Abstract: This present invention relates to pharmacologically potent and stable human fibroblast growth factor 21 (FGF21) proteins, pharmaceutical compositions comprising FGF21 proteins, and methods for treating type 2 diabetes, obesity, dyslipidemia, and/or metabolic syndrome using such proteins.

Abstract: The present invention relates to devices and related methods for treating fistulas such as anal or recto-vaginal fistulas, in particular by the use of a seton to secure a tissue growth promoter such as a growth factor and/or fibrin. The various devices are particularly suitable for positioning tissue growth promoters securely within a fistula. Thus, one device comprises a seton and a tissue growth promoter. Further related aspects of the invention included devices comprising an enclosure provided in between portions of a seton, devices comprising a seton and a plurality of holes for enabling the device to be sutured to tissue, devices comprising a probe and a seton that are releasably connectable end-to-end, devices comprising an attachment device to secure the ends of a seton, and devices comprising a fistula plug adapted to be secured to a section.

Abstract: Described herein is a cell tissue gel cross-linked with a cross-linking agent, and a quenching agent bound to a reactive group of the cross-linking agent.

Abstract: Methods and compositions are described to regenerate cartilage in a partial thickness defect or area of reduced volume of articular cartilage comprising an infiltration suppressor agent and a columnar growth promoting agent.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, wherein the FGF 21 mutant polypeptides comprise two or more mutations, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: The invention relates to an isolated amino acid that can act as an antagonist to FGF signaling, comprising at least a portion of the FGF protein amino acid sequence, and including a mutation in either a) the integrin ?v?3 binding region of FGF-1; or b) the FGFR binding region of FGF-1.

Abstract: Provided are novel biocompatible copolymers and compositions comprising the copolymers. The copolymers are non-toxic and typically have an LCST below 37° C. Compositions comprising the copolymers can be used for wound treatment, as a cellular growth matrix or niche and for injection into cardiac tissue to repair and mechanically support damaged tissue. The copolymers comprise numerous ester linkages so that the copolymers are erodeable in situ. Degradation products of the copolymers are soluble and non-toxic. The copolymers can be amine-reactive so that they can conjugate with proteins, such as collagen. Active ingredients, such as drugs, can be incorporated into compositions comprising the copolymers.

Abstract: Methods of treating metabolic diseases and disorders using a FGF21 polypeptide are provided.

Abstract: Disclosed are an artificial dura mater and manufacturing method thereof. The artificial dura mater includes electrospun layers prepared by electrostatic spinning, at least one of which is a hydrophobic electrospun layer. Further, above the hydrophobic electrospun layer, there can be at least one hydrophilic electrospun layer. A transition layer can be further included between the hydrophobic and the hydrophilic electrospun layers. Additionally, cytokines and/or medicines can be affixed to either or both of the hydrophobic and the hydrophilic electrospun layers, by way of bio-printing. The disclosed artificial dura mater shows good biocompatibility, enhances dural tissue regeneration, achieves excellent repairing effects, prevents adhesion, allows complete absorption, has good mechanical properties, ensures low infection rates, and can be loaded with therapeutic agents.

Abstract: Compositions and methods of using the compositions are provided for forming an embolus within a region of an anatomical lumen for a transitory period in order to achieve a therapeutic effect.

Abstract: A system for growing tissue based upon layers of an inorganic extracellular matrix, wherein each layer of the inorganic matrix is designed to dissolve at a separate rate and result in sequential growth factor delivery upon its dissolution.

Abstract: The invention generally relates to systems (i.e. constructs) for repairing cartilage and methods for preparing the same that introduce a bioactive agent into a culture medium, suspension, scaffold, solution incorporated into the pores of the scaffold, or combinations thereof. The introduction of a bioactive agent promotes production of neo-cartilage (i.e. immature hyaline cartilage) in the system, both ex-vivo and in-vivo.

Abstract: In some aspects, the present invention provides surgical procedures that comprise applying compositions into and/or onto tissue, including supporting tissues (e.g., ligaments, connective tissue, muscles, etc.) for pelvic organs, among other tissues. In other aspects, the present disclosure pertains to compositions that are useful for performing such procedures. In still other aspects, the present disclosure pertains to kits that are useful for performing such procedures.

Abstract: Prolonged or extended release of bioactive protein is achieved using an affinity-based approach which exploits the specific binding of Src homology 3 (SH3) domain with short proline-rich peptides. Specifically, methylcellulose was modified with SH3-binding peptides (MC-peptide) with either a weak affinity or strong affinity for SH3. Controlled release of chondroitinase ABC (ChABC) is also described.

Abstract: The present invention relates to a method of modulating a release of biomolecules having heparin-binding affinity, and more specifically, to a method of modulating a release of biomolecules having heparin-binding affinity, using thiolated heparin adsorbed on metal surface. According to the present invention, it is possible to modulate various biomolecules having heparin-binding affinity such as growth factors spatiotemporally by external electrical stimulations, without causing cytotoxicity and having deteriorating effects on cell activity. Thus, the present invention can be applied for various biomedical and biotechnical fields including drug delivery, biosensor, and cell culture.

Abstract: There is provided a composition for controlling formation and/or stabilization of a blood vessel comprising a first isolated nucleic acid molecule that encodes a FGF-9 polypeptide and optionally one or more isolated nucleic acid molecule that encodes another angiogenic polypeptide. There is provided a composition for controlling formation and/or stabilization of a blood vessel comprising administering an effective amount of a composition comprising an isolated FGF-9 polypeptide and one or more other angiogenic polypeptides. The compositions provided herein may be useful for controlling angiogenesis and/or vasculogenesis.

Abstract: Methods for preventing incisional hernia formation and acute wound failure are described. More particularly, methods are described for preventing incisional hernia formation and acute wound failure by administering a composition comprising basic fibroblast growth factor. In addition, a drug delivery device to administer basic fibroblast growth factor is described.

Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidaemia, obesity, and fatty liver.

Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Abstract: This present invention relates to pharmacologically potent and stable human fibroblast growth factor 21 (FGF21) proteins, pharmaceutical compositions comprising FGF21 proteins, and methods for treating type 2 diabetes, obesity, dyslipidemia, and/or metabolic syndrome using such proteins.

Abstract: This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder—Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.

Abstract: The present invention is directed to novel chimeric fibroblast growth factor (FGF) polypeptides, novel DNA encoding chimeric FGF polypeptides, and to the recombinant production of chimeric FGF polypeptides, and to methods, compositions and assays utilizing chimeric FGF polypeptides for the therapeutic treatment of metabolic-related disorders and other conditions, and for producing pharmaceutically active compositions including chimeric FGF polypeptides, the compositions having therapeutic and pharmacologic properties including those associated with the treatment of metabolic-related disorders and other conditions.

Abstract: The invention is directed to a pharmaceutical composition comprising at least one FGF-21 (fibroblast growth factor 21) compound, at least one GLP-1R (glucagon-like peptide-1 receptor) agonist and optionally at least one anti-diabetic drug and/or at least one DPP-4 (dipeptidyl peptidase-4) inhibitor for the treatment of at least one metabolic syndrome and/or atherosclerosis, in particular diabetes, dyslipidemia, obesity and/or adipositas. The invention is also directed to a pharmaceutical composition comprising at least one FGF-21 (fibroblast growth factor 21) compound, at least one DPP-4 (dipeptidyl peptidase-4) inhibitor and optionally GLP-1R (glucagon-like peptide-1 receptor) agonist and/or at least one at least one anti-diabetic drug for the treatment of at least one metabolic syndrome and/or atherosclerosis, in particular diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: The present invention provides a unit dose comprising 0.2 ?g/kg to 36 ?g/kg of a recombinant FGF or an angiogenically active fragment or mutein thereof. Also provided is a pharmaceutical composition comprising an angiogenically effective dose of an FGF or an angiogenically active fragment or mutein thereof, and a pharmaceutically acceptable carrier. Also provided is a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of said patient a safe and angiogenically effective dose of a recombinant FGF of any of SEQ ID NOS:1-3, 5, 8-10, or 12-14, or an angiogenically active fragment or mutein thereof.

Abstract: A synthetic, flexible tissue matrix and methods for repairing hyaline cartilage defects in a joint using the flexible tissue matrix are described. The flexible tissue matrix includes a high molecular weight polycaprolactone polymer entangled with a polysaccharide such as hyaluronic acid. In the methods, autologous bone mesenchymal stem cells are introduced to a joint by a microfracturing technique, and a membrane made of the flexible matrix is applied to the joint. Cartilage which forms in the joint is hyaline cartilage rather than fibrocartilage.

Abstract: The present invention provides a FGF21 molecule covalently attached to the combining site of an antibody via a linker, wherein the linker is covalently attached to the side chain of a linking residue within FGF21. Various uses of the compounds are provided, including methods to prevent or treat diabetes or diabetes-related conditions.

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: Disclosed are a novel therapeutic agent and a novel treatment method for cancer. Specifically disclosed are: a targeting agent for a cell selected from the group consisting of a cancer cell and a cancer-associated fibroblast, which comprises a retinoid; a substance delivery carrier for the cell, which comprises the targeting agent; an anti-cancer composition utilizing the targeting agent or the carrier; an anti cancer-associated fibroblast composition; and a method for treatment of cancer.

Abstract: The invention relates to the field of pharmaceutical formulations. More particularly it is directed to freeze-dried formulations of Fibroblast Growth Factor 18 (FGF-18) compound and to methods of producing such formulations. The freeze-dried formulations according to the invention are stable upon storage for an appropriate period of time. They can be used, after reconstitution, for the treatment of cartilage disorders such as osteoarthritis or cartilage injury.

Abstract: The invention provides hydrogels and methods for their use in treating disorders of the retina such as age-related macular degeneration (AMD).

Abstract: The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes.

Abstract: System and methods for isolation of collagen and other fibrous tissue from adipose tissue are described herein. The method of the present invention isolates the collagen from adipose tissue by sonication. The tissue to be sonicated is placed in a container or a flow cell transparent to ultrasound waves. After sonication the sonicated material is filtered out through the bottom of the flow cell and the sonicated collagen is trapped in the filter, which may be taken for further processing. The isolated collagen can then be combined with a suitable carrier for re-injection to correct various tissue defects such as wrinkles, to form a carrier for the stem cells, a filler, and matrix for new collagen production by injecting into the desired area of the host.

Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Abstract: A flowable biomedical implant for application to a bone defect to promote bone growth is provided. The flowable biomedical implant comprises a carrier matrix including a biodegradable polysaccharide and ceramic material. An impermeable membrane can be integrally formed at the surface of the carrier matrix by applying a crosslinking agent to the biodegradable polysaccharide mixed with ceramic materials.

Abstract: Using betaKlotho or a substance that increases or inhibits betaKlotho activity as an agent for controlling the activity of FGF21 mediated by an FGF receptor, the present invention provides a pharmaceutical composition comprising such betaKlotho or such substance as an active ingredient, particularly, a pharmaceutical composition for anti-metabolic syndrome, and further particularly, a pharmaceutical composition for therapeutic or preventive use associated with the control of blood glucose level. In addition, the present invention provides a screening system for each of a substance that enhances or suppresses betaKlotho activity, an FGF21-like active substance, and a betaKlotho-like active substance, which uses a cell system that has expressed an FGF receptor and/or betaKlotho on the surface thereof.

Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF21 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Abstract: The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Abstract: The invention provides a particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, including i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 70 weight percent based on the total weight of the particulate composition; ii) a monocalcium phosphate monohydrate powder; and iii) a ?-tricalcium phosphate powder having a median particle size of less than about 20 microns. Bone graft substitute cements made therefrom, a bone graft substitute kit comprising the particulate composition, methods of making and using the particulate composition, and articles made from the bone graft substitute cement are also provided.

Abstract: The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of Alzheimer's diseases.

Abstract: An injector system for delivery of a pharmacological agent to biological tissue having a plurality of needles arranged in an array, a plurality of reservoirs configured to receive a pharmacological composition therein, the reservoirs being in fluid communication with a respective one of the plurality of needles, a pneumatic pressure source, a pneumatic drive system that is configured to induce a first discharge of the pharmacological composition out of the reservoirs and needles in a plurality of delivery modes, agent delivery volume control means for controlling volume of the pharmacological composition discharged from the needles, and a control system having actuation control means for controlling said pneumatic drive system. The control system is programmed to control the delivery modes.

Abstract: The invention provides compositions and methods to form pores in situ within hydrogels following hydrogel injection. Pores formed in situ via degradation of sacrificial porogens within the surrounding hydrogel facilitate recruitment or release of cells. Disclosed herein is a material that is not initially porous, but which becomes macroporous over time.

Abstract: It has been discovered that that certain growth factors can delay the ossification of a tissue site, such as a cranial suture, via the promotion of fibroblast differentiation and/or inhibition of osteoblast differentiation. Provided herein are methods for treating bone formation conditions or disorders, such as synostotic conditions, or ectopic mineralization conditions, via administration of compositions comprising connective tissue growth factor (CTGF), and optionally other growth factors or fibroblast or progenitor cells, to a tissue site of a subject in need thereof.

Abstract: A method for preparing polymer microparticles with a reduced initial burst, and the polymer microparticles prepared thereby, the method including: contacting polymer microparticles with an alcohol aqueous solution, the polymer microparticles prepared thereby, and use for drug delivery of the polymer microparticles.

Abstract: The present invention provides methods for diagnosing mental disorders. The invention also provides methods of identifying modulators of mental disorders as well as methods of using these modulators to treat patients suffering from mental disorders.

Abstract: A novel approach for inhibiting FGF2/FGFR1-mediated signalling is presented which is based on FGFR1 mutations to introduce higher affinity for the natural GAG co-receptors into the soluble part of the FGF1 receptor, preferably into the D2/D3 domains.

Abstract: The invention is directed to a fusion protein comprising at least one FGF-21 (fibroblast growth factor-21) compound and at least one GLP-1R (glucagon-like peptide-1 receptor) agonist as well as to pharmaceutical compositions, medical uses and methods of treatment involving the fusion protein, particularly in the field of diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric form of thyroid hormone, or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

Abstract: The compositions and methods of the present invention relate to the co-delivery of a molecule and a polypeptide to cells to improve the therapeutic efficacy of the molecules. In one embodiment of the invention, the invention may improve delivery of growth factors by co-delivering these growth factors with their receptors and co-receptors, such as syndecans. Co-delivery of growth factors with syndecans, for example, may protect growth factors from proteolysis, enhance their activity, and target the growth factors to the cell surface to facilitate growth factor signaling. This novel approach to growth factor therapy could be extended to other systems and growth factors enabling the enhancement of multiple signaling pathways to achieve a desired therapeutic outcome.

Abstract: The invention relates to a viral-safe platelet extract, to its preparation and use. The extract comprises a mixture of biologically active platelet derived factors. Advantageously, the extract comprises a balanced proportion of the factors and is non-clottable.

Abstract: Provided is a method of causing a cell to migrate to a scaffold and there differentiate to form adipose or adipose-like cells or tissue. Also provided is a method of treating a mammal that has a tissue defect. Further provided is a tissue scaffold comprising a cell homing composition and an adipogenic composition. Additionally, a method of making a tissue scaffold capable of recruiting a cell and differentiating the recruited cell to form adipose or adipose-like cells or tissue is provided.