Abstract: Methods for reducing the severity of an arthritic condition or repairing an osteochondral defect are carried out by administering to a subject compositions comprising a member of the matrilin family of proteins, e.g., a matrilin protein, fragment thereof, or nucleic acid encoding the protein or fragment.

Abstract: This invention relates to articular cartilage mimetics and processes to make them using a composite of and electrospun fiber and a hydrogel.

Abstract: Neo-cartilage constructs suitable for implantation into a joint cartilage lesion in situ and a method for repair and restoration of function of injured, traumatized, aged or diseased cartilage. The construct comprises at least chondrocytes incorporated into a support matrix processed according to the algorithm comprising variable hydrostatic or atmospheric pressure or non-pressure conditions, variable rate of perfusion, variable medium composition, variable temperature, variable cell density and variable time to which the chondrocytes are subjected.

Abstract: The invention provides biomatrix compositions comprising cross-linked lactoferrin, either alone or in combination with other organic or inorganic components. Also provided are methods of making and using the biomatrix compositions. As described herein, cross-linked lactoferrin biomatrix retains the bioactivities of the lactoferrin molecule. The biomatrix composition can act as a matrix for cell adhesion and growth and is particularly useful in musculoskeletal tissue regeneration. The biomatrix compositions can be pre-formed or injectable and can act as a cell, drug or protein delivery vehicle.

Abstract: The present invention relates to the expression and regulating growth factors in chrondrocytes and developing cartilage, particularly granulin-epithelin precursor (GEP). The invention relates to the modulation and manipulation of these growth factors, GEP, and/or the molecules they interact with, for instance COMP, in cartilage disorders, including arthritis. Assays and screening methods for the determination of the expression and activity of GEP, or of GEP-COMP, are provided, including for screening for the presence or extent of cartilage or arthritic disease and for identifying modulators or compounds/agents for treatment or prevention of cartilage or arthritic diseases.

Abstract: A method of fabricating a collagen structure, is disclosed. The method comprises applying onto a surface in a layerwise manner acidic solutions of liquid crystalline collagen and a crosslinker to form a layered structure. The acidic solutions that correspond to at least two adjacent layers have different concentrations of the crosslinker therein.

Abstract: The present invention provides methods of repairing and regenerating cartilage tissue by administering into the cartilage or the area surrounding the cartilage a composition comprising a therapeutically effective amount of a morphogenic protein.

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: This invention relates to a novel use of IL-1?-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1? ligand-IL-1 receptor interaction, IL-1? antibodies or IL-1 receptor antibodies, e.g. IL-1? binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1? binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1? ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Abstract: Provided herein are compositions and methods related to promoting protection or repair of articular cartilage and/or musculoskeletal soft tissue by contacting the cartilage, tissues or cellular components thereof with a parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor agonist or releasing factor.

Abstract: FGF18 is known to stimulate the proliferation of chondrocytes, resulting in increased cartilage formation. When hyaluronic acid is administered in addition to FGF18, the effects on chondrocyte proliferation and production of matrix were found to be greater than administration of FGF18 or hyaluronic acid alone.

Abstract: An article comprising two chemically grafted polymer layers comprising a hydrogel layer and an end-functionalized polyurethane layer. The invention also includes methods of making and using the article.

Abstract: The present invention relates to novel drug depot implant designs for optimal delivery of therapeutic agents to subjects. The invention provides a method for alleviating pain associated with neuromuscular or skeletal injury or inflammation by targeted delivery of one or more therapeutic agents to inhibit the inflammatory response which ultimately causes acute or chronic pain. Controlled and directed delivery can be provided by drug depot implants, comprising therapeutic agents, specifically designed to deliver the therapeutic agent to the desired location by facilitating their implantation, minimizing their migration from the desired tissue location, and without disrupting normal joint and soft tissue movement.

Abstract: The present invention relates to pharmaceutical compositions for a combination therapy with a cytokine antagonist and a corticosteroid. By means of the combination therapy diseases such as osteoarthritis, tendon injuries and/or degenerative spinal diseases can be treated.

Abstract: The present invention relates to peptides or fragments thereof, which peptides bind to mesenchymal stem cells. The present invention also relates to a method for identifying, isolating, specifically selecting and/or enriching mesenchymal stem cells, wherein the peptides, or fragments thereof, are employed for specifically binding to the mesenchymal stem cells. Also, the present invention relates to the use of the peptides of the invention, or fragments thereof, and of the mesenchymal stem cells isolated with the peptides of the invention, or fragments thereof, for treating, injuries and/or degenerated bone, cartilage or tissues.

Abstract: Therapeutic and cosmetic uses and applications of calreticulin are provided. In particular, the invention relates to therapeutic and cosmetic uses and applications of calreticulin to a patient in need of such treatment including in tissue repair, wound healing, ulcers, reducing scar formation, and reducing or eliminating wrinkles.

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: Disclosed herein are novel peptide amphiphile molecules and compositions composed of a peptide sequence that non-covalently binds the growth factor TGF-?1. Also disclosed are methods of using these peptide amphiphiles to create a gel scaffold in situ that enhances articular cartilage regeneration when used in combination with microfracture. Significant improvement in tissue quality and overall O'Driscoll histological scores were observed in rabbits with full thickness articular cartilage defects treated with the TGF-binding peptide amphiphile. The gel can further serve as a delivery vehicle for recombinant TGF-?1 protein growth factor. Scaffolds that localize and retain chondrogenic growth factors may synergistically enhance cartilage repair when combined with microfracture, by inducing bone marrow mesenchymal stem cells into chondrogenic differentiation. This invention represents a promising new biomimetic approach to enhance current techniques of articular cartilage regeneration in the clinical setting.

Abstract: The present invention relates to a novel composition comprising an implant, scaffold or construct bound to a biological or chemical moiety. The bound moiety has the ability to bind to a component of the extracellular matrix of biological tissue, allowing the implant to be bound to the biological tissue in a short period of time after implantation. The invention also relates to the use and manufacture of this novel composition, as well as a novel use for the protein CNA.

Abstract: Disclosed are novel methods of maintaining articular cartilage health in an atraumatic, non-diseased joint of a mammal, either human or non-human. The methods involve injecting into the joint capsule of the mammal an amount of a lubricin polypeptide to prevent shear-induced chondrocyte apoptosis and to maintain a lubricin-expressing phenotype of chondrocytes.

Abstract: An artificial cartilage comprising 15-95% by mass of collagen, 4.9-70% by mass of proteoglycan, and 0.1-20% by mass of hyaluronic acid.

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 peptides and antibodies which bind to melanoma inhibitory activity protein and the uses of such peptides and antibodies. The invention also relates to nucleic acids coding for such peptides or antibodies. The invention also relates to pharmaceutical compositions comprising such peptides or antibodies or such nucleic acids. The present invention also relates to small molecule compounds which bind to melanoma inhibitory activity protein and to uses of such small molecule compounds. Moreover, the present invention also relates to a method of preventing dimerization and/or aggregation of melanoma inhibitory activity (MIA) protein. The invention is based on the identification of the relevant sites of interaction of the MIA protein with the inhibitory peptides/antibodies.

Abstract: The present invention provides a biocompatible material in the form of a water insoluble cross-linked gel, which contains a stable complex of TNF-stimulated gene 6 protein (TSG-6) and hyaluronan.

Abstract: The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

Abstract: This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Abstract: The present invention encompasses methods and compositions for generating a biomimetic proteoglycan. The invention includes methods of treating a disease, disorder, or condition of soft tissue using a biomimetic proteoglycan.

Abstract: Compositions and methods are provided for promoting elastin fiber formation (elastogenesis) in a cell, including methods that comprise contacting a cell that is capable of elastogenesis with (i) a mutated biglycan polypeptide that lacks chondroitin sulphate proteoglycan chains, (ii) a versican V3 isoform polypeptide that lacks most or all of the polypeptide regions encoded by one or more of exons 4, 5 or 6 or by exons 9-10 or 11-13, and/or with (iii) metastatin.

Abstract: Provided herein are methods and devices for inducing the formation of functional replacement nonarticular cartilage tissues and ligament tissues. These methods and devices involve the use of osteogenic proteins, and are useful in repairing defects in the larynx, trachea, interarticular menisci, intervertebral discs, ear, nose, ribs and other fibrocartilaginous tissues in a mammal.

Abstract: A carrier matrix may be delivered to a target position within a patient in a minimally invasive manner by first cutting a collagen sponge sheet into a plurality of relatively small pieces. These pieces are sized so that, when wet, they are capable of flowing through a cannula and/or reduced-diameter syringe tip. The pieces are placed into a syringe and wetted, say with a morphogenic solution, and optionally mixed with a bulking material, which is similarly sized to fit through the cannula. The thoroughly mixed and wetted product forms a viscous aggregate which may then be injected into the patient at the target site.

Abstract: The present invention relates to pharmaceutical compositions for a combination therapy with a cytokine antagonist and a corticosteroid. By means of the combination therapy diseases such as osteoarthritis, tendon injuries and/or degenerative spinal diseases can be treated.

Abstract: The present invention relates to the expression and regulating growth factors in chrondrocytes and developing cartilage, particularly granulin-epithelin precursor (GEP). The invention relates to the modulation and manipulation of these growth factors, GEP, and/or the molecules they interact with, for instance COMP, in cartilage disorders, including arthritis. Assays and screening methods for the determination of the expression and activity of GEP, or of GEP-COMP, are provided, including for screening for the presence or extent of cartilage or arthritic disease and for identifying modulators or compounds/agents for treatment or prevention of cartilage or arthritic diseases.

Abstract: A method and a composition for photochemical cross linking of collagen by photoactive agent in-vivo are presented. The method includes a non-toxic photoactive formulation of the composition with collagen, which is administered to treatment area locally; followed by irradiation with suitable wavelength. In one of the embodiment liposomal formulated mTHPC is added to the collagen and is irradiated with a 652 nm laser, resulting in producing efficient collagen scaffolds with strengthen and stabilized microstructure, thus improving the physiochemical properties of the collagen scaffold. It improves the thermostability, mechanical property and swelling ratio of newly formed scaffold. Photochemical cross-linked collagens shows antimicrobial effect, when irradiated with suitable wavelength it disinfects the treatment site and curbs microbial growth.

Abstract: The present invention describes a new bioresorbable filler constituted by hyaluronic acid and/or the derivatives thereof structured with/in phospholipid liposomes, which increase the residence time of the starting polymer in situ. Said fillers described herein are substantially intended to increase the soft tissues in aesthetic surgery and dermocosmetics for the correction of mild to medium defects, but because of their special characteristics they can also be used in other fields of application.

Abstract: Subjects lacking Nfat1 display osteoarthritis in weight-bearing joints. Osteoarthritic changes associated with Nfat1 deficiency are characterized by articular cartilage degradation, articular chondrocyte proliferation/clustering, progressive articular surface destruction, periarticular chondro-osteophyte formation, and exposure of thickened subchondral bone. Methods of treating osteoarthritis, methods of diagnosis and early prediction of the onset of osteoarthritis, and methods for screening drug candidates that may be useful for treatment of osteoarthritis are presented.

Abstract: The present invention provides a peptide comprising an amino acid sequence of SEQ ID NO: 1, a variant thereof and a pharmaceutically acceptable salt thereof. A novel peptide of the present invention, a variant thereof and a pharmaceutically acceptable salt thereof are effective for treating and/or preventing degenerative disc diseases, treating body organ fibrosis, treating cancer and/or treating glomerulosclerosis, and are effective for the inhibition of TGF-beta1 signaling.

Abstract: This invention relates to oral and intra-articular formulations based on sulphated hyaluronic acid which are effective in the treatment of degenerative osteoarthritis.

Abstract: Provided herein are methods for enhancing bone mineralization for bone repair or regeneration and compositions and grafts therefor. Methods for screening agents that enhance or modulate NELL-1 gene expression or NELL-1 protein production in a cell are also provided.

Abstract: Novel peptides are described which comprise an amino acid motif selected from the group consisting of “PG”, “GP”, “PI” and “IG” and having up to 10 amino acids upstream and/or downstream of the amino acid motif, wherein “P” in the motif is proline or hydroxyproline and the peptide stimulates the development, maintenance and repair of bone, cartilage and associated connective tissue. The invention further relates to pharmaceutical compositions of these peptides, as well as therapeutic and prophylactic uses of such peptides.

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: A carrier matrix may be delivered to a target position within a patient in a minimally invasive manner by first cutting a collagen sponge sheet into a plurality of relatively small pieces. These pieces are sized so that, when wet, they are capable of flowing through a cannula and/or reduced-diameter syringe tip. The pieces are placed into a syringe and wetted, say with a morphogenic solution, and optionally mixed with a bulking material, which is similarly sized to fit through the cannula. The thoroughly mixed and wetted product forms a viscous aggregate which may then be injected into the patient at the target site.

Abstract: An object of the present invention is to enable the repair and regeneration of articular cartilage, which could not be achieved by conventional therapies, and to provide a safe and inexpensive agent that is effective for the treatment of joint diseases such as osteoarthritis. According to the present invention, a combined formulation for simultaneously, separately, or sequentially administering a hyaluronic acid and an animal mucin-type glycoprotein for the treatment of joint diseases is provided.

Abstract: Provided are a substrate for cartilage cultivation, which exhibits high safety and has a growth promoting effect on cartilage cells, and a method for cartilage regeneration treatment. The substrate for cartilage cultivation containing artificial collagen, in particular, an artificial collagen aqueous solution has a growth promoting effect on cartilage cells. A cartilage regeneration effect is obtained by the intraarticular injection of the substrate in and around a cartilage defect site.

Abstract: The applications and medical devices of Midkine in the field of biotechnology are described in this invention. This invention describes the applications of the protein as follow in (a) or (b) in preparing drugs for promoting cartilage growth or treating cartilage diseases, the protein as a growth factor for promoting chondrocyte proliferation, or medical devices containing this protein: (a) the protein whose amino acid sequence is shown as SEQ ID NO.1; (b) the proteins whose amino acid sequence have at least 60% homology comparing with amino acid sequence described in (a) and have activity for promoting proliferation of chondrocyte. The protein described in this invention promotes proliferation of three types of chondrocytes and is used for preparing drugs for treating cartilage disease. It may provide new therapy for treating cartilage diseases clinically, and new technology for expansion of chondrocytes in vitro for cartilage tissue engineering.

Abstract: This invention relates, in part, to unique and newly identified genetic polynucleotides involved in the process of bone remodeling; variants and derivatives of the polynucleotides and corresponding polypeptides; uses of the polynucleotides, polypeptides, variants and derivatives; and methods and compositions for the amelioration of symptoms caused by bone remodeling disorders. Disclosed in particular are, the isolation and identification of polynucleotides, polypeptides, variants and derivatives involved in osteoclast activity, validation of the identified polynucleotides for their potential as therapeutic targets and use of the polynucleotides, polypeptides, variants and derivatives for the amelioration of disease states and research purposes.

Abstract: The present invention concerns improved osteoinductive materials comprising matrix materials and morphogenetic proteins, wherein depending on the subject matter the proteins may be dimeric or monomeric proteins. The osteoinductive materials according to the present invention have improved properties. The invention further concerns methods for producing the respective improved osteoinductive materials.

Abstract: A linear or cyclic peptide and the use of said peptide in medicine and especially in the manufacture of a medicament for the treatment and/or prophylaxis of a disease associated with inflammatory mediated cartilage destruction. The minimal core sequence of the linear or cyclic peptide is WLEAK (SEQ ID No. 1). Alternatives are WLEAR (SEQ ID NO. 17) and WLDAK (SEQ ID No. 18).

Abstract: The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGF?). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

Abstract: The present invention provides a storage-stable composition containing a parathyroid hormone-related protein (PTHrP) analogue and methods of using a PTHrP analogue and the PTHrP compositions described herein to treat osteoporosis, to increase bone mass or to increase bone quality. The composition is storage stable, in sterile form, and in general may be stored at room temperature for at least several weeks to allow convenient parenteral administration to human patients.

Abstract: A carrier matrix may be delivered to a target position within a patient in a minimally invasive manner by first cutting a collagen sponge sheet into a plurality of relatively small pieces. These pieces are sized so that, when wet, they are capable of flowing through a cannula and/or reduced-diameter syringe tip. The pieces are placed into a syringe and wetted, say with a morphogenic solution, and optionally mixed with a bulking material, which is similarly sized to fit through the cannula. The thoroughly mixed and wetted product forms a viscous aggregate which may then be injected into the patient at the target site.