receptive to the growth of new host bone and "osteoconduction” as the mechanism or result.
- the whole bone suitable for making the demineralized bone particles of this invention can be donor bone from any source.
- autogenic, allogenic or xenogenic bone can be used with autogenic and allogenic bone being preferred.
- An especially useful source of xenogenic tissue can be porcine, equine, or bovine.
- the bone can be cortical, cancellous or corticocancellous.
- the preferred bone is cortical allogenic bone, e.g., femur, tibia, fibula, radius, ulna, etc..
- the bone utilized as the starting, or stock, material will range in size from relatively small pieces of bone to bone of such dimensions as to be recognizable as to its anatomical origin.
- the pieces or sections of whole bone stock can range from about 1 to about 400 mm, and preferably from about 5 to about 100 mm, in median length, from about 0.5 to about 20 mm, and preferably from about 2 to about 10 mm, in median thickness and from about 1 to about 20 mm, and preferably from about 2 to about 10 mm, in median width.
- the bone is obtained from the donor, it is processed, e.g., cleaned, disinfected, defatted, etc., using methods well known in the art.
- the entire bone can then be demineralized or, if desired, the bone can just be sectioned before demineralization.
- the entire bone or one or more of its sections is then subjected to demineralization in order to reduce the inorganic content to a low level, e.g., to contain less than about 10% by weight, preferably less than about 5 % by weight and more preferably less than about 1 % by weight, residual calcium.
- Demineralization of the bone can be accomplished in accordance with known and conventional procedures.
- Demineralization procedures remove the inorganic mineral component of bone by employing acid solutions. Such procedures are well known in the art, see for example, Reddi et al., Proceeding of the National Academy of Sciences of the United States of America 69, pp.1601-1605 (1972), incorporated herein by reference.
- the strength of the acid solution, the shape and size of the bone and the duration of the demineralization procedure will determine the extent of demineralization. Generally speaking larger bone portions as compared to small particles will require more lengthy and vigorous demineralization.
- Guidance for specific parameters for the demineralization of different size bone can be found in U.S. Patent No.
- a useful defatting/disinfectant solution is an aqueous solution of ethanol, the ethanol being a good solvent for lipids and the water being a good hydrophilic carrier to enable the solution to penetrate more deeply into the bone particles.
- the aqueous ethanol solution also disinfects the bone by killing vegetative microorganisms and viruses.
- At least about 10 to about 40 weight percent by weight of water i.e., about 60 to about 90 weight percent of defatting agent such as alcohol
- a useful concentration range of the defatting solution is from about 60 to 85 weight percent alcohol or about 70 weight percent alcohol.
- An alternative or supplemental defatting solution is made from a surfactant such as Triton X- 100 at a concentration of 0.1 % to 10% in water.
- the demineralized bone is rinsed with sterile water for injection to remove residual amounts of acid and thereby raise the pH.
- the bone is subdivided into demineralized bone particles of desired configuration and size.
- Useful for the subdivision of the demineralized bone are machines or instruments known to the arts of , e. shredding, milling, pressing, shaving, machining, extruding and/or cutting, of hard or brittle materials such as wood, plastics, soft metals, ceramics and the like. Particularly preferred are mills, including impact mills, grating mills, shearing mills and cutting mills. Many of the preferred instruments for the subdivision of the demineralized bone will fragment the demineralized bone, by cutting or separating the demineralized material in direction parallel to the underlying collagen fibers
- Particularly preferred types of equipment or machine useful for shredding, cutting hard or brittle materials such as wood, plastics, soft metals that can be used to subdivide the demineralized bone include impact mills, grating mills, shearing mills and cutting mills. Many preferred cutting and milling instruments and or machine will fragment the demineralized bone, by cutting or separating the demineralized material in direction parallel or nearly parallel to the underlying collagen fibers. Mills, presses and extruders are particularly useful in this regards.
- An impact mill has blunt rotors or swinging hammers that move at high speed and subdivide the demineralized bone stock by impacting upon the bone shattering it into fragmentary particles.
- the bone tends to shatter along the lines of the natural collagen bundles constituting the microstructure of the bone.
- Similar mills with sharp cutting rotors tend to chop the bone into somewhat symmetric particles as opposed to the fibrous particles obtained with an impact mill.
- Impact speed is a factor that influences the result. Too low a speed may cause the bone to plastically deform rather than shatter into particles as required. This and similar factors involved in the operation of a particular type or model of impact mill to provide demineralized bone fibers can be optimized employing routine experimentation.
- a shearing mill subdivides demineralized bone stock by tearing the bone apart.
- the tearing action tends to preferentially break the bone apart at its weakest point.
- the junctions between demineralized collagen bundles represent weak points and the result is the production of fiber type particles.
- the spindle element of a lathe can be adapted to carry a rotary grinding wheel whose circumferential surface is studded with projecting cutting elements. As the bone stock is pressed against the rotating wheel, the cutting elements produce fiber-type particles. In this type of particle-forming operation, the resulting fibrous particles are not separated along the lines of natural collagen bundles.
- Still other apparatus useful in milling bone particles according to the invention includes mills available from IKA® Works (Wilmington, NC) such as the model A 10 IKA-Analytical Mill or the model M 20 IKA-Universal Mill. Such mills have cooling connections and are suitable for the grinding of hard and brittle substances with a maximum grain size of 6 - 7 mm. It has been determined that a stainless steel star-shaped cutter provides particles of a useful size.
- Other milling machines useful in the practice of the invention herein include drum cutter bone mills such as those available from Tracer Designs, Inc. (Santa Paula, CA), e.g., its bone mill model BM1000.
- a particularly effective method for subdividing demineralized bone stock is to subject the bone to pressing.
- the simplest pressing technique is to apply pressure to the unconstrained demineralized bone. Examples include pressing the bone using a mortar and pestle, applying a rolling/pressing motion such as is generated by a rolling pin, or pressing the bone pieces between flat or curved plates. These flattening pressures cause the bone fibers to separate.
- pressing demineralized bone in accordance with the present invention provides intact natural bone collagen fibers, (not composite fibers made from joined short fiber sections) that can be as long as the fibers in the demineralized bone stock from which they were obtained.
- Another pressing technique involves mechanically pressing demineralized bone which is constrained within a sealed chamber having a hole (or a small number of holes) in its floor or bottom plate.
- the separated fibers extrude through the holes with the hole diameter limiting the maximum diameter of the extruded fibers.
- this constrained technique results in fibers that are largely intact (as far as length is concerned) but separated bone collagen bundles.
- the demineralized bone is first pressed into an initially separated mass of fibers while in the unconstrained condition and thereafter these fibers are constrained within the sealed chamber where pressing is continued.
- pressing of demineralized bone to provide demineralized bone particles can be carried out at from about 1,000 to about 40,000psi, and preferably at from about 5,000 to about 20,000psi.
- a mass of bone particles in which at least about 80 weight percent, preferably at least about 90 weight percent and most preferably at least about 95 weight percent, of the particles possess a median length of from about 2 to about 300 mm or greater, preferably a median length of from about 5 to about 50 mm, a median thickness of from about 0.5 to about 15 mm, preferably a median thickness of from about 1 to about 5 mm, a median width of from about 2 to about 35 mm, preferably a median width of from about 2 to about 20 mm and a median length to thickness ratio and/or a median length to width ratio of from about 2 to 200, preferably from about 10 to about 100.
- the mass of bone particles can be graded or sorted into different sizes, e.g., by screening, and or any less desirable size(s) of bone particles that may be present can be reduced or eliminated.
- the demineralized bone particles can be utilized as is or stored under aseptic conditions, advantageously in a lyophilized or frozen state, for use at a later time.
- the demineralized bone particles of this invention find use as, or in implants, for a variety of orthopedic procedures where they participate in the bone healing/repair process through one or more mechanisms such as osteogenesis, osteoinduction and osteoconduction.
- the demineralized bone particles can be used as is, or formed into a variety of product types such as a gel, putty, or sheet.
- the demineralized bone particles can optionally be admixed with one or more substances such as adhesives, fillers, plasticizers, flexibilizing agents, biostatic/biocidal agents, surface active agents, binding and bonding agents, and the like, prior to, during, or after shaping the particles into a desired configuration.
- Suitable adhesives, binding agents and bonding agents include acrylic resins, cellulosics, bioresorbable polymers such as polyesters, polycarbonates, polyarylates and polyfomarates. Specifically, tyrsine, polycarbonates, tyrosine polyarylates, polyglycolides, polylactides, glycolide-lactide copolymer, etc.
- Suitable fillers include bone powder, demineralized bone powder, hydroxyapatite, etc.
- Suitable plasticizers and flexibilizing agents include liquid polyhydroxy compounds such as glycerol, monacetin, diacetin, etc.
- Suitable biostatic/biocidal agents include antibiotics, providone, sugars, etc.
- Suitable surface-active agents include the biocompatible nonionic, cationic, anionic and amphoteric surfactants.
- the demineralized bone particles can be modified in one or more ways, e.g., their protein content can be augmented or modified as described in U.S. Patent Nos. 4,743,259 and 4,902,296, the contents of which are incorporated by reference herein.
- Any of a variety of medically and/or surgically useful substances can be incorporated in or associated with the bone particles either before, during or after their formation.
- one or more of such substances can be introduced into the demineralized bone particles, e.g., by soaking or immersing the bone particles in a solution or dispersion of the desired substance(s).
- Medically/surgically useful substances which can be readily combined with the demineralized bone particles of this invention include, e.g., collagen, insoluble collagen derivatives, etc., and soluble solids and/or liquids dissolved therein, e.g., antiviricides, particularly those effective against HIV and hepatitis; antimicrobials and or antibiotics such as erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracyclines, viomycin, chloromycetin and streptomycins, cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamicin, etc.; biocidal/biostatic sugars such as dextrose, glucose, etc.; amino acids, peptides, vitamins, inorganic elements, co-factors for protein synthesis; hormones; endocrine tissue or tissue fragments; synthesizers; enzymes such as collagenase, peptidases, oxidases
- EXAMPLE 1 A right diaphysis (99g) of human donor origin was divided lengthwise into four sections. The total weight of all the sections was 94 g. The bone sections were placed in a 2-liter container along with 1410 ml of a 0.6 N HC1 solution. After approximately 6 hours the solution was removed and replaced with another 1410-ml portion of the acid solution. The bone sections and second aliquot of acid solution were subjected to mild vortexing with a magnetic stirrer for two days. The bone sections were demineralized until they were completely translucent without any visible mineralized areas indicating substantially complete demineralization. The demineralized bone sections were then rinsed with water until the pH of the rinse water was above 4.0.
- the demineralized bone sections were then soaked in 70% ethanol for 1 hour.
- the demineralized bone sections were cut with scissors to fit into a model M 20 IKA-Universal Mill and processed in the mill for about 30 seconds to produce demineralized bone particles in the form of fibers (yield 17.98g, 1 lOcc).
- the fibers were then frozen and lyophilized for about 12-15 hours.
- COMPARATIVE EXAMPLE 119 g of mineralized human donor bone was milled in the milling machine described in U.S. Patent No. 5,607,269 to provide a quantity of mineralized bone particles in the form of fibers.
- the mineralized fibers were then subjected to a demineralization process described as follows. Allogenic cortical bone is placed in a reactor. A 0.6 N solution of HCl at 15 ml per gram of bone is introduced into the reactor, the demineralization reaction proceeding for 1 to 2 hours. Following drainage of the HCl, the bone is covered with 0.6 N HCl /20 ppm-2000 ppm nonionic surfactant solution for 24 to 48 hours.
- 0.6 N HCl at 15 ml per gram of bone is introduced into the reactor, the demineralization reaction proceeding for another 40 to 50 minutes resulting in substantially complete demineralization of the starting cortical bone.
- the demineralized bone is rinsed three times with water for injection at 15 ml per gram bone weight with the water for injection being replaced at 15-minute intervals.
- the demineralized bone is covered with alcohol and allowed to soak for at least 30 minutes. The alcohol is then drained and the bone is rinsed with water for injection. The demineralized bone is then subdivided in the bone milling apparatus of U.S. Patent No.
- This material was then ["fluffed up”] and pressed again employing similar pressures as before.
- the pressing operation was again repeated yielding a mass of coarse bundles of fibers that were not completely separated from each other.
- the yield of fibers was about 50 wt.% based on the volume of the [starting demineralized bone sections] and many of the fibers possessed lengths that were nearly as great as the natural fibers of the bone stock.
- the fibers ranged in length from 10-15mm, with some fibers in the range of from 20-25mm, and possessed diameters of about 2mm. Material that was not in fiber form remained in bundled fiber clumps.
- the fibers were further subdivided in an impact mill for [30 seconds] resulting in a reduction of the diameters of many of the fibers and fiber bundles without, however, significantly reducing their length.
- the fibers continued to fall within the aforesaid range of length but their diameters were now within the range of from about 0.5 to about 2mm.
- EXAMPLE 3 Demineralized fibula cross sections, about 25 mm in length, were placed in a series of 29mm diameter press cells possessing single orifices in their bottoms having diameters of 1, 2 and 3mm, respectively. Under pressures of from 5,000- 10,000psi, the demineralized bone sections subdivided into fibers which extruded through the orifices. Yields of demineralized fiber were on the order of nearly 100 wt.% in almost every case; little or no bone remained in the cells.
- EXAMPLE 4 A cell pressing procedure similar to that of Example 4 was carried out on demineralized bone sections of from 4 to 8mm in length in a 29mm diameter press cell having a single orifice of 0.75mm diameter.
- the bone sections subdivided into fibers that ranged in length from 25 to 50% of the length of the bone sections from which they were obtained. Yield of fiber was about 50wt.%.
- the fibers ranged in length from about l-5mm and possessed a diameter of about 0.5mm.
- Example 7 The pressing operations described in Example 5 were substantially repeated but were preceded by a preliminary pressing carried out in a Carver press at 15,000psi.
- the resulting demineralized bone fibers possessed smaller diameters, and consequently, greater length to diameter ratios, than the fibers obtained in Example 6.
- Substantially fully demineralized whole fibula shafts were subdivided into fibrous particles employing a Tracer (rotary grater) mill. Fiber length was about 5mm, diameter was about 0.5mm and fiber yield was about 70 wt.%.
- Example 8 was repeated but with fibula sections of 4-8mm in length. Fiber length was about 3-5mm, diameter was about 0.5mm and fiber yield was about 50 wt.%.
- EXAMPLE 9 A model M5A Fitzpatrick Mill was employed to subdivide substantially fully demineralized bovine bone chips of 4- 10mm into fibrous particles having a length of about l-2mm and a diameter of about 0.2-0.7mm in a yield of about 70 wt. %.
- Example 9 was repeated but employing a model M 20 IKA-Universal Mill to subdivide the demineralized bovine bone chips.
- the fibers in the fiber-fraction produced by the mill had a length of about l-2mm, a diameter of about 0.5-lmm and the fiber yield was about 10%.
- Example 9 was repeated but employing a Megatron homogenizer (Glen Mills Inc., Maywood, NJ).
- the resulting fibers produced in a yield of about 70 wt.%, possessed a length of about l-3mm and a diameter of about 0.2-0.5mm.
Abstract
Description
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Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01991103A EP1347793A2 (en) | 2000-12-14 | 2001-12-14 | Method of making demineralized bone particles |
US10/433,588 US7323193B2 (en) | 2001-12-14 | 2001-12-14 | Method of making demineralized bone particles |
CA002431030A CA2431030A1 (en) | 2000-12-14 | 2001-12-14 | Method of making demineralized bone particles |
KR10-2003-7007988A KR20030074660A (en) | 2000-12-14 | 2001-12-14 | Method of making demineralized bone particles |
AU2002230852A AU2002230852A1 (en) | 2000-12-14 | 2001-12-14 | Method of making demineralized bone particles |
JP2002549301A JP2004515318A (en) | 2000-12-14 | 2001-12-14 | Method for producing demineralized bone particles |
US11/951,084 US7939108B2 (en) | 2000-12-14 | 2007-12-05 | Method of making demineralized bone particles |
US13/010,084 US8529962B2 (en) | 2000-12-14 | 2011-01-20 | Method of making demineralized bone particles |
US14/021,179 US8753689B2 (en) | 2001-12-14 | 2013-09-09 | Method of making demineralized bone particles |
Applications Claiming Priority (2)
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US25565200P | 2000-12-14 | 2000-12-14 | |
US60/255,652 | 2000-12-14 |
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US10433588 A-371-Of-International | 2001-12-14 | ||
US11/951,084 Continuation US7939108B2 (en) | 2000-12-14 | 2007-12-05 | Method of making demineralized bone particles |
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WO2002047732A2 true WO2002047732A2 (en) | 2002-06-20 |
WO2002047732A3 WO2002047732A3 (en) | 2002-12-27 |
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PCT/US2001/048384 WO2002047732A2 (en) | 2000-12-14 | 2001-12-14 | Method of making demineralized bone particles |
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EP (1) | EP1347793A2 (en) |
JP (1) | JP2004515318A (en) |
KR (1) | KR20030074660A (en) |
AU (1) | AU2002230852A1 (en) |
CA (1) | CA2431030A1 (en) |
WO (1) | WO2002047732A2 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103998070A (en) * | 2011-09-29 | 2014-08-20 | Cg生物技术有限公司 | Manufacturing method for fibrous demineralized bone matrix |
US9028859B2 (en) | 2006-07-07 | 2015-05-12 | Advanced Cardiovascular Systems, Inc. | Phase-separated block copolymer coatings for implantable medical devices |
US9610383B2 (en) | 2010-10-27 | 2017-04-04 | Cosmobiomedicare Co., Ltd. | Method for producing a bone transplant material, and bone transplant material produced by same |
AU2015215864B2 (en) * | 2009-08-03 | 2017-04-13 | Osteotech, Inc. | Bone matrix compositions and methods |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101398406B1 (en) * | 2011-09-29 | 2014-05-28 | (주)시지바이오 | Bone-repair composition |
US20170319626A1 (en) * | 2016-05-09 | 2017-11-09 | Warsaw Orthopedic, Inc. | Osteoinductive fibrous bone chips |
KR102581755B1 (en) | 2021-09-06 | 2023-09-22 | 주식회사 써지덴트 | Bone graft material manufacturing apparatus and manufacturing method |
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US5053049A (en) * | 1985-05-29 | 1991-10-01 | Baxter International | Flexible prostheses of predetermined shapes and process for making same |
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US5290558A (en) * | 1989-09-21 | 1994-03-01 | Osteotech, Inc. | Flowable demineralized bone powder composition and its use in bone repair |
JPH0497747A (en) * | 1990-08-17 | 1992-03-30 | Osteotech Inc | Artificial bone for transplanting application |
US5507813A (en) * | 1993-12-09 | 1996-04-16 | Osteotech, Inc. | Shaped materials derived from elongate bone particles |
US5607269A (en) * | 1995-11-21 | 1997-03-04 | Osteotech, Inc. | Bone milling apparatus |
-
2001
- 2001-12-14 AU AU2002230852A patent/AU2002230852A1/en not_active Abandoned
- 2001-12-14 CA CA002431030A patent/CA2431030A1/en not_active Abandoned
- 2001-12-14 WO PCT/US2001/048384 patent/WO2002047732A2/en not_active Application Discontinuation
- 2001-12-14 KR KR10-2003-7007988A patent/KR20030074660A/en not_active Application Discontinuation
- 2001-12-14 JP JP2002549301A patent/JP2004515318A/en not_active Ceased
- 2001-12-14 EP EP01991103A patent/EP1347793A2/en not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5053049A (en) * | 1985-05-29 | 1991-10-01 | Baxter International | Flexible prostheses of predetermined shapes and process for making same |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9028859B2 (en) | 2006-07-07 | 2015-05-12 | Advanced Cardiovascular Systems, Inc. | Phase-separated block copolymer coatings for implantable medical devices |
AU2015215864B2 (en) * | 2009-08-03 | 2017-04-13 | Osteotech, Inc. | Bone matrix compositions and methods |
US9610383B2 (en) | 2010-10-27 | 2017-04-04 | Cosmobiomedicare Co., Ltd. | Method for producing a bone transplant material, and bone transplant material produced by same |
CN103998070A (en) * | 2011-09-29 | 2014-08-20 | Cg生物技术有限公司 | Manufacturing method for fibrous demineralized bone matrix |
EP2762175A4 (en) * | 2011-09-29 | 2015-06-03 | Cg Bio Co Ltd | Manufacturing method for fibrous demineralized bone matrix |
Also Published As
Publication number | Publication date |
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AU2002230852A1 (en) | 2002-06-24 |
JP2004515318A (en) | 2004-05-27 |
KR20030074660A (en) | 2003-09-19 |
CA2431030A1 (en) | 2002-06-20 |
WO2002047732A3 (en) | 2002-12-27 |
EP1347793A2 (en) | 2003-10-01 |
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