83 results about "Bone morphogenetic protein" patented technology

The invention provides an application of bifidobacterium animalis subsp. Lactis CP-9 in preparation of a product for promoting bone growth and development or improving bone health. Long-term research and a large number of experiments show that the bifidobacterium animalis subsp. Lactis CP-9 can improve the bone volume fraction, the bone trabecula thickness, the bone density and the bone volume of an organism, and can also effectively improve the growth hormone level and the insulin-like growth factor 1 level, so that bone growth and development are promoted. Meanwhile, the bifidobacterium animalis subsp. Lactis CP-9 can effectively improve the N-terminal propeptide level, osteocalcin level, bone morphogenetic protein level and osteoprotectin level of I-type procollagen in a body, and remarkably reduce the amino-terminal peptide level of the I-type collagen and the ligand level of nuclear factor kappa B receptor activating factor, so that osteoblast differentiation is promoted, osteoclast differentiation is inhibited, and osteoclast differentiation is inhibited. Furthermore, bone formation is promoted, bone resorption is inhibited, bone metabolism is improved, and finally the effect of improving bone health is achieved.

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 invention discloses a culture system, culture method and application of gastrointestinal tumor chemotherapy drug-resistant organoid, the culture system comprises: a basic culture medium, which is a DMEM / F12 culture medium, and is additionally added with a special growth promoting factor obtained from a natural extract; the multiple growth factors comprise an epidermal growth factor (EGF), a fibroblast growth factor (FGF), a bone morphogenetic protein (BMP) and a vascular endothelial growth factor receptor inhibitor (VEGFRi), and the concentration of each growth factor is accurately screened and optimized; the extracellular matrix is Matrigel modified by physical and chemical methods; the specific additive comprises an antioxidant N-acetylcysteine (NAC). According to the culture system, the culture method and the application of the gastrointestinal tumor chemotherapy drug-resistant organoid, the culture system which is closer to a real environment in vivo is constructed by optimizing basic culture medium components, setting various growth factors and specific additive concentrations and adopting modified Matrigel as an extracellular matrix.

The present invention provides methods of generating bone and cartilage in vivo. The methods include delivering leukocyte cell-derived chemotaxin-1 (LECT-1) biomolecules and bone morphogenetic protein-2 (BMP-2) biomolecules into an in vivo target site, preferably by using biocompatible scaffolds containing the biomolecules.

The present invention provides a pharmaceutical formulation, a pharmaceutical composition, a method for inducing new bone formation and a method for accelerating and enhancing spinal fusion and treating bone defects in a subject. The composition comprises autologous coagulum as the carrier for osteogenic bone morphogenetic protein BMP6, which has no immunogenicity to cause inflammation and ectopic bone formation and presents a higher potency for bone formation and reduction of drug usage.

The present invention relates to an inhibitor of R-spondin 2 and / or R-spondin 3 mediated bone morphogenetic protein (BMP) receptor inhibition for use in treating and / or preventing leukemia in a subject; and to methods, kits, combined preparations, and uses related thereto.

Disclosed herein are methods for treating a disease or disorder of the central or peripheral nervous system by administering to a subject in thereof an agent capable of modulating the activity or expression of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI). Additionally, methods for screening agents capable of modulating the activity or expression of BAMBI are disclosed.

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.

To provide a method for producing a sheet-like cell culture showing a three-layer structure including a cell layer of superficial cells, a cell layer of intermediate cells, and a cell layer of basal cells, in this order. Provided is a method for producing a sheet-like cell culture that includes culturing a progenitor cell population in a second compartment separated from a first compartment via a porous member to form a sheet-like cell culture in the second compartment. The sheet-like cell culture includes a cell layer of superficial cells derived from the progenitor cell population, a cell layer of intermediate cells derived from the progenitor cell population, and a cell layer of basal cells derived from the progenitor cell population, in this order. The first compartment holds an induction medium containing retinoic acid, bone morphogenetic protein (BMP), and fibroblast growth factor (FGF).

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.

The present application belongs to the field of biomedicine, and relates to an inducer for inducing mesenchymal stem cells to differentiate into estradiol-secreting cells. The inducer for inducing mesenchymal stem cells to differentiate into estradiol-secreting cells is based on a human mesenchymal stem cell serum-free culture medium, and is composed of the following components in a mass concentration ratio: bone morphogenetic protein-4 20-60 mg / L, bone morphogenetic protein-7 20-60 mg / L, tretinoin 2-8 mg / L, resveratrol 2-8 mg / L, icariin 2-8 mg / L, benzamide 2-8 ug / L, chloroplatinic acid hexahydrate 2-8 ug / L, ethanolamine 2-8 ug / L, erythropoietin 2-10 ug / L, and vascular endothelial growth factor 2-10 ug / L. The inducer for inducing mesenchymal stem cells to differentiate into estradiol-secreting cells has high induction efficiency.

The present invention provides a method for producing neural crest cells from pluripotent stem cells, the method comprising: a step (1) of subjecting pluripotent stem cells to suspension culture in a culture medium containing an ALK inhibitor and a bone morphogenetic protein; and (2) performing suspension culture in a culture medium containing an ALK inhibitor and a GSK-3beta inhibitor.

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.

The invention relates to the field of bone tissue engineering and regenerative medicine, in particular to non-denatured bone protein calcium superfine powder with bone tissue oriented growth and rapid repair effects and a preparation method and application of the non-denatured bone protein calcium superfine powder, and the non-denatured bone protein calcium superfine powder comprises the following components in percentage by weight: 25%-45% of non-denatured type I collagen, 0.005%-0.05% of bone morphogenetic protein-2, 0.001%-0.02% of transforming growth factor-beta1, 0.01%-0.02% of calcium sulfate, 0.01%-0.02% of calcium sulfate, 0.01%-0.02% of calcium The bone tissue repairing agent is prepared from, by weight, 0.001%-0.02% of basic fibroblast growth factors, 20%-40% of ultramicro hydroxyapatite nanoparticles, 5%-15% of chitosan oligosaccharide, 3%-10% of mannitol calcium complex, 2%-8% of sodium hyaluronate, 0.01%-0.1% of vitamin D3, 0.01%-0.1% of vitamin K2, 5%-15% of chondroitin sulfate, 1%-4% of casein phosphopeptides and the balance auxiliary materials, and directional growth and rapid repairing of bone tissue are promoted.

The invention provides a bone repair material and a preparation method and application thereof, the bone repair material is composed of BMP protein (bone morphogenetic protein), carboxymethyl chitosan and calcium chloride, the carboxymethyl chitosan is crosslinked through calcium chloride to form nanoparticles, and the BMP protein is effectively loaded through electrostatic interaction; the bone repair material has good biocompatibility, biosafety and biodegradability, not only can effectively wrap and protect BMP protein from rapid degradation by enzyme, enhance in-vivo stability of BMP protein and realize continuous and controllable release of BMP protein, but also is beneficial to reduction of oedema and ectopic bone risks due to low-dose medication, and has good application prospects. And finally, by promoting angiogenesis, promoting bone tissue development and relieving inflammation, formation and repair of bones are achieved.

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 application relates to the technical field of orthopedic repair material preparation, and discloses a sterile preparation and injection device for autologous red blood cell drug-loaded blood gel, which comprises a cross bolt mixer, a multimodal injector combined with a composite syringe and a mixing flow channel, the cross bolt is internally integrated with a microfluidic mixing channel, a vertical shaft direction and a coronal shaft direction are respectively connected with a main injector and a drug-loaded injector, when the red blood cell-rich plasma enters the bolt, longitudinal shear force is generated through a spiral flow channel, so that bone morphogenetic protein suspension is vertically injected into a main flow channel through a one-way valve structure, equal ratio mixing of 4:1 is realized in the spiral channel, and the whole mixing process is completed in a closed system. The device has the advantages of realizing accurate and uniform mixing of the red blood cell-rich plasma and the drug in a sterile environment, reducing the risk of bacterial contamination, being capable of directly injecting and filling bone defects for the prepared blood gel, being excellent in biological safety and compatibility, and being low in preparation cost and simple in process.

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 an application of animal Bifidobacterium lactis subspecies CP-9 in the preparation of a product that promotes bone growth and development or improves bone health. After long-term research and a large number of experiments, the present invention found that animal Bifidobacterium lactis subspecies CP-9 can improve the body's bone volume fraction, trabecular thickness, bone density and bone mass, and can also effectively increase the level of growth hormone and insulin-like growth factor 1, thereby promoting bone growth and development. At the same time, animal Bifidobacterium lactis subspecies CP-9 can effectively increase the level of type I procollagen N-terminal propeptide, osteocalcin level, bone morphogenetic protein level, and osteoprotegerin level in the body, and significantly reduce the level of type I collagen amino-terminal peptide and nuclear factor κB receptor activator ligand level, thereby promoting osteoblast differentiation, inhibiting osteoclast differentiation, and then promoting bone formation, inhibiting bone resorption, improving bone metabolism, and ultimately achieving the effect of improving bone health.

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.

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.

The pedicle screw comprises a screw rod and a spherical head connected with the rear end of the screw rod, the interior of the screw rod is hollow, and a hole channel coaxial with the screw rod is formed; a first threaded section and a second threaded section are sequentially arranged outside the screw rod in the direction from the rear end to the front end of the screw rod; the thread pitch of the first thread section is smaller than that of the second thread section; and a plurality of side wall concave holes communicated with the pore passages are formed in the side wall of the screw rod between adjacent threads of the second thread section and are used for enabling bone debris to enter the pore passages. According to the spinal column screw, the side wall concave hole is formed, so that when the screw is screwed into a spinal column, bone chippings can be automatically drawn into the hole channel, the bone chippings and bones loaded in the hole channel form protein contact, bone growth is further promoted, and the problem that the screw is loosened for a patient after a spinal column operation is solved.

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

This invention discloses a reductase mutant and its application in the preparation of S-Bosein. The reductase mutant differs from the amino acid sequence shown in SEQ ID NO:3 in containing one or more amino acid residues at sites Q95, L96, and G190. The reductase mutant of this invention exhibits high substrate conversion and high ee value of S-Bosein when using β-pyruvate as a substrate, making it suitable for industrial production.

To provide pharmaceutical compositions for osteoarthritis treatment, comprising immune-tolerized fetal stem cell-derived extracellular vesicles containing various components that promote hyaline cartilage regeneration and relieve inflammation at higher levels than those stem cell-derived extracellular vesicles obtained under general culture conditions, and thus exhibiting superior hyaline cartilage regeneration and anti-inflammatory efficacy as well as methods for manufacturing the extracellular vesicles and compositions for osteoarthritis treatment using the extracellular vesicles.SOLUTION: These extracellular vesicles derived from immune-tolerized fetal stem cells contain fibroblast growth factor-2 (FGF-2), fibroblast growth factor-7 (FGF-7), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta 1 (TGF-β1), bone morphogenetic protein-4 (BMP-4), bone morphogenetic protein-5 (BMP-5), and bone morphogenetic protein-7 (BMP-7) and HLA-G protein.SELECTED DRAWING: Figure 1