Abstract: Methods for delipidation, viral inactivation and terminal sterilization are provided for bone grafting material. The methods include contacting bone material with an amount of supercritical fluid effective to remove at least lipids and at least contaminants from the bone material, thereby obtaining a terminally sterilized and delipidated bone material. In various embodiments, the substantially terminally sterilized and delipidated bone material is 99.0%, 99.5% or 99.9% free of lipids and contaminants. Contaminants that are removed from bone material by terminal sterilization with supercritical fluid include infectious organisms, such as bacteria, viruses, protozoa, parasites, fungi and mold. Bone material or bone compositions that can be treated with critical or supercritical fluids comprise mineralized or demineralized bone particles, mineralized or demineralized bone matrix, partially demineralized bone matrix or combinations thereof.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2, as do endogenous forms of BBP, and sequence conservation between species results in a variety of useful BBP compositions. BBP increases the over-all osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: An osteoinductive composition, corresponding osteoimplants, and methods for making the osteoinductive composition are disclosed. The osteoinductive composition comprises osteoinductive factors, such as may be extracted from demineralized bone, and a carrier. The osteoinductive composition is prepared by providing demineralized bone, extracting osteoinductive factors from the demineralized bone, and adding the extracted osteoinductive factors to a carrier. Further additives such as bioactive agents may be added to the osteoinductive composition. The carrier and osteoinductive factors may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, can induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation. Also, in some embodiments, the osteoinductive composition can be used as a delivery device to administer bioactive agents.

Abstract: The use of autogenous bone graft is the current gold standard in the 1.5 million bone-grafting surgeries performed annually in the United States. Although this practice has resulted in high rates of fusion success, it is associated with increased operative time and blood loss, along with a significant degree of donor-site morbidity. Additionally, in certain settings such as revision cases, multilevel constructs, or in patients with medical comorbidities, autogenous bone graft may exist in limited quantity and quality. This significant need for a suitable alternative to autogenous bone graft has stimulated great interest in the exploration of bone graft substitutes and extenders.

Abstract: The present invention relates to the clinical application of BBP, alone or in combination with other growth factors, for use in bone healing applications, such as spinal surgery. Additional applications include use in orthopedic implantable prostheses and implantation into other surgical sites (e.g., surgical reconstruction, regional osteopenia, etc.) where bone is desired.

Abstract: The present invention provides methods of improving the osteogenic and/or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and/or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions.

Abstract: An osteoinductive composition, corresponding osteoimplants, and methods for making the osteoinductive composition are disclosed. The osteoinductive composition comprises osteoinductive factors, such as may be extracted from demineralized bone, and a carrier. The osteoinductive composition is prepared by providing demineralized bone, extracting osteoinductive factors from the demineralized bone, and adding the extracted osteoinductive factors to a carrier. Further additives such as bioactive agents may be added to the osteoinductive composition. The carrier and osteoinductive factors may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, can induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation. Also, in some embodiments, the osteoinductive composition can be used as a delivery device to administer bioactive agents.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2, as do endogenous forms of BBP, and sequence conservation between species results in a variety of useful BBP compositions. BBP increases the over-all osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2. BBP increases the overall osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

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: An osteoinductive composition, corresponding osteoimplants, and methods for making the osteoinductive composition are disclosed. The osteoinductive composition comprises osteoinductive factors, such as may be extracted from demineralized bone, and a carrier. The osteoinductive composition is prepared by providing demineralized bone, extracting osteoinductive factors from the demineralized bone, and adding the extracted osteoinductive factors to a carrier. Further additives such as bioactive agents may be added to the osteoinductive composition. The carrier and osteoinductive factors may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, can induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation. Also, in some embodiments, the osteoinductive composition can be used as a delivery device to administer bioactive agents.

Abstract: This disclosure describes systems and methods for providing a novel delivery system for implantation in a patient. Further, this disclosure describes a delivery system including a carrier that is made of at least one monolithic bone tissue for retaining one or more substances.

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: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2. BBP increases the overall osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: Osteoinductive compositions and implants having increased biological activities, and methods for their production, are provided. The biological activities that may be increased include, but are not limited to, bone forming; bone healing; osteoinductive activity, osteogenic activity, chondrogenic activity, wound healing activity, neurogenic activity, contraction-inducing activity, mitosis-inducing activity, differentiation-inducing activity, chemotactic activity, angiogenic or vasculogenic activity, and exocytosis or endocytosis-inducing activity. In one embodiment, a method for producing an osteoinductive composition comprises providing partially demineralized bone, treating the partially demineralized bone to disrupt the collagen structure of the bone, and optionally providing a tissue-derived extract and adding the tissue-derived extract to the partially demineralized bone.

Abstract: Demineralized bone matric (DBM) and native bone morphogenetic protein (nBMP) are complex mixtures of non-collagenous bone proteins. These mixtures contain many of the BMPs that are available as recombinant molecules. Information regarding the presence in these materials of molecules that may affect the availability and activity of the BMPs is very limited. A chemical extraction of DBM, such as using alkali-urea produces a water soluble extractate which inhibits the osteogenic activity of DBM. Noggin, an extracellular BMP ligand antagonist is found in the water soluble extractate from DBM. Differential chemical extraction is a useful means of removing non-osteogenic, or osteogenic inhibitory molecules from DBM and nBMP.

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: 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: 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: In one embodiment, the method comprises providing tissue, preparing the tissue, and treating the tissue to improve remodeling characteristics of the tissue. The tissue may be, for example, cortical bone. Treating the tissue to improve remodeling characteristics may comprise heating the tissue, treating the tissue with a chemical, or other. Heating the tissue may be done in the absence of oxygen and may comprise heating the tissue in a vacuum, heating the tissue in an inert atmosphere, heating the tissue in a reducing atmosphere, coating the tissue with a protective coating and heating the tissue, or other. Further embodiments comprise treating the tissue in supercritical fluids, for example, to dry or virally inactivate the tissue.