440 results about "Bone morphogenetic protein" patented technology

This invention provides a fibrin sealant bandage, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and / or using the unsupplemented or supplemented fibrin sealant bandage.

PCT No. PCT / JP97 / 02858 Sec. 371 Date Oct. 30, 1997 Sec. 102(e) Date Oct. 30, 1997 PCT Filed Aug. 19, 1997 PCT Pub. No. WO98 / 07705 PCT Pub. Date Feb. 26, 1998A compound of the formula: wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; Z1 is a C1-3 alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; Z2 is an optionally substituted C1-3 alkylene group; Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; one of R1 and R2 is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or R1 and R2 taken together with adjacent -c=c- form a ring; and ring A is a benzene ring which may be substituted in addition to R1 and R2; or a salt thereof.

An interbody osteogenic fusion device is provided that includes opposite end pieces with an integral central element. The end pieces are sized to maintain the height of an intervertebral disc space. The central element has a much smaller diameter so that the osteogenic fusion device forms an annular pocke around the central element. An osteogenic material is disposed within the annular pocket between the opposite end pieces. In one embodiment,the osteogenic material constitutes a collagen sheet soaked in asolution containing a bone morphogenetic protein. The osteogenic fusion device is configured so that the osteogenic material is in direct contact with the adjacent vertebral bone. In addition to the enhanced area of contact between the vertebral bone and the fusion material, the inventive osteogenic fusion device reduces stress-shielding and minimizes the radiopacity of the implant so that growth of the fusion mass can be continuously assessed. In yet another embodiment, the osteogenic fusion device includes at least one end piece with a truncated surface. The osteogenic fusion devices of the present invention may be combined with other fusion devices to form an implant system. The implant system includes at least one load bearing member having a truncated surface configured to nest within another load bearing member, preferably the load bearing, osteogenic fusion device of the present invention. The invention also provides implant systems comprising adjacent load bearing members connected to one another to resist lateral separation. Methods of promoting fusion bone growth in the space between adjacent vertebrae utilizing devices and systems of the invention are also described.

This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, antiinflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and / or using the unsupplemented or supplemented fibrin sealant dressing.

Described are osteogenic paste compositions with enhanced osteoinductive properties for use in bone repair. Compositions comprising a quickly resorbable paste carrier, a more slowly resorbed mineral matrix, and Bone Morphogenetic Protein (BMP) or other osteogenic factor are described which enable increased osteoinductive activity while retaining a reliable scaffold for the formation of new bone at the implant site. Methods for making and methods for therapeutic use of the compositions are also disclosed.

The invention is a medical implantable device which is coated by the method according to the invention. The surface of the substrate used for the implantable device, in the raw condition, following a cleaning regime and physiochemical pretreatments, is coated using a biomimetic process in a supersaturated calcium phosphate solution (SCPS) to obtain the desired coating coverage and morphology maintaining a ratio of calcium to phosphorus pH, as well as solution temperature plays a major role in yielding precipitation of the proper phase of CaP so that composition, morphologies, crystal structures, and solubility characteristics are optimal for the deposition process. The biomimetic coating adds the attribute of osteoconductivity to the implant device. To maximize bone growth, the implant must also induce bone growth, or possess the attribute of osteoinductivity. This attribute is acquired by the use of therapeutic agents, i.e. bone morphogenic proteins (BMP), growth factors, stem cells, etc. The preparation of the SCPS solution is slightly altered so that during the immersion of the implant in the SCPS, the therapeutic agents are co-precipitated and bonded with the CaP directly on the underlying surface of the implant device. A final dipping process into a BMP solution provides an initial burst of cellular activity. For delivering stem and / or progenitor cell, after drying the dipped solution of BMP, the cells are cultured on the surface of the implant.

The present invention provides muscle-derived cells, preferably myoblasts and muscle-derived stem cells, genetically engineered to contain and express one or more heterologous genes or functional segments of such genes, for delivery of the encoded gene products at or near sites of musculoskeletal, bone, ligament, meniscus, cartilage or genitourinary disease, injury, defect, or dysfunction. Ex vivo myoblast mediated gene delivery of human inducible nitric oxide synthase, and the resulting production of nitric oxide at and around the site of injury, are particularly provided by the invention as a treatment for lower genitourinary tract dysfunctions. Ex vivo gene transfer for the musculoskeletal system includes genes encoding acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, platelet derived growth factor, transforming growth factor-β, transforming growth factor-α, nerve growth factor and interleukin-1 receptor antagonist protein (IRAP), bone morphogenetic protein (BMPs), cartilage derived morphogenetic protein (CDMPs), vascular endothelial growth factor (VEGF), and sonic hedgehog proteins.

Methods and devices are described for the regulation of bone morphogenetic protein gene expression in bone cells via the application of fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured bone. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased bone tissue that include generating specific and selective electric and electromagnetic signals that generate fields optimized for increase of bone morphogenetic protein gene expression and exposing bone to the fields generated by specific and selective signals so as to regulate bone morphogenetic protein gene expression in such bone tissue. The resulting methods and devices are useful for the targeted treatment of bone fractures, fractures at risk, delayed unions, nonunion of fractures, bone defects, spine fusions, osteonecrosis or avascular necrosis, as an adjunct to other therapies in the treatment of one or all of the above, and in the treatment of osteoporosis.

Methods and devices for culturing human pluripotent stem cells to produce cells of the pancreatic lineage are disclosed. The methods include steps of culturing the stem cells under conditions that induce the expression of mesendoderm / primitive streak and definitive endoderm markers in a chemically defined medium including an effective amount of i) fibroblast growth factor, ii) Activin A, and iii) bone morphogenetic protein. The methods further include the steps of culturing cells under conditions favoring the formation of at least one of intact embryoid bodies and pancreatic progenitor PDX1+ Ins− cells.

Methods and compositions are provided for the treatment of articular cartilage defects and disease involving the combination of tissue, such as osteochondral grafts, with active growth factor. The active growth factor is preferably a composition containing at least one bone morphogenetic protein and a suitable carrier. The method results in the regeneration and / or functional repair of articular cartilage tissue.

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising the epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of the culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in the culture medium.

A cage for facilitating fusion of bones, such as vertebrae, or fusion of adjacent bone surfaces is disclosed. In one form, the cage includes a plurality of spaced apart walls comprising a biodegradable polymeric material (e.g., polycaprolactone); an osteoconductive mineral coating (e.g., a calcium compound) on at least a portion of the walls; and a bioactive agent (e.g., a bone morphogenetic protein) associated with the polymeric material and / or the coating. The bioactive agent is present in amount that induces ossification between the bones or adjacent bone surfaces. The cage may also include a fixation plate connected to at least one of the walls.

The present invention relates to compositions of bone morphogenetic proteins, particularly solid and liquid formulations of such proteins comprising one or more stabilizing excipients. The invention further provides methods of producing the compositions, kits comprising the compositions and methods of using the compositions in the treatment of diseases of skeletal and non-skeletal tissues.

The invention provides pharmaceutical compositions for the treatment of neuroinflammatory or neurodegenerative diseases comprising a single or a combination of several blocking agent(s) of Bone Morphogenic Protein (BMP) signaling. The invention further provides methods of treatment of neuroinflammatory or neurodegenerative diseases comprising administering to a patient in need thereof the pharmaceutical compositions of the invention.

The invention relates to a cell model obtained after targeted knockout of a rabbit BMP2 gene based on CRISPR / Cas9 and application thereof, belonging to the technical field of molecular biology and biomedicine. According to the invention corresponding oligos are synthesized for three targeting sites of the rabbit BMP2 gene on the design principles of CRISPR / Cas9 and are constructed on px458 vectors; and a CRISPR / Cas9 system is constructed directed at the three targeting sites in rabbit mesenchymal stem cells, and the CRISPR / Cas9 system can effectively knock out the rabbit BMP2 gene, is easy to operate and has high rabbit BMP2 gene knockout efficiency. The cell model disclosed in the invention can greatly promote research related to the functions and signaling pathways of the BMP2 gene.

The various embodiments of the present invention are generally directed to systems and methods to affect anatomical structures. More particularly, the various embodiments of the present invention are directed to systems and methods to regenerate bone. An aspect of the present invention comprises a system for affecting an anatomical structure, comprising: a nanofiber mesh configured to substantially conform to an anatomical structure, wherein at least a portion of the nanofiber mesh defines a fillable space; a carrier substance comprising an active agent, such as a bone morphogenetic protein, wherein the carrier substance is disposed within the fillable space.

This invention provides supplemented tissue sealants, methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one cytotoxin or cell proliferation inhibiting composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, drugs, growth factors, interferons, hormones, lipids, deminearlized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

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.

The invention includes biostructures which may be characterized as having substantially all of the organic-solvent-soluble material in the form of a network of irregularly shaped perforated films. The biostructure may further include particles of a substantially-insoluble material, which may be a member of the calcium phosphate family. The biostructure may be osteoconductive. The biostructure may further contain an Active Pharmaceutical Ingredient or other bioactive substance. The API may be a substance which stimulates the production of bone morphogenetic protein, such as Lovastatin or related substances, thereby making the biostructure effectively osteoinductive. One or more of the polymers may have a resorption rate in the human body such as to control the release of the API. Methods of manufacture are also disclosed.

The invention relates to a degradable wound repair material and a preparation method thereof. The degradable wound repair material includes a matrix component and an auxiliary component, wherein the matrix component includes a protein ingredient, and the auxiliary component includes at least one of an antibacterial agent and an active factor. Specifically, the antibacterial agent is a synthetic antibacterial drug, an inorganic antibacterial agent, an organic antibacterial agent, or a natural antibacterial agent, and the active factor is at least one of the following active factors: an epidermal growth factor, an FGF vascular endothelial growth factor, a platelet-derived growth factor, a platelet activating factor, an insulin-like growth factor, a tumor necrosis factor, interleukin, colony stimulating factor-1, various bone morphogenetic proteins or transforming growth factors. By loading the antibacterial agent and active factor component on the basis of the matrix component, the degradable wound repair material provided by the invention can have biological activity on the basis of meeting degradability, can better promote wound repair, and has good anti-infection properties during use.

The invention discloses a method for editing a swine BMP15 (bone morphogenetic protein 15) gene by using CRISPR / Cas9. The method comprises the steps as follows: designing two gRNAs on an exon 1 of theBMP15 of a target swine genome, and constructing pX458 and pX459 vectors respectively, so that the BMP15 gene loses functions due to accurate deletion of DNA fragments. Compared with single gRNA medicated editing, the method has the advantage that the BMP15 gene can lose functions more effectively due to accurate deletion of DNA fragments of the exon.

Osteogenic sponge compositions having enhanced osteoinductive properties for use in bone repair are described. The compositions include a quickly resorbable porous carrier, a more slowly resorbed mineral scaffold and an osteogenic factor, preferably a bone morphogenetic protein. The compositions enable increased osteoinductive activity while retaining a reliable scaffold for the formation of new bone at an implant site. Methods for therapeutic use of the compositions are also described.

This invention provides methods for the localized delivery of supplemented tissue sealants, wherein the supplemented tissue sealants comprise at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are methods of using the site-specific supplemented tissue sealants, including preparation of a biomaterial.

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.

A cage for facilitating fusion of bones, such as vertebrae, or fusion of adjacent bone surfaces is disclosed. In one form, the cage includes a plurality of spaced apart walls comprising a biodegradable polymeric material (e.g., polycaprolactone); an osteoconductive mineral coating (e.g., a calcium compound) on at least a portion of the walls; and a bioactive agent (e.g., a bone morphogenetic protein) associated with the polymeric material and / or the coating. The bioactive agent is present in amount that induces ossification between the bones or adjacent bone surfaces. The cage may also include a fixation plate connected to at least one of the walls.