Abstract: A fibrin adhesive for use in the minimally-invasive treatment of a rupture of a body component formed by hard connective tissue adhesively bonds to that body component. A suitable treatment method features locating the rupture, providing the fibrin adhesive, and supplying the fibrin adhesive at the body component to be treated.

Abstract: Disclosed herein is a use of an amniotic fluid stem cell spheroid in the preparation of a composition or pharmaceutical composition for treating urinary incontinence, wherein said pharmaceutical composition may further comprise hyaluronic acid.

Abstract: A process for purifying fibrinogen from a fibrinogen containing source by precipitation of fibrinogen by a precipitating agent from a fibrinogen containing solution in the presence of one or more chelating agent(s) and removal of the supernatant from the fibrinogen paste, characterised in that fibrinogen is extracted from the paste forming a liquid fraction containing fibrinogen, and an undissolved residue, which is separated from the liquid.

Abstract: The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

Abstract: Aqueous pharmaceutical formulations, for parenteral administration, comprising peptidomimetic macrocycle or a pharmaceutically acceptable salt thereof wherein the peptidomimetic macrocycle binds to MDM2 and/or MDMX proteins are disclosed. Also disclosed are methods of treating diseases and disorders using the aqueous pharmaceutical formulations disclosed herein.

Abstract: The present invention relates to compressed bone-based products and methods to make the same. The maintained compressed state of the product serves to enhance the product's inherent osteoconductivity.

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. Described herein is an artificial mammalian skin substitute product, comprising: (a) optionally, but in some embodiments preferably, a first (“hypodermis-like”) layer comprising live mammalian adipocytes (e.g., induced pre-adipocytes) in a first hydrogel carrier; (b) a second (“dermis-like”) layer contacting or directly contacting the first layer and comprising live mammalian fibroblast cells and' live mammalian follicle dermal papilla cells in combination in a second hydrogel carrier; (c) a third (“epidermis-like”) layer contacting or directly contacting the second layer (i.e.

Abstract: The present disclosure relates to cartilage repair compositions and methods for modifying the proteoglycan content of the compositions. Specifically, the methods relate to serum free, collagen free neocartilage made from chondrocytes that can be used for implants. Proteoglycans, such as aggrecan and sulfated glycosaminoglycan are used and the content modified using temperature changes.

Abstract: The inventions provided herein relate to dissolvable hydrogel compositions and methods of uses, e.g., but not limited to, in wound management. Accordingly, methods for wound management involving the dissolvable hydrogel compositions are also provided herein. In some embodiments, the dissolvable hydrogel composition comprises an adhesive thioester hydrogel, which can facilitate adherence of the dissolvable hydrogen composition to a surface (e.g., a wound) and can be controllably dissolved later upon addition of a thiolate compound to release the dissolvable hydrogel composition from the surface (e.g., the wound).

Abstract: The present subject matter is directed to a method of manufacturing and purifying an intraveneous injection of prothrombin complex concentration (PCC) from plasma Fraction III, comprising reconstituting a Fraction III paste in a buffer to create a Fraction III suspension; adjusting pH and temperature of the Fraction III suspension; performing PEG precipitation; centrifuging the Fraction III suspension and collecting a supernatant; filtering the supernatant; performing solvent detergent virus inactivation of the supernatant; undergoing weak anion exchange chromatography of the supernatant; twice washing and eluting two to three times; ultra-filtering the supernatant; adjusting pH of the supernatant; adjusting activity of a human factor IX of the supernatant; performing aseptic filtration and nano filtration for virus removal; and filling and lyophilizing to obtain the intraveneous injection of PCC.

Abstract: A method for preparing a highly concentrated fibrinogen solution includes adding amino acid or amino acid derivatives, and/or salts to a lowly concentrated fibrinogen solution, followed by a ultra-filtration concentration. Factor XIII can be added either before or after the ultra-filtration to give a fibrin sealant component 1 containing the highly concentrated fibrinogen solution. The fibrin sealant component 1 could be preserved for a long time at room temperature and be used without a reconstitution. Fibrin sealant component 2 is a solution containing thrombin and calcium. A fibrin sealant product may be provided in a vial type in which the fibrin sealant components 1 and 2 are each filled in separate vials or in a re-filled syringe type wherein the fibrin sealant components 1 and 2 are each filled in separate syringes connected with each other to be instantly used.

Abstract: The present invention relates to polypeptides which include tenth fibronectin type III domains (10Fn3) that binds to serum albumin, with south pole loop substitutions. The invention further relates to fusion molecules comprising a serum albumin-binding 10Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.

Abstract: The invention relates to aryl and heteroaryl-fused tetrahydro-1,4-oxazepine amide derivatives of general formula (1), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates processes for manufacture of the compounds according to the invention.

Abstract: The present invention relates to methods for the treatment, prevention and diagnosis of peripheral T cell lymphoma using compounds that specifically bind KIR3DL2. The invention also relates to use of antibodies that specifically bind KIR3DL2 in diagnostic and theranostic assays in the detection and treatment of peripheral T cell lymphoma.

Abstract: Orthopedic fastener devices for fixation of fractured bones are disclosed. The orthopedic fastener device is in the form of an orthopedic fastener having an IM nail coated on its external surface with a bioabsorbable or biodegradable hydrogel. Also disclosed are hydrogel coated orthopedic fastener devices in the form of a K-wire or bone screw, a method for stabilizing a fractured long bone fracture by inserting an orthopedic fastener into the medullary canal of the bone and a kit for fastener implantation.

Abstract: Orthopedic fastener devices for fixation of fractured bones are disclosed. The orthopedic fastener device is in the form of an orthopedic fastener having an IM nail coated on its external surface with a bioabsorbable or biodegradable hydrogel. Also disclosed are hydrogel coated orthopedic fastener devices in the form of a K-wire or bone screw, a method for stabilizing a fractured long bone fracture by inserting an orthopedic fastener into the medullary canal of the bone and a kit for fastener implantation.

Abstract: Fibrin-specific imaging agents that contain at least two imaging reporters are described, as well as methods of making and using the contrast agents.

Abstract: A system and method for transcellular transport of compositions containing agents (e.g., research, analytical, reporter or molecular probes, diagnostic and therapeutic agents, biologically active agents, research agents, analytical agents, imaging agents, monitoring agents, enzymes, proteins, peptides, nucleic acids, lipids, sugars, hormones, lipoproteins, chemicals, viruses, bacteria, cells, including modified cells, biosensors, markers, antibodies and/or ligands) across the gastrointestinal epithelial layer including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes an anti-ICAM antibody targeting moiety, specific for targeting ICAM-1. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: A fibrinogen with reduced half-life and low sialic acid content as a result of recombinant expression or enzymatic and chemical removal. The fibrinogen is useful in treating or effecting prophylaxis of bleeding particularly in situations of an acute nature in which a high initial dose and rapid decline to normal or below normal levels is desirable.

Abstract: Fibrin-specific imaging agents that contain at least two imaging reporters are described, as well as methods of making and using the contrast agents.

Abstract: The present invention provides a hemostatic porous sponge comprising a matrix of a fibrous biomaterial and particles of a fluid absorbing, particulate material adhered to said matrix material, a method of producing these sponges and their use for wound healing.

Abstract: Disclosed are solid dressings for treated wounded tissue in mammalian patients, such as a human, comprising a haemostatic layer consisting essentially of fibrinogen and a fibrinogen activator, wherein the fibrinogen is present in an amount between 3.0 mg/cm2 of the wound facing surface of the dressing and 13.0 mg/cm2 of the wound facing surface of the dressing. Also disclosed are methods for treating wounded tissue.

Abstract: The present invention provides a process or preparing an extracellular matrix composition which comprises: (a) mixing an aqueous solution of fibrinogen with a coagulating agent and a bulking agent and a foaming agent; (b) causing the mixture to foam and coagulate; (c) incubating the mixture obtained in step (b) with a cross-linking agent; and (d) washing the cross-linked composition obtained in step (c) to remove the cross-linking agent. Wherein the foaming agent consists of or comprises one or more surfactant agent(s) from the class of sugar-surfactants. The invention also relates to the formulation mixture as such, and to the products of the process.

Abstract: The invention generally relates to dextran fibers which are preferably electrospun and devices formed from such fibers. In particular, such devices may include substances of interest (such as therapeutic substances) associated with the electrospun fibers. Upon exposure to a liquid the electrospun fibers dissolve immediately and the substances of interest are released into the liquid. Exemplary devices include bandages formed from electrospun dextran fibers and associated agents that promote hemostasis, such as thrombin and fibrinogen.

Abstract: A method for preparing a haemostatic and adhesive durable scaffold useful for promoting wound healing, and the scaffold so prepared, are provided. The scaffold made of fibrinogen and chitosan is produced by electrospinning techniques, resulting in a material with enhanced endurance, applicable in various medical purposes including surgery, tissue regeneration, burns, injuries, and the like. The scaffold is produced in the absence of biocatalysts, in particular thrombin.

Abstract: Tissue patches and associated systems and methods are described. Certain embodiments are related to inventive systems and methods in which tissue patches can be made quickly and robustly without the use of complicated fabrication or sterilization equipment.

Abstract: The invention provides methods and compositions for wound treatment and/or blood clot formation, e.g., arresting the flow of blood from an open wound. The methods and compositions provide for promoting and accelerating wound healing and optionally provide for inhibition of microbial infection and/or a local analgesic effect.

Abstract: A system for harvesting a fibrin clot and depositing that fibrin clot into a wound site during a surgical procedure, the system comprising: (i) blood drawing apparatus for drawing blood; (ii) extraction apparatus for extracting fibrin from blood so as to form a fibrin clot; (iii) configuring apparatus for molding, cutting and shaping the fibrin clot into a desired configuration; and (iv) dispensing apparatus for reliably and controllably dispensing the fibrin clot at a selected location in the body.

Abstract: Surgical procedures of the breast where an adhesive is applied to fixate a reshaped and/or relocated portion of breast tissue.

Abstract: Compositions that include fibrin microthreads are provided. The compositions can include one or more therapeutic agents including cytokines and interleukins, extracellular matrix proteins and/or biologically active fragments thereof (e.g., RGD-containing peptides), hormones, vitamins, nucleic acids, chemotherapeutics, antibiotics, and cells. Also provided are methods of making compositions that include fibrin microthreads. Also provided are methods for using the compositions to repair or ameliorate damaged or defective organs or tissues.

Abstract: The present invention relates generally to agents and devices for promoting hemostasis and tissue sealing and, more particularly, to hemostatic pads comprising bioabsorbable scaffolds that can deliver lyophilized hemostasis promoting proteins, such as fibrinogen and thrombin, to a wound site or injured organ or tissue.

Abstract: The invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives.

Abstract: A method of inducing hemostasis in a wound using a hemostatic product. A dextran support is provided. At least one hemostatic agent stabilizer is mixed with at least one hemostatic agent to form a hemostatic agent and stabilizer mixture. The at least one hemostatic agent includes at least one of thrombin and fibrinogen. The hemostatic agent and stabilizer mixture is associated with the dextran support. The hemostatic product is applied to the wound in which a bodily fluid is present. The at least one hemostatic agent is released from the hemostatic product to induce hemostasis in the wound.

Abstract: Blood-derived plastic articles prepared from compositions including blood and, in some embodiments, at least one crosslinking agent and/or at least one biological response modifier, that can be useful for biological applications such as wound repair and tissue grafts; methods of making and using the same; methods for assessing the concentration of a biological response modifier in an article; and systems for preparing blood-derived plastic articles are provided.

Abstract: ClotGel is a single-component hemostatic agent designed for use as an adjunct or primary treatment in moderate intraoperative hemorrhage and in trauma. It can be applied topically to the wound either on the skin in a laparatomy or as non-invasive manner in surgical procedures. Its crosslinking technology generates an adhesive stable fibrin clot using a single component (fibrin II) required for hemostasis. The agent is a mixture of lyophilized polymerized fibrin II and fibrin II monomer which is polymerized and stabilized when in contact with the blood. The attachment properties of the gel, as well as the rapid formation of a fibrin clot, ensures that a strong stable fibrin clot is formed within 1 minute of application.

Abstract: A method for preparing a highly concentrated fibrinogen solution includes adding amino acid or amino acid derivatives, and/or salts to a lowly concentrated fibrinogen solution, followed by a ultra-filtration concentration. Factor XIII can be added either before or after the ultra-filtration to give a fibrin sealant component 1 containing the highly concentrated fibrinogen solution. The fibrin sealant component 1 could be preserved for a long time at room temperature and be used without a reconstitution. Fibrin sealant component 2 is a solution containing thrombin and calcium. A fibrin sealant product may be provided in a vial type in which the fibrin sealant components 1 and 2 are each filled in separate vials or in a re-filled syringe type wherein the fibrin sealant components 1 and 2 are each filled in separate syringes connected with each other to be instantly used.

Abstract: Compositions that include fibrin microthreads are provided. The compositions can include one or more therapeutic agents including cytokines and interleukins, extracellular matrix proteins and/or biologically active fragments thereof (e.g., RGD-containing peptides), hormones, vitamins, nucleic acids, chemotherapeutics, antibiotics, and cells. Also provided are methods of making compositions that include fibrin microthreads. Also provided are methods for using the compositions to repair or ameliorate damaged or defective organs or tissues.

Abstract: There is provided a method of forming a hydrogel, the method comprising: providing a mixture of a polymer comprising a cross-linkable pendant phenolic group, peroxidase, H2O2, fibrinogen, and thrombin, at concentration sufficient to enzymatically cross-link the polymer and to cleave the fibrinogen to yield fibrin; and allowing the mixture to form a hydrogel. There is also provided a hydrogel comprising a cross-linked network of a polymer interpenetrated by fibrin fibers, the polymer cross-linked by oxidative coupling between phenolic groups pendant on the polymer.

Abstract: Compositions are disclosed containing a polymeric mixture diluted into an aqueous solution, which can be usefully applied to any surface mat is hydbcphoixc to act, for example, as an aotifoggiag coating with minimal optical distortion and excellent transparency. The compositions can also be used as lubricious agents on medical implants, shunts, and surgical supplies to minimize tissue trauma, to maximize bio-compatibility, and to increase healing by enhancing better irrigation and flow in adjacent tissue.

Abstract: The application is directed to a fibrin sealant (FIBRINGLURAAS®) consisting of a kit of lyophilized or frozen high concentrate fribinogen in which 5% a1at will be added into the final bulk and or 5% a1at as a diluent for high concentrate fibrinogen and new found proteins kh30, kh31, kh32, kh44, kh46, kh47, and kh52 in which the kh good healthy cells are present, either non-heated or heating to at least 1° C. and above, preferably at least 101° C., and lyophilized or frozen thrombin used to compound glue membrane, the diameter of which is less than 10 micrometers the actual size of the glue membrane of the fibrin sealant (FIBRINGLURAAS®) is from 0.6 ?m, to 101° C. heating 0.

Abstract: The present invention provides a method for manufacturing a virus-free protein drug, comprising (a) a filtration step of filtering a virus-containing protein solution through a small-pore size virus removal membrane to obtain a virus-free protein solution, the filtration step (a) comprising (q) a low-pressure filtration step of filtering the solution through the small-pore size virus removal membrane at a filtration pressure of 0.30 kgf/cm2 or lower to obtain the virus-free protein solution, wherein the solution prior to filtration in the low-pressure filtration step (q) has a pH (X) and a salt ionic strength (Y (mM)) that satisfy the following equations 1 and 5: 0?Y?150X?590 (Equation 1) and 3.5?X?8.0 (Equation 5) or the following equations 4 and 5: Y=0 (Equation 4) and 3.5?X?8.0 (Equation 5).

Abstract: ClotGel is a single-component hemostatic agent designed for use as an adjunct or primary treatment in moderate intraoperative hemorrhage and in trauma. It can be applied topically to the wound either on the skin in a laparatomy or as non-invasive manner in surgical procedures. Its crosslinking technology generates an adhesive stable fibrin clot using a single component (fibrin II) required for hemostasis. The agent is a mixture of lyophilized polymerized fibrin II and fibrin II monomer which is polymerized and stabilized when in contact with the blood. The attachment properties of the gel, as well as the rapid formation of a fibrin clot, ensures that a strong stable fibrin clot is formed within 1 minute of application.

Abstract: A fibrin wound dressing is made by mixing quantities of fibrinogen solution and thrombin solution with air. The resulting foam is very light weight, and with the proper attention to the amount of thrombin, is also sufficiently viscous to rest on a vertical surface without dripping. The wound dressing may also be formulated for its ability to continue migration of healing substances, such as PDGF, from the dressing to the wound site. Thrombin substitutes, such as other clotting proteins, may be used instead of thrombin. The resulting foam may also be lyophilized or ground and lyophilized for later reconstitution. A therapeutic drug or other additive may also be added to the wound dressing.

Abstract: A composition including a peptide sequence of the formula ?X1-X2, the peptide sequence corresponding to an amino acid sequence of a fibrin beta chain fragment of a Bbeta chain of fibrinogen, wherein X1 represents an N-terminal end of the peptide sequence, and X2 represents a C-terminal end of the peptide sequence, wherein the peptide sequence includes additional amino acids between X1 and X2, wherein the peptide sequence may contain a non-naturally occurring amino acid residue, wherein the peptide sequence is other than a wild-type ?15-42 monomer sequence per se, and wherein the peptide sequence is other than (?15-66)2 dimer having two chains with each chain limited to wild type amino acids ?15-65 and each chain further including a non-naturally occurring Gly at position 66 of each chain. Methods for treatment and pharmaceutical combinations may include a polypeptide agent such as Thymosin beta 4.

Abstract: A hemostatic product that includes a dextran support, at least one hemostatic agent and at least one hemostatic agent stabilizer. The at least one hemostatic agent is selected from the group consisting of thrombin and fibrinogen. The at least one hemostatic agent is associated with the dextran support. The at least one hemostatic agent stabilizer is associated with the at least one hemostatic agent.

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 herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Therapeutic agents with improved fibrinogen binding properties are described. The agents are suitable for use as artificial platelets, or for formation of biogels. Methods and intermediates for producing the agents, cross-linking agents for use in the methods, and biogels formed from, or comprising the agents, are also described.

Abstract: A composition and a method effective in the production of the composition. The composition is a ready-to-use aqueous suspension in large and small quantities comprising human-fibrinogen-coated human-albumin spheres and the supernatant, said suspension being useful for the treatment of thrombocytopenic patients.

Abstract: The present invention relates to the use of plasminogen and plasmin as agents for enhancing healing of tympanic membrane perforations or other wounds, and for reducing scars or necrotic tissue forming during wound healing. The invention also relates to a method for screening of compounds which enhance wound healing by evaluating the healing of tympanic membrane perforations in an animal model.