An injectable bone repair material containing bioactive glass and a method for preparing the same

Abstract

The present application relates to a kind of injectable bone repair material containing bioactive glass and its preparation method, belong to bone repair material technical field, material includes composite inorganic phase powder, hydrogel precursor liquid and injection medium;Composite inorganic phase powder includes bioactive glass, hydroxyapatite whisker and L-arginine;Hydrogel precursor liquid includes oxidized hyaluronic acid, modified gelatin and phosphate buffer solution.Bioactive glass is with mesoporous bioactive glass as core, strontium-doped hydroxyapatite as intermediate layer, nanoscale silicon dioxide as shell of core-shell structure, and shell surface is grafted with mercapto and loaded with zinc ion.Oxidized hyaluronic acid is obtained by oxidizing sodium hyaluronate with sodium periodate.Modified gelatin is obtained by modifying gelatin with chitosan oligosaccharide, EDC·HCl, N-hydroxysuccinimide system.The present application realizes the integration of minimally invasive injection, controllable degradability, bionic mechanics and active osteogenesis through multi-component modification and synergistic effect.

Description

Technical Field

[0001] This invention belongs to the field of bone repair materials technology, specifically relating to an injectable bone repair material containing bioactive glass and its preparation method. Background Technology

[0002] For bone tissue integrity loss caused by bone trauma, autologous bone, allogeneic bone, and synthetic bone repair materials are currently the mainstream repair solutions. Autologous bone transplantation has excellent osteoconductivity, osteoinduction, and biocompatibility, with no risk of immune rejection, but it has drawbacks such as limited sources, secondary damage to the donor site, and limited bone harvest. Allogeneic and xenograft bone can solve the problem of insufficient donors, but they have safety risks such as immune rejection, pathogen transmission, and decreased osteoinduction activity, which limits their clinical application. Synthetic bone repair materials use calcium phosphate, polylactic acid, hydroxyapatite, etc. as base materials, relying on osteoconductivity to provide a scaffold for osteoblast adhesion and proliferation. They have high biocompatibility and abundant sources, making them the core choice for replacing transplanted bone at present. Some materials achieve functional optimization through growth factor loading and are widely used in the repair of bone defects in non-weight-bearing areas.

[0003] However, existing synthetic bone repair materials still suffer from multiple technical and efficacy limitations in clinical applications. Traditional solid porous scaffold materials have a fixed shape, making them unsuitable for irregular, cavitary, or minimally invasive bone defects. They require intraoperative shaping and cutting, increasing the difficulty of operation and resulting in poor compatibility with minimally invasive implantation. Most materials lack in-situ osteogenic activity, possessing only simple osteoconduction properties, leading to slow bone integration and low new bone formation efficiency. The degradation rate of some polymeric substrates does not match the bone regeneration rate; excessively rapid degradation can cause scaffold collapse, while excessively slow degradation can result in foreign body retention and local inflammatory reactions. Furthermore, conventional materials lack antibacterial and anti-inflammatory capabilities, easily inducing postoperative infection and leading to repair failure. Inorganic ceramic materials are brittle, and their mechanical strength does not match that of natural bone, making them unsuitable for weight-bearing bone defect scenarios.

[0004] Therefore, it is necessary to improve and develop new bone repair materials, optimize their dispersibility, mechanical properties and drug release characteristics, and make up for the shortcomings of existing bone repair materials in terms of formability, activity, degradability and mechanical properties, so as to provide a new solution with high efficiency, safety and adaptability for minimally invasive bone defect repair. Summary of the Invention

[0005] To address the problems of poor shape adaptability, degradation and mechanical limitations, and poor repair effects in existing bone repair materials, this invention provides an injectable bone repair material containing bioactive glass and its preparation method. Through multi-level composite and multi-dimensional synergistic design of core-shell structured inorganic phase, dynamically cross-linked hydrogel, and functional fillers, it solves the core pain points of traditional bone repair materials, such as poor shape adaptability, mismatch between degradation and bone regeneration rates, low osteogenic activity, and insufficient mechanical properties. Simultaneously, it achieves integration of minimally invasive injectability, gel-forming properties, controllable degradation, biomimetic mechanical properties, and active osteogenic properties. The specific technical solution is as follows:

[0006] An injectable bone repair material containing bioactive glass, comprising a composite inorganic phase powder, a hydrogel precursor solution, and an injection medium; the composite inorganic phase powder comprises bioactive glass, hydroxyapatite whiskers, and L-arginine; the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and phosphate buffer. The bioactive glass is a core-shell structure with mesoporous bioactive glass as the core, strontium-doped hydroxyapatite as the middle layer, and nano-silica as the outer shell, and the outer shell surface is grafted with thiol groups and loaded with zinc ions. The preparation of the bioactive glass includes: reacting hexadecyltrimethylammonium bromide, triethyl phosphate, tetraethyl orthosilicate, and calcium nitrate in deionized water to prepare a precipitate, followed by calcination to prepare MBG microspheres; preparing an aqueous solution containing Ca(NO3)2 and Sr(NO3)2 as growth solution A; preparing an aqueous solution containing (NH4)2HPO4 as growth solution B; reacting MBG microspheres, growth solution A, and growth solution B in deionized water to prepare MBG-SrHA microspheres; stirring MBG-SrHA microspheres and a tetraethyl orthosilicate ethanol solution in an ethanol aqueous solution to prepare MBG-SrHA@nSiO2 core-shell microspheres; reacting MBG-SrHA@nSiO2 core-shell microspheres and 3-mercaptopropyltrimethoxysilane in anhydrous toluene to prepare MBG-SrHA@nSiO2-SH modified microspheres; mixing MBG-SrHA@nSiO2-SH modified microspheres and a zinc acetate ethanol solution, and stirring in the dark to prepare bioactive glass. The oxidized hyaluronic acid is prepared by oxidizing sodium hyaluronate in deionized water with sodium periodate and then quenching it with ethylene glycol in a mass ratio of (0.9-1.1):(0.30-0.34):(0.18-0.22). The modified gelatin is a powder obtained by modifying gelatin, chitosan oligosaccharide, EDC·HCl, and N-hydroxysuccinimide in deionized water at pH 4.5–5.0. The modified gelatin is prepared by modifying chitosan oligosaccharide, N-hydroxysuccinimide, and EDC·HCl in a mass ratio of (1.8–2.2): (0.8–1.2): (0.8–1.5): (0.2–0.4).

[0007] Furthermore, in the above-mentioned bone repair material, the bone repair material includes a composite inorganic phase powder, a hydrogel precursor liquid, and an injection medium in a mass ratio of (1-1.2):(1.5-2):(0.9-1.3).

[0008] Furthermore, in the above-mentioned bone repair material, the composite inorganic phase powder includes bioactive glass, hydroxyapatite whiskers and L-arginine in a mass ratio of (17-21):(5-8):(0.1-0.3).

[0009] Furthermore, in the above-mentioned bone repair material, the hydrogel precursor solution includes oxidized hyaluronic acid, modified gelatin, and phosphate buffer solution with a mass ratio of (1.0-1.2):(0.7-0.9):(20-25).

[0010] Furthermore, in the above-mentioned bone repair material, the injection medium is a phosphate buffer solution with a pH of 7.2 to 7.4.

[0011] Furthermore, in the aforementioned bone repair material, the preparation method of the bioactive glass includes: cetyltrimethylammonium bromide: triethyl phosphate: tetraethyl orthosilicate: 10wt%–15wt% calcium nitrate aqueous solution = (1.8–2.2):(2.3–2.7):(8.5–10):(70–80) mass ratio, reacting in deionized water at pH 10.5–11.5 to prepare a precipitate, calcining at 620℃–680℃ for 4–6 hours to prepare a median particle size of 1μm–3.5μm and a specific surface area >200m². 2 / g MBG microspheres; prepare growth solution A with an aqueous solution containing 0.7mol / L~0.9mol / L Ca(NO3)2 and 0.15mol / L~0.25mol / L Sr(NO3)2; prepare growth solution B with an aqueous solution containing 0.4mol / L~0.6mol / L (NH4)2HPO4; prepare MBG-SrHA microspheres by reacting in deionized water at 90℃~95℃ and pH10.4~10.8 according to the mass ratio of MBG microspheres:growth solution A:growth solution B = (0.8~1.2):(35~45):(35~45); prepare MBG-SrHA microspheres by stirring in an ethanol aqueous solution at pH8.8~9.6 according to the mass ratio of MBG-SrHA microspheres:8vol%~10vol% tetraethyl orthosilicate in ethanol = (4.5~5.5):(10~12). rHA@nSiO2 core-shell microspheres; MBG-SrHA@nSiO2-SH modified microspheres were prepared by reacting MBG-SrHA@nSiO2 core-shell microspheres with 3-mercaptopropyltrimethoxysilane in anhydrous toluene at a mass ratio of (3.5–4.5): (0.7–0.9); and bioactive glass was prepared by mixing MBG-SrHA@nSiO2-SH modified microspheres with an ethanol solution of 0.04 mol / L–0.06 mol / L zinc acetate in an ethanol solution at a mass ratio of (2.8–3.2): (90–110) and stirring in the dark.

[0012] Furthermore, in the above-mentioned bone repair material, the preparation method of the bioactive glass includes the following steps: N1: Following the mass ratio of hexadecyltrimethylammonium bromide:triethyl phosphate:ethyl orthosilicate:10wt%–15wt% calcium nitrate aqueous solution = (1.8–2.2):(2.3–2.7):(8.5–10):(70–80), hexadecyltrimethylammonium bromide was dissolved in deionized water, and the pH was adjusted to 10.5–11.5. Triethyl phosphate, ethyl orthosilicate, and 10wt%–15wt% calcium nitrate aqueous solution were added dropwise under stirring for 1–1.5 hours. The mixture was then aged, centrifuged, and the precipitate was collected, washed, vacuum dried, and calcined at 620℃–680℃ for 4–6 hours to obtain a median particle size of 1 μm–3.5 μm and a specific surface area >200 m². 2 / g MBG microspheres; N2: Prepare an aqueous solution containing 0.7 mol / L to 0.9 mol / L Ca(NO3)2 and 0.15 mol / L to 0.25 mol / L Sr(NO3)2 as growth solution A; prepare an aqueous solution containing 0.4 mol / L to 0.6 mol / L (NH4)2HPO4 as growth solution B; disperse MBG microspheres in deionized water according to the mass ratio of MBG microspheres: growth solution A: growth solution B = (0.8 to 1.2): (35 to 45): (35 to 45), add growth solution A while stirring, adjust the pH to 10.4 to 10.8, raise the temperature to 90℃ to 95℃, add growth solution B while stirring, maintain the pH at 10.4 to 10.8, stir and react for 22 to 26 hours, centrifuge, collect the precipitate, wash to pH 6.8 to 7.2, vacuum dry to obtain MBG-SrHA microspheres; N3: MBG-SrHA microspheres were dispersed in an ethanol-water solution at a mass ratio of (4.5-5.5):(10-12) of 8 vol%-10 vol% tetraethyl orthosilicate in ethanol solution. The pH was adjusted to 8.8-9.6. 8 vol%-10 vol% tetraethyl orthosilicate in ethanol solution was added dropwise while stirring at 30-35℃. The mixture was stirred for 5-7 hours, centrifuged, the precipitate was collected, washed, and vacuum dried to obtain MBG-SrHA@nSiO2 core-shell microspheres. N4: MBG-SrHA@nSiO2 core-shell microspheres were dispersed in anhydrous toluene according to the mass ratio of MBG-SrHA@nSiO2 core-shell microspheres: 3-mercaptopropyltrimethoxysilane = (3.5~4.5): (0.7~0.9). 3-mercaptopropyltrimethoxysilane was added, and nitrogen gas was introduced for protection. The mixture was stirred and refluxed at 100℃~110℃ for 10h~14h. After centrifugation, washing, and vacuum drying, MBG-SrHA@nSiO2-SH modified microspheres were obtained. N5: Mix MBG-SrHA@nSiO2-SH modified microspheres with 0.04mol / L to 0.06mol / L zinc acetate in an ethanol solution at a mass ratio of (2.8 to 3.2): (90 to 110). Stir in the dark for 10 to 14 hours, centrifuge, collect the precipitate, wash, and vacuum dry to obtain bioactive glass.

[0013] In step N1 of the above-mentioned method for preparing bioactive glass, hexadecyltrimethylammonium bromide is dissolved in 100 to 150 times its mass of deionized water, and the pH is adjusted to 10.5 to 11.5 with ammonia. Triethyl phosphate is added dropwise under stirring at 150 to 200 rpm, and stirring is continued for 30 to 40 minutes after the addition is complete. Then, tetraethyl orthosilicate is added dropwise, and stirring is continued for 30 to 40 minutes after the addition is complete. Finally, a 10 wt% to 15 wt% calcium nitrate aqueous solution is added dropwise, and stirring is continued for 1 hour. After 1.5 hours, statically age at 90℃-95℃ for 45-50 hours, naturally cool to room temperature, centrifuge at 7500-8500rpm for 10-15 minutes, collect the precipitate, wash alternately with anhydrous ethanol and deionized water 2-4 times each, vacuum dry at 55℃-65℃ for 10-14 hours, and calcine at 620℃-680℃ for 4-6 hours under nitrogen protection with a heating rate of 1.5℃ / min-2.5℃ / min, to obtain a median particle size of 1μm-3.5μm and a specific surface area >200m². 2 / g MBG microspheres.

[0014] In step N2 of the above-mentioned method for preparing bioactive glass, MBG microspheres are uniformly dispersed in 90 to 100 times their mass of deionized water. Under stirring at 300 to 350 rpm, growth solution A is added, and the pH is adjusted to 10.4 to 10.8 with ammonia. The temperature is raised to 90 to 95°C, and under continuous stirring, growth solution B is added. During this process, the pH is maintained at 10.4 to 10.8 with ammonia or dilute nitric acid. The reaction is carried out under continuous stirring for 22 to 26 hours. The mixture is then naturally cooled to room temperature, centrifuged at 7500 to 8500 rpm for 10 to 15 minutes, and the precipitate is collected. The precipitate is washed with deionized water until the pH is adjusted to 6.8 to 7.2, and then vacuum dried at 75 to 85°C for 22 to 26 hours to obtain MBG-SrHA microspheres.

[0015] In step N3 of the above-mentioned method for preparing bioactive glass, MBG-SrHA microspheres are uniformly dispersed in 30 to 40 times their mass of a 75 vol% to 80 vol% aqueous ethanol solution. The pH is adjusted to 8.8 to 9.6 with ammonia. Under stirring conditions of 30 to 35°C and 150 to 200 rpm, an 8 vol% to 10 vol% ethanol solution of tetraethyl orthosilicate is added dropwise. After the addition is complete, stirring is continued for 5 to 7 hours. The mixture is then centrifuged at 7500 to 8500 rpm for 10 to 15 minutes, and the precipitate is collected. It is washed 2 to 4 times with deionized water and vacuum dried at 55 to 65°C for 7 to 9 hours to obtain MBG-SrHA@nSiO2 core-shell microspheres.

[0016] In step N4 of the above-mentioned method for preparing bioactive glass, MBG-SrHA@nSiO2 core-shell microspheres are uniformly dispersed in 30 to 40 times their mass of anhydrous toluene. 3-Mercaptopropyltrimethoxysilane is added, and nitrogen gas is introduced for protection. The mixture is stirred at 100 to 110°C and 150 to 200 rpm, and refluxed for 10 to 14 hours. After cooling to room temperature, the mixture is centrifuged at 7500 to 8500 rpm for 10 to 15 minutes. The mixture is washed 1 to 3 times with toluene and 2 to 4 times with anhydrous ethanol. It is then vacuum dried at 45 to 55°C for 9 to 11 hours to obtain MBG-SrHA@nSiO2-SH modified microspheres.

[0017] Furthermore, in the above-mentioned bone repair material, the preparation method of the oxidized hyaluronic acid includes the following steps: sodium hyaluronate is added to deionized water according to the mass ratio of sodium hyaluronate: sodium periodate: ethylene glycol = (0.9~1.1):(0.30~0.34):(0.18~0.22), and stirred. Sodium periodate is added, and the mixture is stirred continuously at room temperature in the dark for 5h~7h. Ethylene glycol is added, and the mixture is stirred. The mixture is then dialyzed with flowing deionized water in the dark using a MWCO 3500 dialysis membrane, freeze-dried, and pulverized to obtain oxidized hyaluronic acid.

[0018] Furthermore, in the above-mentioned bone repair material, the preparation method of the modified gelatin includes the following steps: According to the mass ratio of gelatin:chitosan oligosaccharide:EDC·HCl:N-hydroxysuccinimide = (1.8~2.2):(0.8~1.2):(0.8~1.5):(0.2~0.4), gelatin is added to deionized water at 40℃~45℃ and stirred to dissolve. Chitosan oligosaccharide is added, and the pH is adjusted to 4.5~5.0. Under stirring at 35℃~40℃, N-hydroxysuccinimide is added and stirred to dissolve. EDC·HCl is added in 3~4 equal portions, with an interval of 1h~1.5h between each portion. After the addition is complete, the mixture is stirred and reacted for 4h~6h. The pH is adjusted to 6.8~7.2. Dialysis with flowing deionized water is performed using a MWCO 8000~10000 dialysis membrane. The mixture is then freeze-dried and pulverized to obtain the modified gelatin.

[0019] The preparation method of the above-mentioned injectable bone repair material containing bioactive glass includes the following steps: S1: Bioactive glass, hydroxyapatite whiskers, and L-arginine are mixed evenly according to the mass ratio to obtain a composite inorganic phase powder; S2: Add the modified gelatin to the phosphate buffer solution according to the mass ratio, stir and dissolve at 40℃~45℃, cool down to 35℃~40℃, add oxidized hyaluronic acid and stir to dissolve evenly to obtain the hydrogel precursor solution. S3: According to the mass ratio, first mix the composite inorganic phase powder with the injection medium to form a uniform suspension; then mix it with the hydrogel precursor liquid at a temperature below 30°C until uniform, and defoam under vacuum to form an injectable sol-like material.

[0020] This invention provides an injectable bone repair material containing bioactive glass and its preparation method, with the following beneficial effects: I. The injectable bone repair material of this invention solves the core pain points of traditional bone repair materials, such as poor shape adaptability, mismatch between degradation and bone regeneration rate, low osteogenic activity, and insufficient mechanical properties, through multi-level composite and all-dimensional synergistic design of core-shell inorganic phase, dynamic cross-linked hydrogel, and functional filler. At the same time, it achieves the integration of minimally invasive injection, gel formation, controllable degradation, biomimetic mechanical properties, and active osteogenic properties. It also has excellent biocompatibility, hydrophilicity, and protein adsorption capacity, and can adapt to the repair of irregular, cavitary, and minimally invasive bone defects, providing an efficient, safe, and highly adaptable solution for minimally invasive bone defect repair.

[0021] II. In the preparation of core-shell structured bioactive glass, the mesoporous MBG core: through calcination and median particle size control, a high specific surface area mesoporous structure is formed, realizing Ca... 2+ Si 3+ P 5+ The slow, sustained release of plasma activates osteogenic signaling pathways, exhibiting dual activity in osteoconduction and osteoinduction. The SrHA intermediate layer, synthesized hydrothermally, achieves uniform strontium doping, biomimetically matching the natural bone mineral phase while bidirectionally regulating bone metabolism and promoting osteoblast differentiation. It also enhances the lattice stability of apatite, improving the material's mechanical properties. The nSiO2 shell, encapsulated in a sol-gel process, forms a dense nano-silica layer, enabling precise control of the degradation rate and ensuring a high degree of matching between material degradation and bone regeneration rates, preventing scaffold collapse or foreign body retention. Thiol grafting and zinc ion loading, modified with silane and light-shielded complexation, provide site-specific anchoring points for zinc ions, enabling controlled, sustained release. This inhibits local inflammation, reduces postoperative infection risk, and synergistically enhances osteogenic activity with osteogenic ions.

[0022] III. In the preparation of oxidized hyaluronic acid, aldehyde active sites are introduced into the hyaluronic acid molecular chain to provide a reaction basis for in-situ crosslinking with modified gelatin; at the same time, the biocompatibility and hydrophilicity of hyaluronic acid are preserved, and the cell affinity of the material is enhanced.

[0023] IV. In the preparation of modified gelatin, the introduction of chitosan oligosaccharides not only improves the hydrophilicity and degradation uniformity of gelatin, avoiding rapid dissolution of pure gelatin, but also increases the amino sites on the molecular chain, improving the cross-linking efficiency with oxidized hyaluronic acid; the coupling agent system of EDC·HCl and N-hydroxysuccinimide ensures the high efficiency of the modification reaction and the stability of the product.

[0024] Fifth, hydroxyapatite whiskers, as a mechanical reinforcing phase, improve the compressive strength and elastic modulus of the material, compensating for the brittleness of hydrogels and bioglasses, making the material's mechanical properties close to those of cancellous bone, and suitable for repairing bone defects in non-load-bearing areas. L-arginine, as a functional small molecule, not only provides alkaline regulation for the local microenvironment, mitigating the impact of acidic byproducts from material degradation on the osteogenic microenvironment, but also improves local microcirculation and promotes angiogenesis.

[0025] In summary, the composite inorganic phase powder, hydrogel precursor solution, and injection medium are compounded in a specific ratio, with each component complementing and promoting the others to form a closed-loop performance optimization system.

[0026] The surface functional groups (thiol groups, hydroxyl groups) of the core-shell structured bioactive glass form hydrogen bonds and weak chemical bonds with the aldehyde and amino groups of the hydrogel, achieving uniform dispersion and firm binding of the inorganic phase in the three-dimensional network of the hydrogel. This avoids particle aggregation, sedimentation, or interfacial debonding, improving both the injectability and mechanical homogeneity of the material while ensuring the stability of ion release. MBG releases Ca... 2+ Si 3+ P 5+ SrHA releases Sr 2+ and the load of Zn 2+ The synergistic upregulation of alkaline phosphatase activity by multiple ions promotes collagen synthesis and mineralized nodule formation, upgrading the material from traditional passive filling to active osteogenic processes. The whisker toughening effect of hydroxyapatite whiskers, the particle reinforcement effect of core-shell bioactive glass, and the three-dimensional network support effect of hydrogel work together to enhance the compressive strength and elastic modulus of the material, compensating for the mechanical shortcomings of a single phase and matching the mechanical properties of cancellous bone. The degradation rate control of the nSiO2 shell, the mild hydrolysis of the hydrogel, and the alkalinity regulation of L-arginine work together to match the degradation rate with the bone regeneration rate, maintain a stable pH within the physiological range, avoid inflammatory reactions caused by the accumulation of acidic byproducts, and ensure a healthy physiological microenvironment for bone repair. The high biocompatibility, low hemolysis rate, and non-cytotoxicity of oxidized hyaluronic acid-modified gelatin hydrogel provide a safe carrier environment for the functional expression of the inorganic phase, achieving a synergistic effect of carrier safety and high functional efficiency. Detailed Implementation

[0027] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these embodiments.

[0028] Glossary: ​​MBG is mesoporous bioactive glass; SrHA is strontium-doped hydroxyapatite; nSiO2 is nano-silica; SH is mercapto; Zn is zinc; MBG-SrHA@nSiO2-SH-Zn is bioactive glass, specifically zinc-complexed mercapto-modified core-shell mesoporous bioactive glass microspheres; CTAB is hexadecyltrimethylammonium bromide; TEP is triethyl phosphate; TEOS is tetraethyl orthosilicate; MPTMS is 3-mercaptopropyltrimethoxysilane; OHA is oxidized hyaluronic acid; Gel-COS is modified gelatin; EDC·HCl is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; MWCO is molecular weight cutoff.

[0029] Example 1 An injectable bone repair material containing bioactive glass, comprising a composite inorganic phase powder in a mass ratio of 1.1:1.8:1.2, a hydrogel precursor solution, and an injection medium; the composite inorganic phase powder comprises bioactive glass, hydroxyapatite whiskers, and L-arginine in a mass ratio of 19:7:0.2; the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and pH 7.3 phosphate buffer in a mass ratio of 1.1:0.8:23; and the injection medium is pH 7.3 phosphate buffer.

[0030] The preparation method of bioactive glass (MBG-SrHA@nSiO2-SH-Zn) includes the following steps: N1: Prepare the following mixture by mass ratio: hexadecyltrimethylammonium bromide (CTAB): triethyl phosphate (TEP): tetraethyl orthosilicate (TEOS): 12wt% calcium nitrate aqueous solution = 2.0:2.5:9.2:75; Dissolve hexadecyltrimethylammonium bromide in 120 times its mass of deionized water, adjust the pH to 11.0 with ammonia, add triethyl phosphate dropwise while stirring at 180 rpm, and continue stirring for 35 min after the addition is complete. Then add tetraethyl orthosilicate dropwise, and continue stirring for 3 min after the addition is complete. After 5 min, 12 wt% calcium nitrate aqueous solution was added dropwise, and stirring was continued for 1 h. Static aging was carried out at 90℃~95℃ for 48 h, followed by natural cooling to room temperature. The precipitate was collected by centrifugation at 8000 rpm for 12 min, and washed three times each with anhydrous ethanol and deionized water (each wash solution was 5 times the volume of the precipitate). The precipitate was then vacuum dried at 60℃ for 12 h, and calcined at 650℃ for 5 h under nitrogen protection at a rate of 2.0℃ / min to remove the CTAB template, yielding a median particle size of 2.3 μm and a specific surface area of ​​238 m². 2 / g MBG microspheres; N2: Prepare an aqueous solution containing 0.8 mol / L Ca(NO3)2 and 0.2 mol / L Sr(NO3)2 as growth solution A; prepare an aqueous solution containing 0.5 mol / L (NH4)2HPO4 as growth solution B; prepare materials according to the mass ratio of MBG microspheres: growth solution A: growth solution B = 1:40:40; uniformly disperse MBG microspheres in 95 times their mass of deionized water, add growth solution A under stirring at 320 rpm, adjust the pH to 10.6 with ammonia water, raise the temperature to 90℃~95℃, add growth solution B under continuous stirring, during which the pH is maintained in the range of 10.4~10.8 with ammonia water or dilute nitric acid, continuously stir and react for 24 h, cool naturally to room temperature, centrifuge at 8000 rpm for 12 min, collect the precipitate, wash with deionized water to pH 7.0, vacuum dry at 80℃ for 24 h to form SrHA shell, and obtain MBG-SrHA microspheres; N3: Prepare materials according to the mass ratio of MBG-SrHA microspheres: 9 vol% tetraethyl orthosilicate ethanol solution = 5:11; uniformly disperse MBG-SrHA microspheres in 35 times their mass of 78 vol% ethanol aqueous solution, adjust the pH to 9.2 with ammonia water, add 9 vol% tetraethyl orthosilicate ethanol solution dropwise under the temperature range of 30℃~35℃ and stirring at 180 rpm, continue stirring for 6 h after the addition is complete, centrifuge at 8000 rpm for 12 min, collect the precipitate, wash 3 times with deionized water, and vacuum dry at 60℃ for 8 h to form a SiO2 outer shell layer, and obtain MBG-SrHA@nSiO2 core-shell microspheres; N4: Prepare materials according to the mass ratio of MBG-SrHA@nSiO2 core-shell microspheres: 3-mercaptopropyltrimethoxysilane (MPTMS) = 4:0.8; uniformly disperse MBG-SrHA@nSiO2 core-shell microspheres in 35 times their mass of anhydrous toluene, add 3-mercaptopropyltrimethoxysilane, purge with nitrogen for protection, stir at 180 rpm in the temperature range of 100℃~110℃, reflux for 12 h to achieve mercaptosilane modification, cool to room temperature, centrifuge at 8000 rpm for 12 min, wash twice with toluene and three times with anhydrous ethanol to remove unreacted silane, and vacuum dry at 50℃ for 10 h to obtain MBG-SrHA@nSiO2-SH modified microspheres; N5: By mass ratio, MBG-SrHA@nSiO2-SH modified microspheres: 0.05 mol / L zinc acetate ethanol solution = 3:100. Add MBG-SrHA@nSiO2-SH modified microspheres to 0.05 mol / L zinc acetate ethanol solution, stir at 120 rpm for 12 h under light-protected conditions to achieve zinc ion complexation and loading adsorption. Centrifuge at 8000 rpm for 12 min, collect the precipitate, wash with deionized water until no zinc ions are detected in the eluent, and vacuum dry at 50℃ for 12 h to obtain MBG-SrHA@nSiO2-SH-Zn, i.e., bioactive glass.

[0031] The preparation method of the oxidized hyaluronic acid (OHA) includes the following steps: Prepare materials according to the mass ratio of sodium hyaluronate:sodium periodate:ethylene glycol = 1:0.32:0.2; add sodium hyaluronate to 100 times its mass of deionized water, stir at 130 rpm for 35 min, add sodium periodate, stir continuously at room temperature in the dark for 6 h, add ethylene glycol, stir continuously for 30 min to quench, dialyze with flowing deionized water using a MWCO3500 dialysis membrane in the dark for 76 h, freeze dry, pulverize and pass through a 200-mesh sieve to obtain oxidized hyaluronic acid.

[0032] The preparation method of the modified gelatin (Gel-COS) includes the following steps: Prepare materials according to the mass ratio of gelatin:chitosan oligosaccharide:EDC·HCl:N-hydroxysuccinimide = 2:1:1.3:0.3; add gelatin to 28 times its mass of deionized water at 43℃, stir and dissolve at 120 rpm; add chitosan oligosaccharide, adjust the pH to 4.8 with 0.12 mol / L hydrochloric acid, and continuously stir at 35℃~40℃; add N-hydroxysuccinimide and stir to dissolve; add EDC·HCl in 3 equal portions, with an interval of 1 hour between each portion; after the addition is complete, continue stirring and react for 5 hours; adjust the pH to 7.0 with 0.12 mol / L sodium hydroxide aqueous solution; dialyze with flowing deionized water using a MWCO 8000 dialysis membrane for 60 hours (with 7 water changes during this period); freeze-dry; pulverize and pass through a 200-mesh sieve to obtain the modified gelatin.

[0033] The preparation method of the above-mentioned injectable bone repair material containing bioactive glass includes the following steps: S1: Bioactive glass, hydroxyapatite whiskers, and L-arginine are mixed evenly according to the mass ratio to obtain a composite inorganic phase powder; S2: Add the modified gelatin to the pH 7.3 phosphate buffer solution according to the mass ratio, stir and dissolve at 42℃, cool to 38℃, add oxidized hyaluronic acid and stir to dissolve evenly to obtain the hydrogel precursor solution. S3: According to the mass ratio, first mix the composite inorganic phase powder with the injection medium to form a uniform suspension; then mix it with the hydrogel precursor liquid at 28℃ and 80rpm until uniform, and defoam under vacuum to form an injectable sol-like material.

[0034] Example 2 An injectable bone repair material containing bioactive glass, comprising a composite inorganic phase powder in a mass ratio of 1:2:0.9, a hydrogel precursor solution, and an injection medium; the composite inorganic phase powder comprises bioactive glass, hydroxyapatite whiskers, and L-arginine in a mass ratio of 21:5:0.3; the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and pH 7.2 phosphate buffer in a mass ratio of 1.0:0.9:20; and the injection medium is pH 7.2 phosphate buffer.

[0035] The preparation method of bioactive glass (MBG-SrHA@nSiO2-SH-Zn) includes the following steps: N1: Prepare the following mixture by mass ratio: hexadecyltrimethylammonium bromide (CTAB): triethyl phosphate (TEP): tetraethyl orthosilicate (TEOS): 10wt% calcium nitrate aqueous solution = 1.8:2.7:8.5:80; Dissolve hexadecyltrimethylammonium bromide in 100 times its mass of deionized water, adjust the pH to 11.5 with ammonia, add triethyl phosphate dropwise while stirring at 150 rpm, and continue stirring for 40 min after the addition is complete. Then add tetraethyl orthosilicate dropwise, and continue stirring for 30 min after the addition is complete. After a period of time, 10 wt% calcium nitrate aqueous solution was added dropwise, and the mixture was stirred continuously for 1.5 h. The mixture was then statically aged at 90℃–95℃ for 45 h, naturally cooled to room temperature, centrifuged at 8500 rpm for 10 min, and the precipitate was collected. It was washed four times each with anhydrous ethanol and deionized water (each wash solution being four times the volume of the precipitate). The precipitate was then vacuum dried at 65℃ for 10 h, and calcined at 620℃ for 6 h under nitrogen protection with a heating rate of 2.5℃ / min to remove the CTAB template, yielding a median particle size of 1.0 μm and a specific surface area of ​​245 m². 2 / g MBG microspheres; N2: Prepare an aqueous solution containing 0.7 mol / L Ca(NO3)2 and 0.25 mol / L Sr(NO3)2 as growth solution A; prepare an aqueous solution containing 0.4 mol / L (NH4)2HPO4 as growth solution B; prepare materials according to the mass ratio of MBG microspheres: growth solution A: growth solution B = 1.2:35:45; uniformly disperse MBG microspheres in 90 times their mass of deionized water, add growth solution A under stirring at 350 rpm, adjust the pH to 10.4 with ammonia, raise the temperature to 90℃~95℃, add growth solution B under continuous stirring, maintain the pH in the range of 10.4~10.8 with ammonia or dilute nitric acid, continuously stir and react for 26 h, cool naturally to room temperature, centrifuge at 7500 rpm for 15 min, collect the precipitate, wash with deionized water to pH 6.8, vacuum dry at 85℃ for 22 h to form SrHA shell, and obtain MBG-SrHA microspheres; N3: Prepare materials according to the mass ratio of MBG-SrHA microspheres: 8 vol% tetraethyl orthosilicate ethanol solution = 4.5:12; uniformly disperse MBG-SrHA microspheres in 30 times their mass of 80 vol% ethanol aqueous solution, adjust the pH to 8.8 with ammonia water, add 8 vol% tetraethyl orthosilicate ethanol solution dropwise under the temperature range of 30℃~35℃ and stirring at 200 rpm, continue stirring for 5 h after the addition is complete, centrifuge at 8500 rpm for 10 min, collect the precipitate, wash 4 times with deionized water, and vacuum dry at 55℃ for 9 h to form a SiO2 outer shell layer, and obtain MBG-SrHA@nSiO2 core-shell microspheres; N4: Prepare materials according to the mass ratio of MBG-SrHA@nSiO2 core-shell microspheres: 3-mercaptopropyltrimethoxysilane (MPTMS) = 3.5:0.9; uniformly disperse MBG-SrHA@nSiO2 core-shell microspheres in 30 times their mass of anhydrous toluene, add 3-mercaptopropyltrimethoxysilane, purge with nitrogen for protection, stir at 200 rpm in the temperature range of 100℃~110℃, reflux for 10 h to achieve mercaptosilane modification, cool to room temperature, centrifuge at 8500 rpm for 10 min, wash 3 times with toluene and 2 times with anhydrous ethanol to remove unreacted silane, and vacuum dry at 55℃ for 9 h to obtain MBG-SrHA@nSiO2-SH modified microspheres; N5: By mass ratio, MBG-SrHA@nSiO2-SH modified microspheres: 0.04 mol / L zinc acetate ethanol solution = 2.8:110. MBG-SrHA@nSiO2-SH modified microspheres were added to 0.04 mol / L zinc acetate ethanol solution and stirred at 100 rpm for 14 h under light-protected conditions to achieve zinc ion complexation and loading adsorption. After centrifugation at 7500 rpm for 15 min, the precipitate was collected and washed with deionized water until no zinc ions were detected in the eluent. After vacuum drying at 45℃ for 14 h, MBG-SrHA@nSiO2-SH-Zn, i.e., bioactive glass, was obtained.

[0036] The preparation method of the oxidized hyaluronic acid (OHA) includes the following steps: Prepare materials according to the mass ratio of sodium hyaluronate:sodium periodate:ethylene glycol = 0.9:0.34:0.18; add sodium hyaluronate to 110 times its mass of deionized water, stir at 120 rpm for 40 min, add sodium periodate, stir continuously at room temperature in the dark for 5 h, add ethylene glycol, stir continuously for 35 min to quench, dialyze with flowing deionized water using a MWCO3500 dialysis membrane in the dark for 72 h, freeze dry, pulverize and pass through a 250 mesh sieve to obtain oxidized hyaluronic acid.

[0037] The preparation method of the modified gelatin (Gel-COS) includes the following steps: Prepare materials according to the mass ratio of gelatin:chitosan oligosaccharide:EDC·HCl:N-hydroxysuccinimide = 1.8:1.2:0.8:0.4; add gelatin to 25 times its mass of deionized water at 45℃, stir and dissolve at 100 rpm, add chitosan oligosaccharide, adjust the pH to 4.5 with 0.15 mol / L hydrochloric acid, continuously stir at 35℃~40℃, add N-hydroxysuccinimide and stir to dissolve, add EDC·HCl in 4 equal portions, with an interval of 1 hour between each portion, and continue stirring for 6 hours after the addition is complete, adjust the pH to 7.2 with 0.1 mol / L sodium hydroxide aqueous solution, dialyze with flowing deionized water using a MWCO 8000 dialysis membrane for 72 hours (with 8 water changes during this period), freeze-dry, pulverize and pass through a 250-mesh sieve to obtain the modified gelatin.

[0038] The preparation method of the above-mentioned injectable bone repair material containing bioactive glass includes the following steps: S1: Bioactive glass, hydroxyapatite whiskers, and L-arginine are mixed evenly according to the mass ratio to obtain a composite inorganic phase powder; S2: Add the modified gelatin to the pH 7.2 phosphate buffer solution according to the mass ratio, stir and dissolve at 45°C, cool to 40°C, add oxidized hyaluronic acid and stir to dissolve evenly to obtain the hydrogel precursor solution. S3: According to the mass ratio, first mix the composite inorganic phase powder with the injection medium to form a uniform suspension; then mix it with the hydrogel precursor liquid at 29°C and 60 rpm until uniform, and defoam under vacuum to form an injectable sol-like material.

[0039] Example 3 An injectable bone repair material containing bioactive glass, comprising a composite inorganic phase powder in a mass ratio of 1.2:1.5:1.3, a hydrogel precursor solution, and an injection medium; the composite inorganic phase powder comprises bioactive glass, hydroxyapatite whiskers, and L-arginine in a mass ratio of 17:8:0.1; the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and pH 7.4 phosphate buffer in a mass ratio of 1.2:0.7:25; and the injection medium is pH 7.4 phosphate buffer.

[0040] The preparation method of bioactive glass (MBG-SrHA@nSiO2-SH-Zn) includes the following steps: N1: Prepare the following mixture by mass ratio: hexadecyltrimethylammonium bromide (CTAB): triethyl phosphate (TEP): tetraethyl orthosilicate (TEOS): 15wt% calcium nitrate aqueous solution = 2.2:2.3:10:70; Dissolve hexadecyltrimethylammonium bromide in 150 times its mass of deionized water, adjust the pH to 10.5 with ammonia, add triethyl phosphate dropwise while stirring at 200 rpm, and continue stirring for 30 min after the addition is complete. Then add tetraethyl orthosilicate dropwise while stirring for 40 min after the addition is complete. After a period of time, 15 wt% calcium nitrate aqueous solution was added dropwise, and the mixture was stirred continuously for 1 hour. The mixture was then statically aged at 90℃–95℃ for 50 hours, naturally cooled to room temperature, and centrifuged at 7500 rpm for 15 minutes. The precipitate was collected and washed twice alternately with anhydrous ethanol and deionized water (each time using 6 times the volume of the precipitate). The precipitate was then vacuum dried at 55℃ for 14 hours and calcined at 680℃ for 4 hours under nitrogen protection at a rate of 1.5℃ / min to remove the CTAB template, yielding a median particle size of 3.5 μm and a specific surface area of ​​219 m². 2 / g MBG microspheres; N2: Prepare an aqueous solution containing 0.9 mol / L Ca(NO3)2 and 0.15 mol / L Sr(NO3)2 as growth solution A; prepare an aqueous solution containing 0.6 mol / L (NH4)2HPO4 as growth solution B; prepare materials according to the mass ratio of MBG microspheres: growth solution A: growth solution B = 0.8:45:35; uniformly disperse MBG microspheres in 100 times their mass of deionized water, add growth solution A under stirring at 300 rpm, adjust the pH to 10.8 with ammonia, raise the temperature to 90℃~95℃, add growth solution B under continuous stirring, maintain the pH in the range of 10.4~10.8 with ammonia or dilute nitric acid, and continue stirring for 22 h. Cool naturally to room temperature, centrifuge at 8500 rpm for 10 min, collect the precipitate, wash with deionized water to pH 7.2, and vacuum dry at 75℃ for 26 h to form SrHA shell, thus obtaining MBG-SrHA microspheres; N3: Prepare materials by mass ratio of MBG-SrHA microspheres: 10 vol% tetraethyl orthosilicate ethanol solution = 5.5:10; uniformly disperse MBG-SrHA microspheres in 40 times their mass of 75 vol% ethanol aqueous solution, adjust pH to 9.6 with ammonia water, add 10 vol% tetraethyl orthosilicate ethanol solution dropwise under temperature range of 30℃~35℃ and stirring at 150 rpm, continue stirring for 7 h after the addition is complete, centrifuge at 7500 rpm for 15 min, collect the precipitate, wash twice with deionized water, and vacuum dry at 65℃ for 7 h to form SiO2 outer shell layer, thus obtaining MBG-SrHA@nSiO2 core-shell microspheres; N4: Prepare materials according to the mass ratio of MBG-SrHA@nSiO2 core-shell microspheres: 3-mercaptopropyltrimethoxysilane (MPTMS) = 4.5:0.7; uniformly disperse MBG-SrHA@nSiO2 core-shell microspheres in 40 times their mass of anhydrous toluene, add 3-mercaptopropyltrimethoxysilane, purge with nitrogen for protection, stir at 150 rpm in the temperature range of 100℃~110℃, reflux for 14 h to achieve mercaptosilane modification, cool to room temperature, centrifuge at 7500 rpm for 15 min, wash once with toluene, wash four times with anhydrous ethanol to remove unreacted silane, vacuum dry at 45℃ for 11 h to obtain MBG-SrHA@nSiO2-SH modified microspheres; N5: By mass ratio, MBG-SrHA@nSiO2-SH modified microspheres: 0.06 mol / L zinc acetate ethanol solution = 3.2:90. Add MBG-SrHA@nSiO2-SH modified microspheres to 0.06 mol / L zinc acetate ethanol solution, stir at 150 rpm for 10 h under light-protected conditions to achieve zinc ion complexation and loading adsorption. Centrifuge at 8500 rpm for 10 min, collect the precipitate, wash with deionized water until no zinc ions are detected in the eluent, and vacuum dry at 55℃ for 10 h to obtain MBG-SrHA@nSiO2-SH-Zn, i.e., bioactive glass.

[0041] The preparation method of the oxidized hyaluronic acid (OHA) includes the following steps: Prepare materials according to the mass ratio of sodium hyaluronate:sodium periodate:ethylene glycol = 1.1:0.3:0.22; add sodium hyaluronate to 90 times its mass of deionized water, stir at 150 rpm for 30 min, add sodium periodate, stir continuously at room temperature in the dark for 7 h, add ethylene glycol, stir continuously for 25 min to quench, dialyze with flowing deionized water using a MWCO3500 dialysis membrane in the dark for 80 h, freeze dry, pulverize and pass through a 200-mesh sieve to obtain oxidized hyaluronic acid.

[0042] The preparation method of the modified gelatin (Gel-COS) includes the following steps: Prepare materials according to the mass ratio of gelatin:chitosan oligosaccharide:EDC·HCl:N-hydroxysuccinimide = 2.2:0.8:1.5:0.2; add gelatin to 30 times its mass of deionized water at 40℃, stir and dissolve at 150 rpm, add chitosan oligosaccharide, adjust the pH to 5.0 with 0.1 mol / L hydrochloric acid, continuously stir at 35℃~40℃, add N-hydroxysuccinimide and stir to dissolve, add EDC·HCl in 3 equal portions, with an interval of 1.5 h between each portion, and continue stirring for 4 h after the addition is complete, adjust the pH to 6.8 with 0.15 mol / L sodium hydroxide aqueous solution, dialyze with flowing deionized water using a MWCO 10000 dialysis membrane for 48 h (with 6 water changes during this period), freeze-dry, pulverize and pass through a 200-mesh sieve to obtain the modified gelatin.

[0043] The preparation method of the above-mentioned injectable bone repair material containing bioactive glass includes the following steps: S1: Bioactive glass, hydroxyapatite whiskers, and L-arginine are mixed evenly according to the mass ratio to obtain a composite inorganic phase powder; S2: Add the modified gelatin to the pH 7.4 phosphate buffer solution according to the mass ratio, stir and dissolve at 40°C, cool to 35°C, add oxidized hyaluronic acid and stir to dissolve evenly to obtain the hydrogel precursor solution. S3: According to the mass ratio, first mix the composite inorganic phase powder with the injection medium to form a uniform suspension; then mix it with the hydrogel precursor liquid at 26℃ and 100rpm until uniform, and defoam under vacuum to form an injectable sol-like material.

[0044] The sol-like materials prepared in the above embodiments are compatible with 18G to 21G needles.

[0045] The raw materials used in the above embodiments are sourced as follows: Hydroxyapatite whiskers are from Shanghai Buwei Applied Materials Technology Co., Ltd., 30nm-100nm grade. L-arginine (L-2-amino-5-guanidinovalerate) is from Ruichengkang Pharmaceutical Technology (Shaanxi) Co., Ltd. Cetyltrimethylammonium bromide (CTAB) has a purity of ≥99%. Triethyl phosphate (TEP) has a purity of ≥99%. Tetraethyl orthosilicate (TEOS) has a purity of ≥99%. 3-Mercaptopropyltrimethoxysilane (MPTMS, silane coupling agent KH-590) has a purity of ≥99%. Sodium hyaluronate is from Aivit (Shanghai) Pharmaceutical Technology Co., Ltd., molecular weight 500,000-1,490,000, injection grade. Sodium periodate has a purity of ≥99%. Ethylene glycol has a purity of ≥99%. Gelatin is type B gelatin, sourced from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd. Chitosan oligosaccharides were sourced from Sichuan Huatang Jurui Biotechnology Co., Ltd. EDC·HCl, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, was sourced from Shanghai Puzhen Biotechnology Co., Ltd. N-hydroxysuccinimide had a purity of over 99%.

[0046] Comparative Example 1 The difference from Example 1 is that the mass ratio of bioactive glass, hydroxyapatite whiskers, and L-arginine in the composite inorganic phase powder is 24:2:0.2.

[0047] Comparative Example 2 The difference from Example 1 is that the bioactive glass (MBG-SrHA@nSiO2-SH-Zn) is replaced with MBG microspheres.

[0048] Comparative Example 3 The difference from Example 1 is that the bioactive glass (MBG-SrHA@nSiO2-SH-Zn) is replaced with MBG-SrHA microspheres.

[0049] Comparative Example 4 The difference from Example 1 is that the bioactive glass (MBG-SrHA@nSiO2-SH-Zn) is replaced with MBG-SrHA@nSiO2 core-shell microspheres.

[0050] Comparative Example 5 The difference from Example 1 is that the N3 step (SiO2 coating is not performed) is omitted in the preparation of bioactive glass (MBG-SrHA@nSiO2-SH-Zn).

[0051] Comparative Example 6 The difference from Example 1 is that the N4 step (mercaptosilane modification is not performed) is omitted in the preparation of bioactive glass (MBG-SrHA@nSiO2-SH-Zn).

[0052] Comparative Example 7 The difference from Example 1 is that sodium hyaluronate is used instead of oxidized hyaluronic acid.

[0053] Comparative Example 8 The difference from Example 1 is that the modified gelatin uses gelatin instead of gelatin.

[0054] I. Cytotoxicity test: Sample preparation: Gel samples from each example and comparative example were added to serum-free DMEM medium at a ratio of 0.2 g / mL and extracted at 37°C for 24 h. The supernatant was collected by centrifugation and filtered through a 0.22 μm filter membrane for sterilization, serving as the 100% extract stock solution. The stock solution was diluted to a 50% concentration with serum-free DMEM medium to form the experimental group.

[0055] Detection method: Mouse osteoblast progenitor cells MC3T3-E1 were used at a concentration of 5 × 10⁻⁶. 3 Cells were seeded at a density of 1 cell / well in 96-well plates. After 24 hours of culture, the medium was replaced with medium containing 50% sample extract (experimental group); a blank group was prepared using serum-free DMEM medium; and a negative control group was prepared using high-density polyethylene (Wuhan Nengren Pharmaceutical Chemical Co., Ltd.) extract. After 48 hours of further culture, 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C in the dark for 2 hours. The absorbance (OD value) was measured at 450 nm using a microplate reader. Cell viability (%) = (OD value of experimental group - OD value of blank group) / (OD value of negative control group - OD value of blank group) × 100%.

[0056] II. Hemolytic performance test: Sample preparation: After gel solidification, the sample was cut into particles <2mm. The positive control group was distilled water; the negative control group was 0.9% (w / v) physiological saline.

[0057] Detection method: Fresh anticoagulated rabbit blood was taken and diluted at a ratio of blood to physiological saline of 4:5 (v / v). 0.2g of sample particles and 10mL of physiological saline were added to each experimental tube; 10mL of physiological saline was added to the negative control tube; and 10mL of distilled water was added to the positive control tube. All tubes were preheated in a 37℃ water bath for 30 minutes, and then 0.1mL of diluted anticoagulated blood was added to each. After gentle mixing, the tubes were incubated in a 37℃ water bath for 60 minutes. The tubes were centrifuged at 1500rpm for 10 minutes, and the supernatant was measured at a wavelength of 545nm to determine the OD value. Hemolysis rate (%) = (OD value of experimental group - OD value of negative control) / (OD value of positive control - OD value of negative control) × 100%.

[0058] III. Simultaneous detection of pH stability and in vitro degradation performance: Sample preparation: Fresh sol from each example and comparative example was injected into a mold and gelled at 37°C for 24 hours to prepare cylindrical samples with a diameter of 10 mm × 10 mm. After freeze-drying, the samples were weighed (W0).

[0059] Extraction medium: Tris-HCl buffer solution at pH 7.4 containing 0.1% (w / v) NaN3 antibacterial agent.

[0060] Test method: Place the sample in a 50 mL centrifuge tube and add 30 mL of extraction medium. Place in a constant temperature shaker at 37℃ and 100 rpm. Take samples on days 7, 14, and 28, and measure the pH of the extract using a pH meter. Remove the sample, gently rinse three times with deionized water, freeze-dry to constant weight, and weigh W. n Replace with an equal amount of fresh extraction medium after each sampling. Cumulative mass loss rate over 28 days (%) = (W0 - W) n ) / W0×100%.

[0061] IV. Compression mechanical property testing: Sample preparation: Fresh sol from each example and comparative example was injected into a mold and gelled at 37°C for 24 hours to form cylindrical samples with a diameter of 10 mm × 10 mm. The samples were then equilibrated with PBS for 24 hours.

[0062] Test method: A universal testing machine was used to perform uniaxial compression tests on cylindrical specimens at a compression rate of 1 mm / min under conditions of 25℃ and 55% humidity, and the stress-strain curves were recorded. The peak stress before the first stress drop was taken as the compressive strength (kPa), and the elastic modulus (kPa) was calculated in the linear segment of strain 0-10%.

[0063] V. Material Surface Hydrophilicity Test: Sample preparation: Fresh sol from each example and comparative example was injected into a mold and gelled at 37°C for 24 hours to form a Φ10mm×2mm round sample, which was then freeze-dried.

[0064] Detection method: Using a contact angle meter, 2 μL of deionized water was dropped onto a flat surface of the sample at 25℃. The droplet morphology was automatically captured, and the static water contact angle was calculated 5 seconds after the droplet contacted the surface. Five different locations were measured for each sample.

[0065] VI. Protein Adsorption Performance Testing: Sample preparation: The gel sample was made into a 10mm×10mm×1mm sheet, freeze-dried and weighed precisely W.

[0066] Detection method: Immerse the sample in 5.0 mL of 1.0 mg / mL bovine serum albumin (BSA) PBS solution and shake at 37℃, 60 rpm, and 20 mm amplitude for 24 h for adsorption. After removing the sample, centrifuge at 10℃, 8000×g for 10 min and collect the supernatant. Use a BCA protein concentration assay kit to determine the residual BSA concentration C1 (mg / mL) in the supernatant. Simultaneously determine the concentration C0 (mg / mL) of the original BSA solution without sample. Protein adsorption amount (mg / g) = (C0 - C1) × 5.0 / W.

[0067] VII. In vitro osteogenic differentiation performance assessment: Sample preparation: 100 μL of sol material was injected into the bottom of a 48-well plate and gelled at 37°C and 5% CO2 for 2 h to form a hydrogel membrane; the gel membrane was gently washed twice with PBS buffer to equilibrate, and then sterilized by UV for 30 min.

[0068] Detection method: MC3T3-E1 cells were cultured at 5×10⁻⁶ cells / year. 4 Cells were seeded at a density of cells / well on the surface of a hydrogel membrane. After 24 hours of cell adhesion, the medium was replaced with osteogenic induction medium (DMEM containing 10% FBS, 50 μg / mL ascorbic acid, 10 mM β-glycerophosphate sodium, and 100 nM dexamethasone). After 7 and 14 days of culture, cells were lysed, and ALP activity was measured using an alkaline phosphatase (ALP) activity assay kit. Total protein content was determined using the BCA method and normalized. Results are expressed as ALP activity per unit protein (U / mg protein). The control group consisted of cells cultured on ordinary tissue culture plates.

[0069] Table 1. Test Results (Average Values)

[0070] Note 1: In the in vitro osteogenic differentiation performance assessment, the average ALP activity (U / mg protein) of the control group (cells cultured on ordinary tissue culture plastic plates) was 1.82 at 7 days and 3.31 at 14 days.

[0071] Note 2: All data are the average of 3 parallel samples.

[0072] The results above show that the comprehensive performance advantages of Examples 1 to 3 stem from the multi-level composite and all-dimensional synergistic design of the core-shell inorganic phase, the dynamic cross-linked hydrogel, and the functional filler. Each component complements and enhances the effect from the perspectives of structure, function, and biocompatibility, thus solving the shortcomings of traditional bone repair materials in terms of formability, activity, degradation, and mechanical properties.

[0073] The multi-level functions of core-shell bioactive glass (MBG-SrHA@nSiO2-SH-Zn): The mesoporous bioactive glass (MBG) core provides a high specific surface area and mesoporous channels, enabling the sustained release of ions such as calcium, silicon, and phosphorus, activating osteogenic signaling pathways, and possessing both osteoconductive and osteoinductive activities. The strontium-doped hydroxyapatite (SrHA) intermediate layer achieves a biomimetic match with the natural bone mineral phase, with sustained release of strontium ions regulating bone metabolism, promoting osteoblast differentiation, and simultaneously enhancing the lattice stability of apatite and improving the material's mechanical properties. The nano-silica (nSiO2) shell controls degradation, ensuring a precise match between the material's degradation rate and bone regeneration rate. Thiol grafting provides site-specific complexation sites for zinc ions, enabling controlled sustained release of zinc ions rather than rapid loss due to physical adsorption, while also inhibiting local inflammatory responses.

[0074] The compatibility of oxidized hyaluronic acid-modified gelatin hydrogel: The aldehyde groups of oxidized hyaluronic acid bond with the amino groups of modified gelatin, achieving rapid in-situ cross-linking at physiological temperatures and pH. This results in a sol state before injection, suitable for minimally invasive injections and filling irregular bone defects. After injection, it rapidly gels and solidifies without the need for additional cross-linking agents, exhibiting excellent biocompatibility. Chitosan oligosaccharide-modified gelatin enhances the hydrophilicity, cell affinity, and degradation uniformity of the hydrogel, avoiding injection difficulties caused by rapid dissolution of pure gelatin or excessively high viscosity of pure hyaluronic acid. The three-dimensional network of the hydrogel ensures uniform dispersion of the inorganic phase powder, preventing particle agglomeration and sedimentation, and improving the injectability and mechanical uniformity of the material.

[0075] Synergistic effect of composite inorganic phase and functional small molecules: Hydroxyapatite whiskers, as a mechanically reinforcing phase, directionally improve the compressive strength and elastic modulus of the material, compensating for the brittleness of hydrogels and bioglasses, making the material's mechanical properties close to those of cancellous bone, suitable for repairing bone defects in non-load-bearing areas. L-arginine provides alkaline regulation to the local microenvironment, mitigating the effects of acidic byproducts from material degradation, while improving local microcirculation, promoting angiogenesis, providing nutrients and oxygen to newly formed bone tissue, and solving the vascularization problem in bone repair. Inorganic phase ions (Ca... 2+ 、Sr 2+ SiO3 2- It works synergistically with zinc ions to upregulate alkaline phosphatase (ALP) activity, promote collagen synthesis and mineralized nodule formation, thus upgrading the material from a simple passive filler to an active osteogenic agent.

[0076] Closed-loop design for biosafety and performance: The material is non-cytotoxic throughout the process, and the hemolysis rate is far below the qualified standards for medical implant materials. The high specific surface area and strong hydrophilicity bring excellent protein adsorption capacity. Ion slow release and gentle hydrolysis of hydrogel ensure that the pH remains stable within the physiological range throughout the process, without local acidosis, avoiding inflammatory reactions and cell damage, and ensuring the physiological microenvironment for bone repair.

[0077] In Comparative Example 1, the proportion of inorganic phase components was unbalanced. The inorganic phase proportion deviated from the optimal synergistic range, with an excessively high proportion of bioactive glass and an excessively low proportion of hydroxyapatite whiskers, leading to a comprehensive deterioration in dispersibility, structural stability, and ion release kinetics. The whisker reinforcement effect was weakened, the compatibility between the hydrogel network and the inorganic phase decreased, and the mechanical properties of the material were reduced. Excessive bioactive glass resulted in locally high ion concentrations, generating micro-irritation that increased cytotoxicity and hemolysis rate. The excessively high proportion of inorganic phase degradation led to insufficient hydrogel support, rapid structural disintegration, and the accumulation of acidic products, resulting in a decrease in pH and an accelerated degradation rate. Particle aggregation increased the number of dense areas on the material surface, reduced effective adsorption sites, decreased hydrophilicity and protein adsorption capacity, and insufficient synergistic osteogenic activity.

[0078] Comparative Example 2 used only MBG microspheres. Lacking key modifications such as core-shell structure protection, strontium functionalization, and thiol-complexed zinc, it only retained the basic mesoporous framework of MBG, resulting in a complete loss of activity, stability, and interfacial compatibility. The lack of an outer protective layer led to excessively rapid degradation of MBG, a sharp increase in localized silicon and calcium ion concentrations, and a disrupted microenvironment. The lack of surface functionalization resulted in poor compatibility with hydrogels, weak interfacial bonding, delayed cross-linking reactions, and debonding between particles and the organic phase, leading to extremely poor mechanical properties. Pure MBG had a single surface functional group, making mesopores prone to collapse and blockage, resulting in low specific surface area utilization and reduced hydrophilicity and protein adsorption capacity. Without strontium doping and zinc ion-promoted proliferation, it only possessed simple osteoconductive activity, exhibiting low osteogenic induction activity.

[0079] Comparative Example 3 used MBG-SrHA microspheres. Strontium doping brought some improvement in osteogenic and mechanical properties, outperforming pure MBG, but lacked the stabilizing effect of the nSiO2 outer layer and the functionalization of zinc thioglycolate, leading to uncontrolled degradation. The SrHA shell had many pores and weak barrier properties, failing to effectively slow down the degradation of the MBG core layer, resulting in a significant decrease in pH and a high mass loss rate; the particle surface lacked a dense nSiO2 layer, resulting in weak binding force with the hydrogel, making the particles prone to relative slippage under stress, and the material's mechanical properties were relatively low; although strontium ions could enhance alkaline phosphatase activity, the lack of synergistic osteogenic effects of zinc ions and structural stabilization of nSiO2 resulted in low osteogenic activity.

[0080] Comparative Example 4 used MBG-SrHA@nSiO2 core-shell microspheres. The nSiO2 shell effectively slowed down the degradation of the core layer, resulting in a better degradation rate and pH stability compared to Comparative Examples 2 and 3. While structurally stable, it lacked functionality, only providing osteoconduction and structural support. The surface lacked thiol modification, making it unable to load zinc ions; it also lacked thiol functional groups, resulting in only physical entanglement between the particles and the hydrogel, without chemical or hydrogen bonding enhancement, leading to generally poor interfacial compatibility; the surface was uniform but lacked active sites, limiting protein adsorption and mechanical enhancement effects; although structural stability resulted in good cell compatibility, the lack of zinc ion activation of key osteogenic pathways resulted in generally poor osteogenic activity.

[0081] Comparative Example 5: The nSiO2 coating step was omitted. The core-shell structure was destroyed, losing the slow-release regulation and structural protection of nSiO2, resulting in explosive ion release and decreased structural stability. The MBG-SrHA core was directly exposed, leading to rapid degradation, high material mass loss, and a sharp drop in pH. Excessive exposure of zinc ion loading sites caused excessively rapid release. The mesoporous structure was destroyed by rapid degradation, reducing the specific surface area and effective adsorption sites, thus decreasing hydrophilicity and protein adsorption capacity. The particle surface was rough and uneven, prone to aggregation, and the dispersion stability decreased. Without the protection of the nSiO2 shell, the particle strength was low, easily broken under stress, and could not effectively enhance the hydrogel, resulting in reduced material mechanical properties.

[0082] In Comparative Example 6, the mercaptosilane modification step was omitted. Without the mercapto group as an anchoring site for zinc ions, the zinc ions cannot stably complex and are only physically adsorbed and rapidly lost, resulting in a loss of the material's core function. Zinc ions cannot be stably and sustainedly released, resulting in a short effective duration, weak differentiation-promoting effect on osteoblasts, and a slight decrease in osteogenic activity. The mercapto group forms hydrogen bonds with the carboxyl group of oxidized hyaluronic acid and the amino group of modified gelatin, enhancing the interfacial bonding between the inorganic phase particles and the organic phase of the hydrogel. Without the bonding effect of the mercapto group, the particles easily settle, the phase separates, and the interfacial compatibility is poor. The lack of active functional groups such as mercapto groups on the surface reduces cell affinity and protein binding ability.

[0083] In Comparative Example 7, oxidized hyaluronic acid was replaced with ordinary sodium hyaluronate. Ordinary sodium hyaluronate lacks aldehyde groups and cannot bond with the amino groups of modified gelatin, causing the in-situ cross-linking system of the hydrogel to fail, resulting in a decline in all functions including injection, molding, support, and controlled release. Unoxidized hyaluronic acid has high viscosity and poor flowability; it lacks chemical cross-linking and is only physically mixed, failing to form an effective three-dimensional network, resulting in poor gel strength; the loose network leads to rapid hydrolysis of the material, exposing and disintegrating the inorganic phase, resulting in a fast degradation rate and a decrease in pH; the lack of effective cross-linking results in the lowest mechanical properties of the material among all groups; the discontinuous network leads to a small effective specific surface area, reduced hydrophilicity and protein adsorption capacity; rapid structural disintegration causes uncontrolled release of ions and functional components, leading to microenvironment collapse and ultimately poor osteogenic activity.

[0084] In Comparative Example 8, the modified gelatin was replaced with ordinary gelatin. Ordinary gelatin, without chitosan oligosaccharide modification, exhibited a comprehensive decline in cross-linking activity, structural stability, and biocompatibility. Pure gelatin had lower hydrophilicity and reactivity than modified gelatin, resulting in decreased cross-linking efficiency with oxidized hyaluronic acid, poor flowability, and uneven gelation. Pure gelatin also exhibited faster enzymatic and hydrolytic rates, making its structure easily eroded, and the inorganic phase lost its protective coating, leading to faster material degradation and a lower pH. Lacking the rigidity and multiple amino sites of chitosan oligosaccharides, the hydrogel network density and strength were insufficient, reducing mechanical properties. The lack of highly hydrophilic and biorecognition sites on the surface of chitosan oligosaccharides reduced hydrophilicity and protein adsorption capacity. The adhesion-promoting effect of chitosan oligosaccharides was absent, and the microenvironment regulation ability decreased, ultimately resulting in decreased osteogenic activity of the material.

Claims

1. An injectable bone repair material containing bioactive glass, characterized in that, The bone repair material comprises a composite inorganic phase powder, a hydrogel precursor solution, and an injection medium; the composite inorganic phase powder comprises bioactive glass, hydroxyapatite whiskers, and L-arginine in a mass ratio of (17-21):(5-8):(0.1-0.3); the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and phosphate buffer. The bioactive glass is a core-shell structure with mesoporous bioactive glass as the core, strontium-doped hydroxyapatite as the middle layer, and nano-silica as the outer shell, and the outer shell surface is grafted with thiol groups and loaded with zinc ions. The oxidized hyaluronic acid is prepared by oxidizing sodium hyaluronate in deionized water with sodium periodate and then quenching it with ethylene glycol in a mass ratio of (0.9-1.1):(0.30-0.34):(0.18-0.22). The modified gelatin is a powder obtained by modifying gelatin, chitosan oligosaccharide, EDC·HCl, and N-hydroxysuccinimide in deionized water at pH 4.5–5.

0. The modified gelatin is prepared by modifying chitosan oligosaccharide, N-hydroxysuccinimide, and EDC·HCl in a mass ratio of (1.8–2.2): (0.8–1.2): (0.8–1.5): (0.2–0.4).

2. The injectable bone repair material containing bioactive glass according to claim 1, characterized in that, The bone repair material comprises a composite inorganic phase powder, a hydrogel precursor solution, and an injection medium in a mass ratio of (1-1.2):(1.5-2):(0.9-1.3); the hydrogel precursor solution comprises oxidized hyaluronic acid, modified gelatin, and a pH 7.2-7.4 phosphate buffer in a mass ratio of (1.0-1.2):(0.7-0.9):(20-25); and the injection medium is a pH 7.2-7.4 phosphate buffer.

3. The injectable bone repair material containing bioactive glass according to claim 1, characterized in that, The preparation method of the bioactive glass includes: hexadecyltrimethylammonium bromide: triethyl phosphate: tetraethyl orthosilicate: 10wt%~15wt% calcium nitrate aqueous solution = (1.8~2.2):(2.3~2.7):(8.5~10):(70~80) mass ratio, reacting in deionized water at pH 10.5~11.5 to prepare a precipitate, calcining at 620℃~680℃ for 4h~6h to prepare a median particle size of 1μm~3.5μm and a specific surface area >200m². 2 / g MBG microspheres; prepare growth solution A with an aqueous solution containing 0.7mol / L~0.9mol / L Ca(NO3)2 and 0.15mol / L~0.25mol / L Sr(NO3)2; prepare growth solution B with an aqueous solution containing 0.4mol / L~0.6mol / L (NH4)2HPO4; prepare MBG-SrHA microspheres by reacting in deionized water at 90℃~95℃ and pH10.4~10.8 according to the mass ratio of MBG microspheres:growth solution A:growth solution B = (0.8~1.2):(35~45):(35~45); prepare MBG-SrHA microspheres by stirring in an ethanol aqueous solution at pH8.8~9.6 according to the mass ratio of MBG-SrHA microspheres:8vol%~10vol% tetraethyl orthosilicate in ethanol = (4.5~5.5):(10~12). rHA@nSiO2 core-shell microspheres; MBG-SrHA@nSiO2-SH modified microspheres were prepared by reacting MBG-SrHA@nSiO2 core-shell microspheres with 3-mercaptopropyltrimethoxysilane in anhydrous toluene at a mass ratio of (3.5–4.5): (0.7–0.9); and bioactive glass was prepared by mixing MBG-SrHA@nSiO2-SH modified microspheres with an ethanol solution of 0.04 mol / L–0.06 mol / L zinc acetate in an ethanol solution at a mass ratio of (2.8–3.2): (90–110) and stirring in the dark.

4. An injectable bone repair material containing bioactive glass according to claim 1 or 3, characterized in that, The method for preparing the bioactive glass includes the following steps: N1: Following the mass ratio of hexadecyltrimethylammonium bromide:triethyl phosphate:ethyl orthosilicate:10wt%–15wt% calcium nitrate aqueous solution = (1.8–2.2):(2.3–2.7):(8.5–10):(70–80), hexadecyltrimethylammonium bromide was dissolved in deionized water, and the pH was adjusted to 10.5–11.

5. Triethyl phosphate, ethyl orthosilicate, and 10wt%–15wt% calcium nitrate aqueous solution were added dropwise under stirring for 1–1.5 hours. The mixture was then aged, centrifuged, and the precipitate was collected, washed, vacuum dried, and calcined at 620℃–680℃ for 4–6 hours to obtain a median particle size of 1 μm–3.5 μm and a specific surface area >200 m². 2 / g MBG microspheres; N2: Prepare an aqueous solution containing 0.7 mol / L to 0.9 mol / L Ca(NO3)2 and 0.15 mol / L to 0.25 mol / L Sr(NO3)2 as growth solution A; prepare an aqueous solution containing 0.4 mol / L to 0.6 mol / L (NH4)2HPO4 as growth solution B; disperse MBG microspheres in deionized water according to the mass ratio of MBG microspheres: growth solution A: growth solution B = (0.8 to 1.2): (35 to 45): (35 to 45), add growth solution A while stirring, adjust the pH to 10.4 to 10.8, raise the temperature to 90℃ to 95℃, add growth solution B while stirring, maintain the pH at 10.4 to 10.8, stir and react for 22 to 26 hours, centrifuge, collect the precipitate, wash to pH 6.8 to 7.2, vacuum dry to obtain MBG-SrHA microspheres; N3: MBG-SrHA microspheres were dispersed in an ethanol-water solution at a mass ratio of (4.5-5.5):(10-12) of 8 vol%-10 vol% tetraethyl orthosilicate in ethanol solution. The pH was adjusted to 8.8-9.

6. 8 vol%-10 vol% tetraethyl orthosilicate in ethanol solution was added dropwise while stirring at 30-35℃. The mixture was stirred for 5-7 hours, centrifuged, the precipitate was collected, washed, and vacuum dried to obtain MBG-SrHA@nSiO2 core-shell microspheres. N4: MBG-SrHA@nSiO2 core-shell microspheres were dispersed in anhydrous toluene according to the mass ratio of MBG-SrHA@nSiO2 core-shell microspheres: 3-mercaptopropyltrimethoxysilane = (3.5~4.5): (0.7~0.9). 3-mercaptopropyltrimethoxysilane was added, and nitrogen gas was introduced for protection. The mixture was stirred and refluxed at 100℃~110℃ for 10h~14h. After centrifugation, washing, and vacuum drying, MBG-SrHA@nSiO2-SH modified microspheres were obtained. N5: Microspheres modified with MBG-SrHA@nSiO2-SH: A 0.04 mol / L to 0.06 mol / L zinc acetate ethanol solution was mixed in a mass ratio of (2.8 to 3.2): (90 to 110), stirred in the dark for 10 to 14 hours, centrifuged, the precipitate was collected, washed, and vacuum dried to obtain bioactive glass.

5. The injectable bone repair material containing bioactive glass according to claim 4, characterized in that, In N1, hexadecyltrimethylammonium bromide is dissolved in 100 to 150 times its mass of deionized water. The pH is adjusted to 10.5 to 11.5 with ammonia. Triethyl phosphate is added dropwise while stirring at 150 to 200 rpm. After the addition is complete, stirring is continued for 30 to 40 minutes. Then, tetraethyl orthosilicate is added dropwise while stirring is continued for 30 to 40 minutes. Finally, a 10 wt% to 15 wt% calcium nitrate aqueous solution is added dropwise while stirring is continued for 1 to 1.5 hours. Static aging at 90℃~95℃ for 45h~50h, naturally cooled to room temperature, centrifuged at 7500rpm~8500rpm for 10min~15min, collected the precipitate, washed alternately with anhydrous ethanol and deionized water 2~4 times each, vacuum dried at 55℃~65℃ for 10h~14h, and calcined at 620℃~680℃ for 4h~6h under nitrogen protection with a heating rate of 1.5℃ / min~2.5℃ / min to obtain a median particle size of 1μm~3.5μm and a specific surface area >200m². 2 / g MBG microspheres.

6. The injectable bone repair material containing bioactive glass according to claim 4, characterized in that, In N2, MBG microspheres were uniformly dispersed in 90 to 100 times their mass of deionized water. Under stirring at 300 to 350 rpm, growth solution A was added, and the pH was adjusted to 10.4 to 10.8 with ammonia. The temperature was raised to 90 to 95°C, and growth solution B was added while stirring continuously. During this process, the pH was maintained at 10.4 to 10.8 with ammonia or dilute nitric acid. The reaction was carried out with continuous stirring for 22 to 26 hours. The mixture was then allowed to cool naturally to room temperature, centrifuged at 7500 to 8500 rpm for 10 to 15 minutes, and the precipitate was collected. The precipitate was washed with deionized water until the pH was adjusted to 6.8 to 7.2, and then vacuum dried at 75 to 85°C for 22 to 26 hours to obtain MBG-SrHA microspheres.

7. The injectable bone repair material containing bioactive glass according to claim 4, characterized in that, In N3, MBG-SrHA microspheres were uniformly dispersed in 30 to 40 times their mass of a 75 vol% to 80 vol% ethanol aqueous solution. The pH was adjusted to 8.8 to 9.6 with ammonia. Under stirring conditions of 30 to 35°C and 150 to 200 rpm, an 8 vol% to 10 vol% tetraethyl orthosilicate ethanol solution was added dropwise. After the addition was complete, stirring was continued for 5 to 7 hours. The mixture was then centrifuged at 7500 to 8500 rpm for 10 to 15 minutes. The precipitate was collected, washed 2 to 4 times with deionized water, and vacuum dried at 55 to 65°C for 7 to 9 hours to obtain MBG-SrHA@nSiO2 core-shell microspheres. In N4, MBG-SrHA@nSiO2 core-shell microspheres were uniformly dispersed in 30 to 40 times their mass of anhydrous toluene. 3-Mercaptopropyltrimethoxysilane was added, and the mixture was purged with nitrogen. The mixture was stirred at 100 to 110 °C and 150 to 200 rpm, and refluxed for 10 to 14 hours. After cooling to room temperature, the mixture was centrifuged at 7500 to 8500 rpm for 10 to 15 minutes. The microspheres were washed 1 to 3 times with toluene and 2 to 4 times with anhydrous ethanol. After drying under vacuum at 45 to 55 °C for 9 to 11 hours, MBG-SrHA@nSiO2-SH modified microspheres were obtained.

8. The injectable bone repair material containing bioactive glass according to claim 1, characterized in that, The preparation method of the oxidized hyaluronic acid includes the following steps: Sodium hyaluronic acid:sodium periodate:ethylene glycol in a mass ratio of (0.9-1.1):(0.30-0.34):(0.18-0.22), sodium hyaluronic acid is added to deionized water and stirred. Sodium periodate is added and stirred continuously at room temperature in the dark for 5-7 hours. Ethylene glycol is added and stirred. The mixture is then dialyzed with flowing deionized water in the dark using a MWCO 3500 dialysis membrane. The mixture is then freeze-dried and pulverized to obtain oxidized hyaluronic acid.

9. The injectable bone repair material containing bioactive glass according to claim 1, characterized in that, According to the mass ratio of gelatin:chitosan oligosaccharide:EDC·HCl:N-hydroxysuccinimide = (1.8~2.2):(0.8~1.2):(0.8~1.5):(0.2~0.4), gelatin was added to deionized water at 40℃~45℃ and stirred to dissolve. Chitosan oligosaccharide was added, and the pH was adjusted to 4.5~5.

0. Under stirring at 35℃~40℃, N-hydroxysuccinimide was added and stirred to dissolve. EDC·HCl was added in 3~4 equal portions, with an interval of 1h~1.5h between each portion. After the addition was completed, the reaction was stirred for 4h~6h. The pH was adjusted to 6.8~7.

2. Dialysis with flowing deionized water was performed using a MWCO 8000~10000 dialysis membrane. The gelatin was then freeze-dried and pulverized to obtain modified gelatin.

10. The method for preparing an injectable bone repair material containing bioactive glass as described in claim 2, characterized in that, Includes the following steps: S1: Bioactive glass, hydroxyapatite whiskers, and L-arginine are mixed evenly according to the mass ratio to obtain a composite inorganic phase powder; S2: Add the modified gelatin to the phosphate buffer solution according to the mass ratio, stir and dissolve at 40℃~45℃, cool down to 35℃~40℃, add oxidized hyaluronic acid and stir to dissolve evenly to obtain the hydrogel precursor solution. S3: According to the mass ratio, first mix the composite inorganic phase powder with the injection medium to form a uniform suspension; then mix it with the hydrogel precursor liquid at a temperature below 30°C until uniform, and defoam under vacuum to form an injectable sol-like material.

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