Injectable light-cured hydrogel capable of resisting inflammation and promoting vascularized tissue regeneration
By developing an injectable optical solid hydrogel with calcium phosphorus and phosphorus pool and sulfur quantum dots, the existing bone regeneration material is solved in irregular osteophytic defect filling and promoting the lack of bone regeneration. Immune regulation, vascular and bone integration repair, significantly improved the repair effect of infectious bone defects.
Patent Information
- Application Number
- CN202411552190.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-01
- Publication Date
- 2025-01-28
- Estimated Expiration
- 2044-11-01
AI Technical Summary
Existing bone regeneration materials have problems with insufficient shape adaptability and adhesion in filling irregular bone defects, and lack effective antibacterial, immune regulation and pro-angiogenic properties, which limits their application in complex clinical situations.
The development of an anti -inflammatory tissue regeneration can be injected with the injectable light curing hydrogel. The hydrogel is carried on the calcium, phosphorus vanguard and sulfur quantum dot, which causes curing technology through light to realize the release of biological activity ingredients in situ. Promote bone regeneration.
This hydrogel can quickly inject and fully fill the area of irregular bone defects. Through the biological activity ingredients released in situ, antibacterial, immune regulation, vascular and bone integration repair, which significantly improves the repair effect of infectious bone defects Essence
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Figure CN119367599A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of biomedical materials, and in particular to an injectable photocurable hydrogel capable of resisting inflammation and promoting vascularized tissue regeneration. Background Art
[0002] Critical-sized bone defects are defined as defects that cannot spontaneously achieve bone integration without further surgical intervention. In clinical reconstruction, autologous bone transplantation is regarded as the gold standard, but its application is limited by the limited bone source and possible complications of the donor site. Compared with autologous grafts, allogeneic grafts have solved the problem of limited sources, but they still have some limitations, including the risk of immune rejection, the possibility of pathogen infection transmission, as well as low osteoinductive / osteoconductive activity and high cost, which limit their widespread clinical application. In addition, the challenges faced by xenografts include the difficulty of integration with host tissues and obvious graft rejection. In order to overcome these difficulties, researchers have developed a series of biomaterials as substitutes for bone grafts, including metals / alloys, bioceramics and polymers, which have gradually received attention in bone tissue engineering. Nevertheless, these materials are not without disadvantages: metal materials may cause chronic inflammation due to their non-degradability; bioceramics have problems such as brittleness, difficulty in processing and insufficient mechanical properties; and synthetic polymer materials may release toxic byproducts during degradation. More importantly, many existing bone regeneration materials lack shape adaptability and adhesion, which may become a limiting factor in some surgically difficult areas, such as the treatment of patients with cleft lip and palate. For these complex clinical situations, injectable materials show great advantages due to their ability to quickly adapt to irregular shapes. However, pure hydrogels often have poor immunomodulatory, pro-angiogenic and osteoinductive properties, which may limit their ability to effectively regenerate infected bone defects. Summary of the invention
[0003] In order to solve the above technical problems, the purpose of the present invention is to provide an injectable photocurable hydrogel with anti-inflammatory and pro-vascularized tissue regeneration, which can release sulfur quantum dots and calcium phosphate oligomers as bioactive components in situ, and synergistically promote the healing of infected bone defects through multiple effects of antibacterial, immunomodulatory, angiogenesis and osteogenesis.
[0004] The technical solution of the present invention to solve the above technical problems is as follows: an injectable photocurable hydrogel with anti-inflammatory and pro-vascularized tissue regeneration is provided, which is a methacrylic anhydride gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots.
[0005] Furthermore, the content of calcium phospho-oligomers is 5-20 wt %; the concentration of sulfur quantum dots is 0.1-10 mg / mL; and the concentration of methacrylic anhydride gelatin is 5-25 g / mL.
[0006] Furthermore, the preparation method of the injectable photocurable hydrogel for anti-inflammatory and pro-vascularized tissue regeneration is as follows: dissolving methacrylic anhydride-treated gelatin in a phosphate buffer solution, then adding calcium phosphate oligomers and sulfur quantum dots, and then adding a photoinitiator and mixing evenly, and finally curing under ultraviolet light or blue light.
[0007] Furthermore, the amount of photoinitiator added is 5-20 mg / mL.
[0008] Further, it is cured under irradiation with light having a wavelength of 300-500 nm.
[0009] Methacrylic anhydride gelatin is prepared by the following method: 5-25% (w / v) gelatin is added to PBS buffer and stirred to dissolve at 40-60°C; then 1-2% (w / v) methacrylic anhydride is added and vigorously stirred at 50°C for 3-5h; then preheated PBS buffer is added to the above solution to terminate the reaction; the obtained solution is placed in a 14000-20000Da dialysis bag, dialyzed at 40-50°C for one week, and then freeze-dried to obtain methacrylic anhydride gelatin.
[0010] Further, calcium phosphate oligomers are prepared by the following method:
[0011] (1) dissolving calcium chloride in anhydrous ethanol, adding triethylamine solution to prepare calcium solution;
[0012] (2) dispersing a phosphoric acid solution in anhydrous ethanol to obtain a phosphorus liquid;
[0013] (3) adding the phosphorus solution obtained in step (2) to the calcium solution obtained in step (1) to react and obtain calcium-phosphorus oligomers.
[0014] Furthermore, sulfur quantum dots are prepared by the following method: sublimated sulfur is added to ethylenediamine and stirred, and then a solvent thermal reaction is carried out at a temperature of 100-200°C for 4-6 hours, and after cooling, hydrogen peroxide is added dropwise with stirring until the solution is clear and transparent, and then concentrated by rotary evaporation, ethanol precipitation, washing and vacuum drying are carried out in sequence to obtain sulfur quantum dots.
[0015] The present invention also provides the use of the above-mentioned injectable light-curable hydrogel for anti-inflammatory and promoting vascularized tissue regeneration in the preparation of a product for treating infectious bone defect repair.
[0016] The present invention has the following beneficial effects:
[0017] 1. The hydrogel of the present invention is easy to prepare quickly and has good shear thinning properties. It can be injected into irregular bone defect areas and fully fill them. After further curing and cross-linking by light irradiation, the repair of infectious critical-size irregular bone defects can be achieved by in situ sustained release of bioactive components.
[0018] 2. The sulfur quantum dots loaded by the hydrogel of the present invention have good antibacterial and immunomodulatory properties. In the acidic microenvironment of early bacterial infection, the sulfur quantum dots released by the hydrogel can effectively remove bacteria, prevent bacteria from directly attacking osteoblasts and promote osteoclast activation, reshape the osteogenic microenvironment, and at the same time, its excellent immunomodulatory properties can promote the later tissue repair ability and enhance the bone regeneration ability.
[0019] 3. The sulfur quantum dots and calcium phosphate oligomers loaded in the hydrogel of the present invention can effectively improve the migration activity of endothelial cells through synergistic action, and promote their development towards angiogenesis, which is beneficial to improving the bone repair effect. In bone tissue engineering, vascularization is a key technology, which can supply blood and oxygen to cells in the tissue engineering construct and ensure the survival of tissue engineered bone. Vascular endothelial growth factor is a major participant in angiogenesis. It can induce the migration and proliferation of endothelial cells by regulating the release of osteogenic growth factor and paracrine signals, and indirectly stimulate osteogenesis. The hydrogel of the present invention promotes angiogenesis not only directly affects the regeneration and repair of bone tissue, but also promotes the healthy development of bone tissue through coupling with osteogenesis.
[0020] 4. The hydrogel of the present invention fills the bone defect area by injection and releases the active ingredients of sulfur quantum dots and calcium phosphate oligomer functional nanoparticles in situ, achieving antibacterial, immunomodulatory, angiogenic and osteogenic integrated repair, and effectively solving the problems of existing bioactive materials that cannot effectively fill irregular bone defects, have single functionality and poor bone induction performance. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 The graphs are the test results of the injectability, curing ability and curing time of each group of hydrogels;
[0022] Figure 2 The results of alkaline phosphatase expression assay under different concentrations of calcium phosphate oligomer hydrogels are shown;
[0023] Figure 3 is the scanning electron microscopy image of each group of hydrogels;
[0024] Figure 4 The graphs show the test results of the antibacterial ability of each group of hydrogels against Staphylococcus aureus;
[0025] Figure 5 The results of the effects of each group of hydrogels on the alkaline phosphatase activity of BMSCs cells are shown in the figure;
[0026] Figure 6 The graphs are the results of endothelial cell migration tests for each group of hydrogel pairs;
[0027] Figure 7 The test results of endothelial cell vascular tubular structure formation for each group of hydrogel pairs are shown;
[0028] Figure 8 The graphs show the test results of each group of hydrogels promoting bone regeneration in animals;
[0029] Fig. 9 The results of immunofluorescence and immunohistochemistry staining of the defect area are shown. DETAILED DESCRIPTION
[0030] The principles and features of the present invention are described below, and the examples are only used to explain the present invention and are not used to limit the scope of the present invention. If no specific conditions are specified in the embodiments, they are carried out according to normal conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.
[0031] Example 1
[0032] An injectable photocurable hydrogel (GCS) for anti-inflammatory and pro-vascularized tissue regeneration, which is a methacrylic anhydride gelatin hydrogel loaded with calcium phospho-oligomers (CPO) and sulfur quantum dots (SQDs);
[0033] The preparation method is as follows: 0.15 g of methacrylic anhydride gelatin is dissolved in 1 mL of phosphate buffer solution, and then 0.05 g of calcium phosphate oligomer and 1.5 mg of sulfur quantum dots are added, and then 0.01 g of photoinitiator is added and mixed evenly, and finally cured under blue light irradiation for 1 minute.
[0034] The methacrylic anhydride gelatin is prepared by the following method: 25% (w / v) gelatin is added to PBS buffer and stirred to dissolve at 50°C; then 2% (w / v) methacrylic anhydride is added and vigorously stirred at 50°C for 4 hours; then preheated PBS buffer is added to the above solution to terminate the reaction; the obtained solution is loaded into a 16000Da dialysis bag, dialyzed at 50°C for one week, and then freeze-dried to obtain methacrylic anhydride gelatin.
[0035] Wherein, calcium phosphate oligomer is prepared by the following method:
[0036] (1) dissolving calcium chloride in anhydrous ethanol, adding triethylamine solution to prepare calcium solution;
[0037] (2) dispersing a phosphoric acid solution in anhydrous ethanol to obtain a phosphorus liquid;
[0038] (3) adding the phosphorus solution obtained in step (2) to the calcium solution obtained in step (1) to react and obtain calcium phosphate oligomer (CPO).
[0039] Among them, sulfur quantum dots are prepared by the following method: 20% (w / v) sublimed sulfur is added to ethylenediamine and stirred, and then a solvent thermal reaction is carried out at a temperature of 150°C for 5 hours. After cooling, hydrogen peroxide is added dropwise with stirring until the solution is clear and transparent, and then concentrated by rotary evaporation, ethanol precipitation, washing and vacuum drying are carried out in sequence to obtain sulfur quantum dots (SQDs).
[0040] Example 2
[0041] An injectable photocurable hydrogel for anti-inflammatory and pro-vascularized tissue regeneration, which is a methacrylic anhydride gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots;
[0042] The content of calcium phosphate oligomers is 15wt%; the concentration of sulfur quantum dots is 8mg / mL; the concentration of methacrylic anhydride gelatin is 20g / mL;
[0043] The preparation method is as follows: dissolving methacrylic anhydride gelatin in a phosphate buffer solution, then adding 0.05g of calcium phosphate oligomer and sulfur quantum dots, then adding a photoinitiator at a rate of 10mg / mL and mixing evenly, and finally curing under ultraviolet light.
[0044] Example 3
[0045] An injectable photocurable hydrogel for anti-inflammatory and pro-vascularized tissue regeneration, which is a methacrylic anhydride gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots;
[0046] The content of calcium phosphate oligomers is 5wt%; the concentration of sulfur quantum dots is 0.1mg / mL; the concentration of methacrylic anhydride gelatin is 5g / mL;
[0047] The preparation method is as follows: dissolving methacrylic anhydride gelatin in a phosphate buffer solution, then adding calcium phosphate oligomers and sulfur quantum dots, then adding a photoinitiator at a rate of 5 mg / mL and mixing evenly, and finally curing under ultraviolet light.
[0048] Example 4
[0049] An injectable photocurable hydrogel for anti-inflammatory and pro-vascularized tissue regeneration, which is a methacrylic anhydride gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots;
[0050] The content of calcium phosphate oligomers is 20wt%; the concentration of sulfur quantum dots is 10mg / mL; the concentration of methacrylic anhydride gelatin is 25g / mL;
[0051] The preparation method is as follows: dissolving methacrylic anhydride gelatin in a phosphate buffer solution, then adding calcium phosphate oligomers and sulfur quantum dots, then adding a photoinitiator at 20 mg / mL and mixing evenly, and finally curing under blue light irradiation.
[0052] Comparative Example 1
[0053] Methacrylic anhydride gelatin hydrogel (GelMA) is prepared by dissolving 0.15 g of methacrylic anhydride gelatin in 1 mL of phosphate buffer solution, adding 0.01 g of photoinitiator and mixing evenly, and curing under blue light for 1 min.
[0054] Comparative Example 2
[0055] A hydrogel loaded with calcium phosphate oligomers (GelMA / 5CPO), wherein the preparation method comprises the following steps: dissolving 0.15 g of methacrylic anhydride-treated gelatin in 1 mL of phosphate buffer solution, then adding 0.05 g of calcium phosphate oligomers and mixing, then adding 0.01 g of a photoinitiator and mixing evenly, and curing by irradiating under blue light for 1 min.
[0056] Comparative Example 3
[0057] A hydrogel loaded with calcium phosphate oligomers (GelMA / 10CPO), wherein the preparation method comprises the following steps: dissolving 0.15 g of methacrylic anhydride-treated gelatin in 1 mL of phosphate buffer solution, then adding 0.1 g of calcium phosphate oligomers and mixing, then adding 0.01 g of a photoinitiator and mixing evenly, and curing by irradiating under blue light for 1 min.
[0058] Comparative Example 4
[0059] A hydrogel loaded with calcium phosphate oligomers (GelMA / 15CPO), wherein the preparation method comprises the following steps: dissolving 0.15 g of methacrylic anhydride-treated gelatin in 1 mL of phosphate buffer solution, then adding 0.15 g of calcium phosphate oligomers and mixing, then adding 0.01 g of a photoinitiator and mixing evenly, and curing by irradiating under blue light for 1 min.
[0060] Comparative Example 5
[0061] A hydrogel loaded with calcium phosphate oligomers (GelMA / 20CPO), wherein the preparation method comprises the following steps: dissolving 0.15 g of methacrylic anhydride-treated gelatin in 1 mL of phosphate buffer solution, then adding 0.2 g of calcium phosphate oligomers and mixing, then adding 0.01 g of a photoinitiator and mixing evenly, and curing by irradiating under blue light for 1 min.
[0062] Comparative Example 6
[0063] A hydrogel loaded with sulfur quantum dots (GelMA / SQDs), the preparation method of which is as follows: 0.15g of methacrylic anhydride gelatin is dissolved in 1mL of phosphate buffer solution, then 1.5mg of sulfur quantum dots are added and mixed, and then 0.01g of photoinitiator is added and mixed evenly, and the mixture is cured by irradiating under blue light for 1min.
[0064] Test Example 1 CPO concentration screening
[0065] (1) Comparative Examples 1-5 were compared in terms of injectability, curing ability and curing time. The results are as follows Figure 1 shown.
[0066] Depend on Figure 1 It can be seen that, except for the GelMA / 20CPO group, other GelMA hydrogels loaded with different proportions of CPO can be injected and cured, and the cross-linking time of UV and blue light increases slightly with the increase of CPO concentration, proving that the injectable hydrogel was successfully synthesized.
[0067] (2) ALP activity is related to the mineralization of bone tissue and is one of the effective indicators of early osteogenic differentiation. Its activity can be characterized by detecting the content of p-nitrophenyl phosphate converted to p-nitrophenol catalyzed by alkaline phosphatase per minute. The optimal CPO content was selected by qualitative and quantitative analysis of ALP expression caused by early osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The results are as follows Figure 2 As shown, * indicates a significance level of 0.01, ** indicates a significance level of 0.001, and *** indicates a significance level of 0.0001.
[0068] Depend on Figure 2 It can be seen that regardless of whether BMSCs were differentiated for 7 days or 14 days, the expression level of ALP in the GelMA / 5CPO test group was the most significant, with significant statistical differences, proving the excellent effect of GelMA / 5CPO in promoting osteogenic differentiation in vitro.
[0069] Test Example 2 Morphology and structure observation
[0070] The five hydrogels of Example 1 (GCS), Comparative Example 1 (GelMA), Comparative Example 2 (GelMA / 5CPO) and Comparative Example 6 (GelMA / SQDs) were observed using a scanning electron microscope. The SEM characterization results are shown in Figure 3 shown.
[0071] Depend on Figure 3 It can be seen that each component GelMA hydrogel has a representative porous sponge-like structure, indicating that the loading of SQDs and CPO has no negative impact on the excellent water absorption capacity of the original hydrogel.
[0072] Moreover, according to the results of energy spectrum (EDS) element mapping analysis, sulfur (S), calcium (Ca) and (P) elements are evenly distributed in GCS. The results show that SQDs and CPO are evenly distributed in the hydrogel network without phase separation and particle aggregation. GCS can be considered as a homogeneous hydrogel on a macro scale.
[0073] Test Example 3: Antibacterial activity and osteogenic differentiation of mesenchymal stem cells
[0074] (1) The antibacterial performance test was carried out on the hydrogels of Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 6 respectively. The results are as follows Figure 4 shown.
[0075] Depend on Figure 4 It can be seen that for the five hydrogels of GelMA, GelMA / 5CPO, GelMA / SQDs and GCS, GelMA / SQDs and GCS hydrogels containing SQDs components showed excellent antibacterial properties against Staphylococcus aureus, with an antibacterial rate of up to 99% compared with the control group.
[0076] (2) ALP, as an important mineralizing enzyme, can decompose organic phosphorus to produce inorganic phosphorus during bone formation and regeneration, promote mineral deposition and hydroxyapatite formation, and is an important indicator of osteoblast differentiation in the pre-osteoblast stage. Therefore, BMSCs cells were co-cultured with the extracts of the hydrogels of Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 6 for 7 days and 14 days, respectively, and the expression of ALP activity in the cells was observed. The results are as follows: Figure 5 As shown, * indicates a significance level of 0.01, and ** indicates a significance level of 0.001.
[0077] Depend on Figure 5 It can be seen that the most positive ALP expression was observed in the GelMA / 5CPO group, followed by the GCS and GelMA / SQDs groups, and very little ALP positive expression was observed in the control group and the GelMA group. This result shows that the calcium and phosphate ions released from the hydrogel can effectively promote the early osteogenic differentiation of BMSCs. Although the ALP activity of BMSCs was weakened to a certain extent after combining with sulfur quantum dots, it still has a better osteogenic differentiation effect than the GelMA group.
[0078] Experimental Example 4 Endothelial cell migration and vascular tubular structure formation experiment
[0079] (1) During bone tissue regeneration, endothelial progenitor cells and stem cells are initially stimulated to secrete angiogenic factors to achieve vascular regeneration, while stem cells further differentiate into osteoblasts to form vascularized bone structures. Therefore, bone repair materials should first stimulate endothelial cells to form a vascular network in the defect area, and then promote osteoprogenitor cells or osteoblasts to synthesize bone extracellular matrix to achieve bone tissue regeneration. The effects of various components on cell migration activity were studied by scratch experiments. The results are as follows: Figure 6 shown.
[0080] Depend on Figure 6It can be seen that as the culture time increases, the cells in each group migrate to the scratch area to varying degrees. At the same culture time, the scratch area of the GelMA / 5CPO and GCS groups containing calcium phosphate oligomers is smaller than that of the other groups. At the same time, the same regular experimental results were observed after 6h and 12h of culture.
[0081] (2) The formation of HUVECs tubular network structure is a morphological feature of endothelial cells developing into angiogenesis. Matrigel can support HUVECs to form tubular structure. HUVECs cells were inoculated on Matrigel and co-cultured with the extracts of each group of hydrogels for 8 hours and then observed. The results are as follows: Figure 7 shown.
[0082] Depend on Figure 7 It can be seen that HUVECs in each group can form tubular structures of varying degrees of completeness in the matrix gel. The number of nodes, number of grids, and total area of grids in the tubular structures formed by HUVECs co-cultured with the extract of the GCS group were higher than those in other groups. The above results show that the simultaneous loading of calcium phosphate oligomers and sulfur quantum dots on GelMA hydrogel can effectively promote the migration of HUVECs and the formation of tubular structures.
[0083] Test Example 5 Bone tissue regeneration performance test
[0084] (1) Different hydrogels were implanted into the femoral limit defect model of rats. The skull repair effect was observed after 4 and 8 weeks. Micro-CT new bone reconstruction and quantitative statistical results were also observed. Figure 8 As shown in the figure, a is the Micro-CT image of skull repair in each group after 4 weeks, b is the comparison chart of bone analysis data in each group after 4 weeks, c is the Micro-CT image of skull repair in each group after 8 weeks, d is the comparison chart of bone analysis data in each group after 8 weeks, * indicates a significant level of 0.01, ** indicates a significant level of 0.001, and *** indicates a significant level of 0.0001.
[0085] Depend on Figure 8 It can be seen that compared with the GelMA / 5CPO and GelMA / SQDs groups, a large amount of new bone was formed in the defect area of the GCS group, almost completely covering the defect area, indicating that the GelMA hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots simultaneously has a good effect in guiding bone tissue regeneration and has broad application prospects in the field of infectious tissue repair.
[0086] (2) The phenotypic reprogramming of macrophages around the hydrogel was further observed by immunofluorescence experiments on the defect area, and the levels of bone metabolism markers were analyzed by immunohistochemical staining. Fig. 9 shown.
[0087] Depend on Fig. 9It can be seen that the number of Arg-1 positive cells (i.e., M2 phenotype macrophages) around the GelMA / SQDs group increased significantly compared with the control group and the GelMA group. In contrast, the staining results of iNOS positive cells (i.e., M1 phenotype macrophages) showed an opposite trend. This verifies the excellent immunomodulatory properties of SQDSs in vivo, which is essential for guiding later bone regeneration. The results of immunohistochemical staining showed that the expression of osteocalcin (OCN) and TRAP was observed in the infected bone defect area treated with SQDs, and the expression level of OCN in the GelMA / SQDs group was significantly increased compared with other groups. In addition, a large number of positive osteoclasts were observed in the control group and the GelMA group. In contrast, the osteoclast activation in the GelMA / SQDs group was the lowest. The results show that GelMA / SQDs can effectively remove bacteria in the acidic microenvironment of early bacterial infection, prevent bacteria from directly attacking osteoblasts and promote osteoclast activation. After successful bacteria removal, the infected acidic microenvironment was alleviated, and GelMA / SQDs further improved the bone immune microenvironment damage caused by infection, ultimately enhancing bone regeneration capacity.
[0088] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. An injectable photocurable hydrogel for anti-inflammatory and pro-vascularized tissue regeneration, characterized in that: Methacrylic anhydride-treated gelatin hydrogel loaded with calcium phospho-oligomers and sulfur quantum dots.
2. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularization tissue regeneration according to claim 1, characterized in that: The content of the calcium phosphate oligomer is 5-20wt%; the concentration of the sulfur quantum dots is 0.1-10mg / mL; and the concentration of the methacrylic anhydride gelatin is 5-25g / mL.
3. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularization tissue regeneration according to claim 1, characterized in that: The preparation method is as follows: dissolving methacrylic anhydride gelatin in a phosphate buffer solution, then adding calcium phosphate oligomers and sulfur quantum dots, then adding a photoinitiator and mixing evenly, and finally curing under ultraviolet light or blue light.
4. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularized tissue regeneration according to claim 3, characterized in that: The added amount of the photoinitiator is 5-20 mg / mL.
5. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularization tissue regeneration according to claim 3, characterized in that: Curing under light with a wavelength of 300-500nm.
6. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularization and tissue regeneration according to claim 1, characterized in that: The calcium phosphate oligomer is prepared by the following method: (1) dissolving calcium chloride in anhydrous ethanol, adding triethylamine solution to prepare calcium solution; (2) dispersing a phosphoric acid solution in anhydrous ethanol to obtain a phosphorus liquid; (3) adding the phosphorus solution obtained in step (2) to the calcium solution obtained in step (1) to react and obtain calcium-phosphorus oligomers.
7. The injectable photocurable hydrogel for anti-inflammatory and promoting vascularization and tissue regeneration according to claim 1, characterized in that: The sulfur quantum dots are prepared by the following method: adding sublimed sulfur to ethylenediamine and stirring, then performing a solvent thermal reaction at a temperature of 100-200° C. for 4-6 hours, cooling, stirring, and dripping hydrogen peroxide until the solution is clear and transparent, and then sequentially performing rotary evaporation concentration, ethanol precipitation, washing, and vacuum drying to obtain the sulfur quantum dots.
8. Use of the anti-inflammatory and pro-vascularized tissue regeneration injectable photocurable hydrogel according to any one of claims 1 to 7 in the preparation of a product for treating infected bone defect repair.
Citation Information
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