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CN-122005923-A - Bone-like organic matrix composite fiber material for repairing bone defect, and preparation method and application thereof

CN122005923ACN 122005923 ACN122005923 ACN 122005923ACN-122005923-A

Abstract

The invention belongs to the technical field of biomedical materials, and discloses a bone-like organic matrix composite fiber material for repairing bone defects, and a preparation method and application thereof. The bone-like organic matrix composite fiber material is a composite fiber film formed by core-shell structure composite fiber yarn prepared by coaxial electrostatic spinning, wherein the core of the core-shell structure composite fiber yarn is compounded by polycaprolactone, mesoporous bioactive glass and multicomponent glycosaminoglycan, the shell of the core-shell structure composite fiber yarn is compounded by polycaprolactone, silk fibroin and nerve growth factor, and the multicomponent glycosaminoglycan comprises, by mass, 6-27 parts of hyaluronic acid, 28-39 parts of chondroitin sulfate, 4-24 parts of dermatan sulfate, 1-29 parts of heparin, 14-42 parts of heparan sulfate and 0.16-0.41 part of keratan sulfate. The bone-like organic matrix composite fiber material has good application prospect in preparing medicines or medical instruments for promoting bone defect repair.

Inventors

  • WANG XIAOYAN
  • YANG YING
  • Lin Kunlu
  • LIU LONG
  • LIU HAOMING
  • MAO HANYUE

Assignees

  • 中国人民解放军国防科技大学

Dates

Publication Date
20260512
Application Date
20260323

Claims (10)

  1. 1. The bone-like organic matrix composite fiber material for repairing bone defects is characterized by being a composite fiber membrane formed by core-shell structure composite fiber yarns prepared by coaxial electrostatic spinning, wherein the core of the core-shell structure composite fiber yarns is obtained by compounding polycaprolactone, mesoporous bioactive glass and multicomponent glycosaminoglycan, and the shell of the core-shell structure composite fiber yarns is obtained by compounding polycaprolactone, silk fibroin and nerve growth factor, and the multicomponent glycosaminoglycan comprises, by mass, 6-27 parts of hyaluronic acid, 28-39 parts of chondroitin sulfate, 4-24 parts of dermatan sulfate, 1-29 parts of heparin, 14-42 parts of heparan sulfate and 0.16-0.41 part of keratan sulfate.
  2. 2. The bone-like organic matrix composite for repairing bone defects according to claim 1, wherein the composite fiber membrane is in a three-dimensional network structure, the fiber diameter of the core-shell structure composite fiber filaments is 80-120nm, and the diameter ratio of the inner core to the outer shell is 1:1.8-2.4.
  3. 3. The bone-mimicking organic matrix composite material for bone defect repair according to claim 1, wherein the multicomponent glycosaminoglycan comprises the following components, by mass, 14 parts of hyaluronic acid, 39 parts of chondroitin sulfate, 18 parts of dermatan sulfate, 10 parts of heparin, 19 parts of heparan sulfate and 0.33 part of keratan sulfate.
  4. 4. The bone-like organic matrix composite fiber material for repairing bone defects according to claim 1, wherein the mass ratio of polycaprolactone, mesoporous bioactive glass and multicomponent glycosaminoglycan in the core of the core-shell structured composite fiber yarn is 38-42:3-5:0.5-1.5.
  5. 5. The bone-like organic matrix composite for repairing bone defects according to claim 1, wherein the mass ratio of polycaprolactone, silk fibroin and nerve growth factor in the shell of the core-shell structure composite fiber yarn is 3800-4200:80-120:0.13-0.15.
  6. 6. A method of preparing a simulated bone organic matrix composite for repair of bone defects as claimed in any of claims 1-5, comprising the steps of: (1) Preparing a polycaprolactone hexafluoroisopropanol solution; (2) Dispersing mesoporous bioactive glass in the polycaprolactone hexafluoroisopropanol solution obtained in the step (1), adding multicomponent glycosaminoglycan, standing for adsorption to obtain a core solution; (3) Adding silk fibroin and nerve growth factor solution into polycaprolactone hexafluoroisopropanol solution to obtain shell solution; (4) And respectively stirring the core solution and the shell solution uniformly, then carrying out coaxial electrostatic spinning, and collecting to obtain a composite fiber membrane formed by core-shell structure composite fiber filaments, namely the bone-like organic matrix composite fiber material for repairing bone defects.
  7. 7. The method for preparing a bone-like organic matrix composite material for repairing bone defects according to claim 6, wherein in the step (1), the mass fraction of polycaprolactone in the polycaprolactone hexafluoroisopropanol solution is 8-12%, the concentration of the hexafluoroisopropanol solution is 0.1-0.2g/mL, in the step (2), the dosage ratio of the polycaprolactone hexafluoroisopropanol solution, the mesoporous bioactive glass and the multicomponent glycosaminoglycan is 2-4 mL:15-25 mg:3-8 mg, and the standing adsorption temperature is 3-5 ℃.
  8. 8. The method for preparing the bone-like organic matrix composite fiber material for repairing bone defects according to claim 6, wherein in the step (2), the preparation method of the mesoporous bioactive glass comprises the steps of mixing magnesium nitrate and calcium nitrate according to a molar ratio of 1:2-4, adding tetraethoxysilane and triethyl phosphate, stirring, adjusting the pH to 9-11, standing for precipitation, centrifuging, washing, drying and calcining, wherein the multicomponent glycosaminoglycan is prepared by mixing, by mass, 6-27 parts of hyaluronic acid, 28-39 parts of chondroitin sulfate, 4-24 parts of dermatan sulfate, 1-29 parts of heparin, 14-42 parts of heparan sulfate and 0.16-0.41 part of keratan sulfate.
  9. 9. The method according to claim 6, wherein in the step (3), the nerve growth factor solution is at a concentration of 0.08-0.12. Mu.g/. Mu.L, the polycaprolactone hexafluoroisopropanol solution, the silk fibroin and the nerve growth factor solution are used in a ratio of 2-4 mL:3-8 mg:60-80. Mu.L, the stirring time is 30-40min, and the coaxial electrospinning condition is that the solution is sprayed outwards at a propelling speed of 0.7-0.8mL/h while an uninterrupted voltage of 18-22kV is supplied to the needle tip, the distance between the needle tip and the collector is 15-20cm, and the collector is tin paper with an area of 18-20cm 2 .
  10. 10. Use of a bone-like organic matrix composite for bone defect repair according to any of claims 1-5 for the preparation of a product for promoting bone defect repair, wherein the product for promoting bone defect repair is a medicament or a medical device.

Description

Bone-like organic matrix composite fiber material for repairing bone defect, and preparation method and application thereof Technical Field The invention belongs to the technical field of biomedical materials, and particularly relates to a bone-like organic matrix composite fiber material for repairing bone defects, and a preparation method and application thereof. Background The large bone defect caused by high-energy injuries such as wound, tumor excision, war injury and the like is a serious challenge facing the clinical orthopaedics and military medical field. At present, autologous bone grafting is regarded as a 'gold standard', but has limited sources and is accompanied by secondary operation trauma, and allogeneic bone grafting has the risks of immune rejection and disease transmission. Bone tissue engineering is an emerging solution, the core of which is to construct bioactive scaffolds that mimic the natural extracellular matrix to guide cellular behavior and promote bone regeneration. Glycosaminoglycans (Glycosaminoglycan, glycosaminoglycans) are an important class of linear acidic polysaccharides in the extracellular matrix of bone tissue, which are widely present in cell membranes and matrices by covalent binding to core proteins to form proteoglycans. A great deal of research shows that glycosaminoglycans, such as heparan sulfate, chondroitin sulfate, heparin and the like, can be combined with key growth factors through specific sulfation modes, so that the glycosaminoglycans not only can be protected from degradation, but also can promote the interaction between the glycosaminoglycans and a receptor, thereby precisely regulating and controlling osteogenic differentiation signal paths. However, glycosaminoglycans in natural bone matrix are complex systems that coexist and function in a variety and proportion. The current research focuses on the osteogenic effect of a single GAG, and the optimal formulation of multicomponent glycosaminoglycans and the molecular mechanism behind it have not been studied. The traditional trial-and-error method searches the optimal proportion in the high-dimensional formula space, has high cost and long period, and is difficult to realize efficient screening. The rise of artificial intelligence may provide a break for this bottleneck problem, and machine learning is a core technology of artificial intelligence, which can learn complex rules from massive data and build high-precision models, and has shown great potential in the field of material science. For example, the "mesenchymal stem cell differentiation prediction" framework developed by Zhou et al, constructs a gene expression reference frame based on public RNA-seq data, successfully predicts biomaterial-induced stem cell lineage homing by using K-nearest neighbor algorithm, and has an accuracy rate as high as 90.63%. This demonstrates the effectiveness of transcriptome data-based machine learning models in the assessment of biomaterial function. On the other hand, li et al constructed libraries containing 2304 dipeptides by combinatorial chemistry and successfully predicted their ability to self-assemble into hydrogels using machine learning (e.g., gradient lifting algorithms), providing examples for predicting macroscopic behavior of materials by chemical features. Disclosure of Invention The invention aims to solve the technical problems and overcome the defects and shortcomings in the background art, and provides a bone-like organic matrix composite fiber material for repairing bone defects, and a preparation method and application thereof. In order to solve the technical problems, the technical scheme provided by the invention is as follows: The invention provides a bone-like organic matrix composite fiber material for repairing bone defects, which is a composite fiber membrane formed by core-shell structure composite fiber filaments prepared by coaxial electrostatic spinning, wherein the core of the core-shell structure composite fiber filaments is compounded by polycaprolactone, mesoporous bioactive glass and multicomponent glycosaminoglycan, and the shell of the core-shell structure composite fiber filaments is compounded by polycaprolactone, silk fibroin and nerve growth factor, and the multicomponent glycosaminoglycan comprises, by mass, 6-27 parts of hyaluronic acid, 28-39 parts of chondroitin sulfate, 4-24 parts of dermatan sulfate, 1-29 parts of heparin, 14-42 parts of heparan sulfate and 0.16-0.41 part of keratan sulfate. The bone-like organic matrix composite fiber material further comprises a three-dimensional net-shaped composite fiber membrane, wherein the fiber diameter of the core-shell structure composite fiber yarn is 80-120nm, and the diameter ratio of the inner core to the outer shell is 1:1.8-2.4. Further, the multicomponent glycosaminoglycan comprises, by mass, 14 parts of hyaluronic acid, 39 parts of chondroitin sulfate, 18 parts of dermatan sulfate, 10 parts of heparin, 19 parts o