31 results about "Heparin Binding Growth Factor" patented technology

Formulations, kits and methods for bone or cartilage repair, including treatment of osteogenic defects, including formulations of synthetic heparin-binding growth factor analogs, non-ionic polymers, gelling agents and calcium-containing agents.

The present invention relates to a heparin-derivatized collagen matrix comprising a fragment of heparin covalently linked to a collagen scaffold, wherein the fragment of heparin has molecular weight of less than about 15 kDa, and at least one heparin-binding growth factor (HBGF) or heparin-binding adeno-associated virus (HB-AAV) or a combination thereof and methods for promoting bone growth, bone repair, cartilage repair, bone development, neo-angiogensis, wound healing, tissue engraftment and muscle tissue regeneration and / or tissue augmentation comprising administering a heparin-derivatized collagen matrix that includes at least one heparin-binding growth factor or heparin-binding adeno-associated virus or a combination thereof.

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The invention provides synthetic heparin-binding growth factor analogs of formulas I or II as given in the specification, having two peptide chains branched from a dipeptide branch moiety composed of at least one and preferably two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

The invention provides a coating and a method for coating medical devices with synthetic heparin-binding growth factor analogs, the coating and method including at least one heparin-binding growth factor analog with a region of amino acid residues binding a heparin-binding growth factor receptor, a hydrophobic linker region and a heparin-binding region, and further including heparin or an analog thereof. Also provided are medical devices, including aneurysm coils, coated with synthetic heparin-binding growth factor analogs, the coating further including heparin or an analog thereof.

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and / or remodeling and / or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and / or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

The present invention provides a heparin binding growth factor analog of any of formula I-VIII and methods and uses thereof.

Methods for extracting heparin-binding growth factors from whole blood comprising contacting whole blood with a heparin-conjugated system to immobilize a conjugated fraction comprising the heparin-binding growth factors; separating a non-conjugated fraction from the system; and releasing the heparin-binding growth factors are provided. Kits include a heparin-conjugate immobilized to the surface of a substrate; and a device to withdraw whole blood from a human or animal subject. Methods of promoting tissue health with the growth factors are also provided.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and / or remodeling and / or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and / or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

New uses of proteoglycans to bind and present growth factors, methods of accelerating wound, tissue or bone repair using such proteoglycans, pharmaceutical compositions of such proteoglycans, and scaffolds coated with such proteoglycans are disclosed. The proteoglycan of the invention is derived from domain I or perlecan.

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and / or remodeling and / or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and / or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

The invention relates to a membrane which can be used for cultivating adherent or suspension cells, in particular adherent cells, wherein said membrane allows for the adhesion and proliferation of the cells due to modification of the membrane surface with a combination of at least one extracellular matrix protein, at least one extracellular matrix (proteo-) glycan, and at least one heparin-binding growth factor. The invention further relates to a method for preparing said modified or coated membrane which can be used for the cultivation of cells, in particular adherent cells, and to methods of using such membrane for the cultivation of cells, in particular adherent cells.

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and / or remodeling and / or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and / or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

Preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent and compositions containing such preparations are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as bFGF, or another heparin-binding growth factor, cytokine, or growth factor coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Substantially pure heparin-binding growth factor polypeptides (HBGFs), nucleic acids encoding the HBGFs and antibodies which bind to the HBGFs of the invention are provided. The HBGF polypeptides are useful in methods for the induction of bone, cartilage and tissue formation, growth and development of the endometrium and in the acceleration of wound healing.

The present invention relates to a heparin-derivatized collagen matrix comprising a fragment of heparin covalently linked to a collagen scaffold, wherein the fragment of heparin has molecular weight of less than about 15 kDa, and at least one heparin-binding growth factor (HBGF) or heparin-binding adeno-associated virus (HB-AAV) or a combination thereof and methods for promoting bone growth, bone repair, cartilage repair, bone development, neo-angiogensis, wound healing, tissue engraftment and muscle tissue regeneration and / or tissue augmentation comprising administering a heparin-derivatized collagen matrix that includes at least one heparin-binding growth factor or heparin-binding adeno-associated virus or a combination thereof.

Provided is a method for inducing pluripotent stem cells to differentiate into somatic cells in a culture medium containing a heparin binding growth factor, the method comprising bringing cells into contact with a conjugate of a laminin E8 fragment and a growth factor binding domain-containing fragment of a heparan sulfate proteoglycan. According to the present invention, pluripotent stem cells can be induced to differentiate into any desired somatic cells in a highly efficient manner.

Midkine (MK), which is a retinoic acid-inducible heparin-binding growth factor, enhances neutrophilic migration and exists in an inflammatory state at a high concentration. The midkine or its inhibitors can be used for treating neutrophilic functional disorders or inflammatory diseases.

A method for enhancing chondrogenesis in a subject in need thereof comprises administering to the subject an effective amount of a pharmaceutical composition comprising a growth factor bound to hyaluronic acid (HA)-based hydrogel particles (HGPs). The hyaluronic acid (HA)-based hydrogel particles (HGPs) are conjugated with a heparan sulfate proteoglycan (HSPG). Related medicaments and methods for preparing the medicaments are provided.