Antibacterial hydrogel with wet surface adhesion

Abstract

The application discloses an antibacterial hydrogel with wet surface adhesion, which comprises oxidized hyaluronic acid, carboxymethyl chitosan and polyvinylpyrrolidone; aldehyde groups in the oxidized hyaluronic acid and amino groups in the carboxymethyl chitosan are crosslinked to form Schiff base bonds; and carbonyl groups in the polyvinylpyrrolidone molecules form hydrogen bonds with hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively; and the antibacterial hydrogel is obtained through a Schiff base bond-hydrogen bond synergistic double-network crosslinking form. The application introduces a synergistic mechanism of Schiff base bonds and hydrogen bonds, so that the hydrogel has excellent mechanical properties, antibacterial properties and wet surface adhesion.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, and particularly relates to an antibacterial hydrogel with wet surface adhesion. BACKGROUND

[0002] Antibacterial hydrogels, as a kind of water-based material with significant antibacterial activity, have attracted widespread attention in the biomedical field in recent years. Hydrogels have a hydrated structure similar to biological tissues, and can maintain a high water content in a physiological environment, thereby simulating the properties of in vivo tissues. They are usually formed by cross-linking of natural or synthetic high molecular materials, and have good biocompatibility, flexibility, biodegradability and high hydrophilicity, which makes them have important application potential in the fields of wound dressings, drug delivery systems, tissue engineering and cell culture. Antibacterial hydrogels not only play a key role in traditional medical fields such as wound repair and tissue engineering, but also play a key role in modern antibacterial therapy, especially in the face of the increasingly serious global problem of antibiotic resistance, as a substitute material.

[0003] With the increasing problem of antibiotic resistance, traditional antibacterial treatment methods are facing increasing challenges. The overuse of antibiotics has led to the emergence of multiple drug-resistant bacteria (MDR), which not only have resistance to traditional antibiotics, but also can cause serious hospital-acquired infections. According to the data of the World Health Organization (WHO), antibiotic resistance causes millions of deaths worldwide each year, and this number is expected to continue to rise. In order to address this problem, researchers have made a lot of efforts in developing materials to replace antibiotics. Antibacterial hydrogels, as a new type of therapeutic material, have become an important means to cope with antibiotic resistance because they can release antibacterial agents locally through physical or chemical means, enhance local immune response and directly inhibit bacterial growth.

[0004] Carboxymethyl chitosan (CMC) is a water-soluble derivative obtained by carboxymethylation of chitosan, which has the basic properties of chitosan, such as excellent biocompatibility, non-toxicity and good biodegradability. Chitosan, as a natural polymer, has been widely used in the research of biomedical materials. However, the solubility of chitosan is poor, especially in water, which limits its widespread use in some applications. In order to overcome this shortcoming, researchers have introduced hydrophilic carboxymethyl groups through chemical modification methods (such as carboxymethylation), which significantly improve its water solubility and biocompatibility, and enhance its performance in medical applications.

[0005] The water-solubility and biocompatibility of CMC make it an important material for preparing antibacterial hydrogels. In the preparation process of hydrogels, CMC can be used together with other materials through physical cross-linking or chemical cross-linking to enhance the mechanical properties and antibacterial activity of hydrogels. The carboxyl groups (-COOH) of CMC not only provide strong hydrophilicity, but also form cross-linking reactions with other molecules having active groups (such as amino groups, aldehyde groups, etc.), thereby enhancing the stability of the hydrogel. In addition, CMC itself has certain natural antibacterial properties, which can inhibit the growth and reproduction of bacteria. Studies have shown that CMC hydrogels can exert antibacterial effects through their hydrophilic environment, interaction with bacterial cell walls, and release of active substances.

[0006] In the preparation of antibacterial hydrogels, commonly used cross-linking agents such as glutaraldehyde (GA) or ultraviolet light irradiation cross-linking can effectively cross-link the hydrogels and enhance their mechanical properties, but these cross-linking agents often have certain toxicity and can cause performance degradation of the hydrogels after long-term use. Glutaraldehyde, as a traditional cross-linking agent, is known to have certain cytotoxicity, which can have adverse effects on living organisms. In order to overcome these problems, in recent years, more and more research has focused on non-toxic, low-cost and environmentally friendly natural cross-linking agents. For example, by introducing Schiff base reactions (such as the reaction of aldehyde groups with amino groups), a new cross-linking strategy has been developed, which can not only avoid the toxicity problems caused by traditional chemical cross-linking agents, but also effectively improve the biocompatibility of hydrogels. In addition, Schiff base compounds also have good antibacterial and antifungal effects.

[0007] However, despite the great progress in antibacterial performance and biodegradability of antibacterial hydrogels, the adhesion of traditional hydrogel materials on wet surfaces (such as bleeding wounds, wound surfaces, etc.) remains a challenge. Especially in the fields of medical devices, wound dressings and tissue engineering. The wound surface often has a wet environment with bleeding, exudate, etc. The adhesion ability of the hydrogel in this environment directly determines whether it can effectively seal the wound, maintain the antibacterial effect, promote healing and prevent secondary infection. Traditional wound dressings such as gauze and tape, although they can temporarily cover the wound, often lack good adhesion to wet surfaces, and cannot effectively maintain the stability of the hydrogel on the wound surface. In addition, the wound surface often contains body fluids or blood, and the hydrogel is easily swollen or hydrated in these wet environments, causing changes in the surface tension of the hydrogel, thereby losing effective adhesion. SUMMARY

[0008] The present application aims to overcome the above-mentioned deficiencies and provides an antibacterial hydrogel with wet surface adhesion. By introducing a synergistic mechanism of Schiff base bonds and hydrogen bonds, the hydrogel simultaneously has excellent mechanical properties, antibacterial properties and wet surface adhesion.

[0009] To achieve the above object, the present application provides the following technical solutions: An antibacterial hydrogel with wet surface adhesion, comprising oxidized hyaluronic acid, carboxymethyl chitosan and polyvinylpyrrolidone, the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan are crosslinked to form a Schiff base bond, and the carbonyl groups in the polyvinylpyrrolidone molecules form hydrogen bonds with the hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively, and the antibacterial hydrogel is obtained through the Schiff base bond-hydrogen bond synergistic double network crosslinking form, and the general structure is as follows:

[0010]

[0011] wherein 60 < n1 < 300, 20 < n2 < 110, 100 < n3 < 1500, the molding temperature in the crosslinking reaction is 25-55℃, the molding humidity is 40-60% R.H., and the molding time is 24-48 hours.

[0012] As an improvement, the preparation of the antibacterial hydrogel comprises the following steps:

[0013] S1: Dissolving hyaluronic acid in water to prepare a hyaluronic acid aqueous solution, adding sodium periodate and stirring to form oxidized hyaluronic acid, purifying by dialysis to obtain an oxidized hyaluronic acid solution;

[0014] S2: Adding carboxymethyl chitosan to deionized water or hydrochloric acid solution, stirring until completely dissolved to form a carboxymethyl chitosan solution;

[0015] S3: Adding polyvinylpyrrolidone to deionized water, stirring until completely dissolved to form a polyvinylpyrrolidone solution;

[0016] S4: Mixing the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution and the polyvinylpyrrolidone solution in proportion;

[0017] S5: Pouring the uniformly stirred mixed solution into a mold, performing crosslinking reaction to form a Schiff base bond between the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan, and hydrogen bonds between the carbonyl groups in the polyvinylpyrrolidone molecules and the hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively, and then taking out the molded hydrogel from the mold to obtain the final antibacterial hydrogel product.

[0018] As an improvement, the mass concentration of the hyaluronic acid aqueous solution in step S1 is 1-2%, the mass concentration of sodium periodate is 1-4%, and the stirring time is 6-12 hours and the stirring temperature is 20-50℃.

[0019] As an improvement, the dialysis purification in step S1 is performed by a molecular weight cutoff membrane with a molecular weight of 3500-5000 Da.

[0020] As an improvement, the mass concentration of carboxymethyl chitosan in step S2 is 3-7%, the concentration of hydrochloric acid solution is 0.1-0.5 mol / L, the stirring time is 2-4 hours, and the stirring temperature is room temperature.

[0021] As an improvement, the mass concentration of polyvinylpyrrolidone in step S3 is 10-30%, the stirring time is 2-3 hours, and the stirring temperature is room temperature.

[0022] As an improvement, the ratio of oxidized hyaluronic acid solution: carboxymethyl chitosan solution: polyvinylpyrrolidone solution in step S4 is 1:1:1 to 1:3:4.

[0023] Compared with the prior art, the present application has the advantages of:

[0024] The present application develops a low-toxicity, degradable, wet-surface-applicable antibacterial hydrogel based on oxidized hyaluronic acid (OHA), carboxymethyl chitosan (CMC) and polyvinylpyrrolidone (PVP), which has good biocompatibility and is suitable for medical and drug delivery fields;

[0025] In the hydrogel system, the aldehyde group in oxidized hyaluronic acid and the amino group in carboxymethyl chitosan can form a stable covalent crosslinking network through Schiff base bond, enhancing the mechanical strength and structural integrity of the hydrogel, while the polyvinylpyrrolidone molecular chain is rich in carbonyl and nitrogen atoms, which can form a large number of hydrogen bond interactions with the hydroxyl groups in oxidized hyaluronic acid and carboxymethyl chitosan, further stabilizing the network structure at the molecular level, thereby forming a "Schiff base bond-hydrogen bond synergistic" double network system. This synergistic crosslinking mechanism effectively improves the strength, flexibility and durability of the hydrogel;

[0026] When the mass ratio of oxidized hyaluronic acid solution: carboxymethyl chitosan solution: polyvinylpyrrolidone solution is in the range of 1:1:1 to 1:3:4, the aldehyde group in the Schiff base bond and the active structure of oxidized hyaluronic acid can better covalently react with the amine group in the bacterial cell wall, destroy the cell membrane structure and hinder its metabolic process, thereby achieving excellent antibacterial effect. At the same time, the polar structure of polyvinylpyrrolidone can also better maintain the hydration state of the hydrogel surface, improving its adhesion to wet tissue surfaces, preventing the hydrogel from falling off due to friction or body fluid flushing, prolonging the service life and preventing infection;

[0027] In summary, by introducing the synergistic mechanism of Schiff base bond and hydrogen bond, the hydrogel simultaneously possesses excellent mechanical properties, antibacterial properties and wet surface adhesion, showing broad clinical application potential. BRIEF DESCRIPTION OF DRAWINGS

[0028] The application will be described in further detail below with reference to the drawings and specific embodiments.

[0029] Figure 1 General structure of the antibacterial hydrogel of the application;

[0030] Figure 2 General structure of the antibacterial hydrogel of the application;

[0031] Figure 3 General structure of the antibacterial hydrogel of the application;

[0032] Figure 4 Comparison chart of Example 1 antibacterial hydrogel after inoculation of Staphylococcus aureus and Escherichia coli with the control group;

[0033] Figure 5 Mechanical property chart of Example 1 antibacterial hydrogel;

[0034] Figure 6 Comparison chart of Example 2 antibacterial hydrogel after inoculation of Staphylococcus aureus and Escherichia coli with the control group;

[0035] Figure 7 Mechanical property chart of Example 2 antibacterial hydrogel;

[0036] Figure 8 Comparison chart of Example 3 antibacterial hydrogel after inoculation of Staphylococcus aureus and Escherichia coli with the control group;

[0037] Figure 9 Mechanical property chart of Example 3 antibacterial hydrogel;

[0038] Figure 10 Storage modulus change chart of hydrogel at different crosslinking temperatures of Example 4;

[0039] Figure 11 Comparison chart of Example 4 antibacterial hydrogel after inoculation of Staphylococcus aureus and Escherichia coli with the control group;

[0040] Figure 12 Mechanical property chart of Example 4 antibacterial hydrogel;

[0041] Figure 13 Comparison chart of Example 5 antibacterial hydrogel when the mass concentration of polyvinylpyrrolidone is 22% after inoculation of Staphylococcus aureus and Escherichia coli;

[0042] Figure 14 Mechanical property chart of Example 5 antibacterial hydrogel when the mass concentration of polyvinylpyrrolidone is 22%;

[0043] Figure 15 Figure 1 is a contrast diagram of antibacterial hydrogel of Example Five inoculated with Staphylococcus aureus and Escherichia coli after different mass concentrations of polyvinylpyrrolidone were added;

[0044] Figure 16 Figure 1 is a schematic diagram of antibacterial hydrogel before gelation, wherein Figure 16 Figure 1 (a) is a schematic diagram of antibacterial hydrogel before gelation under normal placement of the container, Figure 16 Figure 1 (b) is a schematic diagram of antibacterial hydrogel before gelation under inversion of the container;

[0045] Figure 17 Figure 1 is a summary diagram of the mechanical properties of antibacterial hydrogel of Example One to Example Five;

[0046] Figure 18 Figure 1 is a diagram of the adhesion effect of antibacterial hydrogel on biological tissues (different mouse organs), wherein Figure 18 Figure 1 (a) is a diagram of the adhesion effect of antibacterial hydrogel on the heart of a mouse, Figure 18 Figure 1 (b) is a diagram of the adhesion effect of antibacterial hydrogel on the liver of a mouse, Figure 18 Figure 1 (c) is a diagram of the adhesion effect of antibacterial hydrogel on the spleen of a mouse, Figure 18 Figure 1 (d) is a diagram of the adhesion effect of antibacterial hydrogel on the kidney of a mouse, Figure 18 Figure 1 (e) is a diagram of the adhesion effect of antibacterial hydrogel on the lung of a mouse, Figure 18 Figure 1 (f) is a diagram of the adhesion effect of antibacterial hydrogel on the stomach of a mouse. DETAILED DESCRIPTION

[0047] Example One

[0048] S1: 1 g of hyaluronic acid was dissolved in 100 mL of water to prepare a 1% hyaluronic acid aqueous solution, 1.8 g of sodium periodate was added, so that the mass ratio of the hyaluronic acid aqueous solution to the sodium periodate was 1:1.8, the reaction was carried out at 35°C for 6 hours with a stirring speed of 250 rpm / min, so that the aldehyde functional groups were introduced into the molecular structure of the hyaluronic acid to form oxidized hyaluronic acid, which was purified by dialysis through a molecular weight cutoff membrane with a molecular weight of 4500 Da to remove the by-products and unreacted sodium periodate in the reaction, and finally freeze-dried to obtain oxidized hyaluronic acid powder, 0.2 g of the oxidized hyaluronic acid powder was added to 10 mL of deionized water to completely dissolve into a 2% oxidized hyaluronic acid solution;

[0049] S2: 0.5 g of carboxymethyl chitosan was added to 10 mL of deionized water, stirred at room temperature for 4 hours until completely dissolved, forming a light yellow carboxymethyl chitosan solution with a mass concentration of 5%;

[0050] S3: 2g of polyvinylpyrrolidone was added to 10 mL of deionized water, stirred at room temperature for 3 hours to completely dissolve, forming a colorless transparent polyvinylpyrrolidone solution with a mass concentration of 20%;

[0051] S4: The hyaluronic acid oxidized solution, the carboxymethyl chitosan solution, and the polyvinylpyrrolidone solution were mixed in a weight ratio of 1:1:2;

[0052] S5: The uniformly stirred mixed solution was poured into a mold, and a crosslinking reaction was carried out at a temperature of 30°C and a humidity controlled at 40-60% R.H. for 24 hours, so that the aldehyde groups in the hyaluronic acid and the amino groups in the carboxymethyl chitosan formed Schiff base bonds, and the carbonyl groups in the polyvinylpyrrolidone molecules formed hydrogen bonds with the hydroxyl groups in the hyaluronic acid and the carboxymethyl chitosan, respectively. Then the formed hydrogel was taken out of the mold to obtain the final antibacterial hydrogel product.

[0053] As shown in Figures 1 to 5 , Figures 16 to 18 , the hyaluronic acid oxidation reaction conditions were optimized. When the mass ratio of sodium periodate to hyaluronic acid was 1:1.8, the generated oxidized hyaluronic acid introduced more aldehyde groups, the crosslinking performance was improved, and the antibacterial performance was enhanced. The advantages of compounding are that the oxidized hyaluronic acid reacts with the amino groups of carboxymethyl chitosan through aldehyde groups to form a stable crosslinked structure, carboxymethyl chitosan provides antibacterial performance and biocompatibility, and polyvinylpyrrolidone enhances the toughness and stability of the gel. After improvement, the plate counting method was used for antibacterial test, and Staphylococcus aureus and Escherichia coli were inoculated respectively. Compared with the control group, the number of colonies of the sample group was reduced by 68% and 65%.

[0054] Example Two

[0055] The mass ratio of the hyaluronic acid aqueous solution to sodium periodate in step S1 was adjusted to 1:1.7, and the reaction was carried out at 37°C for 9 hours with a stirring speed of 350 rpm / min.

[0056] The remaining steps were consistent with Example One, and thus are not described in detail.

[0057] As shown in Figure 6 , Figure 7 , Figures 16 to 18 , under this condition, the oxidation rate of oxidized hyaluronic acid was improved, and the synergistic effect with carboxymethyl chitosan and polyvinylpyrrolidone enhanced the antibacterial performance. Carboxymethyl chitosan provides strong antibacterial properties, and polyvinylpyrrolidone increases flexibility and elasticity. After improvement, the plate counting method was used to detect the antibacterial effect, and the number of colonies of Staphylococcus aureus and Escherichia coli was reduced by 80% and 78% respectively, which was significantly better than Example One.

[0058] Example Three

[0059] The oxidized hyaluronic acid solution, the carboxymethyl chitosan solution, and the polyvinylpyrrolidone solution are mixed in a weight ratio of 1:2.5:3.5 in the adjusting step S4.

[0060] The mixed solution is poured into a mold in the adjusting step S5, and a cross-linking reaction is performed at a temperature of 37°C and a humidity of 40-60% R.H. for 48 hours, so that Schiff base bonds are formed between the aldehyde groups in the oxidized hyaluronic acid and the amino groups in the carboxymethyl chitosan. The formed hydrogel is taken out of the mold to obtain a final antibacterial hydrogel product.

[0061] The remaining steps are the same as in Example 1, and thus are not described in detail.

[0062] As shown in Figure 8 , Figure 9 , Figures 16 to 18 By optimizing the ratio of the oxidized hyaluronic acid solution: the carboxymethyl chitosan solution: the polyvinylpyrrolidone solution to 1:2.5:3.5 and the cross-linking temperature in step S5 to 37°C and the reaction time to 48 hours, the cross-linking density and the mechanical properties of the hydrogel are enhanced, and the flexibility test shows that the compressive strength is 0.8 MPa, which is increased by 30% compared with Example 1. The antibacterial performance is detected by the plate counting method, and the number of bacteria in the sample group in the Staphylococcus aureus and Escherichia coli experiments is reduced by 87% and 85%, respectively. After the improvement, the material has significant antibacterial performance, and the flexibility and pressure resistance of the material are enhanced.

[0063] Example Four

[0064] This example tests the influence of different cross-linking temperatures on the antibacterial performance of the hydrogel.

[0065] The cross-linking reaction is performed at different temperatures in step S5:

[0066] First group: the cross-linking reaction temperature is 25°C, and the reaction time is 24 hours;

[0067] Second group: the cross-linking reaction temperature is 35°C, and the reaction time is 24 hours;

[0068] Third group: the cross-linking reaction temperature is 45°C, and the reaction time is 24 hours;

[0069] Fourth group: the cross-linking reaction temperature is 50°C, and the reaction time is 24 hours;

[0070] Fifth group: the cross-linking reaction temperature is 55°C, and the reaction time is 24 hours.

[0071] The remaining steps are the same as in Example 1, and thus are not described in detail.

[0072] As shown in Figures 10 to 12 , Figures 16 to 18As shown, the higher the storage modulus (G' value) of the hydrogel, the more stable the hydrogel. Figure 10 The storage modulus variation graph of the hydrogel at different crosslinking temperatures shows that the optimal crosslinking temperature is determined to be 45°C. Under this condition, the reaction between oxidized hyaluronic acid and carboxymethyl chitosan is sufficient, polyvinylpyrrolidone is uniformly dispersed, and stability is further optimized. Antibacterial performance was tested using the plate count method. The hydrogel prepared at 45°C reduced the colony counts of Staphylococcus aureus and Escherichia coli by 91% and 89%, respectively, demonstrating significantly better antibacterial performance than in Example 3. While the crosslinking condition at 50°C slightly improved the antibacterial performance, it slightly decreased the mechanical properties. With increasing temperature, the activation energy of the crosslinking reaction decreases, and the chemical reaction rate increases, thereby promoting the formation of chemical bonds between oxidized hyaluronic acid and carboxymethyl chitosan, and increasing the degree of crosslinking.

[0073] At lower temperatures (e.g., 25°C), the reaction is slow and incomplete, resulting in a loose cross-linked network and poor mechanical strength and antibacterial properties. However, as the temperature gradually increases to 45°C, oxidized hyaluronic acid and carboxymethyl chitosan react fully, resulting in a denser and more stable cross-linked network. Simultaneously, polyvinylpyrrolidone is uniformly dispersed within the network, further enhancing the material's stability and antibacterial properties. However, further increasing the temperature to 50°C or 55°C may trigger over-crosslinking or material degradation, leading to network embrittlement, decreased mechanical properties, or the formation of locally uneven microstructures. Therefore, 45°C has been identified as the optimal crosslinking temperature, balancing the material's structural stability, compositional uniformity, and antibacterial properties while ensuring sufficient crosslinking.

[0074] Example 5

[0075] This embodiment explores the effect of polyvinylpyrrolidone solutions of different mass concentrations on the antibacterial properties of hydrogels.

[0076] In step S3, the mass concentration of the polyvinylpyrrolidone solution is adjusted to 10%, 15%, 20%, 22%, 25%, 27%, and 30%, respectively.

[0077] The remaining steps are the same as in Example 1, so they will not be repeated here.

[0078] like Figures 13 to 18 As shown, experiments determined that an optimal concentration of 22% achieved a balance between antibacterial properties and flexibility. Plate count experiments indicated that under these conditions, the colony counts of Staphylococcus aureus and Escherichia coli were reduced by 94% and 92%, respectively. Simultaneously, the samples maintained good flexibility and transparency, making them suitable for antibacterial dressings or drug carriers.

[0079] With the increase of PVP solution concentration from 10% to 30%, the mechanical properties, antibacterial effect, swelling properties and biocompatibility of the hydrogel showed significant differences. In the low concentration range (10%-15%), the distribution of PVP solution was more uniform, which helped to form a stable cross-linked network. However, due to the low concentration of PVP solution, it was unable to significantly improve the water retention and antibacterial ability of the hydrogel. With the increase of concentration to 20%-25%, PVP solution further penetrated into the cross-linked network, forming a more uniform and dense three-dimensional structure, which could significantly enhance the mechanical strength, swelling capacity and antibacterial performance of the hydrogel. This was because PVP solution could adsorb more water molecules through chelation and further improve the release efficiency of the antibacterial agent as a hydrophilic carrier. However, when the mass concentration of PVP solution continued to increase to 27%-30%, it might cause the opposite effect: the excessive mass concentration of PVP solution might cause excessive distribution of cross-linking points or the formation of uneven microstructure, which would weaken the mechanical properties of the hydrogel, and at the same time, cause the swelling rate to be too high, thus causing the risk of material degradation. In addition, the excessive mass concentration of PVP solution might dilute the effective concentration of the antibacterial component (CMCS), thus reducing the antibacterial effect. Therefore, PVP solution with a mass concentration in the range of 22% was considered to be the optimal choice, which could provide good antibacterial performance and biocompatibility while maintaining the stability of the material structure.

[0080] The above description is only for the best embodiments of the present application, but should not be understood as limiting the claims. The present application is not limited to the above embodiments, and the specific structure allows changes. Any changes made within the scope of the independent claims of the present application are within the scope of the present application.

Claims

1. An antimicrobial hydrogel having wet-surface adhesion, characterized in that, The antibacterial hydrogel comprises oxidized hyaluronic acid, carboxymethyl chitosan and polyvinylpyrrolidone, the aldehyde groups in the oxidized hyaluronic acid and the amino groups in the carboxymethyl chitosan are crosslinked to form Schiff base bonds, and the carbonyl groups in the polyvinylpyrrolidone molecules form hydrogen bonds with the hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively, to obtain the antibacterial hydrogel in a form of Schiff base bond-hydrogen bond synergistic double network crosslinking, and the general structure is as follows: wherein, 60 < n1 < 300, 20 < n2 < 110, 100 < n3 < 1500, the molding temperature in the crosslinking reaction is 25-55℃, the molding humidity is 40-60% R.H., and the molding time is 24-48 hours.

2. The antimicrobial hydrogel with wet-surface adhesion according to claim 1, wherein, The preparation of the antibacterial hydrogel comprises the following steps: S1: dissolving hyaluronic acid in water to prepare a hyaluronic acid aqueous solution, adding sodium periodate to stir to form oxidized hyaluronic acid, purifying by dialysis to obtain an oxidized hyaluronic acid solution; S2: adding carboxymethyl chitosan into deionized water or hydrochloric acid solution, stirring until completely dissolved to form a carboxymethyl chitosan solution; S3: adding polyvinylpyrrolidone into deionized water, stirring until completely dissolved to form a polyvinylpyrrolidone solution; S4: mixing the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution and the polyvinylpyrrolidone solution in proportion; S5: pouring the uniformly stirred mixed solution into a mold, performing crosslinking reaction to form Schiff base bonds between the aldehyde groups in the oxidized hyaluronic acid and the amino groups in the carboxymethyl chitosan, and hydrogen bonds between the carbonyl groups in the polyvinylpyrrolidone molecules and the hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively, then taking out the molded hydrogel from the mold to obtain the final antibacterial hydrogel product.

3. The antimicrobial hydrogel with wet-surface adhesion according to claim 2, wherein, The mass concentration of the hyaluronic acid aqueous solution in step S1 is 1-2%, the mass concentration of the sodium periodate is 1-4%, and the stirring time is 6-12 hours at a stirring temperature of 20-50℃.

4. The antimicrobial hydrogel with wet-surface adhesion according to claim 2, wherein, The dialysis purification in step S1 is performed by a molecular weight cutoff membrane with a molecular weight of 3500-5000 Da.

5. The antimicrobial hydrogel with wet-surface adhesion according to claim 2, wherein, The mass concentration of the carboxymethyl chitosan in step S2 is 3-7%, the concentration of the hydrochloric acid solution is 0.1-0.5 mol / L, and the stirring time is 2-4 hours at room temperature.

6. The antimicrobial hydrogel with wet-surface adhesion according to claim 2, wherein, The mass concentration of the polyvinylpyrrolidone in step S3 is 10-30%, and the stirring time is 2-3 hours at room temperature.

7. The antimicrobial hydrogel with wet-surface adhesion according to claim 2, wherein, The proportion of the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution and the polyvinylpyrrolidone solution in step S4 is 1:1:1 to 1:3:4.

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