An injectable photocured hydrogel for anti-inflammatory pro-angiogenic tissue regeneration
By using injectable photocurable hydrogels loaded with calcium phosphate oligomers and sulfur quantum dots, the shortcomings of existing bone regeneration materials in terms of shape adaptability and bioactivity have been overcome, enabling rapid and effective repair of infected bone defects.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SICHUAN UNIV
- Filing Date
- 2024-11-01
- Publication Date
- 2026-06-30
AI Technical Summary
Existing bone regeneration materials lack shape adaptability and adhesion in critical-sized bone defects, and have poor immunomodulatory, angiogenesis-promoting, and osteoinductive properties, which limits their effective repair of infected bone defects.
An injectable, photocurable hydrogel with anti-inflammatory and pro-angiogenic properties is provided, loaded with calcium phosphate oligomers and sulfur quantum dots, which synergistically promote the healing of infected bone defects through antibacterial, immunomodulatory and osteogenic effects.
It enables rapid preparation and filling of irregular bone defects, and enhances bone regeneration capacity by releasing bioactive components in situ, promoting endothelial cell migration and angiogenesis, thus achieving integrated repair of infected bone defects.
Smart Images
Figure CN119367599B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, specifically to an injectable photocurable hydrogel that promotes anti-inflammatory and angiogenesis tissue regeneration. Background Technology
[0002] Critical-sized bone defects are defined as those that cannot spontaneously integrate without further surgical intervention. In clinical reconstructive surgery, autologous bone grafting is considered the gold standard, but its application is limited by the finite availability of bone and potential complications at the donor site. Compared to autologous grafts, allogeneic grafts, while solving the source limitation problem, still have some limitations, including the risk of immune rejection, the possibility of pathogen transmission, lower osteoinduction / osteoconduction activity, and higher cost, all of which limit their widespread clinical application. Furthermore, xenografts face challenges such as difficulty integrating with host tissue and significant graft rejection. To overcome these challenges, researchers have developed a range of biomaterials as alternatives to bone grafts, including metals / alloys, bioceramics, and polymers, which are gaining increasing attention in bone tissue engineering. However, these materials are not without drawbacks: metallic materials may cause chronic inflammation due to their non-degradability; bioceramics suffer from brittleness, processing difficulties, and insufficient mechanical properties; and synthetic polymers may release toxic byproducts during degradation. More importantly, many existing bone regeneration materials lack shape adaptability and adhesion, which can be a limiting factor in some surgically challenging areas, such as the treatment of cleft lip and palate patients. For these complex clinical situations, injectable materials show great advantages due to their ability to rapidly adapt to irregular shapes. However, pure hydrogels often have poor immunomodulatory, angiogenic, and osteoinductive properties, which may limit their ability to effectively regenerate infected bone defects. Summary of the Invention
[0003] To address the aforementioned technical problems, the present invention aims to provide an injectable photocurable hydrogel that promotes anti-inflammatory and angiogenesis tissue regeneration. This hydrogel can release sulfur quantum dots and calcium phosphate oligomers in situ, thereby synergistically promoting the healing of infected bone defects through multiple effects including antibacterial, immunomodulatory, angiogenesis, and osteoproliferative effects.
[0004] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: an injectable photocurable hydrogel with anti-inflammatory and angiogenic tissue regeneration properties is provided, which is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots.
[0005] Furthermore, the content of calcium phosphorus 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 with anti-inflammatory and angiogenic tissue regeneration properties is as follows: dissolve methacrylic anhydride gelatin in phosphate buffer solution, then add calcium phosphate oligomers and sulfur quantum dots, then add photoinitiator and mix evenly, and finally cure under ultraviolet or blue light irradiation.
[0007] Furthermore, the amount of photoinitiator added is 5-20 mg / mL.
[0008] Furthermore, it is cured under light irradiation with a wavelength of 300-500nm.
[0009] Methacrylic anhydride gelatin was prepared by the following method: 5-25% (w / v) gelatin was added to PBS buffer and stirred at 40-60°C to dissolve; then 1-2% (w / v) methacrylic anhydride was added and stirred vigorously at 50°C for 3-5 hours; subsequently, preheated PBS buffer was added to the above solution to terminate the reaction; the resulting solution was placed in a 14000-20000 Da dialysis bag and dialyzed at 40-50°C for one week, and then freeze-dried to obtain methacrylic anhydride gelatin.
[0010] Furthermore, the calcium-phosphorus oligomers are prepared by the following method:
[0011] (1) Dissolve calcium chloride in anhydrous ethanol and add triethylamine solution to prepare calcium solution;
[0012] (2) Disperse the phosphoric acid solution in anhydrous ethanol to prepare phosphoric acid solution;
[0013] (3) Add 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 were prepared by the following method: sublimed sulfur was added to ethylenediamine and stirred, and then a solvothermal reaction was carried out at 100-200℃ for 4-6 hours. After cooling, hydrogen peroxide was added dropwise with stirring until the solution was clear and transparent. Then, the solution was concentrated by rotary evaporation, precipitated with ethanol, washed and dried under vacuum to obtain sulfur quantum dots.
[0015] This invention also provides the application of the above-mentioned anti-inflammatory and angiogenic tissue regeneration injectable photocurable hydrogel in the preparation of products for the treatment of infected bone defects.
[0016] The present invention has the following beneficial effects:
[0017] 1. The hydrogel of this 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, it can repair infectious critical-size irregular bone defects by in-situ sustained release of bioactive components.
[0018] 2. The sulfur quantum dots loaded on the hydrogel of this invention exhibit good antibacterial and immunomodulatory properties. In the acidic microenvironment of early bacterial infection, the sulfur quantum dots released by the hydrogel can effectively eliminate bacteria, prevent bacteria from directly attacking osteoblasts and promote osteoclast activation, thus reshaping the osteogenic microenvironment. At the same time, its excellent immunomodulatory properties can promote subsequent tissue repair capabilities, thereby enhancing bone regeneration.
[0019] 3. The sulfur quantum dots and calcium phosphate oligomers loaded in the hydrogel of this invention, through synergistic effects, can effectively enhance the migration activity of endothelial cells and promote their angiogenesis, thus improving bone repair. In bone tissue engineering, vascularization is a key technology, providing blood and oxygen supply to cells within the tissue-engineered structure and ensuring the survival of the engineered bone. Vascular endothelial growth factor (VEGF) is a major participant in angiogenesis; it can induce endothelial cell migration and proliferation by regulating the release of osteogenic growth factor (OGF) and paracrine signaling, and indirectly stimulate osteoogenesis. The angiogenesis-promoting effect of the hydrogel of this invention not only directly affects bone tissue regeneration and repair but also, through its coupling effect with bone formation, jointly promotes the healthy development of bone tissue.
[0020] 4. The hydrogel of this invention fills the bone defect area by injection and releases sulfur quantum dots and calcium phosphate oligomer functional nanoparticles in situ, achieving integrated repair of antibacterial, immune regulation, angiogenesis and osteogenic effects. It effectively solves the problems of existing bioactive materials being unable to effectively fill irregular bone defects, having single function and poor osteoinductive properties. Attached Figure Description
[0021] Figure 1 The graph shows the test results of injectability, curing ability and curing time for each group of hydrogels;
[0022] Figure 2 Figure 1 shows the results of alkaline phosphatase expression assay under hydrogels containing different concentrations of calcium-phosphorus oligomers.
[0023] Figure 3 Scanning electron microscope images of each group of hydrogels;
[0024] Figure 4 Figure 1 shows the test results of the antibacterial ability of each group of hydrogels against Staphylococcus aureus.
[0025] Figure 5 Figure showing the effect of each group of hydrogels on alkaline phosphatase activity in BMSCs cells;
[0026] Figure 6 Figure 1 shows the endothelial cell migration test results for each hydrogel pair.
[0027] Figure 7 The results of the test for the formation of endothelial vascular tubular structures in each group of hydrogel pairs are shown in the figure.
[0028] Figure 8 Figure 1 shows the experimental results of each group of hydrogels promoting bone regeneration in animals.
[0029] Figure 9 The image shows the results of immunofluorescence and immunohistochemical staining of the defect area. Detailed Implementation
[0030] The principles and features of this invention are described below. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available products.
[0031] Example 1
[0032] An injectable photocurable hydrogel (GCS) with anti-inflammatory and pro-angiogenic tissue regeneration properties is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphate oligomers (CPO) and sulfur quantum dots (SQDs).
[0033] The preparation method is as follows: 0.15g of methacrylic anhydride gelatin is dissolved in 1mL of phosphate buffer solution, then 0.05g of calcium phosphate oligomer and 1.5mg of sulfur quantum dots are added, followed by 0.01g of photoinitiator. The mixture is then thoroughly mixed and cured under blue light irradiation for 1min.
[0034] The methacrylic anhydride gelatin was prepared by the following method: 25% (w / v) gelatin was added to PBS buffer and stirred at 50°C to dissolve; then 2% (w / v) methacrylic anhydride was added and stirred vigorously at 50°C for 4 hours; then preheated PBS buffer was added to the above solution to terminate the reaction; the resulting solution was placed in a 16000 Da dialysis bag, dialyzed at 50°C for one week, and then freeze-dried to obtain the methacrylic anhydride gelatin.
[0035] The calcium-phosphorus oligomers are prepared by the following method:
[0036] (1) Dissolve calcium chloride in anhydrous ethanol and add triethylamine solution to prepare calcium solution;
[0037] (2) Disperse the phosphoric acid solution in anhydrous ethanol to prepare phosphoric acid solution;
[0038] (3) Add the phosphorus solution obtained in step (2) to the calcium solution obtained in step (1) to react and obtain calcium phosphorus oligomer (CPO).
[0039] The sulfur quantum dots were prepared by the following method: 20% (w / v) sublimed sulfur was added to ethylenediamine and stirred. Then, a solvothermal reaction was carried out at 150°C for 5 hours. After cooling, hydrogen peroxide was added dropwise with stirring until the solution was clear and transparent. Then, the solution was concentrated by rotary evaporation, precipitated with ethanol, washed and dried under vacuum to obtain sulfur quantum dots (SQDs).
[0040] Example 2
[0041] An injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphorus oligomers and sulfur quantum dots.
[0042] The calcium phosphorus oligomer content is 15 wt%; the sulfur quantum dot concentration is 8 mg / mL; and the methacrylic anhydride gelatin concentration is 20 g / mL.
[0043] The preparation method is as follows: dissolve methacrylic anhydride gelatin in phosphate buffer solution, then add 0.05g of calcium phosphate oligomer and sulfur quantum dots, then add photoinitiator at 10mg / mL and mix evenly, and finally cure under ultraviolet light.
[0044] Example 3
[0045] An injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphorus oligomers and sulfur quantum dots.
[0046] The calcium phosphorus oligomer content is 5 wt%; the sulfur quantum dot concentration is 0.1 mg / mL; and the methacrylic anhydride gelatin concentration is 5 g / mL.
[0047] The preparation method is as follows: dissolve methacrylic anhydride gelatin in phosphate buffer solution, then add calcium phosphate oligomer and sulfur quantum dots, then add photoinitiator at 5 mg / mL and mix evenly, and finally cure under ultraviolet light.
[0048] Example 4
[0049] An injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphorus oligomers and sulfur quantum dots.
[0050] The calcium phosphorus oligomer content is 20 wt%; the sulfur quantum dot concentration is 10 mg / mL; and the methacrylic anhydride gelatin concentration is 25 g / mL.
[0051] The preparation method is as follows: dissolve methacrylic anhydride gelatin in phosphate buffer solution, then add calcium phosphate oligomer and sulfur quantum dots, then add photoinitiator at 20 mg / mL and mix evenly, and finally cure under blue light irradiation.
[0052] Comparative Example 1
[0053] The preparation method of methacrylic anhydride gelatin hydrogel (GelMA) is as follows: 0.15g of methacrylic anhydride gelatin is dissolved in 1mL of phosphate buffer solution, 0.01g of photoinitiator is added and mixed evenly, and then cured by irradiation under blue light for 1min.
[0054] Comparative Example 2
[0055] A hydrogel loaded with calcium phosphate oligomers (GelMA / 5CPO) is prepared by dissolving 0.15g of methacrylic anhydride gelatin in 1mL of phosphate buffer solution, then adding 0.05g of calcium phosphate oligomers and mixing, then adding 0.01g of photoinitiator and mixing evenly, and curing under blue light for 1min.
[0056] Comparative Example 3
[0057] A hydrogel loaded with calcium phosphate oligomers (GelMA / 10CPO) is prepared by dissolving 0.15g of methacrylic anhydride gelatin in 1mL of phosphate buffer solution, then adding 0.1g of calcium phosphate oligomers and mixing, then adding 0.01g of photoinitiator and mixing evenly, and curing under blue light for 1min.
[0058] Comparative Example 4
[0059] A hydrogel loaded with calcium phosphate oligomers (GelMA / 15CPO) is prepared by dissolving 0.15g of methacrylic anhydride gelatin in 1mL of phosphate buffer solution, then adding 0.15g of calcium phosphate oligomers and mixing, then adding 0.01g of photoinitiator and mixing evenly, and curing under blue light for 1min.
[0060] Comparative Example 5
[0061] A hydrogel loaded with calcium phosphate oligomers (GelMA / 20CPO) is prepared by dissolving 0.15g of methacrylic anhydride gelatin in 1mL of phosphate buffer solution, then adding 0.2g of calcium phosphate oligomers and mixing, then adding 0.01g of photoinitiator and mixing evenly, and curing under blue light for 1min.
[0062] Comparative Example 6
[0063] A hydrogel loaded with sulfur quantum dots (GelMA / SQDs) is prepared by dissolving 0.15g of methacrylic anhydride gelatin in 1mL of phosphate buffer solution, then adding 1.5mg of sulfur quantum dots and mixing, then adding 0.01g of photoinitiator and mixing evenly, and curing under blue light for 1min.
[0064] Experimental 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 As 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. The crosslinking time under ultraviolet and blue light increases slightly with the increase of CPO concentration, which proves that the injectable hydrogel has been successfully synthesized.
[0067] (2) ALP activity is related to bone mineralization and is one of the effective indicators of early osteogenic differentiation. Its activity can be characterized by detecting the amount of p-nitrophenyl phosphate converted to p-nitrophenol by alkaline phosphatase per minute. Qualitative and quantitative analysis of ALP expression induced by early osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was performed to select the optimal CPO content. 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 differentiated for 7 or 14 days, the expression level of ALP was the most significant in the GelMA / 5CPO experimental group, showing a significant statistical difference, which proves the excellent effect of GelMA / 5CPO in promoting osteogenic differentiation in vitro.
[0069] Observation of morphology and structure in Experiment Example 2
[0070] Five hydrogels—Example 1 (GCS), Comparative Example 1 (GelMA), Comparative Example 2 (GelMA / 5CPO), and Comparative Example 6 (GelMA / SQDs)—were observed using scanning electron microscopy. The SEM characterization results are as follows: Figure 3 As shown.
[0071] Depend on Figure 3 It can be seen that each component of the 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] Furthermore, energy dispersive spectroscopy (EDS) elemental mapping analysis showed that sulfur (S), calcium (Ca), and phosphorus (P) elements were uniformly distributed in the GCS. The results indicate that SQDs and CPO were uniformly distributed within the hydrogel network without phase separation or particle aggregation, suggesting that the GCS can be considered a homogeneous hydrogel on a macroscopic scale.
[0073] Experimental Example 3: Detection of antibacterial properties and the ability to promote osteogenic differentiation of mesenchymal stem cells
[0074] (1) Antibacterial properties were tested on the hydrogels of Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 6, respectively. The results are as follows: Figure 4 As shown.
[0075] Depend on Figure 4 It can be seen that among the five hydrogels, GelMA, GelMA / 5CPO, GelMA / SQDs and GCS, the GelMA / SQDs and GCS hydrogels containing the SQDs component showed excellent antibacterial properties against Staphylococcus aureus, with an antibacterial rate as high as 99% compared to the control group.
[0076] (2) ALP, as an important mineralizing enzyme, can decompose organic phosphorus and produce inorganic phosphorus during bone formation and regeneration, promoting mineral deposition and hydroxyapatite formation. It is an important indicator of pre-osteogenic differentiation of osteoblasts. Therefore, BMSCs cells were co-cultured in the extracts of hydrogels from Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 6 for 7 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 The study showed that the GelMA / 5CPO group exhibited the highest ALP positive expression, followed by the GCS and GelMA / SQDs groups. ALP positive expression was minimal in the control and GelMA groups. These results indicate that calcium and phosphorus ions released from the hydrogel effectively promote early osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Although binding to sulfur quantum dots somewhat weakened ALP activity in BMSCs, it still demonstrated a better osteogenic differentiation-promoting effect compared to the GelMA group.
[0078] Experiment 4: Endothelial Cell Migration and Vascular Tube Formation
[0079] (1) During bone tissue regeneration, endothelial progenitor cells and stem cells are initially stimulated to secrete angiogenic factors to achieve angiogenesis, 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 each component on cell migration activity were studied through scratch assays, and the results are as follows: Figure 6 As shown.
[0080] Depend on Figure 6It was observed that, with increasing culture time, cells in each group migrated to the scratched area to varying degrees. At the same culture time, the scratch areas of the GelMA / 5CPO and GCS groups containing calcium phosphate oligomers were smaller than those of the other groups. Furthermore, the same trend was observed after 6 h and 12 h of culture.
[0081] (2) The formation of the tubular network structure of HUVECs is a morphological feature of endothelial cell angiogenesis, and matrix gel can support the formation of tubular structures by HUVECs. HUVECs were seeded onto matrix gel and co-cultured with the extracts of each group of hydrogels for 8 hours, and the results were observed as follows: Figure 7 As shown.
[0082] Depend on Figure 7 It was found that HUVECs in each group could form tubular structures with varying degrees of integrity in the matrix gel. The number of nodes, the number of grids, and the total grid area of the tubular structures formed by HUVECs co-cultured with the GCS extract were all higher than those in other groups. These results indicate that simultaneously loading calcium phosphate oligomers and sulfur quantum dots onto GelMA hydrogel can effectively promote the migration of HUVECs and the formation of tubular structures.
[0083] Experimental Example 5: Detection of Bone Tissue Regeneration Performance
[0084] (1) Different hydrogels were implanted into a rat femoral bone defect model. The skull repair effect was observed after 4 and 8 weeks. Micro-CT bone regeneration and quantitative statistical results are as follows: Figure 8 As shown in the figure, a is the Micro-CT image of cranioplasty in each group after 4 weeks, b is the comparison of bone analysis data in each group after 4 weeks, c is the Micro-CT image of cranioplasty in each group after 8 weeks, and d is the comparison of bone analysis data in each group after 8 weeks. * indicates a significance level of 0.01, ** indicates a significance level of 0.001, and *** indicates a significance level of 0.0001.
[0085] Depend on Figure 8 It can be seen that, compared with the GelMA / 5CPO and GelMA / SQDs groups, the GCS group showed a large amount of new bone formation in the defect area, almost completely covering the defect area. This indicates that the GelMA hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots has a good guiding effect on bone tissue regeneration and has broad application prospects in the field of infectious tissue repair.
[0086] (2) Immunofluorescence experiments were performed on the defect area to further observe the phenotypic reprogramming of macrophages around the hydrogel, and the levels of bone metabolism markers were analyzed by immunohistochemical staining. The results are as follows: Figure 9 As shown.
[0087] Depend on Figure 9The results showed that, compared with the control group and the GelMA group, the number of Arg-1 positive cells (i.e., M2 phenotype macrophages) was significantly increased in the GelMA / SQDs group. In contrast, the staining results of iNOS positive cells (i.e., M1 phenotype macrophages) showed the opposite trend. This verifies the superior immunomodulatory properties of SQDs in vivo, which is crucial for guiding later bone regeneration. Immunohistochemical staining results showed that osteocalcin (OCN) and TRAP expression were observed in the infected bone defect area treated with SQDs, and the OCN expression level was significantly increased in the GelMA / SQDs group compared with other groups. In addition, a large number of positive osteoclasts were observed in the control group and the GelMA group, but the osteoclast activation level was the lowest in the GelMA / SQDs group. The results indicate that GelMA / SQDs can effectively clear bacteria in the acidic microenvironment of early bacterial infection, prevent bacteria from directly attacking osteoblasts, and promote osteoclast activation. After successfully eliminating the bacteria, the acidic microenvironment of the infection was alleviated, and GelMA / SQDs further improved the bone immune microenvironment damage caused by the 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 modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. The application of an injectable photocurable hydrogel with anti-inflammatory and pro-vascularizing tissue regeneration properties in the preparation of products for the treatment of infected bone defects, wherein the injectable photocurable hydrogel with anti-inflammatory and pro-vascularizing tissue regeneration properties is a methacrylic anhydride-modified gelatin hydrogel loaded with calcium phosphate oligomers and sulfur quantum dots. The content of the calcium phosphorus oligomer is 5-20 wt%; the concentration of the sulfur quantum dots is 0.1-10 mg / mL; and the concentration of the methacrylic anhydride gelatin is 5-25 g / mL.
2. The application of the injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties as described in claim 1 in the preparation of products for the treatment and repair of infected bone defects, characterized in that, The preparation method is as follows: dissolve methacrylic anhydride gelatin in phosphate buffer solution, then add calcium phosphate oligomer and sulfur quantum dots, then add photoinitiator and mix evenly, and finally cure under ultraviolet or blue light irradiation.
3. The application of the injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties as described in claim 2 in the preparation of products for the treatment and repair of infected bone defects, characterized in that... The amount of photoinitiator added is 5-20 mg / mL.
4. The application of the injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties as described in claim 2 in the preparation of products for the treatment and repair of infected bone defects, characterized in that, Curing is carried out under light irradiation with a wavelength of 300-500 nm.
5. The application of the injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties as described in claim 1 in the preparation of products for the treatment and repair of infected bone defects, characterized in that... The calcium-phosphorus oligomer was prepared by the following method: (1) Dissolve calcium chloride in anhydrous ethanol, add triethylamine solution to prepare calcium solution; (2) Disperse the phosphoric acid solution in anhydrous ethanol to prepare phosphoric acid solution; (3) Add the phosphorus solution obtained in step (2) to the calcium solution obtained in step (1) to react and obtain calcium phosphorus oligomers.
6. The application of the injectable photocurable hydrogel with anti-inflammatory and pro-angiogenic tissue regeneration properties as described in claim 1 in the preparation of products for the treatment and repair of infected bone defects, characterized in that, The sulfur quantum dots were prepared by the following method: sublimed sulfur was added to ethylenediamine and stirred, and then a solvothermal reaction was carried out at 100-200℃ for 4-6 h. After cooling, hydrogen peroxide was added dropwise with stirring until the solution was clear and transparent. Then, the solution was concentrated by rotary evaporation, precipitated with ethanol, washed and dried under vacuum to obtain sulfur quantum dots.