Enzyme-photothermal synergistic composite hydrogel, preparation method and application thereof

Abstract

This application discloses a composite hydrogel based on enzyme-photothermal synergy, its preparation method, and its application, belonging to the field of biomedical materials technology. The composite hydrogel of this application comprises sodium carboxymethyl cellulose, dopamine, and glucose oxidase, with a mass ratio of sodium carboxymethyl cellulose to dopamine of (5~20):1; and a mass ratio of sodium carboxymethyl cellulose to glucose oxidase of (2000~500):1. This composite hydrogel introduces dopamine (DA) and glucose oxidase (GOx) into the system, possessing both enzyme-responsive activity and photothermal properties, exhibiting multiple functions such as excellent adhesion, self-healing properties, injectability, antibacterial activity, antioxidant properties, and promotion of wound healing.

Description

Technical Field

[0001] This application belongs to the field of medical biomaterials technology, and specifically relates to a composite hydrogel based on enzyme-photothermal synergy, its preparation method and its application. Background Technology

[0002] Diabetic wounds are a common chronic complication of diabetes. Due to the imbalance of the pathological microenvironment caused by hyperglycemia, they are characterized by slow healing, susceptibility to infection, and high recurrence rates, severely impacting patients' quality of life and increasing the medical burden. The core reason for their difficulty in healing lies in the interplay of multiple pathological factors: the high-glycemic environment provides suitable growth conditions for pathogens, easily inducing infection and forming antibiotic-resistant biofilms, continuously exacerbating the inflammatory response; simultaneously, hyperglycemia induces excessive accumulation of reactive oxygen species, causing oxidative stress damage, accompanied by the deposition of advanced glycation end products (AGEs), which damage collagen and growth factor activity, leading to stagnation of the healing process.

[0003] Sodium carboxymethyl cellulose hydrogel is an ideal dressing substrate due to its excellent biocompatibility and strong water absorption; however, traditional products have limited functionality and insufficient mechanical properties. Existing composite hydrogels are mostly simple mixtures of components, with unclear enzyme-photothermal synergistic mechanisms, and suffer from biocompatibility issues and complex preparation processes. Developing composite hydrogels that combine synergistic antibacterial, microenvironment regulation, and regeneration-promoting functions is key to overcoming the bottlenecks in diabetic wound treatment. Summary of the Invention

[0004] Purpose of the invention: This application aims to overcome the shortcomings of existing wound dressings, such as insufficient antibacterial effect, easy drug resistance, and single function, and to provide a composite hydrogel based on enzyme-photothermal synergy, which realizes the dual synergistic effect of enzyme-responsive antibacterial and near-infrared photothermal sterilization, while having good biocompatibility and repair-promoting ability, to meet the clinical treatment needs of diabetic infected wounds and chronic wounds.

[0005] Technical solution: This application provides a composite hydrogel based on enzyme-photothermal synergy, comprising sodium carboxymethyl cellulose, dopamine and glucose oxidase, wherein the mass ratio of sodium carboxymethyl cellulose to dopamine is (5~20):1; and the mass ratio of sodium carboxymethyl cellulose to glucose oxidase is (2000~500):1.

[0006] The composite hydrogel of this application solves the technical problems of low antibacterial efficiency, easy development of drug resistance, and inability to simultaneously achieve antibacterial and tissue repair effects in existing wound dressings. It exhibits a synergistic antibacterial effect against common clinical pathogens. Glucose secreted from the wound triggers glucose oxidase to catalyze the production of hydrogen peroxide. Bacterial catalase catalyzes the production of oxygen from the hydrogen peroxide, and the oxygen induces in-situ polymerization of dopamine to form polydopamine. Polydopamine kills bacteria through physical action and achieves photothermal sterilization under 808nm near-infrared light irradiation. The composite hydrogel of this application has excellent wound healing effects, and is particularly suitable for the repair and treatment of diabetic infected wounds and chronic wounds.

[0007] In some embodiments, the mass ratio of sodium carboxymethyl cellulose to dopamine is any value or a range of any two values ​​from 5:1, 10:1, and 20:1.

[0008] In some embodiments, the mass ratio of sodium carboxymethyl cellulose to glucose oxidase is any value or a range of any two values ​​from 2000:1, 1500:1, 1000:1, and 500:1.

[0009] In some embodiments, the sodium carboxymethyl cellulose is activated.

[0010] In some embodiments, the sodium carboxymethyl cellulose is activated by 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide.

[0011] The enzyme-photothermal synergistic composite hydrogel (CDG) of this application uses sodium carboxymethyl cellulose (CMC-Na) as a substrate and constructs a cross-linked network by activating carboxyl groups through EDC / NHS. The hydrogel system contains dopamine (DA) and glucose oxidase (GOx), which can generate polydopamine in situ within the wound microenvironment, forming a composite system with both enzyme-responsive activity and photothermal properties.

[0012] In some embodiments, the molar ratio of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) to N-hydroxysuccinimide (NHS) is (1~2):1.

[0013] In some embodiments, the concentration of EDC in the system is 5-20 mmol / L, and the concentration of NHS in the system is 5-15 mmol / L.

[0014] This application also provides a method for preparing the above-mentioned enzyme-photothermal synergistic composite hydrogel, including the following steps: (S1) Prepare a sodium carboxymethyl cellulose solution with a mass concentration of 1%~5%, and stir magnetically at room temperature until completely dissolved to obtain a CMC-Na-based solution; (S2) Add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide to the sodium carboxymethyl cellulose solution described in step (S1), and stir at 20℃~30℃ to activate the carboxyl groups for 0.5~2h. (S3) Add dopamine and glucose oxidase sequentially to the activated solution in step (S2), stir and mix evenly, and then adjust the pH of the system to 6.5~7.5; (S4) Allow the mixture obtained in step (S3) to stand for 2 to 6 hours to solidify and form a composite hydrogel, thus obtaining the target product.

[0015] In some embodiments, the mass concentration of the sodium carboxymethyl cellulose solution is 1% to 5%. The mass concentration of the sodium carboxymethyl cellulose solution can be any value or a range of any two of the following: 1%, 2%, 3%, 4%, and 5%.

[0016] In some embodiments, the amount of glucose oxidase added is 1-5 mg per 100 mL of sodium carboxymethyl cellulose solution.

[0017] In some embodiments, in step (S3), the reagent used to adjust the pH is a 1 mol / L NaOH solution or a 1 mol / L HCl solution, and the stirring rate is 100~300 r / min.

[0018] This application also provides the application of the above-mentioned enzyme-photothermal synergistic composite hydrogel or the enzyme-photothermal synergistic composite hydrogel prepared by the above-mentioned preparation method in antibacterial materials and antibacterial coatings for medical devices.

[0019] In some embodiments, the above-described enzyme-photothermal synergistic composite hydrogel is used in the preparation of wound dressings, which include wound dressings for diabetic infections and wound dressings for chronic wounds.

[0020] In some embodiments, the application further includes photothermal sterilization under 808nm near-infrared light irradiation.

[0021] In some embodiments, the composite hydrogel of this application exhibits good biocompatibility. Specifically, L929 mouse fibroblasts were used to evaluate the biocompatibility and cell migration ability of the hydrogel. The hydrogel extract was prepared at a ratio of 1g hydrogel to 10mL culture medium, extracted at 37°C in the dark for 24 hours, and used after filtration and sterilization. The experimental results showed that the hydrogel extract had no significant toxicity to L929 mouse fibroblasts and could significantly promote cell proliferation and migration.

[0022] Beneficial Effects: This application provides a composite hydrogel based on enzyme-photothermal synergy, its preparation method, and its application. The composite hydrogel of this application uses biocompatible and biodegradable CMC-Na as a substrate. A hydrogel network is constructed through an EDC / NHS activation system, and dopamine and glucose oxidase are introduced into the system. A mild reaction forms a composite hydrogel possessing both enzyme-responsive activity and photothermal properties. This method is simple, mild, green, and safe. The resulting hydrogel exhibits multiple functions, including excellent adhesion, self-healing, injectability, antibacterial properties, antioxidant properties, and promotion of wound healing. This application utilizes glucose in the wound microenvironment and catalase secreted by bacteria to trigger in-situ polymerization of dopamine to generate polydopamine, achieving synergistic bactericidal effects of enzyme-responsive antibacterial and near-infrared photothermal therapy, effectively avoiding antibiotic resistance problems. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The composite hydrogel prepared in the embodiments of this application is shown in (A) as a scanning electron microscope image of the hydrogel after freeze-drying, and (B) as an X-ray diffraction pattern of the hydrogel. Figure 2 A schematic diagram illustrating the self-healing properties of the CDG composite hydrogel prepared in this application; Figure 3 A schematic diagram showing the photothermal cycling stability of the CDG composite hydrogel prepared in this application; Figure 4 The results of the effect of different glucose oxidase contents on the photothermal temperature rise of the hydrogel prepared in this application; Figure 5 The quantitative statistical results of the effect of different glucose oxidase contents in the hydrogel prepared in this application on the corresponding temperature of the hydrogel; Figure 6 Scanning electron micrographs of Staphylococcus aureus and Escherichia coli after co-culturing with hydrogels; Figure 7 This is a schematic diagram of the antibacterial plate of the hydrogel of this application against Staphylococcus aureus and Escherichia coli; Figure 8 This is a schematic diagram of CCK-8 cell proliferation in the hydrogel of this application; Figure 9 This is a schematic diagram of cell viability and death staining of the hydrogel in this application; Figure 10The results of the cell scratch test for the hydrogel of this application; Figure 11 The results show the quantitative statistical results of cell migration rate of the hydrogel at 24h and 48h in this application. Detailed Implementation

[0025] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application. In addition, in the description of this application, the term "comprising" means "including but not limited to". The terms first, second, third, etc. are used only as illustrative purposes and do not impose numerical requirements or establish an order. Various embodiments of this application may exist in the form of a range; it should be understood that the description in the form of a range is only for convenience and conciseness and should not be construed as a hard limitation on the scope of this application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single values ​​within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which applies regardless of the range. Additionally, whenever a range of numbers is specified in this document, it means including any referenced numbers (fractions or integers) within the range referred to.

[0026] Example 1: Preparation of enzyme-photothermal synergistic composite hydrogel (CDG) This embodiment uses sodium carboxymethyl cellulose (CMC-Na) as the substrate. A cross-linked network is constructed by activating carboxyl groups using EDC / NHS, and dopamine and glucose oxidase (GOx) are introduced into the system. The specific preparation process is as follows: (1) Prepare a 2% sodium carboxymethyl cellulose (CMC-Na) solution: Weigh 2g of CMC-Na and dissolve it in 98mL of deionized water. Stir magnetically at room temperature until completely dissolved to obtain CMC-Na base solution.

[0027] (2) Add EDC and NHS to the CMC-Na base solution in step (1) to make the final concentration of EDC 10 mmol / L, the final concentration of NHS 8 mmol / L, and the molar ratio of EDC to NHS 1.25:1. Stir and activate at 25°C for 1 h.

[0028] (3) Add 0.2g of dopamine (DA) to the activated solution in step (2), the mass ratio of CMC-Na to DA is 10:1, then add 2mg of glucose oxidase (2mg per 100mL CMC-Na solution), stir and mix evenly, then adjust the pH of the system to 7.0 with 1mol / L NaOH solution, and stir at a rate of 200r / min.

[0029] (4) Let the mixture obtained in step (3) stand for 4 hours to react and solidify to form a composite hydrogel, thus obtaining the target product.

[0030] Comparative Example 1: Preparation of hydrogels (CMC) without dopamine and glucose oxidase The difference between this comparative example and Example 1 is that dopamine and glucose oxidase are not added in step (3), while the other preparation steps and parameters are the same as in Example 1.

[0031] Comparative Example 2: Preparation of hydrogels (CD) without glucose oxidase The difference between this comparative example and Example 1 is that glucose oxidase is not added in step (3), while the rest of the preparation steps and parameters are the same as in Example 1.

[0032] Figure 1 The corresponding figure (A) is a scanning electron microscope (SEM) image of the hydrogel after freeze-drying in Example 1 of this application. The enzyme-photothermal synergistic composite hydrogel has an interconnected three-dimensional porous network structure with uniform cross-linking and stable structure, and has good pore connectivity and material transport performance. Figure 1 Figure (B) shows the elemental analysis (EDS) of the enzyme-photothermal synergistic composite hydrogel prepared in Example 1. The results show that the hydrogel surface mainly contains characteristic elements such as C, O, N, Na, and S. The elements are evenly distributed without obvious enrichment or aggregation, indicating that dopamine and glucose oxidase have been successfully loaded and uniformly dispersed in the CMC-Na cross-linked network. The composite system has good compatibility and uniform structure, providing a stable structural basis for realizing the enzyme-photothermal synergistic function.

[0033] Example 2: Performance Testing (1) Self-healing performance test: To verify the self-healing performance of the CDG composite hydrogel of this application, the CDG composite hydrogel prepared in Example 1 of this application (stained red and brown respectively) was completely cut with a scalpel to form two independent halves of hydrogel; then the cuts of the two halves were precisely fitted together, and the self-healing process was observed under the conditions of room temperature, no additional pressure, and no external stimulation. The test results are as follows: Figure 2 As shown. From Figure 2The results show that after cutting, the cuts of the red and brown hydrogels are clear and the cross-sections are complete; after bonding, the interface of the hydrogels spontaneously fuses in a short time, and the red and brown parts are seamlessly combined to form a complete and uniform integrated hydrogel with no obvious interface traces; the healed hydrogel can withstand external forces such as lifting and bending by tweezers, and there is no cracking or falling off at the interface, and the mechanical properties are well restored.

[0034] (2) Photothermal stability test: The photothermal performance of the CDG composite hydrogel prepared in Example 1 of this application was characterized. The CDG composite hydrogel was irradiated three times using an 808nm near-infrared laser (each irradiation lasted 5 minutes, followed by natural cooling to room temperature), and the temperature changes were recorded. The results are as follows: Figure 3 As shown, during the three cycles, the highest heating temperature of the hydrogel remained stable at around 41°C without significant decay, indicating that the CDG composite hydrogel prepared in Example 1 of this application has excellent photothermal stability and can achieve repeatable and stable photothermal response, providing a guarantee for multiple antibacterial treatments.

[0035] (3) Antibacterial performance test: Scanning electron micrographs of bacteria co-cultured with hydrogel in different treatment groups, such as Figure 6 As shown in the figure, the bacteria in the Control group (control group) were intact, plump, smooth, and well-structured; the bacteria in the CMC group showed no obvious damage; the bacteria in the CD group showed slight shrinkage; the bacterial cell membranes in the CDG group were significantly ruptured, shrunken, and leaked contents; the bacterial structure in the CDG+NIR group (near-infrared light irradiation, 808nm) was completely destroyed, collapsed, and disintegrated, showing the most significant killing effect.

[0036] Using the plate coating method, Staphylococcus aureus ( S.aureus Gram-positive bacteria), Escherichia coli ( E. coli Using Gram-negative bacteria as model strains, the in vitro antibacterial properties of the CDG composite hydrogel prepared in Example 1 of this application, the CMC hydrogel prepared in Comparative Example 1, and the CD hydrogel prepared in Comparative Example 2 were evaluated. A blank control group (Control group) and a CDG combined with 808nm near-infrared light irradiation group (CDG+NIR group) were also set up. The test results are as follows: Figure 7 As shown. Staphylococcus aureus: In the blank control group and CMC group, the colony count grew densely; in the CD group, the colony count decreased significantly; in the CDG group, the colony count decreased further and significantly; and in the CDG+NIR group, there were almost no viable colonies, demonstrating a near-complete bactericidal effect. Escherichia coli: In the blank control group and CMC group, the colony count increased significantly; in the CD group, the colony count decreased significantly; in the CDG group, only a very small number of colonies remained; and in the CDG+NIR group, there were no visible viable bacteria, demonstrating excellent antibacterial effects.

[0037] Cell proliferation and biocompatibility testing: Figure 8To evaluate the cell compatibility of the hydrogel using the CCK-8 assay, L929 mouse fibroblasts were used as a model to detect cell proliferation activity on days 1, 3, and 5 after treatment with CMC, CD, and CDG hydrogel extracts. The results showed that the OD values ​​of all three cell groups increased continuously with prolonged culture time. The proliferation activity of the CDG group was slightly lower than that of the CMC and CD groups, but there was no statistically significant difference (p>0.05). This confirms that the CDG composite hydrogel prepared in this application has no significant cytotoxicity, excellent biocompatibility, and can support normal fibroblast proliferation, meeting the biosafety requirements for medical dressings.

[0038] Cell viability staining assay: Figure 9 To observe the viability of L929 cells, a Live / Dead fluorescence staining method was used, where green fluorescence represented live cells and red fluorescence represented dead cells. Results showed that all groups were dominated by green live cells, with only a very small number of red dead cells. The cells exhibited normal morphology and good spread. Compared with the Control group, no hydrogel groups showed significant cytotoxicity, indicating that this enzyme-photothermal synergistic hydrogel has excellent biocompatibility, effectively supports cell growth and proliferation, and meets the biosafety requirements for medical wound dressings.

[0039] Cell migration assay: The effect of hydrogel on the migration ability of L929 cells was evaluated using a scratch assay. A blank control group (Control group), CMC group, CD group, and CDG group were set up. The results are as follows: Figure 10 and Figure 11 As shown, Figure 10 Micrographs of a cell scratch assay. Figure 11 The results of quantitative statistical analysis of cell migration rates at 24 h and 48 h in the cell scratch assay were presented. Compared with the Control group, the CMC group slightly promoted cell migration, the CD group showed a more significant promoting effect, and the CDG group exhibited the strongest migration ability and the fastest scratch healing. The migration rates at both 24 h and 48 h were in the order of CDG > CD > CMC > Control, indicating that the enzyme-photothermal synergistic hydrogel can significantly promote fibroblast migration, accelerate the re-epithelialization process of the wound, and facilitate the rapid repair of diabetic infected wounds.

[0040] Example 3: Effect of different CMC-Na concentrations on hydrogel properties Following the preparation method of Example 1, CMC-Na solutions with mass concentrations of 1%, 2%, 3%, 4%, and 5% were prepared respectively. The remaining steps and parameters were the same as in Example 1. The effects of different CMC-Na concentrations on the mechanical properties and swelling properties of the hydrogel were investigated.

[0041] The results showed that as the CMC-Na concentration increased from 1% to 5%, the compressive modulus of the hydrogel gradually increased from 12.5 kPa to 45.8 kPa, while the swelling ratio gradually decreased from 850% to 420%. When the CMC-Na concentration was 2%–3%, the hydrogel exhibited both good mechanical strength (compressive modulus 22.3–28.6 kPa) and suitable swelling properties (swelling ratio 580%–650%). The results indicate that the overall performance is optimal within the CMC-Na concentration range of 2%–3%.

[0042] Example 4: Effect of different dopamine addition amounts on hydrogel properties Following the preparation method of Example 1, the mass ratio of CMC-Na to dopamine was set to 30:1, 20:1, 10:1, 5:1, and 2:1 (corresponding to dopamine addition amounts of 0.067g, 0.1g, 0.2g, 0.4g, and 1.0g, and CMC-Na of 2g each). The remaining steps and parameters were the same as in Example 1. The effects of different dopamine addition amounts on the adhesion and photothermal properties of the hydrogel were investigated.

[0043] The adhesion performance was tested using the lap shear method to determine the adhesion strength of the hydrogel to pigskin. The results showed that when the mass ratio of CMC-Na to dopamine was 30:1, the adhesion strength was 8.2 kPa. As the dopamine ratio increased, the adhesion strength gradually increased, reaching 32.5 kPa at a mass ratio of 5:1. Further increasing to 2:1, the adhesion strength reached 34.1 kPa, with the rate of increase slowing down. The photothermal performance test results showed that under 808 nm near-infrared light irradiation (1 W / cm², 10 min), the temperature rise values ​​of the hydrogels were as follows: 30:1 group (ΔT = 12.3℃), 20:1 group (ΔT = 18.6℃), 10:1 group (ΔT = 28.4℃), 5:1 group (ΔT = 35.2℃), and 2:1 group (ΔT = 36.1℃). Considering both adhesion and photothermal properties, the optimal mass ratio of CMC-Na to dopamine is 10:1 to 5:1.

[0044] Example 5: Effect of different glucose oxidase addition amounts on the enzyme response performance of hydrogels Following the preparation method of Example 1, the amount of glucose oxidase (GOx) added was set to 1 mg (CDG-1), 2 mg (CDG-2), and 4 mg (CDG-3) per 100 mL CMC-Na solution, with 2 g of CMC-Na for each case. The remaining steps and parameters were the same as in Example 1. The effect of different GOx addition amounts on the photothermal properties of the hydrogel was investigated. Figure 4 Photothermal heating-time curves of hydrogels with different GOx additions under 808 nm near-infrared light irradiation; Figure 5The highest temperatures reached by each group of hydrogels upon reaching equilibrium were quantitatively analyzed. With the increase of GOx addition in the system, the heating rate and final equilibrium temperature of the hydrogels under near-infrared irradiation gradually increased, showing a clear dose-dependent enhancement trend. This indicates that the enzymatic reaction involving GOx can effectively regulate and improve the photothermal conversion efficiency of the hydrogel, providing a temperature basis for achieving efficient enzyme-photothermal synergistic antibacterial activity.

[0045] The results above demonstrate that the composite hydrogel of this application uses biocompatible and biodegradable sodium carboxymethyl cellulose (CMC-Na) as the substrate. A hydrogel network is constructed using an activation system of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Dopamine (DA) and glucose oxidase (GOx) are introduced into the system, forming a composite hydrogel with both enzyme-responsive activity and photothermal properties through a mild reaction. The composite hydrogel prepared in this application, based on enzyme-photothermal synergy, possesses both enzyme-responsive activity and photothermal properties. Furthermore, through selection of components and proportions, the obtained hydrogel exhibits multiple functions including excellent adhesion, self-healing properties, injectability, antibacterial properties, antioxidant properties, and promotion of wound healing. Moreover, the preparation method of the composite hydrogel in this application is simple, mild, and environmentally friendly.

[0046] In the above embodiments, the descriptions of each embodiment have different focuses. For parts not described in detail in a certain embodiment, please refer to the relevant descriptions in other embodiments.

[0047] The above provides a detailed description of a composite hydrogel based on enzyme-photothermal synergy, its preparation method, and its application, as provided in the embodiments of this application. Specific examples have been used to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this application. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the ideas of this application. Therefore, the content of this specification should not be construed as a limitation of this application.

Claims

1. A composite hydrogel based on enzyme-photothermal synergistic effect, characterized in that, It includes sodium carboxymethyl cellulose, dopamine, and glucose oxidase, wherein the mass ratio of sodium carboxymethyl cellulose to dopamine is (5~20):1; and the mass ratio of sodium carboxymethyl cellulose to glucose oxidase is (2000~500):

1.

2. The composite hydrogel based on enzyme-photothermal synergy according to claim 1, characterized in that, The sodium carboxymethyl cellulose is activated.

3. The composite hydrogel based on enzyme-photothermal synergy according to claim 2, characterized in that, The sodium carboxymethyl cellulose is activated by 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide.

4. The composite hydrogel based on enzyme-photothermal synergy according to claim 3, characterized in that, The molar ratio of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride to N-hydroxysuccinimide is (1~2):

1.

5. The method for preparing the composite hydrogel based on enzyme-photothermal synergy according to claim 1, characterized in that, Includes the following steps: (S1) Prepare a sodium carboxymethyl cellulose solution with a mass concentration of 1%~5%, and stir magnetically at room temperature until completely dissolved to obtain a CMC-Na-based solution; (S2) Add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide to the sodium carboxymethyl cellulose solution described in step (S1), and stir at 20℃~30℃ to activate the carboxyl groups for 0.5~2h. (S3) Add dopamine and glucose oxidase sequentially to the activated solution in step (S2), stir and mix evenly, and then adjust the pH of the system to 6.5~7.5; (S4) Allow the mixture obtained in step (S3) to stand for 2 to 6 hours to solidify and form a composite hydrogel, thus obtaining the target product.

6. The method for preparing the composite hydrogel based on enzyme-photothermal synergy according to claim 5, characterized in that, The mass concentration of the sodium carboxymethyl cellulose solution is 1% to 5%.

7. The method for preparing the composite hydrogel based on enzyme-photothermal synergy according to claim 5, characterized in that, The amount of glucose oxidase added is 1-5 mg per 100 mL of sodium carboxymethyl cellulose solution.

8. The application of a composite hydrogel based on enzyme-photothermal synergy as described in any one of claims 1 to 4, or a composite hydrogel based on enzyme-photothermal synergy prepared by the preparation method as described in any one of claims 5 to 7, in antibacterial materials and antibacterial coatings for medical devices.

9. The application according to claim 8, characterized in that, The application of the enzyme-photothermal synergistic composite hydrogel in the preparation of wound dressings, including wound dressings for diabetic infections and wound dressings for chronic wounds.

10. The application according to claim 8, characterized in that, The application also includes photothermal sterilization under 808nm near-infrared light irradiation.

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