Abstract: Described are bone generation matrixes having an admixture of demineralized bone matrix (DBM) particles and/or bone chips in combination with at least one binding agent selected from the group consisting of alginate, lectin, pectin, gellan gum, starch, collagen and combinations thereof in an aqueous solvent, wherein the DBM particles and/or bone chips are present in an amount of at least 65% by dry weight and the ratio of the aqueous solvent to the dry weight of the DBM particles/bone chips and at least one binding agent is between about 1:1 to about 1:6.

Abstract: This invention includes the composition of organ grafts accommodated prior to transplantation and therefore resistant to rejection by preformed antibodies. Accommodation is achieved within the donor animal by administration of sub-lethal levels of accommodation inducing factors derived from animals sensitized to the donor.

Abstract: The present invention encompasses an osteogenic composition comprising mesenchymal stem cells pre-cultured in the presence of an agent that accelerates canonical Wnt signaling therein. Also, provided are osteogenic compositions incorporated into a biocompatible gel. The present invention provides methods for treating bone degeneration or injury associated with a pathophysiological condition in a mammal or for accelerating repair of a skeletal injury in a mammal by administering to the mammal or contacting the site of injury with the osteogenic composition.

Abstract: A flowable, injectable composite that comprises mineralized allograft bone; and at least one degradable polyurethane that has a quasi-prepolymer and a resin mix, the resin mix having a polyester polyol and a catalyst; wherein the composite has a compression strength of greater than about 10 MPa and a modulus of greater than about 1 GPa.

Abstract: A method for promoting bone formation is provided. More specifically, a method for promoting bone formation by promoting osteoclast formation is provided. In one embodiment, an implant comprising an implantable material and an osteoclast stimulating substance is provided.

Abstract: The present invention provides novel methods of forming mineralized gelatin carriers from bone. The present invention further provides mineralized gelatin carriers themselves; bone products that include such mineralized gelatin carriers including DBM bone products; and kits that include mineralized gelatin carriers formed from bone. The present invention further provides methods for making DBM bone products, wherein both the DBM and a mineralized gelatin carrier for the DBM are derived independently from a bone lot.

Abstract: The present invention relates to methods for treating inflammation associated with bone, joint or connective tissue and an implantable controlled-release material capable of providing these anti-inflammatory activities. In particular, the present invention relates to a method for reducing inflammation in a subject's tissue comprising the step of implanting a material comprising allogenic bone gel into or adjacent to said tissue, wherein said allogenic bone gel reduces the inflammation.

Abstract: The present invention provides biocompatible, non-resorbable porous containment structures for containment of bone graft material at a desired location for stimulation of bone growth. The porous containment structures have interconnected pores sized to allow fibrovascular integration with surrounding tissue and conduction of vascular tissue through the structure into the bone graft material.

Abstract: The invention relates to a sheet-form demineralized bone matrix (DBM) composition comprising an aqueous admixture of DBM particles, starch and gelatin, wherein the DBM particles are present in an amount of between about 30% and about 70% by weight, the gelatin is present in an amount between about 10 and about 40% by weight and the starch is present in an amount between about 5% and about 20% by weight, wherein the DBM particles are retained in the form of the resilient sheet.

Abstract: The invention provides methods of repairing damage to, or defects in, mammalian tissues or organs. In these methods, a particulate or non-particulate acellular matrix made from a tissue or organ other than the tissue or organ being repaired is placed in or on the organ or tissue that is being repaired.

Abstract: This invention pertains to the discovery that the human NELL-1 gene induces or upregulates bone mineralization. The NELL-1 gene or gene product thus provides a convenient target for screening for modulators of bone mineralization. In addition, NELL-1 can be used to facilitate repair of bone fractures and/or to generally increase bone density.

Abstract: A covering for delivering a substance or material to a surgical site is provided. The covering, with substance provided therein, may be referred to as a delivery system. Generally, the covering may be a single or multi-compartment structure capable of at least partially retaining a substance provided therein until the covering is placed at a surgical site. Upon placement, the covering may facilitate transfer of the substance or surrounding materials. For example, the substance may be released (actively or passively) to the surgical site. The covering may participate in, control, or otherwise adjust the release of the substance. In various embodiments, the covering may be formed of a collagen material and is suitable for a variety of procedure specific uses.

Abstract: The invention provides for the use of an improved xenograft bone particulate with respect to osteo-integration and bone remodeling, while diminishing the primate-to-pig immunological response using established bone-processing technique. Work was carried out using undecalcified bone to determine immunocompatibilty and bone remodeling potential of processed porcine bone struts following onlay graft implantation. New bone formation was evident, including the infiltration of cellular materials responsible for fusion and bone reconstruction.

Abstract: The invention features bone grafts (such as bone allografts) with reduced protease activity. These bone grafts are useful, for example, in conjunction with a polypeptide of interest (such as platelet derived growth factor) for treating, stabilizing, preventing, and/or delaying a bone, periodontium, ligament, cartilage, or tendon condition in an individual (such as a human). Additionally, the invention provides methods of measuring the protease activity associated with a bone graft, reducing the level of protease activity associated with a bone graft, selecting a bone graft with an acceptable level of protease activity, and methods of administering a bone graft and a polypeptide of interest to an individual.

Abstract: The present invention provides methods for purifying insoluble bone gelatin and uses for insoluble bone gelatin. The process for isolating insoluble bone gelatin from bone tissue includes grinding the bone tissue into bone powder; washing the bone powder with saline; demineralizing the bone tissue; contacting the bone powder with a neutral salt; and contacting the bone powder with a stabilizer. The present invention also discloses an insoluble bone gelatin including about 10 percent growth factor. Insoluble bone gelatin is useful, for example, in preparing impaction bone grafts.

Abstract: The present invention relates to composition useful in growing hair. The compositions are particularly suited for re-growing hair in subjects who have experienced hair loss due to any cause. The compositions comprise essentially the lipoidic fraction of mammalian bone marrow. Methods of using the compositions and processes of preparing the lipoidic fraction for the compositions are also disclosed.

Abstract: A method for making an implantable bone material. The method includes providing a bone composition consisting essentially of demineralized human bone, and irradiating the composition at a temperature less than about 0° C.

Abstract: A cancellous bone graft substitute and a method of manufacturing the cancellous bone graft substitute are provided, and more particularly, a cancellous bone graft substitute and a method of manufacturing the cancellous bone graft substitute by which defatting, demineralizing, cleaning, and sterilizing processes are performed within a short time using a supersonic cabitation without damaging a surface and an inside of a bone tissue so as to further rapidly, effectively supply an allogeneic or xenogeneic bone graft substitute. Internal and external concentrations of Ca++ of the allogeneic or xenogeneic bone graft substitute are effectively removed so as to maintain physical properties of the allogenetic or xenogeneic bone graft substitute.

Abstract: Compositions are provided which stimulate bone growth. Also provided are methods for utilizing the compositions for filling in bone defects, promoting rapid fusion of bone fractures, grafts, and bone-prostheses, and promoting strengthening of osteoporotic bones.

Abstract: A bone grafting material composite is provided. The bone grafting material composite includes a demineralized bone matrix (DBM) and a carboxymethyl cellulose (CMC)/glycerol gel carrier. Due to the CMC/glycerol gel carrier, the implantation ability thereof is better than that of the DBM. Therefore, the bone grafting material composite can be easily used, so that a curative effect can be greatly improved. In addition, since the CMC/glycerol gel is used as a carrier, the composite with a mobility maintained is washed out by water after surgery, so that the composite can be fixed on a damaged portion of a bone.

Abstract: The purpose of this study was to identify the periodontal regeneration factors in enamel protein shown to induce cementum- and osteo-promotive activities in vivo. The cementum regeneration (CR), a part of periodontal regeneration, was examined by using experimental cavities prepared in a buccal dehiscence dog model. The CR activity was found in the aggregate consisted of sheath proteins along with a small amount of amelogenins separated from newly formed secretory enamel. The sheath proteins were purified to be homogeneous, and examined for the alkaline phosphatase (ALP) inducing activity of human periodontal ligament (HPDL) cells. Application of 17 kDa sheath protein induced ALP activity in HPDL cells. Peptides synthesized from the sheath protein sequence also showed ALP inducing activity. The 17 kDa sheath protein has cell differentiation activity.

Abstract: An osteoinductive/osteoconductive composition prepared from a quantity, of demineralized fibrous bone elements possessing an average surface area to volume ratio of about 100:1 to about 20:1, a quantity of mostly shaped regular non-fibrous bone elements possessing an average surface area to volume ratio of about 10:1 or less and a sufficient quantity of biocompatible fluid carrier sufficient to provide the composition as a deformable mass is provided herein. Also provided is a method of using the composition to repair a bone defect site.

Abstract: A pharmaceutical product and a process for bone regeneration and neoformation, which uses sirtuin modulators such as resveratrol and/or trans-resveratrol resulting in the substantial acceleration in the process of integration of biomaterials to the body, substantially shortening the recovery period of the injured or lost organ.

Abstract: A composite material comprising: (i) hyaluronic acid and/or hyaluronic acid derivatives, (ii) demineralised bone and/or biocompatible partially or totally demineralised bone tissue matrix and/or biocompatible and bioresorbable ceramic materials. This material preferably associated with at least one layer comprising a hyaluronic acid derivative may be used in the preparation of bone substitutes or grafts for the regeneration or formation of bone tissue in surgery.

Abstract: The invention relates to a therapeutic composition, a method for producing a therapeutic composition, and the use of a cell-free substance, especially a cell-free bone or cartilage matrix. The disclosed therapeutic composition comprises at least a cell-free substance obtained from stimulated stem cells and/or precursor cells. Immunogenic reactions during in vivo therapeutic use are prevented by the fact that the therapeutic composition is free from cells and contains no typically antigenic cell components. The disclosed composition can therefore be universally used for the therapeutic purposes regardless of the origin of the stem cells and/or precursor cells and utilize the natural regenerative potency thereof in a highly efficient manner for replacing tissue, e.g. for a suitable bone and/or cartilage structure.

Abstract: Bone graft compositions comprising demineralized bone matrix, calcium phosphate, collagen and bioinductive cellular solution. Methods to repair and heal defective and missing bone using the bone graft compositions are also described.

Abstract: The present invention provides a method of promoting bone growth in a subject in need thereof, by administering to the subject a therapeutically effective amount of a compound of Formula I. The present invention also provides methods for the treatment of renal disease and cancer.

Abstract: This invention relates to an osteogenic device for the de novo induction of bone formation in a mammal. The device contains a at least one transforming growth factor—&bgr;3 isoform and a retention matrix. The device is introduced by direct injection or surgical implantation into an area where de novo bone formation is desired and, once implanted, the retention matrix acts to retain the TGF-&bgr;3 isoform at its place of introduction and forms a scaffold for generated bone, the induction of which is promoted by the TGF-&bgr;3 isoform. The device may be used to induce bone growth where bone has been debrided in a surgical procedure and it may also be used to transform neoplastic primary and/or metastatic secondary masses into bone thus facilitating surgical debridement thereof.

Abstract: The present invention provides a method of promoting bone growth in a subject in need thereof, by administering to the subject a therapeutically effective amount of a compound of Formula I. The present invention also provides methods for the treatment of renal disease and cancer.

Abstract: Formed compositions for application to a bone surface of a human or animal subject, comprising: a bone material; and a carrier comprising denatured demineralized bone, where the composition is formed into a shape suitable for administration to the bone. Methods are provided for making formed compositions for application to a bone surface of a human or animal subject comprise mixing a demineralized bone and water; heating the mixture to form a carrier; mixing the carrier with bone to form a moldable composition; and molding the moldable composition to produce a formed composition. Several apparatuses are provided in which to hydrate the formed bone composition. Methods of hydrating a formed bone composition are also provided.

Abstract: Bone graft substitute compositions and methods of making the compositions are disclosed. In some embodiments, a method of making a composition includes contacting a mixing solution with a first mixture having calcium sulfate hemihydrate and a plasticizing material to form a second mixture; waiting a predetermined period of time after forming said second mixture; and then contacting demineralized bone with the second mixture to form the composition. A composition can be formed from a kit including a first mixture having calcium sulfate hemihydrate and a plasticizing substance, a second mixture having demineralized bone, and a mixing solution. The first and second mixtures and the mixing solution are unblended.

Abstract: Disclosed herein is a composition suitable for use in spinal surgery. The composition generally includes a reaction product or settable mixture of first and second components, the first component including a spray-dried inorganic filler, a radical donor, and a pre-polymerized vinyl polymer, and the second component including a radical scavenger, a diluent, a polymerization accelerator, and a reactive monomer. Furthermore, disclosed herein is a method of making the composition, which generally includes mixing the first and second components under conditions suitable to form a curable reaction product.

Abstract: The invention is directed toward an osteochondral repair assembly comprising a shaped allograft construct comprising an unbalanced barbell-shaped cylindrical cancellous bone primary member formed with a mineralized cylindrical base section having a smaller diameter cylindrical stem leading to a second cylindrical section which is demineralized. A mineralized ring-shaped support member is forced over the compressed demineralized second demineralized the aperture of the ring-shaped member to fit around the stem with one ring surface being adjacent the bottom surface to the second cylindrical section and the opposite ring surface being adjacent the upper surface of the mineralized cylindrical base section.

Abstract: The invention relates to methods of improving the osteoinductivity of calcium phosphate materials, to calcium phosphate materials having improved osteoinductivity as well as bone (re)generation scaffolds produced therefrom and to the use of such materials and scaffolds in methods of treatment.

Abstract: The present invention provides a method of promoting bone growth in a subject in need thereof, by administering to the subject a therapeutically effective amount of a compound of Formula I. The compounds include the salts, hydrates and isomers thereof. The present invention also provides methods for the treatment of renal disease and cancer.

Abstract: The present invention relates to an in vitro method of assessing the sensitivity of a subject to a treatment of cancer, which method comprises detecting the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid or an abnormal TLR4 protein expression or activity in a sample from the subject, the presence of said mutated TLR4 nucleic acid or abnormal TLR4 expression or activity being indicative of a resistance to said treatment. The invention further provides compounds for treating or preventing a cancer in a subject having a mutated TLR4 nucleic acid or an abnormal TLR4 protein expression or activity.

Abstract: The present invention relates to a method for preparing a bone graft substitute using bovine bone, and more particularly to a method for preparing a safe bone graft substitute which does not have the risk of infection with bovine spongiform encephalopathy, the method comprising treating bovine bone with sodium hypochlorite and treating the treated bone at a high temperature of more than 600° C. The bone graft substitute does not cause an immune response, because it is prepared by effectively removing lipids and organic substances from bovine bone having a structure very similar to that of the human bone. Also, it has excellent osteoconductivity, and is free of prion, and thus it does not have the risk of infection with bovine spongiform encephalopathy. According to the disclosed invention, the bone graft substitute having such advantages can be prepared in a simple manner.

Abstract: An allograft osteochondral plug is combined with a mixture that includes freeze-milled cartilage particles, and such combination is used to repair defects in articular cartilage. The plug includes an subchondral bone portion and an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans. At least a portion of the plug has a lateral dimension selected to form an interference fit against a tissue layer exposed as a result of a bore formed in a defect area in articular cartilage of a host. The cartilage particle mixture is placed adjacent at least a portion of the plug for promoting cartilage cell migration into (i.e., from the adjacent host cartilage) and proliferation in the bore, and for enhancing tissue integration between the plug and patient (i.e., host) tissue when the plug is inserted into the bore. Methods for surgical implantation of the plug into a patient are also disclosed.

Abstract: A method for purifying bone-derived osteoinductive proteins including a demineralization process, a protein extraction process, a high molecular weight ultrafiltration process, a low molecular weight ultrafiltration process, and a recovery process. The high and low ultrafiltration processes preferably select proteins having a nominal molecular weight between approximately 8 kilodaltons and approximately 100 kilodaltons. Processes of the present invention may be used to recover osteoinductive proteins from bone demineralization waste streams.

Abstract: The invention is directed toward an osteoimplant for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing composition of demineralized allograft bone material mixed with an aqueous phosphate buffered gelatin which when lyophilized to remove water from the composition crosslinks the gelatin to form a solid structure and when rehydrated is flexible

Abstract: The present invention relates to the use of a preparation of an active enamel matrix substance, such as an amelogenin, for the manufacture of a pharmaceutical composition for modulating an immune response. The composition can be used in preventing and/or treating a condition or disease in a mammal that is characterised by said mammal presenting an imbalance in its native immune response to an internal and/or external stimuli, i.e. wherein at least a part of said mammal's immune system is stimulated non-discriminatingly, reacts hypersensitively to said immunogen, or fails to react to said stimuli. Said condition can typically either be systemic or local, such as a systemic and/or post-traumatic whole-body inflammation or an autoimmune disease.

Abstract: Bone matrix compositions and, more specifically, demineralized bone matrix (DBM) having increased osteoinductive capacity and methods for its production are provided. Specifically, DBM derived from cortical bone from the periosteal layer of bone are provided. Compositions comprising a disproportionate amount of DBM prepared from bone derived from the periosteal and/or middle layer of bone are provided. Preparations of and methods of use of periosteal DBM compositions are disclosed.

Abstract: Bone paste compositions are described, which promote bone healing and remodeling by stimulating bone marrow elements using a combination of hemopoietic agents, angiogenic agents and a bone molecular signaling material.

Abstract: A covering for delivering a substance or material to a surgical site is provided. The covering, with substance provided therein, may be referred to as a delivery system. Generally, the covering may be a single or multi-compartment structure capable of at least partially retaining a substance provided therein until the covering is placed at a surgical site. Upon placement, the covering may facilitate transfer of the substance or surrounding materials. For example, the substance may be released (actively or passively) to the surgical site. The covering may participate in, control, or otherwise adjust, the release of the substance.

Abstract: According to the invention preparation for regeneration of bone defects is employed in many branches of medicine, especially in orthopedics, dental surgery, reconstructive surgery, periodonthology and implantology. The preparation has been developed on the basis of inorganic chemical compound naturally occurring, i.e. deproteinized human bone, and on the basis of at least one of inorganic chemical compounds synthetically occurring, i.e. bioglass in the form of granulated high calcium product (54% mol. CaO), obtained with the use of zol-gel method in the system CaO—SiO2—P2O5, of density 2.9082 g/cm3, with phase composition with a dominant glassy phase and beginnings of crystallization of apatite, heat treated at temperature of 800° C., having a specific surface BET 57.8166 m2/g and/or tricalcium phosphate—TCP in the form of granulated product with chemical formula Ca3 (PO4)2. As a component deproteinized particles of human bone are used, favorably with granulation 0.3-0.

Abstract: The invention is directed to a method for treating a tissue or organ in a subject by directly administering an effective amount of an exogenous, decellularized extracellular matrix or a mixture of extracellular matrix and mesenchymal stem cells into the intended site of activity, such as bone marrow cavity. In one embodiment, the invention provides methods of treating bone marrow to increase the number of circulating progenitor and stem cells. In some other embodiments of the invention, the decellularized extracellular matrix to be directly administered is configured to be a time released therapeutic.

Abstract: Disclosed herein are improved osteogenic devices and methods of use thereof for repair of bone and cartilage defects. The devices and methods promote accelerated formation of repair tissue with enhanced stability using less osteogenic protein than devices in the art. Defects susceptible to repair with the instant invention include, but are not limited to: critical size defects, non-critical size defects, non-union fractures, fractures, osteochondral defects, subchondral defects, and defects resulting from degenerative diseases such as osteochondritis dessicans.

Abstract: Tissue repair compositions, particularly bone repair compositions, containing demineralized bone fragments and homogenized connective tissues. The compositions can be used in the form of an injectable gel, an injectable paste, a paste, a putty, or a rehydratable freeze-dried form.

Abstract: An osteoinductive demineralized bone matrix, corresponding osteoimplants, and methods for making the osteoinductive demineralized bone matrix are disclosed. The osteoinductive demineralized bone matrix may be prepared by providing demineralized bone and altering the collagenous structure of the bone. The osteoinductive demineralized bone matrix may also be prepared by providing demineralized bone and compacting the bone, for example via mechanical compaction, grinding into a particulate, or treatment with a chemical. Additives such as growth factors or bioactive agents may be added to the osteoinductive demineralized bone matrix. The osteoinductive demineralized bone matrix may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, may induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation.

Abstract: Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.