89 results about "Bone matrix" patented technology

The invention discloses a biphasic hydrogel scaffold of a bionic bone cartilage matrix as well as a preparation method and application of the biphasic hydrogel scaffold, and belongs to the technical field of tissue engineering. The biphasic hydrogel scaffold of the bionic bone cartilage matrix provided by the invention comprises a hard bone matrix phase and a cartilage matrix phase. Wherein hard chitosan hydrogel with a porous structure is used as a hard bone matrix phase, and soft chitosan hydrogel is used as a cartilage matrix phase. The biphase hydrogel with the asymmetric matrix stiffness and the biochemical microenvironment can effectively release active substances in a controlled mode, the release period exceeds 21 days, the time requirement for osteochondral repair is met, and lasting support is provided for proliferation and differentiation of cells. Meanwhile, the biphase hydrogel provided by the invention has good biological safety, two matrix phases have different mechanical properties, the biphase hydrogel adapts to in-vivo complex physiological and mechanical environments, the fate of stem cells can be directionally regulated and controlled, synchronous regeneration and repair of osteochondral tissues are realized, and the biphase hydrogel has a wide application prospect.

An osteoinductive and osteoconductive composition including DBM fibers having multiple geometries, as well as a method of producing the same are disclose. For example, such a method may include: obtaining bone tissue; cleaning the bone tissue obtained with a plurality of washes; milling the cleaned bone tissue into a plurality of fibers of two or more geometries including a long wide fiber, a long narrow fiber, a short wide fiber, and a short narrow fiber; demineralizing the plurality of fibers of two or more geometries to expose one or more biologically active components; and neutralizing the plurality of demineralized fibers of two or more geometries resulting in demineralized bone matrix.

The invention discloses a method for promoting diabetic fracture healing by using bone marrow mesenchymal stem cell exosomes, which comprises the following steps: separating MSCs (mesenchymal stem cells) from the bone marrow of a diabetic patient, culturing and extracting the exosomes; the method comprises the following steps: extracting an exosome from a bone fracture part, performing quantitative analysis on the extracted exosome, injecting the exosome into the bone fracture part in a manner of intravenous injection, local injection or minimally invasive injection, continuously treating, promoting proliferation and differentiation of osteoblasts by miRNA or mRNA in the exosome through targeting cells, enhancing angiogenesis, and further accelerating fracture healing. According to the exosome, proliferation and differentiation of osteoblasts are promoted through miRNA or mRNA in the exosome, the synthesis capacity of bone matrixes of the osteoblasts is enhanced, so that fracture healing is accelerated, meanwhile, the exosome provides necessary blood supply for fracture healing by adjusting vascular endothelial cells and promoting angiogenesis, and the repair capacity of fracture parts is effectively improved.

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 belongs to the field of biomedical materials and tissue engineering, and particularly relates to an injectable mineralized collagen bone repair composite material loaded with stem cell recruitment factors and osteogenic induction factors and a preparation method of the injectable mineralized collagen bone repair composite material. The composite material is composed of 50%-53% of mineralized collagen matrix particles, 15%-20% of SDF-1alpha loaded heparinized gelatin microspheres, 15%-20% of BMP-2 loaded PDA coated mesoporous silica particles, 8%-10% of an NHS-PEG-NHS cross-linking agent and 4%-6% of glycerin. The composite material can realize time-space sequential regulation and control of'collection first and then differentiation '; a bionic bone matrix microenvironment is provided through the mineralized collagen matrix; the problems of two-factor release conflict and stability are solved; in-vitro experiments show that the material can significantly promote stem cell migration and osteogenic differentiation, and animal experiments prove that the material can recover 82-88% of mechanical properties of bone defect parts. The invention solves the technical problems of insufficient stem cell collection, low osteogenic differentiation efficiency and uncontrollable factor release of the existing bone repair material.

The present disclosure relates to osteoinductive putties and other implantable compositions for repair of bone defects and other medical uses. Specifically, the technology pertains to carriers for use in implantable compositions, such as osteoinductive putties. The osteoinductive putties are made entirely from donor tissue such as demineralized bone matrix, and the putties have excellent physical properties. The present disclosure relates to osteoinductive putties, carriers, compositions, implants, kits, methods of making and methods of using any of the foregoing.

The invention discloses a polysaccharide-tea polyphenol-metal compound, which is formed by dispersing a metal-tea polyphenol nano ligand in polysaccharide gel formed by covalent crosslinking of atractylodes macrocephala polysaccharide and sodium alginate, and the metal-polyphenol nano ligand is a nano complex formed by coordination of tea polyphenol and metal ions. The invention also discloses a preparation method and application thereof. The rhizoma atractylodis macrocephalae polysaccharide-sodium alginate-tea polyphenol derivative-metal composite system disclosed by the invention not only can improve the stability and release behavior of tea polyphenol in vivo, but also can regulate and control an immunometabolism microenvironment in a bone repair process, induce inflammation resolution and promote angiogenesis and bone matrix deposition, so that the bone repair effect is improved. Multiple synergistic effects of inflammation resistance, oxidation resistance, vascularization promotion and osteogenesis induction are realized, so that repair and regeneration of skull defects are remarkably accelerated, and a new intelligent immunometabolism regulation strategy is provided for repair of complex bone defects.

The purpose of the present invention is to three-dimensionally culture osteoblasts produced with a direct conversion technique, and to provide a three-dimensional bone-like tissue composed of the osteoblasts and bone matrix. The present invention relates to, for example, a method for producing an osteoblast-containing three-dimensional cell mass, comprising: a first step for performing direct conversion from somatic cells of mammals into osteoblasts; a second step for subjecting cells having undergone the first step to high-density culture, and forming a cell sheet containing the osteoblasts; and a third step for obtaining an osteoblast-containing three-dimensional cell mass from the cell sheet obtained in the second step.

Provided herein is a bone repair composition that is composed of periosteum containing an angiogenic growth factor(s), cancellous bone chips containing viable osteogenic cells, and, optionally, demineralized bone matrix (DBM) chips. Also provided herein are articles of manufacture and methods of use thereof to treat bone defects.

The invention discloses a preparation method of a porous sponge scaffold loaded with vitamin C microspheres. The method comprises the following steps: firstly, preparing bone matrix gel from cortical bones, then preparing vitamin C microspheres, adding the vitamin C microspheres and BMP protein into the bone matrix gel to form a hydrogel complex loaded with the vitamin C microspheres, freeze-drying, preparing a film, and finally preparing the porous sponge scaffold loaded with the vitamin C microspheres through crosslinking. The porous sponge stent loaded with the vitamin C microspheres, prepared by the invention, can obviously promote proliferation and differentiation of cells and formation of blood vessels under external ultrasonic stimulation, and is expected to be capable of improving accessibility of clinical treatment and improving clinical treatment efficiency when being used in cooperation with operative treatment.

A method for modeling temporomandibular joint osteoarthritis, 6-week-old rats are selected, the rats are confirmed to have entered an anesthetized state before surgery, the rat's mandibular incisors are first checked and confirmed to be normal, the first arm of the device is sleeved on one side of the mandibular incisor, and the palatal side of the maxillary incisor is made to touch the slope surface of the second arm of the device, the device is checked and confirmed to not affect the rat's mandibular movement and occlusion, not significantly raise the bite, have no early contact, and the upper and lower jaw relationship is relatively stable; the device and the mandibular incisor sleeved with the device are fixed; then the rat is put back into the cage, and soft food or powdered feed is given after waking up; the device is removed after being fed for 8 weeks or more. It is verified that the condylar process of the rat changes significantly, the overall condylar process is significantly reduced, the subchondral bone is destroyed, and the expression of the cartilage matrix is also reduced. Thus, a TMJOA rat model exhibiting mandibular retrusion is formed.

The invention discloses a method for improving mineralized collagen performance based on discrete increase of ion concentration, and belongs to the technical field of biological material preparation, and the method comprises the following steps: step 1, preparing a reaction stock solution; 2, preparing a dynamically mineralized collagen solution; and step 3, preparing the bracket with dynamically changed ion concentration. According to the method for improving the performance of the mineralized collagen based on discrete increase of the ion concentration, the nonlinear process of mineralization of natural bones is simulated by dynamically regulating and controlling the ion concentration, more inorganic minerals can be attached to the collagen, and the mineralization degree of the prepared collagen is higher on the micron scale; on the macroscopic scale, the mechanical property of the mineralized collagen is better, the mineral substances are more, and the technical support can be provided for preparing the multi-scale bionic bone matrix material.

The application relates to the technical field of biological medicine, and discloses a preparation method of a bone melon extract powder injection and a pharmaceutical composition, which comprises the following steps: bone raw material pretreatment, bone polypeptide extraction, melon seed raw material pretreatment, melon seed polypeptide extraction, stabilizer composition preparation and freeze-dried preparation; through deep defatting and decalcification treatment on the bone raw material, and in combination with specific condition enzymolysis and two-step ultrafiltration purification processes, non-target impurities in the bone matrix can be removed, and the molecular weight distribution range of the bone polypeptide can be controlled, so that the uniformity and batch consistency of the active ingredient of the bone polypeptide are improved. Meanwhile, the compound protease enzymolysis strategy used in the bone polypeptide extraction can synergistically act on the bone protein, improves the polypeptide yield, and lays a foundation for the stable control of the active ingredient proportion in the final pharmaceutical composition.

The invention provides a composite growth factor composition capable of promoting proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, a method and application. The invention provides the composite growth factor composition by simulating a natural secretion mode of a decalcified bone matrix of the mandible of an SD (Sprague Dawley) rat on the seventh day, the composite growth factor composition comprises BMP-2 (400-600 pg / ml), TGF-beta1 (5-7 ng / ml) and IGF-1 (150-250 ng / ml), and the optimal concentrations are 500 pg / ml, 6 ng / ml and 200 ng / ml respectively. The composition is remarkably superior to a single factor and a high-dosage combination in the aspects of promoting BMSCs proliferation, improving the activity of alkaline phosphatase (ALP) and forming mineralized nodules, meanwhile, the use dosage of growth factors is remarkably reduced, and the risk of side effects such as heterotopic ossification is reduced. The composite growth factor composition has good biocompatibility and safety, and is suitable for the fields of bone tissue engineering, bone defect repair and related regenerative medicine.

The application provides an application of miR-30d-5p and CYP24A1 inhibitor in hormone-induced femoral head necrosis, and belongs to the technical field of biological medicine.The application firstly provides a hormone-induced femoral head necrosis treatment strategy based on miR-30d-5p mimic by determining the molecular mechanism of miR-30d-5p in the regulation of CYP24A1 in the vitamin D metabolic pathway, and the direct effect is to significantly promote osteoblast differentiation and bone matrix mineralization, effectively improve bone microstructure damage and delay the femoral head collapse process; in the application significance, the application provides a new solution to the predicament of the lack of targeted drug treatment in clinic, and lays a conversion foundation for conservative treatment and hip-preserving surgery combined treatment by blocking the disease progression through specific molecular intervention.

The application provides a traditional Chinese medicine granule for improving osteoporosis and a preparation method and application thereof, and belongs to the technical field of medicines. Codonopsis pilosula, drynaria rhizome, epimedium and eucommia are subjected to deep eutectic solvent extraction, purification, and preparation of a traditional Chinese medicine extract, water extraction, dialysis and drying of pilose antler to prepare pilose antler protein peptide; water extraction and alcohol precipitation of cistanche to prepare cistanche polysaccharide; after modification of hydroxyapatite by citric acid, sodium dihydrogen phosphate and beta-cyclodextrin, the product is prepared by inclusion of calcium salt, alpha-cholecalciferol and vitamin D3, and then mixed with the traditional Chinese medicine extract, the pilose antler protein peptide and the cistanche polysaccharide to prepare the traditional Chinese medicine granule for improving osteoporosis. The prepared traditional Chinese medicine granule for improving osteoporosis can promote the synthesis of collagen and bone matrix protein, inhibit bone resorption, promote bone remodeling and enhance the activity of osteoblasts, and has a good improvement effect on osteoporosis, bone fracture and other symptoms, and has a wide application prospect.

An enhanced osteoinductive composition is prepared by subjecting particulate bone to a demineralization process that is optimized based on the particle size. In broad particle size ranges, ground bone is separated by particle size and each size range is subjected to independent demineralization conditions that maintain high levels of endogenous growth factors found in bone. Following demineralization, the size ranges are recombined to create an enhanced osteoinductive composition. In narrow particle size ranges, bone is milled to achieve a predetermined size, and the demineralization process is adjusted to this size range. Size-optimized demineralization is also used to create enhanced demineralized bone matrix particles in the size range of <125 μm. Enhanced osteoinductive compositions using size-optimized demineralization bone matrix and protein isolation and / or bone gelatin creation techniques are disclosed. Tissue repair compositions using the enhanced osteoinductive particles are also disclosed.

The present application provides a method for preparing a decalcified bone matrix, which is combined with specific pre-treatment, disinfection, defatting, decellularization, decalcification, freeze-drying and sterilization methods to better retain the integrity of the bioactive components and structure in the material, especially using the decalcification method of the present application, adding sugars and polyol protein protective agents to traditional decalcification reagents, which can achieve efficient removal of mineral components while reducing the damage to BMP-2 and various cytokines during decalcification. The decalcified bone matrix prepared by the present application retains the spatial structure of the bone intact, has good biocompatibility, biodegradability and bone repair ability, can be used for the repair and reconstruction of bone defects, and has broad application prospects.

The present invention discloses a method for delivering siMMP13 to chondrocytes by targeting peptide-modified Expi293 cell exosomes, comprising the following steps: separating and purifying Expi293 cell exosomes, labeling Expi293 cell exosomes, coupling DSPE-CAP polypeptide with Expi293 cell exosomes in a targeted manner, and then loading siMMP13 into the targeted modified Expi293 cell exosomes by electroporation. The present invention targets and modifies Expi293 cell exosomes to deliver siMMP13 through a chemical modification scheme, has a simple preparation method, high targeting, good aggregation effect at damaged parts, and realizes efficient drug release. Targeted delivery of siMMP13 can inhibit the metabolic decomposition of cartilage matrix, thereby inhibiting the progression of osteoarthritis, and is a drug delivery system with high safety, high targeting, and a wide range of applications.

The invention discloses a peptide-magnesium compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The peptide-magnesium compound is prepared from the following raw materials in parts by mass: 6 to 18 parts of deer heart peptide, 35 to 60 parts of oligopeptide, 21 to 34 parts of organic acid magnesium salt, 0.01 to 0.1 part of vitamin and 60 to 115 parts of water. According to the compound, peptide serves as a carrier and is chelated with organic acid magnesium salt, a thermodynamically stable compound is formed, the absorption rate of magnesium is increased, meanwhile, release of inflammatory factors can be reduced, synthesis of bone matrixes can be promoted, the deer heart peptide and magnesium act synergistically, generation of ATP is promoted, vitamin serves as a coenzyme to optimize magnesium metabolism, and the components act synergistically, so that the effect of improving the magnesium absorption rate is achieved. The peptide-magnesium compound has the effects of improving heart failure, myocardial ischemia, arrhythmia and palpitation, preventing metabolic disorder, improving sleep and preventing and treating osteoporosis and diabetes.

The invention discloses a preparation method of biological glue with a layer-by-layer progressive function, which comprises the following steps: 1) uniformly mixing a silk fibroin solution and tadpole-shaped silk fibroin particles, adding a tannic acid solution, and mixing to form a viscous gel material; and 2) adding a cartilage matrix material / bone repair material into the viscous gel material prepared in the step 1), and uniformly mixing to obtain the biological glue. According to the invention, a reactant formed by the silk fibroin and the tannic acid has strong adhesion in an articular cavity wetting state, and rapid adhesion is realized; meanwhile, a viscous gel material formed by the silk fibroin, the tannic acid and the tadpole-shaped silk fibroin particles provides a three-dimensional environment for cell proliferation, so that the functions of adhesion, migration, differentiation, proliferation and the like of related cells are collected favorably, and the extrinsic repair effect of cartilage is realized; the biological glue is mainly used in the field of osteochondral injury repair, and the function of repairing osteochondral layer by layer is realized by adopting a layer-by-layer injection and rapid adhesion technology.

The invention belongs to the technical field of biomedical materials, and discloses a bone tissue repair material for promoting vascularization and new bone generation and a preparation method thereof. The bone tissue repair material is composed of a decalcified bone matrix and a degradable biological source gel material. The repair material has a loose porous three-dimensional structure similar to that of natural cancellous bone, and the temperature-sensitive gel material filled in the pore structure of the repair material can form gel in situ in vivo and is attached to pores of a decalcified bone matrix, so that cell migration, adhesion and proliferation can be promoted, the degradation rate of gel in vivo can be reduced, and the repair material has a good application prospect. The continuous release of the pro-angiogenesis factor is ensured. Good biocompatibility is achieved, and cytotoxicity and immunogenicity are avoided; meanwhile, in the slow degradation process, angiogenesis promoting factors are continuously released for a long time, and angiogenesis and new bone generation are promoted. Therefore, the implanted biological scaffold prepared from the bone tissue repair material has excellent bone repair and regeneration promotion capability and wide application prospect.

The present application relates to the field of cosmetic technology, and discloses a preparation process of cashmere goat bone-derived elastin and application thereof in cosmetics. The process comprises: defatting cashmere goat bone particles; using composite rumen microbial flora to perform bionic fermentation to destruct bone matrix and expose active sites; adopting neutral protease and specific elastase to perform stepwise directional enzymolysis; performing hydrophilic modification through transglutaminase catalysis of covalent anchoring of polyglutamic acid and elastin polypeptide; and finally, performing multi-stage membrane interception purification and drying. The present application realizes complete retention of the natural cross-linking structure of elastin under mild conditions, significantly improves water solubility, biological activity and transdermal permeability of the elastin, solves the problems of structural damage and pollution caused by traditional chemical methods, and provides a green path for high-value utilization of cashmere goat by-products.

The application relates to an anti-inflammatory and cartilage regeneration promoting material, a preparation method and application thereof, and belongs to the technical field of biomedical materials. The anti-inflammatory and cartilage regeneration promoting material comprises a PLGA (50:50) polymer material, and a huperzine A derivative dimer loaded on the PLGA (50:50) polymer material through 3D printing. The application also provides the use of the anti-inflammatory and cartilage regeneration promoting material in the preparation of anti-inflammatory, cartilage protection or cartilage regeneration promoting drugs. The PLGA / A10E scaffold has good biocompatibility, the PLGA / A10E scaffold degradation release liquid can effectively promote the differentiation of cartilage precursor cells into cartilage, and increase the formation of cartilage collagen matrix and cartilage proteoglycan. The in-vitro degradation liquid of the PLGA / A10E scaffold can promote the expression of SOX9 under non-inflammatory conditions; under LPS-mediated inflammatory conditions, the expression of MMP-13 can be inhibited, thereby promoting the synthesis of cartilage matrix and inhibiting the degradation of cartilage matrix.

The invention discloses an interbody fusion cage based on a Thiessen polygonal gradient porous structure, and belongs to the technical field of biomedical engineering and orthopedic implants. The fusion cage body structure is of a three-dimensional communicated porous structure, the basic topological configuration of the porous structure is a Thiessen polygon, and the porous structure at least has gradient change in the distribution direction from the outer surface to the interior of the porous structure. The outer-layer small hole structure is beneficial for blood-source factors and osteoblasts to quickly enter and attach, so that osteogenesis is started; the inner-layer macroporous structure provides sufficient space for cell deep migration, blood vessel growth and new bone matrix deposition, sufficient osseointegration from outside to inside is finally achieved, the structure highly simulates a natural bone trabecula network, cell siphon attachment and internal connectivity are synergistically optimized through gradient pore design, and a specific post-treatment process is combined, so that the natural bone trabecula network structure is obtained. And the osseointegration performance and safety of the fusion cage are improved.

The invention discloses a bone-blood vessel coupling regeneration material based on S1P modified decellularized fish scale bone meal as well as a preparation method and application thereof, and belongs to the technical field of biology. After the fish scales are treated by a decellularization method, sphingosine-1-phosphoric acid (S1P) is efficiently anchored on the surfaces of the fish scales by utilizing a cationic gelatin middle layer, and a novel bone-blood vessel coupling regeneration material is developed. The bone-blood vessel coupling regeneration material retains natural components and topological structures of fish scales, and can guide ordered deposition of calcium and phosphorus to improve bone matrix density and compression strength; the endogenous bone marrow mesenchymal stem cells and vascular endothelial cells are actively collected to migrate to the center of a defect cavity by loading the S1P to simulate the homing principle of natural stem cells in an organism, osteogenesis and angiogenesis signal channels are synchronously activated, and endogenous bone-blood vessel coupling regeneration is rapidly started. The invention provides an effective strategy for regulating and controlling osteogenesis-angiogenesis coupling for the field of bone injury repair.

An enhanced osteoinductive composition is prepared by subjecting particulate bone to a demineralization process that is optimized based on the particle size. In broad particle size ranges, ground bone is separated by particle size and each size range is subjected to independent demineralization conditions that maintain high levels of endogenous growth factors found in bone. Following demineralization, the size ranges are recombined to create an enhanced osteoinductive composition. In narrow particle size ranges, bone is milled to achieve a predetermined size, and the demineralization process is adjusted to this size range. Size-optimized demineralization is also used to create enhanced demineralized bone matrix particles in the size range of <125 μm. Enhanced osteoinductive compositions using size-optimized demineralization bone matrix and protein isolation and / or bone gelatin creation techniques are disclosed. Tissue repair compositions using the enhanced osteoinductive particles are also disclosed.

The invention relates to the technical field of gene engineering, particularly discloses application of an NSUN2 gene in preparation of a product for diagnosing or treating osteoarthritis, and has the technical key points that the invention reveals that the NSUN2 has a potential value of serving as a clinical diagnosis biomarker; meanwhile, by knockdown and overexpression of the NSUN2 and detection of senescence and cartilage matrix synthesis and catabolism related indexes in cartilage cells, the invention finds that the NSUN2 can inhibit synthesis and secretion of cartilage matrix and promote cartilage senescence, and the increase of the NSUN2 is an important factor causing osteoarthritis, which indicates that the NSUN2 is expected to be used as a target to treat osteoarthritis.

The invention provides a tribenzoyl substituted vakognavine type diterpenoid alkaloid, a preparation method and application of the tribenzoyl substituted vakognavine type diterpenoid alkaloid, and a pharmaceutical composition. After rats are treated by the tribenzoyl substituted vakognavine type diterpenoid alkaloid provided by the invention, the quality reduction trend is obviously relieved, and the foot swelling degree and the arthritis score are obviously reduced; bone loss induced by AIA can be effectively inhibited, and the structural integrity of bone trabecula is protected; cartilage matrix degradation can be inhibited, and cartilage erosion damage is relieved; the anti-inflammatory effect can be achieved by inhibiting the expression of key proinflammatory factors in bone tissues.

Novel methods of creating personalized mesenchymal stem cells from pluripotent stem cells, including the utilization of extracellular matrix components, optionally seeded with exogenous differentiation factors for creation of a substrate for promotion of mesenchymal stem cell formation from pluripotent cell populations. Matrices useful for stimulation of differentiation include decellularized bone matrix, placental matrix, and adipose tissue derived matrix. Growth factors such as BMP2, BMP4, GDF-11, and stem cell factor can be added to said matrix. Stimulation of differentiation can be induced by exposure to conditioned media isolated from mesenchymal stem cells.