An injectable gel loaded with modified silica nanoparticles and its preparation method

Abstract

This invention relates to the field of biomedical materials technology, providing an injectable gel loaded with modified silica nanoparticles and its preparation method, comprising the following steps: preparing aldehyde-modified sodium hyaluronate and hydrazide-modified carboxymethyl chitosan respectively; sequentially preparing dendritic mesoporous silica nanoparticles, calcium ion-impregnated dendritic mesoporous silica nanoparticles, cerium ion and calcium ion-impregnated dendritic mesoporous silica nanoparticles, aminated cerium ion and calcium ion-impregnated dendritic mesoporous silica nanoparticles, and glutathione-grafted aminated cerium ion and calcium ion-impregnated dendritic mesoporous silica nanoparticles; finally preparing an injectable gel loaded with modified silica nanoparticles. This invention forms a hydrogel with excellent stability and self-healing ability, effectively scavenging excessive reactive oxygen species locally, reducing inflammatory responses, and the multi-effect synergistic mechanism of the ion combination helps accelerate the healing of diabetic bone defects.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and particularly relates to an injectable gel containing modified silica nanoparticles and its preparation method. Background Technology

[0002] Hydrogels are widely used in the biomedical field due to their excellent biocompatibility, biodegradability, and hydrophilicity, providing tunable three-dimensional scaffolds for cell adhesion, migration, and differentiation; mesoporous bioglass nanoparticles, due to their unique processing, large specific surface area, high drug loading capacity, and good release performance, are suitable as drug delivery carriers or bio-injection materials; Mg 2+ Ca 2+ and Zn 2+ These substances have effects such as inhibiting osteoclast differentiation and promoting osteoogenesis.

[0003] Diabetes impairs fracture or bone defect healing at various stages in multiple ways, including reduced osteogenic differentiation, decreased angiogenesis, and increased inflammation. A key characteristic of impaired bone healing in diabetic patients is elevated levels of reactive oxygen species (ROS). Excessive ROS production triggers oxidative stress, bone homeostasis imbalance, and subsequent pathological conditions. Studies have shown that upregulation of ROS can delay bone healing by inhibiting the differentiation of bone marrow mesenchymal stem cells (BMSCs) and promoting RANKL-mediated osteoclast activation. Current research in the field of diabetic bone defect repair faces multidimensional technical challenges, primarily focusing on in vivo microenvironment regulation, material delivery, and performance synergistic optimization. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing an injectable gel loaded with modified silica nanoparticles, thereby addressing the problems existing in the background art.

[0005] The present invention is implemented as follows: a method for preparing an injectable gel loaded with modified silica nanoparticles includes the following steps:

[0006] Sodium hyaluronate was dissolved in deionized water to obtain a sodium hyaluronate solution, and then solid sodium periodate was added to obtain aldehyde-modified sodium hyaluronate.

[0007] Carboxymethyl chitosan was dissolved in deionized water to obtain a carboxymethyl chitosan solution, and then solid carbazide was added to obtain carboxymethyl chitosan modified with carbazide.

[0008] Hexadecyltrimethylammonium bromide, sodium dodecylbenzenesulfonate and triethanolamine were dissolved in deionized water to obtain a mixed solution, and tetraethyl orthosilicate was added to obtain dendritic mesoporous silica nanoparticles.

[0009] Solid calcium nitrate was dissolved in deionized water to obtain an aqueous solution of calcium nitrate. Dendritic mesoporous silica nanoparticles were then added to obtain calcium ion-impregnated dendritic mesoporous silica nanoparticles.

[0010] Solid cerium nitrate was dissolved in deionized water to obtain an aqueous solution of cerium nitrate. Calcium ion-impregnated dendritic mesoporous silica nanoparticles were then added to obtain dendritic mesoporous silica nanoparticles impregnated with both cerium and calcium ions.

[0011] Cerium and calcium ion impregnated dendritic mesoporous silica nanoparticles were dispersed in anhydrous ethanol solution, and 3-aminopropyltriethoxysilane was added to obtain aminated cerium and calcium ion impregnated dendritic mesoporous silica nanoparticles.

[0012] Aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles were dispersed in deionized water, and solid glutathione was added to obtain glutathione-grafted aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles.

[0013] Aldehyde-modified sodium hyaluronate and hydrazide-modified carboxymethyl chitosan were dissolved in deionized water to obtain precursor solutions A and B. Precursor solutions A and B were mixed with glutathione-grafted, aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles to form an injectable gel loaded with modified silica nanoparticles.

[0014] Another objective of this invention is to provide an injectable gel loaded with modified silica nanoparticles, which is prepared using the above-described preparation method.

[0015] Another objective of this invention is to provide an application of an injectable gel loaded with modified silica nanoparticles in the preparation of bone repair materials.

[0016] In this invention, sodium hyaluronate modified with aldehyde group and carboxymethyl chitosan modified with hydrazide are spontaneously cross-linked through dynamic hydrazone bonds under neutral physiological conditions to form a hydrogel with excellent stability and self-healing ability. Its self-healing properties can endow the material with injectability and in-situ filling ability, which can fit irregular bone defects and provide a continuous and stable support platform for subsequent active ingredients, significantly enhancing the durability of bone repair.

[0017] The cerium and calcium ion impregnated dendritic mesoporous silica nanoparticles grafted with glutathione prepared in this embodiment of the invention have pH responsiveness. Targeting the weakly acidic microenvironment at the initial bone defect site in diabetic patients, the amide bond connecting glutathione and nanoparticles will rapidly hydrolyze in a weakly acidic environment, allowing glutathione to be rapidly and massively released in the early stages of bone healing. This precise on-demand release strategy will effectively remove excessive reactive oxygen species (ROS) locally, significantly reduce inflammatory response, and create a favorable initial microenvironment for diabetic bone healing.

[0018] In this embodiment of the invention, calcium and cerium ions are loaded onto dendritic mesoporous silica nanoparticles using an optimized impregnation technique. This achieves a high degree of maintenance of the pore structure and dendritic morphology, enabling controllable distribution of ions within and on the surface of the mesoporous channels. This ensures the material's high specific surface area and structural stability, laying the foundation for the controllable release and functional performance of ions.

[0019] This invention selects and synergistically applies calcium and cerium ions, which can play unique and complementary multiple roles in bone repair: calcium ions have a bone-promoting effect that accelerates the healing of bone defects; cerium ions can effectively stimulate the formation of key new blood vessels in and around the bone defect area to solve the core problem of angiogenesis disorders in diabetic patients. Cerium ions themselves also have SOD / CAT enzyme-like activity, which can synergistically enhance the ability to clear ROS with released glutathione and further optimize the repair microenvironment. This multi-effect synergistic mechanism of ion combination may provide new ideas for accelerating the healing of diabetic bone defects. Attached Figure Description

[0020] Figure 1 A flowchart illustrating the preparation process of an injectable gel containing modified silica nanoparticles supported by an embodiment of the present invention.

[0021] Figure 2 The Fourier transform infrared spectrum of the composite gel material obtained in Comparative Example 1 of this invention is shown below.

[0022] Figure 3 This is a scanning electron microscope image of the injectable gel obtained in Example 1 of the present invention;

[0023] Figure 4 This is a transmission electron microscope (TEM) image of the nanoparticles obtained in step S7 of Example 1 of the present invention.

[0024] Figure 5 The X-ray diffraction spectra of nanoparticles obtained in different steps in Example 1 of this invention are shown below.

[0025] Figure 6 The particle size analysis diagrams are shown for the nanoparticles obtained in different steps of Example 1 of the present invention.

[0026] Figure 7 The modulus-amplitude scans are shown for the injectable gels with loaded modified silica nanoparticles obtained in Examples 1-3 of this invention and the gel obtained in Comparative Example 1.

[0027] Figure 8 The compressive stress-strain curves of the injectable gels with loaded modified silica nanoparticles obtained in Examples 1-3 of the present invention and the gel obtained in Comparative Example 1 are shown.

[0028] Figure 9 This is a comparison of the results of RAW264.7 cells scavenging reactive oxygen species (ROS) under a simulated high glucose environment, using injectable gels with modified silica nanoparticles loaded in Examples 1-3 of the present invention and gels obtained in Comparative Example 1.

[0029] Figure 10 This is a comparison of the results of BMSC cell proliferation experiments under a simulated high glucose environment using injectable gels loaded with modified silica nanoparticles obtained in Examples 1-3 of this invention and gels obtained in Comparative Example 1.

[0030] Figure 11 This is a comparison of the results of angiogenesis experiments of HUVEC cells in a simulated high-glucose environment using injectable gels loaded with modified silica nanoparticles obtained in Examples 1-3 of this invention and gels obtained in Comparative Example 1. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0032] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0033] Example 1: An injectable gel loaded with modified silica nanoparticles, the preparation process of which is as follows: Figure 1 As shown, the specific steps include:

[0034] Step S1: Dissolve 1g of sodium hyaluronate (HA) with a molecular weight of 1.0-1.8 MDa in 100mL of deionized water and stir magnetically until completely dissolved to obtain a sodium hyaluronate solution; add 0.16g of sodium periodate to the obtained solution and stir magnetically for 5h in the dark at 25℃, then add 5mL of ethylene glycol and stir magnetically for 1h to terminate the reaction; put the obtained mixed solution into a dialysis bag, dialyze with deionized water for 7 days, and freeze-dry at -80℃ for 3 days to obtain aldehyde-modified sodium hyaluronate (OHA).

[0035] Step S2: Dissolve 1g of carboxymethyl chitosan (CMCS) in 100mL of deionized water and stir magnetically until completely dissolved to obtain a carboxymethyl chitosan solution; add 0.1432g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.0859g of N-hydroxysuccinimide to the obtained solution and stir magnetically until completely dissolved; add 1g of carbohydrazide to the obtained mixed solution and stir magnetically until completely dissolved; stir the obtained mixed solution magnetically at 25℃ for 24h; put the obtained mixed solution into a dialysis bag, dialyze with deionized water for 7 days, and freeze-dry at -80℃ for 3 days to obtain carboxymethyl chitosan modified with carbohydrazide (CMCS-CDH).

[0036] Step S3: Dissolve 1.52 g cetyltrimethylammonium bromide, 0.38 g sodium dodecylbenzenesulfonate, and 0.34 g triethanolamine in 100 mL of deionized water and stir magnetically until completely dissolved. Stir magnetically at 80 °C for 1 h to obtain W1. Add 15.51 mL of tetraethyl orthosilicate dropwise to W1 at a rate of 0.2 mL / min and stir magnetically at 80 °C for 2 h. Remove the organic solvent, centrifuge at 10000 rpm for 10 min, wash three times alternately with ethanol and deionized water, centrifuge to collect the nanoparticles, place them in a vacuum drying oven, and vacuum dry at 60 °C for 24 h to obtain dendritic mesoporous silica nanoparticles (MSN).

[0037] Step S4: Dissolve 1.18g of calcium nitrate in 20mL of deionized water to obtain a calcium nitrate aqueous solution; disperse 0.15g of the dried nanoparticles obtained in step S3 in the calcium nitrate aqueous solution and stir magnetically until the particles are uniformly distributed; stir magnetically at 500rpm for 1h at 25℃; remove the solvent, centrifuge at 10000rpm for 10min, wash three times alternately with water and ethanol, centrifuge to collect the nanoparticles, place them in a vacuum drying oven, and vacuum dry at 60℃ for 24h to obtain calcium ion impregnated dendritic mesoporous silica nanoparticles (MSN / Ca).

[0038] Step S5: Dissolve 0.19 g of cerium nitrate in 20 mL of deionized water to obtain an aqueous solution of cerium nitrate; disperse the dried nanoparticles obtained in step S4 in the aqueous solution of cerium nitrate at a concentration of 16 mg / mL, and magnetically stir until the particles are uniformly distributed; magnetically stir at 500 rpm for 30 min at 25 °C; remove the solvent, centrifuge at 10000 rpm for 10 min, wash three times alternately with water and ethanol, centrifuge to collect the nanoparticles, place them in a vacuum drying oven, and vacuum dry at 60 °C for 24 h to obtain dendritic mesoporous silica nanoparticles (MSN / Ca / Ce) impregnated with cerium ions and calcium ions.

[0039] Step S6: Disperse 50 mg of the dried nanoparticles obtained in step S5 in 50 mL of anhydrous ethanol and stir magnetically until the particles are uniformly distributed; add 100 mL of 3-aminopropyltriethoxysilane to the above solution at a rate of 10 mL / min and stir magnetically at 400 rpm for 24 h at 60 °C; remove the organic solvent, centrifuge at 10000 rpm for 10 min, wash three times alternately with ethanol and deionized water, centrifuge to collect the nanoparticles, place them in a vacuum drying oven, and vacuum dry at 60 °C for 24 h to obtain ammoniated cerium ion and calcium ion impregnated dendritic mesoporous silica nanoparticles;

[0040] Step S7: Disperse 0.5g of the dried nanoparticles obtained in Step S6 in 100mL of deionized water and stir magnetically until the particles are uniformly distributed; add 0.5751g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.3452g of N-hydroxysuccinimide to the mixed solution sequentially and stir magnetically until completely dissolved; add 0.5g of glutathione to the mixed solution and stir magnetically at 500rpm for 24h at 25℃; remove the solvent, centrifuge at 10000rpm for 10min, wash three times alternately with water and ethanol, collect the nanoparticles by centrifugation, and freeze-dry at -80℃ for 3 days to obtain glutathione-grafted, aminated cerium ion and calcium ion impregnated dendritic mesoporous silica nanoparticles (MSN / Ca / Ce / GSH).

[0041] Step S8: Dissolve the aldehyde-modified sodium hyaluronate obtained in step S1 and the acylhydrazine-modified carboxymethyl chitosan obtained in step S2 in deionized water to obtain precursor solutions A and B. Mix precursor solutions A and B with nanoparticles obtained in step S7 at a volume ratio of 1:1 and stir thoroughly for 1 min at a speed of 300 rpm to obtain an injectable gel loaded with modified silica nanoparticles (named OHCC@MSN / Ca / Ce / GSH).

[0042] Example 2: An injectable gel loaded with modified silica nanoparticles, the preparation method of which specifically includes the following steps:

[0043] Steps S1-S6 are the same as steps S1-S6 in Example 1;

[0044] Step S7: Dissolve the aldehyde-modified sodium hyaluronate obtained in Step S1 and the acylhydrazine-modified carboxymethyl chitosan obtained in Step S2 in deionized water to obtain precursor solutions A and B. Mix precursor solutions A and B with nanoparticles obtained in Step S6 at a volume ratio of 1:1 and stir thoroughly for 1 min at a speed of 300 rpm to obtain an injectable gel loaded with modified silica nanoparticles (named OHCC@MSN / Ca / Ce).

[0045] Example 3: An injectable gel loaded with modified silica nanoparticles, the preparation method of which specifically includes the following steps:

[0046] Steps S1-S4 are the same as steps S1-S4 in Example 1;

[0047] Step S5: Disperse 50 mg of the dried nanoparticles obtained in step S4 in 50 mL of anhydrous ethanol and stir magnetically until the particles are uniformly distributed; add 100 mL of 3-aminopropyltriethoxysilane to the above solution at a rate of 10 mL / min and stir magnetically at 400 rpm for 24 h at 60 °C; remove the organic solvent, centrifuge at 10000 rpm for 10 min, wash three times alternately with ethanol and deionized water, centrifuge to collect the nanoparticles, place them in a vacuum drying oven, and vacuum dry at 60 °C for 24 h to obtain aminated calcium ion impregnated dendritic mesoporous silica nanoparticles;

[0048] Step S6: Dissolve the aldehyde-modified sodium hyaluronate obtained in step S1 and the acylhydrazine-modified carboxymethyl chitosan obtained in step S2 in deionized water to obtain precursor solutions A and B. Mix precursor solutions A and B with nanoparticles obtained in step S5 at a volume ratio of 1:1 and stir thoroughly for 1 min at a speed of 300 rpm to obtain an injectable gel loaded with modified silica nanoparticles (named OHCC@MSN / Ca).

[0049] Comparative Example 1: A gel, the preparation method of which specifically includes the following steps:

[0050] Steps S1-S2 are the same as steps S1-S2 in Example 1;

[0051] Step S3: Dissolve the aldehyde-modified sodium hyaluronate obtained in step S1 and the acylhydrazine-modified carboxymethyl chitosan obtained in step S2 in deionized water to obtain precursor solutions A and B. Mix precursor solutions A and B thoroughly at a volume ratio of 1:1 for 1 min at a speed of 300 rpm to obtain an injectable gel (named OHCC) of aldehyde-modified sodium hyaluronate crosslinked with acylhydrazine-modified carboxymethyl chitosan.

[0052] Example 4: Compared with Example 1, the only difference is that in step S8, the volume ratio of precursor solution A and precursor solution B is adjusted to 2:1.

[0053] Example 5: Compared with Example 1, the only difference is that in step S8, the volume ratio of precursor solution A and precursor solution B is adjusted to 1:2.

[0054] Performance Analysis and Testing:

[0055] The gel obtained in Comparative Example 1 was subjected to total reflectance infrared spectroscopy, and the results are as follows: Figure 2 As shown in the figure, HA is sodium hyaluronate; OHA is aldehyde-modified sodium hyaluronate; CMCS is carboxymethyl chitosan; CMCS-CDH is hydrazide-modified carboxymethyl chitosan; OHCC is a composite gel formed by the reaction of OHA and CMCS-CDH; after oxidation, 1735cm -1 The characteristic peak of the C=O double bond appears in the infrared spectrum of aldehyde-modified sodium hyaluronate; after the amidation reaction, the peak is 1712 cm⁻¹. -1 The characteristic peak of HN-C=O appears in the infrared spectrum of hydrazide-modified carboxymethyl chitosan; 1730 cm⁻¹ -1 and 1260cm -1 Two characteristic peaks appeared in the infrared spectrum of the OHCC composite gel, confirming the successful preparation of the composite gel.

[0056] Field emission electron microscopy (FEM) analysis was performed on the gel prepared in Example 1, and the results are as follows: Figure 3 As shown, the gel exhibits an irregular porous microstructure, and the presence of nanoparticles can be clearly observed in the pores.

[0057] Field emission transmission electron microscopy (FTEM) was performed on the nanoparticles obtained in step S7 of Example 1. The results are as follows: Figure 4 As shown, the modified silica nanoparticles still maintain a dendritic structure and their size remains at the nanoscale.

[0058] X-ray diffraction spectroscopy was performed on the modified silica nanoparticles obtained in steps S3, S4, S5, and S7 of Example 1, and the results are as follows: Figure 5 As shown, the crystallinity of the dendritic mesoporous silica nanoparticles remained unchanged after modification with calcium ions, cerium ions, and glutathione.

[0059] The particle size of the modified silica nanoparticles obtained in steps S4, S5, and S7 of Example 1 was analyzed, and the results are as follows: Figure 6As shown, the average particle size of silica nanoparticles impregnated with calcium ions is 208 nm, the average particle size of silica nanoparticles impregnated with calcium and cerium ions is 207 nm, and the average particle size of silica nanoparticles grafted with glutathione and impregnated with calcium and cerium ions is 211 nm. The pore structure and surface area of ​​the modified silica nanoparticles maintain high stability, and their original characteristic structure is not destroyed.

[0060] Modulus-vibration scanning tests were performed on the injectable gels containing modified silica nanoparticles obtained in Examples 1-3 and the gel obtained in Comparative Example 1. The results are as follows: Figure 7 As shown, the storage modulus of the gel group with doped modified nanoparticles is significantly improved compared with that of the pure gel group (OHCC).

[0061] The compressive strength stress-strain tests were performed on the injectable gels with modified silica nanoparticles obtained in Examples 1-3 and the gel obtained in Comparative Example 1. The results are as follows: Figure 8 As shown, the compressive strength of the composite gel group with doped and modified nanoparticles is significantly improved compared with that of the pure gel group (OHCC);

[0062] The in vitro ROS scavenging effect of the composite gel was detected using a ROS kit, and the results are as follows: Figure 9 As shown in the figure, OHCC-L represents the pure gel group cultured in a medium with normal glucose concentration, and OHCC-H represents the pure gel group cultured in a medium with simulated high glucose. The peak curve of the pure gel group is on the far right, indicating that the ROS content in mouse mononuclear macrophage leukemia cells (RAW264.7, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences) is very high under high glucose conditions. The peak curves of the three composite gel groups loaded with modified silica nanoparticles all show a leftward shift. Among them, the curve of the OHCC@MSN / Ca / Ce / GSH group is on the far left, indicating that the ROS content in the RAW264.7 cells in this group is the lowest. Compared with the peak curve of the OHCC-L group, it can be seen that the composite gel loaded with modified silica nanoparticles can effectively remove ROS in cells under high glucose conditions.

[0063] The proliferation of rat bone marrow mesenchymal stem cells (BMSCs, Beijing Vital River Laboratory Animal Technology Co., Ltd.) in composite gels was detected using a CCK-8 assay kit. The results are as follows: Figure 10As shown in the figure, OHCC-L represents the pure gel group cultured in a normal glucose concentration medium, and OHCC-H represents the pure gel group cultured in a simulated high glucose medium. Compared with cells cultured in a normal glucose concentration medium, the three composite gel groups loaded with modified silica nanoparticles can still keep the cells viable in a high glucose environment. Among them, the OHCC@MSN / Ca / Ce / GSH group has the best cell activity.

[0064] The angiogenic capacity of various materials was evaluated using in vitro angiogenesis experiments with human umbilical vein endothelial cells (HUVEC, Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences). The results are as follows: Figure 11 As shown in the figure, OHCC-L represents the pure gel group cultured in a medium with normal glucose concentration, and OHCC-H represents the pure gel group cultured in a medium simulating high glucose concentration. Compared with the angiogenesis ability of endothelial cells cultured in a medium with normal glucose concentration, the angiogenesis ability of the OHCC@MSN / Ca / Ce / GSH group was not affected by the high glucose environment. Moreover, the number of blood vessels and the number of blood vessel nodes were increased compared with the OHCC-L and OHCC-H groups, as well as the OHCC@MSN / Ca and OHCC@MSN / Ca / Ce groups. This proves that the composite gel, after being doped with modified nanoparticles, promotes the angiogenesis ability of endothelial cells in a simulated high glucose environment.

[0065] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing an injectable gel loaded with modified silica nanoparticles, characterized in that, Includes the following steps: Sodium hyaluronate was dissolved in deionized water to obtain a sodium hyaluronate solution, and then solid sodium periodate was added to obtain aldehyde-modified sodium hyaluronate. Carboxymethyl chitosan was dissolved in deionized water to obtain a carboxymethyl chitosan solution, and then solid carbazide was added to obtain carboxymethyl chitosan modified with carbazide. Hexadecyltrimethylammonium bromide, sodium dodecylbenzenesulfonate and triethanolamine were dissolved in deionized water to obtain a mixed solution, and tetraethyl orthosilicate was added to obtain dendritic mesoporous silica nanoparticles. Solid calcium nitrate was dissolved in deionized water to obtain an aqueous solution of calcium nitrate. Dendritic mesoporous silica nanoparticles were then added to obtain calcium ion-impregnated dendritic mesoporous silica nanoparticles. Solid cerium nitrate was dissolved in deionized water to obtain an aqueous solution of cerium nitrate. Calcium ion-impregnated dendritic mesoporous silica nanoparticles were then added to obtain dendritic mesoporous silica nanoparticles impregnated with both cerium and calcium ions. Cerium and calcium ion impregnated dendritic mesoporous silica nanoparticles were dispersed in anhydrous ethanol solution, and 3-aminopropyltriethoxysilane was added to obtain aminated cerium and calcium ion impregnated dendritic mesoporous silica nanoparticles. Aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles were dispersed in deionized water, and solid glutathione was added to obtain glutathione-grafted aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles. Aldehyde-modified sodium hyaluronate and hydrazide-modified carboxymethyl chitosan were dissolved in deionized water to obtain precursor solutions A and B. Precursor solutions A and B were mixed with glutathione-grafted, aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles to form an injectable gel loaded with modified silica nanoparticles.

2. The method for preparing the injectable gel of loaded modified silica nanoparticles according to claim 1, characterized in that, In the step of dissolving sodium hyaluronate in deionized water to obtain a sodium hyaluronate solution, the molecular weight of the sodium hyaluronate is 1.0-1.8 MDa.

3. The method for preparing the injectable gel of supported modified silica nanoparticles according to claim 1, characterized in that, The step of dissolving carboxymethyl chitosan in deionized water to obtain a carboxymethyl chitosan solution and then adding solid carbohydrazine specifically involves first adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide to the carboxymethyl chitosan solution in sequence, and then adding solid carbohydrazine.

4. The method for preparing the injectable gel of supported modified silica nanoparticles according to claim 1, characterized in that, The step of dispersing the aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles in deionized water and adding solid glutathione specifically involves dispersing the aminated cerium and calcium ion-impregnated dendritic mesoporous silica nanoparticles in deionized water, sequentially adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, and then adding solid glutathione.

5. The method for preparing an injectable gel with supported modified silica nanoparticles according to claim 1, characterized in that, In the step of stirring and mixing precursor solutions A and B with cerium and calcium ions grafted with glutathione to form an injectable gel loaded with modified silica nanoparticles, the volume ratio of precursor solution A to precursor solution B is 1-2:1-2; and the concentration (w / v) of the cerium and calcium ions grafted with glutathione is 0.1-0.5%.

6. An injectable gel loaded with modified silica nanoparticles, characterized in that, It is prepared using the preparation method described in any one of claims 1-5.

7. The application of an injectable gel containing loaded modified silica nanoparticles as described in claim 6 in the preparation of bone repair materials.

Images