Abstract: Provided are live, artificial, skin substitute products and methods of making and using the same, such as for wound treatment and compound testing, including compound testing for efficacy, toxicity, penetration, irritation and/or metabolism testing of drug candidates or compositions such as cosmetics.

Abstract: Blends of enzymes of the same enzyme class (same EC number), such as beta-glucuronidase enzyme blends, are provided that exhibit synergistic levels of activity across a range of substrates as compared to the activity levels of each enzyme in the blend individually. The blends also may exhibit a greater effective substrate range, as well as greater effective pH and/or temperature ranges as compared to single enzyme preparations. Predictive methods for determining optimal enzyme blends, methods for preparing enzyme blends, enzyme blend compositions, enzyme blend formulations and methods of using such enzyme blends are provided.

Abstract: Systems and methods for preparing synthetic osteoinductive bone grafts are provided in which a porous ceramic granule, which may be incorporated within a biocompatible matrix material, is loaded with an osteoinductive agent. Loading of granules is facilitated in some cases by the use of low-pH buffers and pre-treatments.

Abstract: The present invention relates to a carrier composition for particulate and granular bone substitute materials which is a hydrogel comprising a mixture of ethylene oxide (EO)-propylene oxide (PO) block copolymers and silica nanoparticles embedded therein. The present invention further relates to a bone substitute material containing osteoconductive and/or osteoinductive particles or granules in addition to the novel carrier composition. Processes for producing the novel carrier composition and the novel bone substitute material are likewise provided in the context of the invention.

Abstract: An implantable composition is provided. The composition comprises porous ceramic granules. The porous ceramic granules comprise hydroxyapatite in an amount of about 8 to about 22 wt. % and beta-tricalcium phosphate in an amount of about 78 to about 92 wt. % based on a total weight of a ceramic granule. The composition includes a collagen carrier, and the porous ceramic granules have an average diameter from about 50 ?m to 800 ?m. Methods of making are also disclosed.

Abstract: Blends of enzymes of the same enzyme class (same EC number), such as beta-glucuronidase enzyme blends, are provided that exhibit synergistic levels of activity across a range of substrates as compared to the activity levels of each enzyme in the blend individually. The blends also may exhibit a greater effective substrate range, as well as greater effective pH and/or temperature ranges as compared to single enzyme preparations. Predictive methods for determining optimal enzyme blends, methods for preparing enzyme blends, enzyme blend compositions, enzyme blend formulations and methods of using such enzyme blends are provided.

Abstract: The invention relates to a composition containing extracts of the fruit of Hovenia dulcis Thunb., gallocatechin, and methyl vanillate as active ingredients for preventing and treating bone disease. The extracts of the fruit of Hovenia dulcis Thunb., the gallocatechin, and the methyl vanillate according to the present invention are natural materials and thus cause no side effects, and may activate the Wnt/?-catenin pathway to promote bone formation rather than inhibiting bone decomposition, and therefore may be effective in treating osteoporosis and related diseases. In addition, the extracts of the fruit of Hovenia dulcis Thunb., the gallocatechin, and the methyl vanillate according to the present invention may have the effects regrowing hair and preventing and treating wounds and metabolic diseases related to the activation of Wnt/?-catenin pathway.

Abstract: A solid dosage form for injection and a method of making said dosage form wherein the dosage form has a moisture content of 5% (w/w) or less. The solid dosage form comprises a dried matrix including a first excipient and 0.01 to 50% (w/w) or more than 50% and up to 80% (w/w) of a therapeutic peptide; and one or more additional excipients and at least 5% (w/w) of CMC, based on the total weight of the solid dosage form, wherein the dosage form has a width of 0.5 mm to 2 mm.

Abstract: Provided herein are new compositions and methods to target pharmaceutical agents to pathological areas by utilizing fusion polypeptides. These fusion polypeptides contain two or more domains: (i) aptamer sequences that bind to exposed collagenous (XC-) proteins present in pathological areas, including cancerous and viral lesions, (ii) immunomodulators, such as cytokines, and optionally (iii) at least one linker joining the two domains or at the terminus of the polypeptide. In some cases, the linker is a rigid linker, e.g., a rigid helical linker. Also provided herein are methods of treating cancer and/or infectious diseases using the new fusion polypeptides.

Abstract: The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.

Abstract: Compositions for the inhibition of SUV39H1 methyltransferase activity and methods of use thereof are provided. The disclosed compositions may be used for treating certain types of cancer, inducing apoptosis in a cancer cell, increasing cell sensitivity to FasL-induced apoptosis, and overcoming cancer cell resistance to apoptosis and/or certain types of cancer immunotherapy.

Abstract: The present invention provides compositions comprising hyaluronan with high elasticity, as well as methods for improving joint function, reducing pain associated with joint function and treating osteoarthritis by introducing into a joint a therapeutically effective amount of a composition comprising hyaluronan with high elasticity.

Abstract: A bone-repairing agent excellent in workability and applicability to clinical surgical techniques and having a drastically enhanced bone formation rate, obtained by including an elastin hydrolysate in a complex of DNA and at least one selected from the group consisting of protamine, a protamine derivative, and a protamine hydrolysate can be provided. A medical or dental material for bone formation using this bone-repairing agent can be provided.

Abstract: Osteogenic compositions include a decellularized extracellular matrix tissue and bone morphogenic protein, preferably BMP-2. The compositions make beneficial use of the BMP, which can be used at relatively low doses and can bind to native components (e.g., native sulfated glycosaminoglycans such as heparin and/or heparan sulfate) remaining in the decellularized extracellular matrix tissue. Methods for preparation and use of such compositions are also described. The compositions and related methods can be used in the treatment of diseased or damaged bone tissue.

Abstract: The invention relates to truncated BMP-4 growth factors and variants thereof. The invention also relates to methods of making and using the truncated BMP-4 growth factors.

Abstract: The invention relates to truncated BMP-7 growth factors and variants thereof. The invention also relates to methods of making and using the truncated BMP-7 growth factors.

Abstract: Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Abstract: The invention relates to a composition comprising an aqueous admixture of ceramic particles, polysaccharide, a therapeutic agent and, optionally, a polymer, and methods of using the same. The present invention provides a flowable bone void filler for use in medical situations where bone regeneration is desired. In an exemplary embodiment the bone void filler comprises a polysaccharide, a ceramic material and a polymer that exhibits thermosetting properties such that it exists as a viscous liquid at room temperatures and as a gel at about body temperature. In another exemplary embodiment the bone void filler comprises a polysaccharide, a ceramic material, a polymer that exhibits thermosetting properties such that it exists as a viscous liquid at room temperature and as a gel at about body temperatures, and a therapeutic agent.

Abstract: Disclosed are a peptide for promoting osteogenesis and vascularization, and the use thereof. The peptide has a low molecular weight so that it can be economically produced. In addition, it promotes osteoblastic differentiation, thus inducing osteogenesis. Further, the peptide can promote the expression of VEGF, resulting in vascularization. Accordingly, the peptide is useful for the delay of the onset of ischemic diseases and the therapy of ischemic diseases.

Abstract: The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto.

Abstract: A malleable bone graft composition is described. The composition comprises: (a) keratose; (b) particulate filler; (c) antibiotic; and (d) water. The invention may be provided in sterile form in an container, and optionally lyophilized. Methods of treating a fracture with such compositions are also described.

Abstract: This invention relates, e.g., to a synthetic compound, Oxy149, having the structure (Formula I) or a bioactive or pharmaceutical composition comprising Oxy149 and a pharmaceutically acceptable carrier. Methods are also disclosed for using the compound or bioactive or pharmaceutical composition to treat a variety of disorders, including e.g. bone disorders, obesity, cardiovascular disorders, and neurological disorders. Oxy149 can be delivered either locally or systemically.

Abstract: A method for identifying a kidney transplant recipient at an increased risk of developing interstitial fibrosis or tubular atrophy which comprises obtaining a post-transplant urine sample from the kidney transplant recipient; measuring the level of clusterin in the urine sample; comparing the level of clusterin in the patient sample to the level of clusterin in a control sample from the urine of a non-fibrotic kidney transplant recipient; diagnosing a kidney transplant recipient with a clusterin level that is significantly higher than the clusterin level in the control as being at an increased risk of developing interstitial fibrosis or tubular atrophy.

Abstract: There is provided a bone filler material comprising a plurality of particles, each particle comprising a biodegradable outer shell and an inner core. There is also provided an implant prepared from the same, methods of using the same and preparing the same.

Abstract: Bone- and metal-targeted polymeric nanoparticles are provided. Exemplary nanoparticles have three main components: 1) a targeting element that can selectively bind to bone, minerals, or metal ions; 2) a layer of stealth to allow the polymer to evade immune response; and 3) a biodegradable polymeric material, forming an inner core which can carry therapeutics or other diagnostics. Preferred nanoparticles contain a blend of target-element polymer conjugate and polymer that optimizes the ligand density on the surface of the nanoparticle to provide improved targeting of the nanoparticle. The ratio of target-element polymer conjugate to polymer can also be optimized to improve the half-life of the nanoparticles in the blood of the subject. The nanoparticles also exhibit prolonged, sustained release of therapeutic agents loaded into the particles.

Abstract: This invention relates, e.g., to a synthetic compound, Oxy133, having the structure [Formula I] or a bioactive or pharmaceutical composition comprising Oxy133 and a pharmaceutically acceptable carrier. Methods are also disclosed for using the compound or bioactive or pharmaceutical composition to treat a variety of disorders, including e.g. bone disorders, obesity, cardiovascular disorders, and neurological disorders.

Abstract: The invention relates to novel biosynthetic growth factor mutants which exhibit improved biological activity.

Abstract: Described herein are methods, uses, and pharmaceutical compositions for treating heart disease that include a bone morphogenetic protein (BMP). In addition, described herein are methods, uses, and compositions for preventing or slowing fibrosis in diseased or injured tissue, and/or for preventing or slowing cell death in diseased or injured tissue.

Abstract: Provided are systems for controlled release of proteins from decomposable thin films constructed by layer-by-layer deposition. Such films generally comprise alternating layers of polymers and proteins, and may further comprise additional layers of polyions. In some embodiments, decomposable thin films and methods of using such films allow proteins to be released over an extended period of time and/or retention of as much as 100% of function of released protein.

Abstract: The present invention relates to a device having osteoinductive and osteoconductive properties in vivo comprising a carrier containing calcium phosphate and an osteoinductive protein, wherein the carrier is homogenously coated with the protein. Moreover, the present invention relates to a method for the production of a device having osteoinductive and osteoconductive properties in vivo. The invention encompasses a pharmaceutical composition comprising the device of the invention or a device which is obtainable by the method of the invention and relates to the use of the device for the preparation of a pharmaceutical composition to be used for bone augmentation, for treating bone defects, for treating degenerative and traumatic disc disease, for treating bone dehiscence or to be used for sinus floor elevation. Finally, the invention relates to a kit comprising the device of the invention or a device which is obtainable by the method of the invention.

Abstract: Disclosed herein are heretofore undescribed preparations of highly concentrated, solubilized proteins, such as but not limited to, Bone Morphogenetic Proteins. Such protein preparations can be formulated in an aqueous carrier at protein concentrations in excess of 10 mg/ml when using the methods of manufacture taught herein. Such methods yield stable protein preparations in either solubilized or lyophilized form. The protein preparations of the present invention are particularly beneficial when administered either locally or systemically, in part, because low administration volumes can be accomplished. This is especially important for local treatment of certain anatomic locations such as, for example, the synovial fluid of a joint when treating osteoarthritis with BMP-7 or the intradiscal space when treating degenerative disc disease with BMP-7.

Abstract: The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

Abstract: The present invention relates to compositions comprising shape memory polymer (SMP) materials and uses thereof. Particularly, although not exclusively, the present invention relates to biocompatible shape memory polymer (SMP) materials and uses thereof in the medical field.

Abstract: Osteogenic implants, carriers and concentrates are described, along with methods of making and using the same. The implants include a carrier and, optionally, an osteoinductive agent. The carrier includes a mineral component, a binder and, optionally, a collagen additive, while the osteoinductive agent may be a protein such as a bone morphogenetic protein.

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: Osteogenic compositions include a decellularized extracellular matrix tissue and bone morphogenic protein, preferably BMP-2. The compositions make beneficial use of the BMP, which can be used at relatively low doses and can bind to native components (e.g., native sulfated glycosaminoglycans such as heparin and/or heparan sulfate) remaining in the decellularized extracellular matrix tissue. Methods for preparation and use of such compositions are also described. The compositions and related methods can be used in the treatment of diseased or damaged bone tissue.

Abstract: The invention relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors. The invention further relates to compositions including a protease and a growth factor comprising a bone morphogenic protein (BMP) or a variant thereof. The invention also relates to methods of using the composition.

Abstract: Disclosed herein are an in situ-forming, bioadhesive hydrogel and the medical uses thereof. Being formed by in situ crosslinking through an enzymatic reaction, the hydrogel has an advantage over conventional bioadhesive hydrogels in terms of biocompatibility. In addition, the in situ-forming bioadhesive hydrogel has excellent biocompatibility and mechanical strength and has excellent tissue adhesiveness thanks to modification with/without dopa derivatives. The hydrogel finds a variety of applications in the biomedical field, including bioadhesives or hemostats, implant substances for tissue regeneration and augmentation, carriers for delivering biologically active materials or drugs, etc.

Abstract: The present invention provides methods of repairing and regenerating cartilage tissue using a soluble morphogenic protein complex comprising (a) a morphogenic protein; and (b) a morphogenic protein pro region isolated from a morphogenic protein, or a conservative substitution variant or a fragment of said pro region, wherein said pro region or variant or fragment is noncovalently linked to the morphogenic protein, and wherein said complex is more soluble in an aqueous solvent than said morphogenic protein alone.

Abstract: The present invention provides a multi-compartment hydrogel, and a sulfated polysaccharide and at least two bioactive polypeptides capable of binding said sulfated polysaccharide, for use in repair or regeneration of a damaged tissue in a mammal. Also provided is a method for constructing the multi-compartment hydrogel. The present invention also provides a method for the repair or regeneration of a damaged tissue in a mammal, and a kit for constructing a multi-compartment hydrogel.

Abstract: The technology described herein relates to treatments for, e.g., diastolic heart failure, cardiac hypertrophy, and related conditions.

Abstract: The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.

Abstract: A bone implant primer is provided. A biodegradable hydrogel component is provided. A plurality of biomolecule release depots are dispersed within the biodegradable hydrogel component wherein the plurality of biomolecule release depots comprise biomolecules for aiding implant osseointegration or biomolecules for mitigation of foreign body response. Different biomolecules may be released by the microspheres at different times.

Abstract: This invention provides a method of promoting bone healing by locally administering a vanadium-based insulin mimetic agent to a patient in need thereof. The invention also provides a new use of insulin-mimetic vanadium compounds for manufacture of medicaments for accelerating bone-healing processes. In addition, the invention also encompasses a bone injury treatment kit suitable for localized administration of insulin-mimetic vanadium compounds or compositions thereof to a patient in need of such treatment.

Abstract: Described are implantable, malleable medical materials comprising mineral particles, insoluble collagen fibers, and a gel-forming polysaccharide component and/or another added gel-former. The malleable medical materials can be used treat bone or other tissue defects in patients, including in conjunction with biologically active factors such as osteogenic proteins. Also described are methods and materials that can be used to prepare the malleable medical materials.

Abstract: Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Abstract: The claimed invention provides a fusion polypeptide comprising a fibrous protein domain and a mineralization domain. The fusion is used to form an organic-inorganic composite. These organic-inorganic composites can be constructed from the nano- to the macro-scale depending on the size of the fibrous protein fusion domain used. In one embodiment, the composites can also be loaded with other compounds (e.g., dyes, drugs, enzymes) depending on the goal for the materials, to further enhance function. This can be achieved during assembly of the material or during the mineralization step in materials formation.

Abstract: Pharmaceutical gels and methods for delivering a therapeutic agent to a target tissue site beneath the skin of a patient are provided, the gel being capable of adhering to the target tissue site and comprising one or more biodegradable depots containing an effective amount of the therapeutic agent. In various embodiments, the gel is sprayable and hardens after contacting the target tissue site.

Abstract: A method of correcting spinal deformity, which includes locating pharmaceutical-loaded implants adjacent to targeted spinal growth plates, and then eluting the pharmaceutical onto the growth plates. Preferably, the method involves correcting spinal deformity by simply inserting a pharmaceutical-eluting pedicle screw onto the concave side of a scoliotic curve. The screw has a cannulated internal reservoir that contains a chondrocyte growth-inducing pharmaceutical (such as a growth factor or small molecule) and at least one fenestration that allows the pharmaceutical to elute onto the vertebral body growth plate.

Abstract: A method for producing core-shell type particles, including: ring-opening polymerizing a ring-opening polymerizable monomer in a first mixture containing the ring-opening polymerizable monomer, porous particles, and a compressive fluid; and injecting a second mixture containing a polymer obtained in the ring-opening polymerizing, the porous particles, and the compressive fluid to thereby granulate into the core-shell type particles.