Abstract: A composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive factors is described. The composition bioerodes in the biological environment of the subject at a controlled rate, thereby releasing the water soluble proteins at a rate which allows them to interact with local cell populations.

Abstract: The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of treatment.

Abstract: The invention is directed to purified and isolated concanavalin A-binding proteins from chondrocytes that are not present in dedifferentiated cells from chondrocytes. The invention is also directed to a purified and isolated chondrocyte membrane protein, (CMP), which is a concanavalin A-binding protein, with a molecular weight of about 76 kD in SDS-PAGE. After treatment with endoglycosidase, CMP has an apparent molecular weight of about 67 kD. The N-terminal amino acid sequence and several internal amino acid sequences are given for CMP. These proteins can be used in assays, methods, or treatments involving differentiation of chondrocytes and the control of cartilaginous osteogenesis.

Abstract: Suturable, biocompatible, control-resorbing membranes are disclosed for use in guided tissue regeneration, comprising a cross-linked collagen material either obtained by crosslinking a starting collagen material in the coagulated state produced by coagulation of a collagen material gel with a coagulating agent or obtained by crosslinking of a sponge of a collagen material on which a collagen material gel has been poured before performing the crosslinking.

Abstract: A formulated biological adhesive composition utilizes tissue transglutaminase in a pharmaceutically acceptable aqueous carrier. The tissue transglutaminase is used in an effective catalytic amount to promote adhesion between tissue surfaces upon treatment thereof by catalyzing the reaction between glutaminyl residues and amine donors of the tissue and/or the enzyme. The carrier contains a divalent metal ion such as calcium to promote said reaction.

Abstract: A composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive factors is described. The composition bioerodes in the biological environment of the subject at a controlled rate, thereby releasing the water soluble proteins at a rate which allows them to interact with local cell populations.

Abstract: A self-supporting composite bioactive material and method of making it, which comprises immersing a body of collagen in a solution comprising a calcium phosphate and a phosphoprotein (preferably containing o-phosphoserine residues) to deposit on the collagen a mineralized layer of calcium phosphate and the phosphoprotein.

Abstract: A biochemically pure polypeptide(s), termed osteogenic growth polypeptide (OGP), which exhibits stimulatory effects on osteoblastic cells, in vivo bone formation and hemopoietic reconstruction. OGP, identified from regenerating bone marrow, has an amino acid sequence ofAla-Leu-Lys-Arg-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-Gly-Gly.

Abstract: A process for the preparation of gelatin from powdered bone, which consists in subjecting the powdered bone to a first treatment with an acid solution at a temperature below ambient temperature in order to solubilize the phosphates, and then to a second treatment with an acid solution at a temperature of between 60.degree. C. and 85.degree. C. in order to isolate a broth from which the gelatin is extracted. Type A gelatin with a gel strength of more than 300 blooms and a gelling time of less than 100 seconds.

Abstract: This invention provides a purified cochlear antigen reactive with an autoantibody associated with autoimmune sensorineuronal hearing loss. The purified antigen is defined as having a molecular weight of about 68,000 daltons as determined by SDS-PAGE analysis under reducing conditions. This invention also provides a method for detecting autoimmune sensorineural hearing loss in a patient. Finally, a kit containing reagents to assay for an antibody associated with autoimmune sensorineural hearing loss in a patient sample is disclosed and claimed by this invention.

Abstract: The invention provides a process for the preparation of high purity bone mineral wherein the organic matter in degreased bone is degraded and solubilized by heating with ammonia or a primary amine, characterized in that the solubilized degradation products are extracted by washing with flowing water at temperatures below 60.degree. C., such heating with primary amine and washing steps optionally being repeated, whereby substantially all organic matter removable by these steps is removed, the bone mineral so treated being heated in air at temperatures of up to 700.degree. C.

Abstract: The method for preparing high grade gelatin with a specific methionine content and with reduced methionine variability from batch to batch and within a single extraction includes controlling the amount of and variability of oxidant present during processing of bone stock into gelatin. Such controls include control of oxidant concentration and range in process water, control of volume of process water used in gelatin-making process and restriction of the range of gelatin extracts used in the product gelatin. Once the aim level of oxidant has been set, the total range of oxidant around the set point should be less than 220 meq per 100 kg dry bone.

Abstract: A composition is disclosed comprising a pharmaceutically acceptable admixture of an osteogenic protein; a porous particulate polymer matrix; an osteogenic protein-sequestering amount of blood clot; and a calcium sulfate hemihydrate-containing substance. Also disclosed are formulations of bone morphogenetic proteins with improved solubility and/or stability characteristics.

Abstract: Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Abstract: The present invention is directed to a novel imidazo [4,5b] pyridinium molecule composed of a lysine and an arginine residue crosslinked with a pentose sugar. The novel imidazo [4,5b] pyridinium compound, referred to as "pentosidine", was isolated from proteineous tissue undergoing advanced glycosylation and is believed to be one of the principal products involved in the nonenzymatic browning and/or aging of proteins. Assaying for the pentosidine molecule makes it possible to assess the degree of aging of proteins in vivo as mediated by pentose induced crosslinking and modulated by disease such as diabetes and nephropathy. In addition, the pentosidine molecule may be utilized through the production of monoclonal antibodies thereto and/or the preparation of test kits, etc. for diagnostic, as well as therapeutic purposes (i.e. development of agents which inhibit the non-enzymatic browning reaction, etc.).

Abstract: A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (.mu.mhos) (1.026.times.10.sup.-2 siemens (S)) to about 11,200 .mu.mhos (1.120.times.10.sup.31 2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 .mu.mhos (3.91.

Abstract: A process for regenerating articular cartilage in a joint including the steps of exposing the joint having a cartilage defect, debriding the entire cartilage layer to the underlying bone-cartilage interface, to expose a plurality of vascular sinusoids in the sub-chondral layer of bone adjoining the joint surface, restoring the smooth contour and topography of the joint to its natural state, surgically closing the joints, and injecting a single dosage of a mixture of purified growth hormone and buffer solution into the joint so as to initiate the regenerative process, said mixture containing a quantity of purified growth hormone (somatotropin) which has been dissolved in a buffer solution.

Abstract: A myogenic protein isolate from mammalian bone is provided that stimulates lineage commitment and differentiation of stem cells in vitro and in vivo. The protein isolate is characterized by its ability to cause muscle stem cell differentiation without excessive proliferation of connective tissue proximal to the delivery site. Treated muscle stem cells differentiate into myotubes and multinucleated structures with minimal formation of scar tissue, resulting in functional muscle tissue restoration in vivo, and therefore useful in the treatment of a number of disorders and injuries. The protein isolate is preferably administered by implanting a bioerodible polymer matrix, preferably a surface erodible polymer such as a polyanhydride or a polyorthoester, interspersed with the protein isolate near the site of muscle injury or degeneration, but can be administered directly to cells cultured in vitro.

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid compositions, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: An aspartic acid rich protein isolated from human urine, as well as proteins having substantial homology thereto and active portions of the foregoing are effective modulators of mineralization in mammals. These proteins and peptides are useful as therapeutic agents, such as in the treatment of kidney stone disease. Hybridoma cell lines capable of producing monoclonal antibodies to these proteins and peptides and monoclonal antibodies produced by these hybridomas are disclosed. These monoclonal antibodies are also useful as therapeutic agents, such as in the treatment of osteoporosis, and further have utility as diagnostic agents. Other uses are also described.

Abstract: A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (.mu.mhos) (1.026.times.10.sup.-2 siemens (S)) to about 11,200 .mu.mhos (1.120.times.10.sup.-2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 .mu.mhos (3.91.

Abstract: Methods and compositions are provided for the treatment and repair of defects in the cartilage or bone of humans and other animals as in full-thickness defects in joints. The defect in bone is filled with a matrix having pores large enough to allow cells to populate the matrix and to form blood vessels. The matrix filling the bone defect contains an angiogenic factor and also contains an osteogenic factor in an appropriate delivery system. To induce cartilage formation, a defect in cartilage is filled with a matrix having pores sufficiently large to allow cartilage repair cells to populate the matrix. The matrix filling the defect in cartilage contains a proliferation agent and also contains a transforming factor in an appropriate delivery system. The matrix may also contain a chemotactic agent to attract cartilage repair cells.

Abstract: Disclosed are (1) osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; (2) DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; (3) vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; (4) methods of producing these polypeptide chains using recombinant DNA technology; (5) antibodies specific for these novel polypeptide chains; (6) osteogenic devices comprising these recombinantly produced proteins in association with an appropriate carrier matrix; and (7) methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: The present invention is directed to various processes and devices for utilizing isolated and culturally expanded marrow-derived mesenchymal cells (i.e. mesenchymal stem cells) for treating skeletal and other connective tissue disorders.

Abstract: The present invention is directed to a novel imidazo [4,5b] pyridinium molecule composed of a lysine and an arginine residue crosslinked with a pentose sugar. The novel imidazo [4,5b] pyridinium compound, referred to as "pentosidine", was isolated from proteineous tissue undergoing advanced glycosylation and is believed to be one of the principal products involved in the non-enzymatic browning and/or aging of proteins. Assaying for the pentosidine molecule makes it possible to assess the degree of aging of proteins in vivo as mediated by pentose induced crosslinking and modulated by disease such as diabetes and nephropathy In addition, the pentosidine molecule may be utilized through the production of monoclonal antibodies thereto and/or the preparation of test kits, etc. for diagnostic, as well as therapeutic purposes (i.e. development of agents which inhibit the non-enzymatic browning reaction, etc.).

Abstract: Methods and compositions are provided for the treatment and repair of defects or lesions in the cartilage of humans and other animals. The defect or lesion in the cartilage may be first treated with an enzyme to remove proteoglycans from the defect area. To induce cartilage formation, the defect is filled or otherwise dressed with a biodegradable matrix having pores sufficiently large to allow repair cells to populate the matrix. The matrix filling the defect contains a proliferation agent at a concentration sufficient to stimulate proliferation of repair cells and a transforming factor in an appropriate delivery system to release the transforming factor at a concentration sufficient to transform repair cells in the matrix and defect area into cartilage-producing chondrocytes. The matrix may also contain a chemotactic agent to attract repair cells. The entire treatment may be carried out in a single arthroscopic or open surgical procedure.

Abstract: The present invention is directed to a method and device for enhancing the implantation and differentiation of marrow-derived mesenchymal cells (i.e. mesenchymal stem cells). The method and device of the invention are an effective means for treating skeletal and other connective tissue disorders.

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: A matrix for implantation in a mammalian host comprising biocompatible, mineral-free, insoluble Type-I bone collagen which may be allogenic or xenogenic to the host, and which, when implanted in the host, is biodegradable. The collagen is treated with a collagen fibril modifying substance such as acidified acetonitrile, chloroform, or dichloromethane, or by heating in an aqueous environment to a temperature of 37.degree.-65.degree. C. The treated material undergoes a change in morphology involving a significant increase in its surface area as measured by various methods. Under the scanning electron microscope the material has an "oyster shell" appearance with many pits and micropores.

Abstract: Described is a purified osteogenic factor that when delivered to bone in association with a physiologically acceptable delivery vehicle is capable of inducing new bone growth at the bone surface. The osteogenic factor is water soluble, and is characterized physically by a molecular weight of about 2.5 kD when measured by gel filtration under dissociating conditions and an isoelectric point in the pH range from about 4.6 to 7.2. Use of the purified factor in treating bone defects is described. Also described is a method for obtaining the purified factor from mammalian bone.

Abstract: The invention provides a process for the preparation of high purity bone mineral wherein the organic matter is degraded by heating with ammonia or a primary amine, characterized in that the solubilized degradation products are extracted by washing with flowing water at temperature below 60.degree. C., such heating with primary amine and washing steps optionally being repeated, whereby substantially all organic matter removable by these steps is removed, the bone mineral so treated being heated in air at temperatures between 250.degree. C. and 600.degree. C.

Abstract: The invention relates to a therapeutic composition (especially for bone lesions with cavity formation and parodontitis) containing a growth-stimulating material and a solid carrier, to such a material and to a process for the preparation thereof.

Abstract: A process for extracting type I collagen from an avian source such as poultry feet that incorporates a fibrillar mass of connective tissue as well as bony tissue to yield a collagen product having useful medical and biotechnology applications. In this process, after being cleaned and decontaminated, the poultry feet are comminuted and then enzyme-treated to enhance the yield. The enzyme-treated comminuted material which is rich in collagen is dispersed in an organic acid to cause the fibrillar mass to undergo controlled swelling, after which the mass is separated from the bony tissue and purified to remove non-collangenous material. The purified mass is dried to provide the desired Type I collagen product which may be ground into a powder or formed into a collagen matrix or sponge, depending on the end use therefor.

Abstract: Disclosed are osteogenic devices comprising a matrix containing substantially pure mammalian osteogenic protein and methods of inducing endochondral bone growth in mammals. A partial amino acid sequence, amino acid composition, solubility properties, and various other data characterizing osteogenic protein are also disclosed, as well as a nucleic acid sequences encoding a consensus osteogenic protein.

Abstract: The present invention provides an osteogenically active protein preparation characterized by a molecular weight of from about 31,000 to 34,000 daltons as characterized comprising a subunit identical to or homologous to a subunit in P3 OF 31-34, by non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis and by the characteristic of eluting from a reverse phase high performance liquid chromatography column equilibrated with buffers containing trifluoroacetic acid and acetonitrile by eluting within the concentrations of 35% to 45% acetonitrile. The invention further provides improved methods for isolating such preparations and genes encoding all or a portion of polypeptide subunits of dimers comprising the osteogenic protein preparation.

Abstract: A composition for use in inducing binding between parts of mineralized tissue by regeneration of mineralized tissue on at least one of the parts, containing as an active constituent a protein fraction originating from a precursor to dental enamel, so called enamel matrix;a process for inducing binding between parts of living mineralized tissue by regeneration of mineralized tissue on at least one of the parts using such composition.

Abstract: Methods and artificial matrices for the growth and implantation of cartilaginous structures and surfaces are disclosed. In the preferred embodiments, chondrocytes are grown on biodegradable, biocompatible fibrous polymeric matrices. Optionally, the cells are proliferated in vitro until an adequate cell volume and density has developed for the cells to survive and proliferate in vivo. One advantage of the matrices is that they can be cast or molded into a desired shape, on an individual basis, so that the final product closely resembles a patient's own ear or nose. Alternatively, flexible matrices can be used which can be manipulated at the time of implantation, as in a joint, followed by remodeling through cell growth and proliferation in vivo. The cultured cells can also be maintained on the matrix in a nutrient media for production of bioactive molecules such as angiogenesis inhibiting factor.

Abstract: Disclosed are (1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; (2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, (3) methods of producing osteogenic proteins using recombinant DNA technology, and (4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: Inflammation, acute and/or chronic, is treated with a CIF (TGF-.beta.). The CIF may be administered locally or systemically, depending upon the indication, and does not require coadministration or activator or cofactor for efficacy.

Abstract: Collagen in tactoid form obtained by forming an aqueous solution containing dissolved collagen and a water soluble or miscible polymer adapted to precipitate collagen out of solution in the form of tactoids.

Abstract: A good tissue-affinity and lack of antigenicity are required for the collagen used as the carrier of BMP. Conventional collagens have these properties only insufficiently. When the tyrosine content is below 2 residues/1000 residues, then the above properties of such collagens are good. Moreover, collagens excelling in the above properties can be readily obtained by using proteolytic enzymes.

Abstract: Disclosed is a matrix material for implantation in a mammalian host comprising biocompatible mineral-free type I bone collagen, xenogenic to the host, and biodegradable therewithin. The matrix is manufactured from protein-extracted bone powder treated with certain swelling agents to increase its surface area and porosity. The matrix may be combined with osteogenic protein to induce reliably and reproducibly endochondral bone formation. It also can be used as a surface coat around implantable prosthetic devices to promote cellular ingrowth or as a carrier for sustained release of various therapeutic compositions.

Abstract: Disclosed are osteogenic devices comprising a matrix containing substantially pure mammalian osteogenic protein and methods of inducing endochondral bone growth in mammals. A partial amino acid sequence, amino acid composition, solubility properties, and various other data characterizing osteogenic protein are also disclosed, as well as a nucleic acid sequences encoding a consensus osteogenic protein.

Abstract: A cartilage-inducing factor has been isolated from dentin and characterized as a polypeptide having an apparent molecular weight of 6,000 to 8,500, an isoelectric pH of from 4.5 to 6.5, and, biologically, as being capable of inducing muscle fibroblast cells to produce cartilage-specific proteoglycan and Type II collagen.

Abstract: A polypeptide transforming growth factor found in porcine platelets, having activity in the TGF-.beta. assay and a molecular weight of about 25 kDa. The factor is a heterodimer, one chain of which has an N-terminal sequence very different from human platelet TGF-.beta., and the other chain of which has an N-terminal sequence identical to that of human platelet TGF-.beta.. The factor is purified using gel filtration and reverse phase HPLC.

Abstract: A method for producing an ossein hydroxyapatite compound from bones or fetal and young animals is described. The compound so produced stimulates chondrocytes and osteoblasts and is useful in the treatment of osteoarthritis, osteoporosis, bone and cartilage defects, and in the healing of bone fractures.

Abstract: A defect is provided in cartilage or bone, or both, to excise damaged or pathological tissue, and it is filled with an implant having capability for complete regeneration of the skeletal tissue as a chondrogenic or osteogenic phenotype. The implant comprises cells expressing a chondrocyte phenotype (80.times.10.sup.6 cells/ml) embedded in a biocompatible matrix having about 20% serum, which provides a permissive environment for maturation and transformation of the implant to a fully integrated state with the surrounding tissue. A portion of the implant may comprise a bone segment or a bone substitute.

Abstract: A grafting material comprising milled bone which has an initial coating of guanidine-extracted bone proteins which are dialyzed from solution. Unbound bone proteins are removed and this augmented milled bone is lyophized. A subsequent coat of anti-coagulated plasma containing plasma proteins is applied to the augmented milled bone. The unbound plasma proteins are removed from the coating by rinsing.

Abstract: A process for the preparation of undenaturated triple helix collagen, starting form animal tendons or cutis, by extraction with diluted organic acids, precipitation with salts, optional gelation and/or lyophilization, tangential filtration.The obtained collagen shows favorable purity characteristics, is not allergenic and more effective in the healing processes than collagens obtained by known methods.