89 results about "Bone morphogenesis" patented technology

The invention relates to bone paste for repairing bone wounds and a preparation method of the bone paste, and belongs to the technical field of biomedical material manufacturing. The bone paste is prepared from nanoscale calcium-phosphorus biphase ceramic, biomimetic mineralized collagen fiber, biodegradable polymer, modified hyaluronic acid, beta-cyclodextrin coated recombinant human bone morphogenetic protein-7, an angiogenesis accelerant and an immunoregulation additive according to a certain proportion. The nano-scale calcium-phosphorus dual-phase ceramic is hydroxyapatite and beta-tricalcium phosphate dual-phase ceramic; the biomimetic mineralized collagenous fiber is prepared by mixing type I collagen freeze-dried fiber with hydroxypropyl chitosan and performing mineralization; the modified hyaluronic acid is hyaluronic acid-sulfydryl and hyaluronic acid-hydrazide; the angiogenesis accelerant is a polylactic acid sustained release microsphere loaded with tanshinone and hydroxyl polyethylene glycol biotin; the immunoregulation additive is disodium glycyrrhizinate, lentinan and astragalus polysaccharide. The bone paste can effectively improve the bone induction capacity, promote vascularization generation and reduce the immunogenicity risk.

The invention discloses an active bone defect repair material and a preparation method thereof. The bone defect repair material is prepared by compounding collagen extracted from an animal source, a calcined bone matrix and bone morphogenetic protein composite microspheres and molding through a photocuring 3D printing technology. From the perspective of bionics, collagen is used as a framework material, a calcined bone matrix with low immunogenicity is used as a hard material to enhance mechanical support of the material, and bone morphogenetic protein composite microspheres have a synergistic effect, so that undifferentiated mesenchymal stem cells are guided to develop towards a specific direction in a long-acting manner. After the active bone defect repair material is implanted into a bone defect part, a microenvironment beneficial to cell adhesion and proliferation is provided for cells, and meanwhile, bone morphogenetic protein is slowly released and can act on the bone defect part for a long time, so that the differentiation and maturation process of osteoblasts is effectively promoted, and bone repair of the bone defect part is promoted.

The present invention relates to a bone trauma repair bone paste and a preparation method thereof, belonging to the technical field of biomedical material manufacturing. The bone paste of the present invention is prepared by mixing nano calcium phosphate biphasic ceramics, biomimetic mineralized collagen fibers, biodegradable polymers, modified hyaluronic acid, β-cyclodextrin-coated recombinant human bone morphogenetic protein-7, angiogenesis promoters and immunomodulatory additives in a certain proportion; the nano calcium phosphate biphasic ceramics are hydroxyapatite and β-tricalcium phosphate biphasic ceramics; the biomimetic mineralized collagen fibers are prepared by mineralizing freeze-dried fibers of type I collagen admixed with hydroxypropyl chitosan; the modified hyaluronic acid is hyaluronic acid-thiol and hyaluronic acid-hydrazide; the angiogenesis promoter is a polylactic acid sustained-release microsphere loaded with tanshinone and hydroxy polyethylene glycol biotin; the immunomodulatory additive is disodium glycyrrhizinate, lentinan and astragalus polysaccharide. The bone paste can effectively improve the bone induction ability, promote angiogenesis and reduce the risk of immunogenicity.

The invention relates to the technical field of biology, in particular to a method for producing a platelet quality control product by using iPS cells and the platelet quality control product, and the method comprises the following steps: controlling overexpression of a specific gene in the iPS cells by using a gene editing technology to obtain an iPS cell line containing the specific iPS cells; a differentiation procedure is started by adding a culture medium containing a tetracycline derivative, and meanwhile, a fibroblast growth factor 2 and a bone morphogenetic protein 4 are added to promote mesoderm differentiation; growth factors and tetracycline derivatives are added to induce overexpression of specific gene segments and promote formation of specific megakaryocytes; adding an AhR antagonist and a ROCK inhibitor into the recovered specific megakaryocyte, and culturing to obtain platelets; and screening a platelet standard substance based on platelet functions and preparing the platelet standard substance into a quality control substance.

The present invention relates to a composition for preventing or treating metabolic diseases, which contains bone morphogenetic protein 10 (BMP10) as an active ingredient. It has been confirmed that BMP10-treated mouse embryonic mesenchymal cell line C3H10T1 / T2 cells promoted brown fat differentiation, and increased brown fat differentiation of stromal vascular fraction adipose stem cells isolated from subcutaneous adipose tissue. It has also been confirmed that BMP10-treated animal models of obesity induced weight loss, improved insulin resistance, and changes in blood lipid levels resulted. Therefore, the composition containing BMP10 as an active ingredient can be used as a preventive or therapeutic agent for metabolic diseases, including obesity, diabetes, and dyslipidemia.

The invention discloses a bone repair material as well as a preparation method and application thereof. The bone repair material is prepared from recombinant human collagen, recombinant human bone morphogenetic protein 2 and hydroxyapatite, wherein the ratio of the inorganic matter to the organic matter in the bone repair material is (64-66): (36-34). The bone repair material disclosed by the invention takes the recombinant human collagen as a core raw material, so that the components and the structure of the prepared material are ensured to be highly consistent with those of natural bone tissues; secondly, by adding the recombinant human bone morphogenetic protein 2, the osteogenic activity of the material is further enhanced. The finally obtained recombinant human collagen active bone repair material completely retains the triple helix structure of the recombinant human collagen, so that the recombinant human collagen active bone repair material has complete biological activity, and also has the outstanding advantages of good osteogenic activity, no disease and virus transmission risk and no immunogenicity.

The present invention relates to a method for assessing myocardial infarction comprising the steps of determining the amount of a first biomarker in a sample of a subject, said first biomarker being a cardiac Troponin, determining the amount of a second biomarker in a sample of the subject, wherein said second biomarker is selected from the group consisting of: a BMP10-type peptide (Bone Morphogenic Protein 10-type peptide), FGF23 (Fibroblast growth factor 23), a BNP-type peptide, cardiac myosin binding protein C (cMyBPC) and ANG2 (Angiopoietin 2), comparing the amounts of the biomarkers to references for said biomarkers and / or calculating a score for assessing myocardial infarction based on the amounts of the biomarkers, and assessing said subject based on the comparison and / or the calculation. The invention also relates to the use of a first biomarker being a cardiac Troponin and a second biomarker selected from the group consisting of: a BMP10-type peptide (Bone Morphogenic Protein 10-type peptide), FGF23 (Fibroblast growth factor 23), a BNP-type peptide, cardiac myosin binding protein C (cMyBPC) and ANG2 (Angiopoietin 2), or at least one detection agent for said first biomarker and at least one detection agent for said second biomarker for assessing myocardial infarction. Moreover, the invention further relates to a computer-implemented method for assessing myocardial infarction and a device and a kit for assessing myocardial infarction.

The invention relates to the technical field of biology, and discloses a culture medium system for pluripotency maintenance and directional induction of embryonic stem cells and application of the culture medium system. 0.5 to 0.8 part of tetramethylenediamine; 0.2 to 0.5 part of corpus luteum hormone; 1-2 parts of a vitamin mixture; 2-4 parts of bovine serum albumin; 0.5 to 1.0 part of sodium bicarbonate; 0.2 to 0.4 part of an antibiotic mixed solution; 1 to 2 parts of biotin; 0.5 to 1.0 part of bone morphogenetic protein; and 0.1 to 0.2 part of magnesium ethylene diamine tetraacetate. A multi-factor regulation and control system is constructed, signal inhibition, a three-dimensional scaffold and a metabolic regulation module are combined, pluripotency of the embryonic stem cells is stably maintained, culture uniformity, structural support and differentiation resistance are remarkably improved, and the technical bottleneck of a traditional system in the aspects of induction efficiency and stability is broken through.

Methods of improving PD-1 based immunotherapy in a subject suffering from a solid cancer, comprising decreasing bone morphogenetic protein 1 (BMP1) levels or function in T cells or in a tumor microenvironment (TME) or extracellular matrix (ECM) of the solid cancer are provided. Methods of treating a solid cancer comprising administering a PD-1 based immunotherapy and decreasing BMP1 levels or function in T cells or a TME or ECM of the solid cancer are also provided. Antibody drug conjugates comprising an anti-PDl blocking antibody and a BMP1 inhibiting small molecule or antibody or antigen binding fragment thereof small molecule inhibitor and pharmaceutical compositions for use in the methods of the invention are also provided.

The application provides a DNA tetrahedron-based complex and a preparation method and application thereof, and belongs to the field of medicines. The application designs a functionalized DNA tetrahedron complex modified bioactive composite hydrogel scaffold containing BMP-2, combines the functionalized BMP-2 binding peptide with the tetrahedron framework structure with unique three-dimensional spatial structure and fine programmability through a chemical clicking mode, and further prepares the composite hydrogel scaffold by combining with methacrylated hyaluronic acid. The functionalized DNA tetrahedron complex realizes the performance of efficiently capturing BMP-2, and the composite hydrogel scaffold realizes the targeted capture of endogenous BMP-2 in the early stage of bone defect and stimulates the osteogenic differentiation of stem cells to promote in-situ osteogenesis, avoids a series of complications caused by the delivery of exogenous bone morphogenetic protein-2, and solves the problems of poor in-vivo stability, safety and high cost, and has a good application prospect.

A suture anchor includes an implanted portion configured to insert within an opening formed in bone of a patient and exposed portion configured to remain exposed. One or more sutures are laced through at least the implanted portion and possibly the exposed portion. Once tensioned, the suture causes the implanted portion to wedge within the opening and resist removal. The exposed portion may be placed over and / or around tissue and the suture may be passed through the tissue and knotted to secure the tissue to the suture anchor. The implanted portion may be infused with bone growth factors and the exposed portion may be infused with healing factors, such as Bone Morphogenic Protein-2 (BMP-2) and Platelet Rich Plasma (PRP).

The application provides a bone morphogenetic protein BMP-2 recombinant protein, and the amino acid sequence of the BMP-2 recombinant protein is shown as SEQ ID No. 1. The coding gene, the expression plasmid, the prokaryotic expression vector and the prokaryotic expression method are also disclosed. The prokaryotic expression system is adopted, and a solubilization tag is creatively introduced, so that the inclusion body expression is converted into soluble expression. The BMP-2 is expressed in the form of inclusion body in the prokaryotic system, the protein is converted into soluble expression by adding the solubilization tag, the difficulty of protein separation and purification is reduced, the purification cycle is shortened, and the purification efficiency is improved.

A method of differentiating pluripotent stem cells into hemangioblasts comprising incubating the pluripotent stem cells in a first serum-free differentiation medium comprising bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor (VEGF) and stem cell factor (SCF) to induce differentiation of the pluripotent stem cells into hemangioblasts or hemangioblast-containing embryoid bodies is provided. The hemangioblasts or embryoid bodies may be cultured in a second differentiation medium comprising at least granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF) and interleukin-3 (IL-3) for a period of time sufficient to generate alveolar-like macrophages.

A composition comprising primed extracellular vesicles and a biologically or pharmaceutically acceptable carrier, wherein the primed extracellular vesicles comprise an upregulated miRNA, and a fold change of the upregulated miRNA of the primed extracellular vesicles compared to miRNA of naturally occurring extracellular vesicles is greater than 1. A method for preventing, treating, or ameliorating a bone defect or a dental defect comprising administering the composition to a subject in need thereof. A method for producing the composition, comprising: cultivating a stem cell in a culture medium containing a Polygonum multiflorum Thunb extract and at least one selected from the group consisting of baicalin and bone morphogenetic protein 6 to obtain a cell culture.

The invention relates to the technical field of oral medical materials, in particular to a tissue regeneration-guided oral repair membrane and a preparation method thereof. Comprising an outer layer and an inner layer, wherein the outer layer is a porous scaffold layer formed by a degradable polymer A, and the polymer A is selected from at least one of polylactic acid, polyglycolic acid, polycaprolactone or a copolymer thereof; the inner layer is loaded with a biocompatible hydrogel layer of a bioactive factor, and the bioactive factor is selected from bone morphogenetic protein, platelet-derived growth factor, vascular endothelial growth factor or a combination thereof. Comprising the following steps: preparing an outer layer solution; forming an outer-layer stent; preparing an inner layer precursor solution; gradient compounding and interface construction; performing crosslinking and curing; and post-processing. The invention provides a novel repairing film with intelligent degradation adaptability and precise biological factor controlled release capability.

The invention relates to the technical field of biomedical materials, in particular to an fCA-BExo composite material and a preparation method and application thereof. According to the complex, the cobalt-aluminum double hydroxide nanosheets are synthesized, mesenchymal stem cells are induced to secrete exosomes rich in bone morphogenetic proteins, fCA-BExo is formed, and the multiple effects of resisting oxidation, removing ROS, inhibiting inflammatory response and promoting osteogenic differentiation are achieved. The layered structure and surface electron vacancies of the nanosheet bring excellent ROS removal performance and biocompatibility, the exosome synergistically optimizes targeting and osteogenic induction effect, and the bone marrow microenvironment can be significantly improved. The complex can be efficiently dispersed in PBS or normal saline, is applied to osteoporosis diagnosis and treatment, and has the advantages of simplicity and convenience in operation, safety, high efficiency and transformation potential.

The present invention provides antibodies that bind to BMP6 and methods of use. According to certain embodiments of the present invention, the antibodies are fully human antibodies that bind to BMP6. The antibodies of the present invention are useful for inhibiting the binding of BMP6 to hemojuvelin receptors, thereby downregulating the transcription and expression of hepcidin, thereby providing a means for preventing or treating iron deficiency anemia or iron deficiency-related disorders. In some embodiments, the antibodies of the present invention are used to treat at least one symptom or complication of iron deficiency anemia or iron deficiency-related disorders.

The invention discloses siRNA (small interfering Ribonucleic Acid) of targeted bone morphogenetic protein 2, modified siRNA and application of the siRNA. According to the invention, siRNA drug design is carried out by taking the BMP2 gene as a target gene to obtain a series of siRNAs, siRNAs capable of effectively silencing the mRNA expression level of the BMP2 gene are screened from the siRNAs, and part of siRNA sequences can even silence the mRNA level of the BMP2 gene to about 25%. The siRNA sequence is further modified, wherein phosphorylation or phosphorylation analogue modification, skeleton modification, sugar ring modification and basic group modification are carried out on the 5'terminal of the sequence, or cholesterol molecule modification is carried out on the end group of the siRNA. The siRNA sequence is further subjected to cholesterol modification to obtain a human-mouse homologous sequence of the targeted BMP2 gene, and the in-vivo silencing activity of the BMP2 target spot is further researched in a mouse experimental model subsequently.

Provided are a method of producing a human pluripotent stem cell-derived Leydig-like cell (Leydig-like cells) capable of secreting testosterone stably and persistently, and a human pluripotent stem cell-derived Leydig-like cell. Also provided is a human pluripotent stem cell-derived Leydig-like cell that enables long-term maintenance of a Leydig-like cell secreting a sufficient amount of testosterone, and is improved in efficiency of differentiation induction. The method includes the steps of: culturing a human pluripotent stem cell under a culture condition with addition of one or a plurality of kinds selected from the group consisting of: a WNT canonical pathway activator; bone morphogenetic protein 4 (BMP4); and vascular endothelial growth factor (VEGF); and forcedly expressing NR5A1, and is achieved by controlling the timing of addition and removal of cyclic adenosine monophosphate (cAMP), suspension culture, adhesion culture, and the like.

The invention provides a method of producing a population of CD34+ hematopoietic precursor cells. The CD34+ hematopoietic precursor cells are used in methods of producing natural killer (NK), methods of inducing NK cell differentiation from pluripotent stem cells (PSCs), and methods of generating terminally differentiated hematopoietic cells from PSCs. The differentiation of immune cells such as NK cells from PSCs includes the use of a hemogenic endothelium induction cocktail that includes a WNT signaling pathway activator, a bone morphogenetic protein and / or a vascular endothelial growth factor. Also provided is a method of producing hematopoietic stem cells from pluripotent stem cells.

The present invention discloses a method for substantially expanding the population of natural killer (NK) cells through the use of modified cellular culture conditions. By employing a targeted induction cocktail, including a WNT signaling pathway activator and bone morphogenetic protein (BMP), this technique facilitates the differentiation of pluripotent stem cells (PSCs) into NK cells. The core innovation lies in optimizing culture conditions, which significantly enhances the proliferation of NK cells. This approach streamlines the production of NK cells for therapeutic uses, emphasizing the expansion phase within the culture environment.

The present invention provides a method of producing a population of CD34 + hematopoietic precursor cells. Methods of using CD34 + hematopoietic precursor cells for producing natural killer cells (NKs), methods of inducing differentiation of NK cells from pluripotent stem cells (PSCs), and methods of producing terminally differentiated hematopoietic cells from PSCs. Differentiation of immune cells, such as NK cells, from PSC comprises the use of a hematopoietic endothelial induction mixture comprising a WNT signaling pathway activator, a bone morphogenetic protein, and / or a vascular endothelial growth factor. The invention also provides a method for producing hematopoietic stem cells from pluripotent stem cells.

The present invention provides antibodies that bind to BMP6, and methods of use. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to BMP6. The antibodies of the invention are useful for inhibiting binding of BMP6 to the hemojuvelin receptor, thereby down-regulating transcription and expression of hepcidin, thus providing a means of preventing or treating an iron-deficiency anemia or an iron-deficiency related disorder. In some embodiments, the antibodies of the present invention are used in treating at least one symptom or complication of an iron-deficiency anemia or an iron-deficiency related disorder.

The present invention relates to the field of diagnostics. Specifically, it relates to a method for assessing congestion in a subject, the method comprising the steps of determining the amount of a BMP10-type peptide (Bone Morphogenetic Protein Type 10 peptide) in a sample of the subject, and comparing the amount of the BMP10-type peptide to a reference for the BMP10-type peptide, thereby assessing congestion. The invention also considers a method for distinguishing precapillary pulmonary hypertension from postcapillary pulmonary hypertension. Further, the present invention relates to a computer-implemented method of the aforementioned method as well as to a device and a kit for implementing said method. The present invention also generally relates to the use of a BMP10-type peptide or a detection agent therefor in a sample of a subject for assessing hyperemia, or the use of a BMP10-type peptide or a detection agent therefor in a sample of a subject for differentiating pre-capillary pulmonary hypertension from post-capillary pulmonary hypertension.

The invention discloses a porous microsphere system for bone regeneration and preparation and application thereof, and relates to the technical field of biomedical engineering and tissue engineering.The porous microsphere system is characterized in that a porous polylactic acid-glycolic acid copolymer microparticle library with adjustable pore diameters is prepared by combining a one-step emulsification method with a chemical etching process; by using the porous particles with multiple functions and drug-loading active compounds, the material can simultaneously bear the functions of an ECM simulation stent assembly and a self-assembly bone-like micro-tissue delivery carrier; in addition, the particle can also be used as a multifunctional carrier of various bone repair factors, including bone morphogenetic protein (BMP-2), nano-hydroxyapatite (nHA) and human umbilical vein endothelial cells (HUVECs). Precise regulation and control of the pore size of the microspheres are achieved through a one-step emulsification method and a chemical etching process, the microspheres can efficiently load BMP-2, nHA and HUVECs, multiple requirements of bone regeneration are met, and the formed three-dimensional micro-tissue has osteogenic differentiation and vascularization functions and is suitable for in-vitro models and clinical treatment.

This disclosure relates to compounds and compositions for forming bone and methods related thereto. In certain embodiments, the disclosure relates to methods of forming bone comprising implanting a bone graft composition comprising a growth factor such as BMP in a subject at a site of desired bone growth or enhancement in combination with a JAB1 blocker.

The invention belongs to the field of biomedical engineering materials, and particularly relates to injectable 3D porous composite hydrogel with a BMP-2 slow release function as well as a preparation method and application of the injectable 3D porous composite hydrogel. According to the present invention, the porous hyaluronic acid methacrylate hydrogel is developed, and the porous hyaluronic acid methacrylate hydrogel is used for wrapping the adipose-derived stem cells (ADSCs) and the bone morphogenetic protein-2 (BMP-2), such that the porous hyaluronic acid methacrylate hydrogel can be used for preparing the bone morphogenetic protein-2, and the porous hyaluronic acid methacrylate hydrogel can be used for preparing the bone morphogenetic protein-2, and can be used for preparing the bone morphogenetic protein-2, the bone morphogenetic protein-2, the bone morphogenetic protein-2, the bone morphogenetic protein-2, the bone morphogenetic protein-2 and the bone morphogenetic protein-2. In-vitro experiments prove that the ADSCs have remarkable proliferation and directional migration characteristics in the porous hydrogel system. After the ADSCs-loaded composite hydrogel (HMs / MBs / ADSCs) is applied to a rat rotator cuff injury model, a fibrous cartilage transition zone is effectively reconstructed, and the healing of a tenon-bone interface (tenon-bone interface, TBI) is promoted by the ADSCs-loaded composite hydrogel (HMs / MBs / ADSCs). In-vitro sequencing is further combined to find that HMs / MBs / ADSCs regulate and control the paracrine effect of ADSCs through BMP-2, so that the tissue microenvironment is improved to enhance the regeneration efficiency. According to the system disclosed by the invention, a comprehensive pathway of HMs / MBs / ADSCs for promoting tissue regeneration is clarified, a synergistic effect mechanism of BMP-2 and ADSCs is disclosed, and a new insight is provided for a biological mechanism of TBI healing.

This invention discloses a composition for the differentiation of mesenchymal stem cells (ADSCs) into keratinocytes and its application. The composition comprises: a Wnt signaling pathway activator, a TGF-β signaling pathway inhibitor, a bone morphogenetic protein pathway activator, and at least one of retinoic acid and a retinoic acid agonist. The small molecule composition provided by this invention is meticulously designed to gradually guide the fate transition of ADSCs by mimicking key signaling events during embryonic development. This strategy is not a simple compound screening, but a rational design based on a deep understanding of developmental biology, achieving precise regulation of cell lineages in vitro by reproducing the natural developmental process. The composition of this invention is not a simple superposition of components, but rather achieves cell fate transition by precisely regulating the balance of signaling pathway networks.

To provide a bone morphogenetic protein-9 (BMP-9) variant in which heterotopic ossification side effect is alleviated, and a fusion thereof.SOLUTION: Provided are a bone morphogenetic protein-9 (BMP-9) variant expressed by a specific amino acid sequence, BMP-9 variant-Fc fusion protein in which an Fc fragment of immunoglobulin is connected to the BMP-9 variant, and a pharmaceutical composition for treating cardiopulmonary disease which contains the BMP-9 variant or the BMP-9 variant-Fc fusion protein as an active ingredient. The cardiopulmonary disease is one or more kinds selected from the group consisting of cardiac infarction, hypertension, pulmonary hypertension, myocardial fibrosis, and pulmonary fibrosis.SELECTED DRAWING: Figure 4b