224 results about "Bone marrow mesenchymal stem cells" patented technology

The present invention relates to the field of biomedical materials. Particularly provided is a DNA-silk fibroin composite hydrogel microsphere. The DNA-silk fibroin composite hydrogel microsphere is prepared from DNA and silk fibroin on the basis of the micro-fluidic technology by means of combination of self-assembly physical crosslinking and photo-crosslinking. The introduction of a silk fibroin network into the composite hydrogel microsphere can provide mechanical performance for a DNA hydrogel network and reduce the production cost. RGD can remarkably improve the cell loading capability of the microsphere. The hydrogel microsphere can simulate a microenvironment of cartilage tissue by means of three-dimensional loading of high-density cells, so as to enhance substance exchange and signaling between cells, and more effectively promote the proliferation and adhesion of bone marrow mesenchymal stem cells and regulating the chondrogenic differentiation, thus promoting cartilage regeneration and repair, and providing an available material for preparing medicaments or medical instruments for cartilage defect repair.

Disclosed are methods of treating perianal fistula a subject by administering a therapeutic MSC secretome product made by a method comprising culturing bone marrow-derived MSCs under conditions that include oxygen tension below 5% and a culture media with a pH below 7.

Disclosed are methods of improving perioral and face fat graft retention in a subject by administering a therapeutic MSC secretome product made by a method comprising culturing bone marrow-derived MSCs under conditions that include oxygen tension below 5% and a culture media with a pH below 7.

The invention belongs to the technical field of biological medicine, and discloses a high-efficiency vascular endothelial cell targeting vesicle system, which is prepared from hemangioma stem cell derived exosome HemSCs-Exos and bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs, and is characterized in that the endothelial cell targeting vesicle system is prepared from the hemangioma stem cell derived exosome HemSCs-Exos and the bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs; meanwhile, the invention further discloses a preparation method of the vesicle system and application of the vesicle system in promoting proliferation and migration of endothelial cells. Different from existing targeting modification, the ingenious targeting relationship between the BMSCs-ABs and the endothelial cells belongs to non-special modification combination, and is simple and efficient; the fusion between the double EVs has the characteristic of realizing '1 + 1gt, 2', not only retains the treatment components of the HemSCs-Exos and the BMSCs-ABs, but also the fused eHEs has remarkable cell specificity distribution, and the fusion mode is simple and stable.

The invention relates to a two-phase hydrogel system based on space-time gradient regulation and control as well as a preparation method and application of the two-phase hydrogel system. The biphase hydrogel system can also be expressed as a GelMA composite hydrogel scaffold of a porous structure, the whole biphase hydrogel system is of a core-shell structure, the inner layer core mineralizes SilMA hydrogel microspheres, the porous GelMA hydrogel scaffold is used as an outer layer, and the angiogenesis promoting factor dimethyl oxalaminoacetic acid, the human umbilical vein endothelial cells and the bone marrow mesenchymal stem cells are loaded on the outer layer. Wherein the inner-layer core mineralized SilMA hydrogel microspheres realize continuous release of osteogenesis signals by slowly releasing nHAp, and the outer-layer porous GelMA hydrogel stent releases DMOG by rapid degradation to realize early angiogenesis, so that space-time coupling construction of blood vessels and bone tissues is realized. Through differential degradation characteristics of inner and outer layers of hydrogel, precise time sequence cooperative regulation and control of angiogenesis and bone tissue remodeling can be realized, and the bionic property and function integration capability of a vascularized bone organ structure can be improved, so that the clinical transformation potential of the vascularized bone organ structure is improved.

The invention provides application of a deacetylase inhibitor or a derivative thereof and application of a pharmaceutical composition, and belongs to the technical field of biology. The application of the deacetylase inhibitor or the pharmaceutically acceptable derivative thereof comprises the application of the deacetylase inhibitor for preparing a medicine for treating osteoporosis; wherein the deacetylase inhibitor is used for inducing histone acetylation in a cell nucleus. By inducing acetylation of histone in a cell nucleus, the differentiation direction of the bone marrow mesenchymal stem cells is accurately and efficiently controlled, and a treatment scheme for osteoporosis related diseases is developed.

The invention relates to a time sequence degradable orthopedic implant material which comprises a base material and a biodegradable coating formed on the surface of the base material, the surface of the base material is provided with a nanocone array microstructure, the biodegradable coating takes a biodegradable polymer as a matrix and loads a metal element for promoting bone repair, and the metal element is a metal element for promoting bone repair. And the surface of the biodegradable coating is also connected with an anti-inflammatory active factor. According to the invention, grafted anti-inflammatory active factors are matched with the biodegradable coating loaded with metal elements for promoting bone repair, and the sequential active regulation and control of the biological effect of the micro-morphology on the surface of the base material cope with effector cells in different repair stages; the time sequence regulation and control on the macrophage inflammation phenotype and bone marrow mesenchymal stem cell osteogenic differentiation in different stages of bone repair are realized, so that each stage of bone tissue repair is matched, and bone repair and osseointegration are promoted.

The application relates to a cartilage organoid based on a DNA-silk fibroin hybrid hydrogel sustained-release system and a preparation method and application thereof. The DNA-silk fibroin hybrid hydrogel sustained-release system is a hydrogel system after a DNA-silk fibroin hybrid hydrogel sustained-release system premixing solution is printed through a digital light processing system, wherein the DNA-silk fibroin hybrid hydrogel sustained-release system premixing solution contains DNA, silk fibroin, acrylated RGD peptide, acrylated polyethylene glycol NHS ester, glucosamine, TD-198946 and 2,4,6-trimethylbenzoyl lithium phosphate. Compared with the prior art, the glucosamine and TD-198946 introduced in the DNA-silk fibroin hybrid hydrogel sustained-release system can significantly improve the cartilage differentiation efficiency of bone marrow mesenchymal stem cells; and the application can be transplanted to a cartilage defect as a cartilage graft to promote cartilage regeneration and repair.

The application discloses a flavonoid compound in eaglewood as well as a preparation method and application of the flavonoid compound, and relates to the technical field of medicines. The application extracts and separates a new compound from natural eaglewood, and the new compound is used in the preparation of anti-osteoporosis drugs. The compound is detected in vitro to obtain an induction effect of the compound on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, so as to affect the formation of osteoclasts. Meanwhile, the compound can promote the bone development of zebra fish through RT-qPCR detection, which indicates that the compound has anti-osteoporosis activity. The separation method of the compound is simple and easy to operate.

The invention belongs to the field of application materials, and particularly relates to Ber-ApoEVs and preparation and application thereof.The Ber-ApoEVs comprise ApoEVs and Ber supported by the ApoEVs, the ApoEVs are bone marrow mesenchymal stem cell-derived apoptosis vesicles, and the Ber is berberine and a derivative thereof. Researches show that brand new Ber-ApoEVs play a synergistic neuroprotective role in the aspects of regulating and controlling polarization of microglial cells, release of inflammatory factors, p38 / MAPK signals and the like, neuroinflammation caused by retinal ischemia reperfusion (IR) can be relieved, retinal neuron apoptosis can be inhibited, and the Ber-ApoEVs can be used for treating glaucoma.

The invention provides a developmental growth plate layered stent as well as a preparation method and application thereof, and belongs to the technical field of bone tissue engineering materials. The developmental growth plate layered stent provided by the invention is divided into three layers, the upper layer is a cartilage cell layer, the middle layer is a blood vessel barrier layer, and the lower layer is an ossification layer. The blood vessel barrier layer can be used as biological glue to bond the upper layer and the lower layer, so that the composite stent is stable in structure and not easy to break; the upper layer contains bone marrow mesenchymal stem cells (BMSCs), and the middle layer and the lower layer are free of cells. Under the condition of in-vitro chondrogenesis induction culture, the BMSCs on the upper layer can penetrate through the middle layer and be colonized on the lower layer, and in the process, part of the BMSCs can be differentiated into cartilage cells. The middle layer containing the platelet reaction protein 1 (TSP1) has a specific intervention effect on cell migration, which is expressed by inhibiting the migration of vascular endothelial cells, but has no influence on the migration of the BMSCs.

Provided is a use of dipsaci radix-derived extracellular vesicle-like nanoparticles (DREVNs) in preparation of a drug for preventing or treating orthopedic diseases. In this application, EVs are creatively extracted from dipsaci radix and purified, and the physiological efficacy of the EVs is studied. It has been found that the EVs can be fully internalized by bone marrow mesenchymal stem cells (BMSCs), can promote the osteogenic differentiation of BMSCs by activating a BMP2 / Smads signaling pathway, promote the calcified nodule formation in BMSCs, and promote the expression of osteogenic differentiation-associated genes ALP, OCN, RUNX2, and COL1, and have bone targetability in vivo. The EVs can be intragastrically administered to alleviate the osteoporosis (OP) in postmenopausal mice. Therefore, the EVs have the potential of being used to prepare drugs for preventing or treating orthopedic diseases, and provide a new strategy for the prevention or treatment of orthopedic diseases.

This invention discloses a composite microsphere loaded with ZIF-8 nanoparticles and stem cell extracellular vesicles, its preparation method, and its applications. The composite microsphere comprises a hydrogel matrix microsphere, and ZIF-8 nanoparticles and small extracellular vesicles derived from bone marrow mesenchymal stem cells uniformly dispersed and encapsulated within the hydrogel matrix microsphere. This invention integrates ZIF-8 nanoparticles and stem cell-derived sEVs into injectable, photocurable GelMA microspheres, constructing an integrated delivery platform capable of sequential release and multi-stage synergistic effects. This platform successfully integrates and leverages three major functions: immunomodulation, stem cell recruitment, and cartilage-induced differentiation, ultimately achieving high-quality functional healing of the tendon-bone interface at both histological and biomechanical levels, providing a highly promising new strategy for the regeneration and repair of interfacial tissues in the musculoskeletal system.

The invention provides hydrogel, a porous titanium / hydrogel composite implant material and a preparation method of the porous titanium / hydrogel composite implant material. The hydrogel is obtained by photo-crosslinking and curing a hydrogel precursor solution containing acrylated beta-cyclodextrin, acrylated alendronate sodium, gelatin and a chemotactic factor. The hydrogel has a porous network structure, high elastic modulus, high fatigue resistance and excellent biocompatibility, and also has the capability of recruiting bone marrow mesenchymal stem cells (BMSCs) and the capability of promoting osteogenic differentiation of the BMSCs; the porous titanium / hydrogel composite implant material prepared from the hydrogel can effectively promote the growth of new bone tissues, has excellent osseointegration capability, obviously improves the osteogenesis repair effect and the osseointegration effect, provides a new treatment approach for the repair treatment of segmental bone defects, and has important medical significance.

The application provides a preparation method of a high-efficiency piezoelectric coating on a titanium implant surface. The preparation method of the application uses a hydrothermal treatment and an in-situ piezoelectric deposition technology to in-situ synthesize a nano strontium titanate-noble metal piezoelectric coating on the titanium implant surface. The coating can generate a piezoelectric potential and active oxygen through ultrasonic driving to degrade extracellular polymers and kill bacteria. In addition, the piezoelectric coating can also promote the osteogenic differentiation of bone marrow mesenchymal stem cells under piezoelectric stimulation, and finally realize the effects of bioactivity, long-acting drug-resistant bacteria and high-efficiency bone integration in the body. The application can provide a new surface treatment technology and research idea for controlling the drug-resistant bacteria infection on the implant surface, help to break through the limitations of the existing theory and technology in removing bacterial infection on the titanium implant surface, and provide beneficial guidance for the control of bacterial biofilm on other parts and the prevention and treatment of related infectious diseases.

The invention provides application of linariin-6-O-glucoside in preparation of a product for preventing and treating osteoporosis, and relates to the field of biological medicine. According to the invention, dyeing experiments of alkaline phosphatase, alizarin red and tartaric acid resistant acid phosphatase prove that the sesaminin-6-O-glucoside has affinity for FPPS receptors, has the capability of promoting bone marrow mesenchymal stem cells to form bone cells, is superior to that of bisphosphate, and can inhibit the generation of osteoclasts; microCT (micro computed tomography) detection results show that the sesaminin-6-O-glucoside has the effect of relieving the osteoporosis and can promote the formation of bone trabecula. According to the application disclosed by the invention, it is proved for the first time that the sesaminin-6-O-glucoside has the effect of resisting osteoclast formation, and meanwhile, the sesaminin-6-O-glucoside also has a better osteogenesis effect, so that a basis is provided for developing the sesaminin-6-O-glucoside as a potential medicine for treating osteoporosis.

The invention provides application of an FZD4 gene. The FZD4 gene is used for regulating osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells. The FZD4 gene in the chicken bone marrow mesenchymal stem cells is over-expressed and is used for promoting osteogenic differentiation and mineralization of the chicken bone marrow mesenchymal stem cells; or / and the FZD4 gene in the chicken bone marrow mesenchymal stem cells is knocked down to inhibit osteogenic differentiation and mineralization of the chicken bone marrow mesenchymal stem cells; the nucleotide sequence of the coding region of the FZD4 gene is as shown in SEQ ID NO. 1. According to the invention, the positive regulation effect of the FZD4 gene in osteogenic differentiation of chicken bone marrow mesenchymal stem cells is determined for the first time, the blank of a bone regulation mechanism of the poultry FZD4 gene is filled, and a new biological preparation target is provided for prevention and treatment of poultry bone diseases; the FZD4 gene can also be used as a molecular marker for breeding chicken varieties with high bone strength.

The invention relates to hydrogel for promoting healing of diabetic wounds as well as a preparation method and application of the hydrogel, and belongs to the technical field of hydrogel dressings. The invention discloses an exosome hydrogel, which is characterized in that exosome is loaded in crosslinked aldehyde hyaluronic acid and carboxymethyl chitosan, the aldehyde hyaluronic acid is grafted with L-arginine, and the exosome is derived from bone marrow mesenchymal stem cells. L-arginine can release nitric oxide under the action of a diabetic wound surface or an inflammation microenvironment to achieve the effects of resisting bacteria and promoting wound surface recovery, and the exosome successfully avoids the risks of cell survival defects, vascular embolism, immunological rejection and the like while retaining powerful bioactive components. The product has excellent antibacterial activity, degradability, tissue adhesion, injectable performance and self-repairing performance, and can be suitable for wounds in different shapes.

The invention discloses a surface-enhanced Raman probe as well as a preparation method and application thereof, and belongs to the technical field of biomedical imaging and stem cell therapy. The preparation method comprises the following steps: coating an ultrathin silver shell layer on the surface of gold nanoparticles to obtain Au-coated Ag particles; 4-sulfydryl phenylboronic acid pinacol ester molecules are modified on the surface of Au (at) Ag to form a Raman report layer, then sulfydryl-polyethylene glycol is introduced to realize biological orthogonal coupling, and the modified SERS probe is obtained through bovine serum albumin modification; jointly incubating the modified SERS probe and the azidation-labeled mouse bone marrow mesenchymal stem cells, so as to form an mmol / LSC-SERS composite probe; the obtained probe has good biocompatibility, stability and anti-interference capability and is suitable for a complex physiological environment, and the preparation method is simple and good in repeatability, is completely carried out in a water phase and does not need an organic solvent.

The invention discloses a siRNA molecule for interfering sheep TBXT gene expression in primary culture of sheep bone marrow mesenchymal stem cells and application of the siRNA molecule, and relates to the technical field of molecules. According to the invention, a method for in-vitro targeting sheep TBXT gene interference siRNA transfected cells is established by synthesizing a specific targeting combination sheep TBXT gene small fragment sequence, and the mRNA expression level of the TBXT gene of sheep bone marrow mesenchymal stem cells can be effectively interfered. A further research proves that the proliferation efficiency of the sheep bone marrow mesenchymal stem cells is obviously reduced after the TBXT gene is interfered. The TBXT gene is helpful for researching the biological function of the TBXT gene participating in embryonic caudal vertebra development regulation, and has good application value for researching the molecular mechanism of the sheep tail type character.

The application discloses application of microRNA-32-5p in preparation of a medicine for preventing and treating osteoporosis, and a medicine composition taking microRNA-32-5p as an active ingredient. It is proved through experiments that knocking out the microRNA-32-5p gene significantly aggravates osteoporosis induced by estrogen deficiency; the microRNA-32-5p plays a bone protection role by promoting osteogenic differentiation of bone marrow mesenchymal stem cells. Therefore, the microRNA-32-5p can be applied to prevention and treatment of osteoporosis as a microRNA medicine.

The invention belongs to the field of biological medicine, and relates to a curcumin-loaded bone marrow mesenchymal stem cell source exosome which is obtained by the following steps: step 1, culturing BMSCs (bone marrow mesenchymal stem cells): simultaneously adding 10% of fetal calf serum and 1% of myclostreptomycin into an MEM culture medium, culturing at 37 DEG C under 5% CO2, and counting and subculturing when the cell density reaches 90%; 2, dissolving Cur in a DMSO solution, preparing a mother solution with the culture medium, and filtering and diluting to 30-50 [mu] g / mL; adding into BMSCs (bone marrow mesenchymal stem cells) with the cell density of 85-100%, and culturing for 12-36 hours; collecting supernate, and carrying out gradient centrifugation to obtain the mesenchymal stem cell source exosome loaded with curcumin. The invention provides a novel administration route which depends on the self function of the mesenchymal stem cell source exosome and the self function of the curcumin at the same time.

The invention belongs to the technical field of biological medicine, and particularly relates to a small-molecule exosome-loaded composition based on bone marrow mesenchymal stem cells and application of the small-molecule exosome-loaded composition. The invention discloses the treatment effect of squalene on osteoarthritis for the first time, and further prepares the squalene-loaded bone marrow mesenchymal stem cell exosome. An in-vitro cell experiment and a model animal experiment prove that the composition has a synergistic treatment effect on osteoarthritis. In-vitro tests prove that the squalene-loaded mesenchymal stem cell exosome can improve the survival rate of inflammatory cartilage cells, inhibit release of proinflammatory factors and restore expression of repair factors. Model animal experiments prove that the squalene-loaded mesenchymal stem cell exosome has the effects of resisting inflammation, easing pain and protecting cartilage in the treatment of osteoarthritis.

The present invention relates to the discovery that different stem cell types (e.g., bone marrow-derived mesenchymal stem cells (RM-MSC) and adipose-derived mesenchymal stem cells (AT-MSC)) undergo large changes in lung epithelial marker 5 expression depending on the substrate on which they are cultured. The present invention includes methods and compositions for differentiating of mesenchymal stem cells, such as bone marrow and adipose tissue mesenchymal stem cells, into lung cells, populations of lung cells, and methods of alleviating or treating a lung defect in a subject in need thereof.

The invention discloses a 3D bio-printing bone marrow mesenchymal stem cell extravascular stent as well as a preparation method and application of the 3D bio-printing bone marrow mesenchymal stem cell extravascular stent. The 3D bio-printing bone marrow mesenchymal stem cell extravascular stent is obtained by performing 3D bio-printing on bio-ink of bone marrow mesenchymal stem cells (BMSCs) containing SIRT3 overexpression, and the bio-ink contains methacrylated hyaluronic acid (HAMA) and methacrylated gelatin (GelMA). The invention further discloses a preparation method of the 3D bio-printing bone marrow mesenchymal stem cell extravascular stent, and the 3D bio-printing bone marrow mesenchymal stem cell extravascular stent has the advantages that the 3D bio-printing bone marrow mesenchymal stem cell extravascular stent is obtained by performing 3D bio-printing on the bio-ink; the effect of improving the long-term patency rate of the vein bridge is evaluated by establishing a rat artery-vein transplantation model. Experimental results show that the 3D bio-printing bone marrow mesenchymal stem cell extravascular stent not only has good structural stability and biocompatibility, but also can significantly improve the long-term patency rate of a venous bridge, promote repair of damaged tissues and enhance the vascular function recovery capability, and has potential application prospects in improving the treatment effect of cardiovascular diseases.

The present application relates to the technical field of biomimetic materials, in particular to a multiphase biomimetic mineralized collagen scaffold, a preparation method and application thereof.The preparation method is as follows: type I collagen solution is self-assembled with solid copper sulfide nanoparticles, and through the technology of liquid phase mineralization, intracellular mineralization of collagen fibrils occurs, forming a multiphase biomimetic mineralized collagen scaffold similar to the nanostructure and Young's modulus of natural bone.The scaffold can improve the energy metabolism of cells by regulating the oxidative phosphorylation of bone marrow mesenchymal stem cells, thereby promoting the osteogenic differentiation of the cells; in addition, the scaffold releases copper ions to simulate enzyme activity, catalyzing the generation of a large amount of active oxygen in bacteria, leading to the rupture of the bacterial membrane and the overflow of the contents, thereby achieving the effect of antibacterial.The scaffold can treat simple bone defects or infected bone defects by regulating the energy metabolism of cells and simulating enzyme activity, thereby providing more new methods for the preparation of drugs for realizing bone regeneration and anti-infection in clinic.

This invention belongs to the field of biomedical technology, specifically relating to the application of mesenchymal stem cells in the preparation of anti-aging drugs. The mesenchymal stem cells are human adipose-derived mesenchymal stem cells (hAMSCs) or mouse bone marrow mesenchymal stem cells (BM-MSCs). This invention utilizes mesenchymal stem cells to regulate senescent stromal cells and the spleen's ECM, improving the thinning stromal state in the tissue microenvironment through multiple targets. Specifically, it improves the aging-related secretory phenotype of stromal cells, enhances mitochondrial activity, strengthens their proliferation capacity, and delays the reduction of collagen secretion. This, in turn, delays the disordered distribution and functional decline of immune cells caused by aging and enhances tissue regeneration capacity, indirectly affecting various other cells in the tissue microenvironment, thus exhibiting an antagonistic effect against systemic organ aging.

The invention discloses a bone targeting forsythiaside A loaded exosome and a preparation method and application thereof, and relates to the technical field of biomedicine.The preparation method comprises the following steps that bone marrow mesenchymal stem cells are separated and cultured, and GLG1 is over-expressed through a molecular cloning technology to obtain GLG1-BMSCs; the exosome GLG1-Exos of the GLG1-BMSCs is collected through an ultracentrifugation method; and loading forsythiaside A into the exosome through an ultrasonic method and an extrusion method to obtain the GLG1-Exos-FTA. The traditional Chinese medicine active ingredient forsythiaside A is loaded, and forsythiaside A is delivered to bone marrow in a targeted manner, so that the effect of preventing and improving diabetic osteoporosis is achieved; due to the targeting effect, the bioavailability of forsythiaside A can be enhanced, and meanwhile, the curative effect of resisting diabetic osteoporosis is improved. Experiments show that the loading rate of forsythiaside A of the GLG1-Exos-FTA reaches 36.9%, the particle size distribution peak value is 122.4 nm, and the GLG1-Exos-FTA has typical exosome characteristics and bone targeting, and can significantly improve the bone microstructure of diabetic osteoporosis mice.

The invention discloses a rehmannia neutral homogeneous polysaccharide as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The polysaccharide mainly comprises galactose, glucose and fructose, the molar ratio of the galactose to the glucose to the fructose is 2.72: 1.17: 1.11, and the weight-average molecular weight of the polysaccharide is 2152 Da. The rehmannia neutral polysaccharide can play a role in treating osteoporosis by increasing bone mineralization amount and bone mineral density; the proliferation and directional osteogenic differentiation of the bone marrow mesenchymal stem cells BMSCs can be promoted, and the obvious application effect is achieved in the aspect of preparing the bone defect treatment medicine through the stem cells. The rehmannia neutral homogeneous polysaccharide shows a huge application prospect in the aspects of preparation of medicines for treating osteoporosis and stem cell treatment (especially bone regeneration treatment based on mesenchymal stem cells). A new candidate substance and a research direction are provided for developing an efficient and safe bone metabolism disease treatment strategy derived from traditional Chinese medicines.

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.