Stimuli-responsive hydrogel for tissue damage repair and preparation method thereof

Abstract

The present application relates to a kind of tissue damage repair with stimulus-responsive hydrogel and its preparation method, the hydrogel includes the following weight parts of component: 6-8 parts of modified isocyanato methyl methacrylate, 2-4 parts of modified chitosan, 0.2-0.3 parts of N,N '-methylene bisacrylamide, 0.1-0.2 parts of ammonium persulfate, 3-5 parts of deionized water;Modified isocyanato methyl methacrylate, modified chitosan is dissolved in deionized water, is stirred uniformly, is prepared into solution, N,N '-methylene bisacrylamide and ammonium persulfate are added, and are stirred uniformly with magnetic stirrer, mixed solution is transferred to closed reaction vessel, nitrogen is imported 10-15min, the reaction vessel is placed in 60-80 DEG C water bath, reaction 30-60min, obtain tissue damage repair with stimulus-responsive hydrogel.The present application hydrogel has multi-stimulus response controlled release mechanism, and dynamic network self-healing performance is good.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a stimulus-responsive hydrogel for tissue damage repair and its preparation method. Background Technology

[0002] Hydrogels are polymeric materials with a three-dimensional network structure. Their unique structure endows them with high hydrophilicity, biocompatibility, and soft physical properties similar to biological tissues. Their network structure can mimic the natural extracellular matrix, providing a microenvironment for cell adhesion, proliferation, and tissue regeneration. Therefore, they are widely used in soft / hard tissue injuries such as trauma and postoperative defects. However, conventional hydrogels only provide physical support and lack active regulation capabilities, making them difficult to respond to changes in the injury microenvironment. Therefore, avoiding this phenomenon is key to solving the problem. For example, patent CN119931096A discloses a method for preparing a low-temperature resistant, high-water-retention, core-shell structured hydrogel. The hydrogel prepared by this invention is green and pollution-free, using polysaccharides, alcohols, and aqueous solutions as raw materials. A shell can be formed on the surface of the hydrogel due to cross-linking, constructing a core-shell structure that improves its water retention and mechanical properties. However, it lacks stimulus-responsive controlled-release function, and the dynamic network self-healing performance needs improvement. Summary of the Invention

[0003] To address the shortcomings of existing technologies, this invention provides a stimulus-responsive hydrogel for tissue damage repair and its preparation method. The hydrogel of this invention has a multi-stimulus-responsive controlled-release mechanism and good dynamic network self-healing properties.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] A stimulus-responsive hydrogel for tissue damage repair comprises the following components by weight: 6-8 parts by weight of modified isocyanate methacrylate, 2-4 parts by weight of modified chitosan, 0.2-0.3 parts by weight of N,N'-methylenebisacrylamide, 0.1-0.2 parts by weight of ammonium persulfate, and 3-5 parts by weight of deionized water;

[0006] The preparation method of the modified isocyanate methacrylate is as follows:

[0007] Step 1: Under inert gas protection, 6-aminopyridine-2-carboxylic acid and triethylamine are added to an organic solvent and stirred evenly in an ice-water bath. Then, isocyanate methacrylate is added dropwise to react. After the reaction is completed, intermediate 1 is obtained through post-treatment.

[0008] Step 2: Under inert gas protection, add intermediate 1,3-aminophenylboronic acid to dimethyl sulfoxide solvent, stir and mix, then add N-hydroxysuccinimide condensing agent to react. After the reaction is completed, post-treatment is performed to obtain modified isocyanate methacrylate.

[0009] The modified chitosan is prepared by:

[0010] S1: Add 4-methylumbelliferone and 3-carboxybenzaldehyde to the reactor, stir until homogeneous, then add concentrated sulfuric acid catalyst to react. After the reaction is completed, the intermediate 2 is obtained through post-treatment.

[0011] S2: Swell the chitosan, then add intermediate 2, stir and mix, adjust the pH, stir the reaction, and after the reaction is completed, obtain modified chitosan through post-processing.

[0012] Furthermore, in step one, the organic solvent is dichloromethane, and the ratio of dichloromethane, 6-aminopyridine-2-carboxylic acid, triethylamine, and isocyanate methacrylate is 120-130mL: 3.45-3.48g: 5.08-5.11g: 5.3-5.5mL.

[0013] Furthermore, in step two, the ratio of dimethyl sulfoxide, intermediate 1,3-aminophenylboronic acid, and N-hydroxysuccinimide is 18-20 mL: 5.4-5.6 g: 2.81-2.84 g: 2.15-2.18 g.

[0014] Furthermore, the post-processing in step one includes rotary evaporation, pH adjustment, filtration, washing, and drying.

[0015] Furthermore, the post-processing in step two includes filtration, washing, column chromatography purification, and drying.

[0016] Further, in S1, the ratio of 4-methylumbelliferone, 3-carboxybenzaldehyde, and concentrated sulfuric acid is 3.52-3.56 g: 3.11-3.15 g: 0.03-0.05 mL.

[0017] Furthermore, in S2, the ratio of chitosan, acetic acid, and intermediate 2 is 3.11-3.15g: 18-20mL: 3.62-3.65g.

[0018] Furthermore, the post-processing in S1 includes cooling to room temperature, washing and drying, filtering, and distillation.

[0019] Furthermore, the post-processing in S2 includes filtration, washing, and drying.

[0020] The present invention also provides a method for preparing the above-mentioned stimulus-responsive hydrogel for tissue damage repair. The method for preparing the stimulus-responsive hydrogel for tissue damage repair is as follows: modified isocyanate methacrylate and modified chitosan are dissolved in deionized water and ultrasonically treated. Then, N,N'-methylenebisacrylamide and ammonium persulfate are added and stirred evenly to obtain a mixed solution. The mixed solution is transferred to a sealed reaction vessel, nitrogen gas is introduced for 10-15 min, and the reaction vessel is placed in a water bath at 60-80℃ for 30-60 min to obtain the stimulus-responsive hydrogel for tissue damage repair.

[0021] The beneficial effects of this invention are as follows:

[0022] In stimulus-responsive hydrogels for tissue damage repair, the combined use of ester groups, phenylboronic acid groups, and Schiff base groups can construct a multi-stimulus-responsive, dynamically adaptive intelligent repair system, achieving precise spatiotemporal controlled release and functional adaptation through synergistic effects. Ester groups can stimulate a response under enzyme overexpression or alkaline conditions, releasing hydrophobic drugs through hydrolysis. Phenylboronic acid groups can stimulate a response under alkaline or high-glucose conditions, releasing metabolically modulating drugs through hydrolysis. Schiff base groups can stimulate a response in the inflammatory microenvironment, releasing antimicrobial peptides, anti-inflammatory drugs, and other medications through hydrolysis. Furthermore, after external force damage, the Schiff base and phenylboronic acid ester bonds preferentially recombine, providing immediate repair, while the covalent bonds of the ester groups maintain the network framework, preventing complete gel disintegration, thus giving the hydrogel excellent dynamic network self-healing properties. Attached Figure Description

[0023] Figure 1 This is the 1H NMR spectrum of intermediate 1 from Example 1;

[0024] Figure 2 This is the 1H NMR spectrum of the modified isocyanate methacrylate from Example 1;

[0025] Figure 3 This is the 1H NMR spectrum of intermediate 2 from Example 1;

[0026] Figure 4 This is the 1H NMR spectrum of the modified chitosan from Example 1. Detailed Implementation

[0027] To better understand the above technical solutions, the following detailed description will be provided in conjunction with the accompanying drawings and specific embodiments. To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] Unless otherwise specified, the experimental methods described in the examples are conventional methods; unless otherwise specified, the reagents and materials are commercially available. Chitosan: 90% deacetylated, manufactured by Adamas. Example 1

[0029] (1) Under nitrogen protection, 3.45 g of 6-aminopyridine-2-carboxylic acid and 5.08 g of triethylamine were added to 120 mL of dichloromethane solvent. The mixture was stirred evenly at 0 °C, and then 5.3 mL of isocyanate methacrylate was added dropwise. The reaction was carried out at room temperature for 90 h. After the reaction was completed, the mixture was rotary evaporated, the pH was adjusted to 2, filtered, washed and dried to obtain intermediate 1. The 1H NMR spectrum of intermediate 1 is shown below. Figure 1 As shown; the reaction process is as follows:

[0030]

[0031] (2) Under nitrogen protection, 5.4 g of intermediate 1 and 2.81 g of 3-aminophenylboronic acid were added to 18 mL of dimethyl sulfoxide solvent and stirred. Then, 2.15 g of N-hydroxysuccinimide condensing agent was added, and the mixture was reacted at 35 °C for 10 h. After the reaction was completed, the mixture was filtered, washed, purified by column chromatography, and dried to obtain modified isocyanate methacrylate. The 1H NMR spectrum of modified isocyanate methacrylate is shown below. Figure 2 As shown; the reaction process is as follows:

[0032]

[0033] (3) Add 3.52 g of 4-methylumbelliferone and 3.11 g of 3-carboxybenzaldehyde to 20 mL of dichloromethane solvent, stir well, then add 0.03 mL of concentrated sulfuric acid catalyst, and react at 80 °C for 5 h. After the reaction is complete, cool to room temperature, wash and dry, filter, and distill to obtain intermediate 2. The 1H NMR spectrum of intermediate 2 is as follows: Figure 3 As shown; the reaction process is as follows:

[0034]

[0035] (4) 3.11 g of chitosan was swollen in 18 mL of 3% acetic acid solution for 1 h, and then 3.62 g of intermediate 2 was added dropwise. The mixture was stirred and the pH was adjusted to neutral. The mixture was magnetically stirred at 50 °C for 4 h. After the reaction was completed, the mixture was filtered, washed and dried to obtain modified chitosan. The 1H NMR spectrum of the modified chitosan is shown below. Figure 4 As shown; the reaction process is as follows:

[0036]

[0037] (5) Dissolve 6 parts by weight of modified isocyanate methacrylate and 2 parts by weight of modified chitosan in 3 parts by weight of deionized water, stir evenly to prepare a solution, add 0.2 parts by weight of N,N'-methylenebisacrylamide and 0.1 parts by weight of ammonium persulfate, stir evenly with a magnetic stirrer, transfer the mixed solution to a sealed reaction vessel, purge with nitrogen for 10 min, place the reaction vessel in a water bath at 60°C, and react for 30 min to obtain a stimulus-responsive hydrogel for tissue damage repair. Example 2

[0038] (1) Under nitrogen protection, 3.48 g of 6-aminopyridine-2-carboxylic acid and 5.11 g of triethylamine were added to 130 mL of dichloromethane solvent and stirred evenly at 5 °C. Then, 5.5 mL of isocyanate methacrylate was added dropwise and the reaction was carried out at room temperature for 100 h. After the reaction was completed, the mixture was rotary evaporated, the pH was adjusted to 2, filtered, washed and dried to obtain intermediate 1.

[0039] (2) Under nitrogen protection, 5.6 g of intermediate 1 and 2.84 g of 3-aminophenylboronic acid were added to 20 mL of dimethyl sulfoxide solvent and stirred. Then, 2.18 g of N-hydroxysuccinimide condensing agent was added and reacted at 40 °C for 12 h. After the reaction was completed, the mixture was filtered, washed, purified by column chromatography, and dried to obtain modified ethyl isocyanate methacrylate.

[0040] (3) Add 3.56 g of 4-methylumbelliferone and 3.15 g of 3-carboxybenzaldehyde to 25 mL of dichloromethane solvent, stir evenly, then add 0.05 mL of concentrated sulfuric acid catalyst, react at 100 °C for 8 h, after the reaction is completed, cool to room temperature, wash and dry, filter, distill to obtain intermediate 2.

[0041] (4) 3.15g of chitosan was swollen in 20mL of 3% acetic acid solution for 2h, and then 3.65g of intermediate 2 was added dropwise. The mixture was stirred and the pH was adjusted to neutral. The mixture was magnetically stirred at 60℃ for 6h. After the reaction was completed, the mixture was filtered, washed and dried to obtain modified chitosan.

[0042] (5) Dissolve 8 parts by weight of modified isocyanate methacrylate and 4 parts by weight of modified chitosan in 5 parts by weight of deionized water, stir evenly to prepare a solution of a certain concentration, add 0.3 parts by weight of N,N'-methylenebisacrylamide and 0.2 parts by weight of ammonium persulfate, stir evenly with a magnetic stirrer, transfer the mixed solution to a sealed reaction vessel, purge with nitrogen for 15 min, place the reaction vessel in a water bath at 80°C, and react for 60 min to obtain a stimulus-responsive hydrogel for tissue damage repair. Example 3

[0043] (1) Under nitrogen protection, 3.46 g of 6-aminopyridine-2-carboxylic acid and 5.1 g of triethylamine were added to 125 mL of dichloromethane solvent and stirred evenly at 2 °C. Then, 5.4 mL of isocyanate methacrylate was added dropwise and reacted at room temperature for 96 h. After the reaction was completed, the mixture was rotary evaporated, the pH was adjusted to 2, filtered, washed and dried to obtain intermediate 1.

[0044] (2) Under nitrogen protection, 5.5 g of intermediate 1 and 2.83 g of 3-aminophenylboronic acid were added to 19 mL of dimethyl sulfoxide solvent and stirred. Then, 2.16 g of N-hydroxysuccinimide condensing agent was added and reacted at 38 °C for 11 h. After the reaction was completed, the mixture was filtered, washed, purified by column chromatography, and dried to obtain modified ethyl isocyanate methacrylate.

[0045] (3) Add 3.54 g of 4-methylumbelliferone and 3.13 g of 3-carboxybenzaldehyde to 22 mL of dichloromethane solvent, stir evenly, then add 0.04 mL of concentrated sulfuric acid catalyst, react at 90 °C for 6 h, after the reaction is completed, cool to room temperature, wash and dry, filter, distill to obtain intermediate 2;

[0046] (4) 3.13g of chitosan was swollen in 19mL of 3% acetic acid solution for 1h, and then 3.63g of intermediate 2 was added dropwise. The mixture was stirred and the pH was adjusted to neutral. The mixture was magnetically stirred at 55℃ for 5h. After the reaction was completed, the mixture was filtered, washed and dried to obtain modified chitosan.

[0047] (5) Dissolve 7 parts by weight of modified isocyanate methacrylate and 3 parts by weight of modified chitosan in 4 parts by weight of deionized water, stir evenly to prepare a solution of a certain concentration, add 0.2 parts by weight of N,N'-methylenebisacrylamide and 0.2 parts by weight of ammonium persulfate, stir evenly with a magnetic stirrer, transfer the mixed solution to a sealed reaction vessel, purge with nitrogen for 12 min, place the reaction vessel in a water bath at 70°C, and react for 45 min to obtain a stimulus-responsive hydrogel for tissue damage repair. Example 4

[0048] (1) Under nitrogen protection, 3.46 g of 6-aminopyridine-2-carboxylic acid and 5.09 g of triethylamine were added to 122 mL of dichloromethane solvent and stirred evenly at 0 °C. Then, 5.4 mL of isocyanate methacrylate was added dropwise and the reaction was carried out at room temperature for 92 h. After the reaction was completed, the mixture was rotary evaporated, the pH was adjusted to 2, filtered, washed and dried to obtain intermediate 1.

[0049] (2) Under nitrogen protection, 5.5 g of intermediate 1 and 2.82 g of 3-aminophenylboronic acid were added to 18 mL of dimethyl sulfoxide solvent and stirred. Then, 2.16 g of N-hydroxysuccinimide condensing agent was added and reacted at 35 °C for 10 h. After the reaction was completed, the mixture was filtered, washed, purified by column chromatography, and dried to obtain modified ethyl isocyanate methacrylate.

[0050] (3) Add 3.54 g of 4-methylumbelliferone and 3.12 g of 3-carboxybenzaldehyde to 20 mL of dichloromethane solvent, stir evenly, then add 0.03 mL of concentrated sulfuric acid catalyst, react at 85 °C for 5 h, after the reaction is completed, cool to room temperature, wash and dry, filter, distill to obtain intermediate 2;

[0051] (4) 3.12g of chitosan was swollen in 18mL of 3% acetic acid solution for 1h, and then 3.63g of intermediate 2 was added dropwise. The mixture was stirred and the pH was adjusted to neutral. The mixture was magnetically stirred at 50℃ for 5h. After the reaction was completed, the mixture was filtered, washed and dried to obtain modified chitosan.

[0052] (5) Dissolve 6 parts by weight of modified isocyanate methacrylate and 3 parts by weight of modified chitosan in 3 parts by weight of deionized water, stir evenly to prepare a solution of a certain concentration, add 0.2 parts by weight of N,N'-methylenebisacrylamide and 0.2 parts by weight of ammonium persulfate, stir evenly with a magnetic stirrer, transfer the mixed solution to a sealed reaction vessel, purge with nitrogen for 10 min, place the reaction vessel in a water bath at 65°C, and react for 40 min to obtain a stimulus-responsive hydrogel for tissue damage repair. Example 5

[0053] (1) Under nitrogen protection, 3.47 g of 6-aminopyridine-2-carboxylic acid and 5.1 g of triethylamine were added to 128 mL of dichloromethane solvent and stirred evenly at 5 °C. Then, 5.4 mL of isocyanate methacrylate was added dropwise and the reaction was carried out at room temperature for 96 h. After the reaction was completed, the mixture was rotary evaporated, the pH was adjusted to 2, filtered, washed and dried to obtain intermediate 1.

[0054] (2) Under nitrogen protection, 5.5 g of intermediate 1 and 2.83 g of 3-aminophenylboronic acid were added to 20 mL of dimethyl sulfoxide solvent and stirred. Then, 2.18 g of N-hydroxysuccinimide condensing agent was added and reacted at 38 °C for 12 h. After the reaction was completed, the mixture was filtered, washed, purified by column chromatography, and dried to obtain modified ethyl isocyanate methacrylate.

[0055] (3) Add 3.55g of 4-methylumbelliferone and 3.14g of 3-carboxybenzaldehyde to 25mL of dichloromethane solvent, stir evenly, then add 0.05mL of concentrated sulfuric acid catalyst, and react at 95℃ for 8h. After the reaction is completed, cool to room temperature, wash and dry, filter, and distill to obtain intermediate 2.

[0056] (4) 3.14 g of chitosan was swollen in 20 mL of 3% acetic acid solution for 2 h, and then 3.65 g of intermediate 2 was added dropwise. The mixture was stirred and the pH was adjusted to neutral. The mixture was magnetically stirred at 60 °C for 6 h. After the reaction was completed, the mixture was filtered, washed and dried to obtain modified chitosan.

[0057] (5) Dissolve 7 parts by weight of modified isocyanate methacrylate and 4 parts by weight of modified chitosan in 4 parts by weight of deionized water, stir evenly to prepare a solution of a certain concentration, add 0.3 parts by weight of N,N'-methylenebisacrylamide and 0.2 parts by weight of ammonium persulfate, stir evenly with a magnetic stirrer, transfer the mixed solution to a sealed reaction vessel, purge with nitrogen for 15 min, place the reaction vessel in a water bath at 75°C, and react for 50 min to obtain a stimulus-responsive hydrogel for tissue damage repair.

[0058] Comparative Example 1

[0059] The difference between this comparative example and Example 5 is that intermediate 1 in (1) is used instead of modified ethyl isocyanate methacrylate.

[0060] Comparative Example 2

[0061] The difference between this comparative example and Example 5 is that chitosan was used instead of modified chitosan.

[0062] Stimulus-Response Controlled Release Function Test:

[0063] Hydrogel samples prepared in Examples 1-5 and Comparative Examples 1-2 were immersed in buffer solutions with different pH conditions (pH 5.0 simulating inflammation, pH 7.4 for normal tissue, and pH 8.0 for diabetic wounds). Samples were taken periodically to determine the drug release amount of each hydrogel sample. The results are shown in Table 1.

[0064] Table 1 pH-responsive drug release test

[0065]

[0066] Matrix metalloproteinases (MMPs) were added to a buffer solution at pH 7.4. The hydrogel samples prepared in Examples 1-5 and Comparative Examples 1-2 were immersed in the buffer solution containing MMPs. Samples were taken periodically to determine the drug release amount of each hydrogel sample. The results are shown in Table 2.

[0067] Table 2 Enzyme-responsive drug release test

[0068]

[0069] Different concentrations of glucose (5 mM, 10 mM, 20 mM) were added to a buffer solution at pH 7.4. The hydrogel samples prepared in Examples 1-5 and Comparative Examples 1-2 were immersed in buffer solutions containing different glucose concentrations. Samples were taken periodically to determine the drug release amount of each hydrogel sample. The results are shown in Table 3.

[0070] Table 3. Glucose-responsive drug release test

[0071]

[0072] As can be seen from Tables 1, 2 and 3, the hydrogels prepared in Examples 1-5 of this invention have a multi-stimulus response controlled release mechanism, among which the hydrogel sample prepared in Example 2 has the best performance.

[0073] Self-healing performance test:

[0074] The hydrogels prepared in Examples 1-5 and Comparative Examples 1-2 were subjected to self-healing performance tests in an enzyme-free and sugar-free environment at pH 7.4, according to ISO 6721-10:2015 "Standard for dynamic mechanical property testing". The results are shown in Table 4.

[0075] Table 4 Self-healing performance test

[0076]

[0077] As can be seen from Table 4, the hydrogels prepared in Examples 1-5 of the present invention have good dynamic network self-healing properties, among which the hydrogel sample prepared in Example 2 has the best self-healing properties.

[0078] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0079] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A stimulus-responsive hydrogel for tissue damage repair, characterized in that, It includes the following components by weight: 6-8 parts by weight of modified isocyanate methacrylate, 2-4 parts by weight of modified chitosan, 0.2-0.3 parts by weight of N,N'-methylenebisacrylamide, 0.1-0.2 parts by weight of ammonium persulfate, and 3-5 parts by weight of deionized water; The preparation method of the modified isocyanate methacrylate is as follows: Step 1: Under inert gas protection, 6-aminopyridine-2-carboxylic acid and triethylamine are added to an organic solvent and stirred evenly in an ice-water bath. Then, isocyanate methacrylate is added dropwise to react. After the reaction is completed, intermediate 1 is obtained through post-treatment. Step 2: Under inert gas protection, add intermediate 1,3-aminophenylboronic acid to dimethyl sulfoxide solvent, stir and mix, then add N-hydroxysuccinimide condensing agent to react. After the reaction is completed, post-treatment is performed to obtain modified isocyanate methacrylate. The modified chitosan is prepared by: S1: Add 4-methylumbelliferone and 3-carboxybenzaldehyde to the reactor, stir until homogeneous, then add concentrated sulfuric acid catalyst to react. After the reaction is completed, the intermediate 2 is obtained through post-treatment. S2: Swell the chitosan, then add intermediate 2, stir and mix, adjust the pH, stir the reaction, and after the reaction is completed, obtain modified chitosan through post-processing.

2. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, In step one, the organic solvent used is dichloromethane, and the ratio of dichloromethane, 6-aminopyridine-2-carboxylic acid, triethylamine, and isocyanate methacrylate is 120-130mL: 3.45-3.48g: 5.08-5.11g: 5.3-5.5mL.

3. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, In step two, the ratio of dimethyl sulfoxide, intermediate 1,3-aminophenylboronic acid, and N-hydroxysuccinimide is 18-20 mL. 5.4-5.6g: 2.81-2.84g: 2.15-2.18g.

4. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, The post-processing in step one includes rotary evaporation, pH adjustment, filtration, washing, and drying.

5. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, The post-processing in step two includes filtration, washing, column chromatography purification, and drying.

6. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, In S1, the ratio of 4-methylumbelliferone, 3-carboxybenzaldehyde, and concentrated sulfuric acid is 3.52-3.56 g: 3.11-3.15 g: 0.03-0.05 mL.

7. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, In step S2, chitosan is swollen in a 3% acetic acid solution; the ratio of chitosan, acetic acid solution, and intermediate 2 is 3.11-3.15g: 18-20mL: 3.62-3.65g.

8. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, The post-processing in S1 includes cooling to room temperature, washing and drying, filtering, and distillation.

9. The stimulus-responsive hydrogel for tissue damage repair according to claim 1, characterized in that, The post-processing in S2 includes filtration, washing, and drying.

10. A method for preparing a stimulus-responsive hydrogel for tissue damage repair according to any one of claims 1-9, characterized in that, The method for preparing the stimulus-responsive hydrogel for tissue damage repair is as follows: Modified isocyanate methacrylate and modified chitosan are dissolved in deionized water and ultrasonically treated. Then, N,N'-methylenebisacrylamide and ammonium persulfate are added and stirred evenly to obtain a mixed solution. The mixed solution is transferred to a sealed reaction vessel, nitrogen gas is introduced for 10-15 minutes, and the reaction vessel is placed in a water bath at 60-80°C for 30-60 minutes to obtain the stimulus-responsive hydrogel for tissue damage repair.

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