Antibacterial hydrogel with wet surface adhesion

Abstract

The invention 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 subjected to cross-linking reaction to form Schiff base bonds, and the Schiff base bonds are subjected to cross-linking reaction to form Schiff base bonds; carbonyl groups in polyvinylpyrrolidone molecules respectively form hydrogen bonds with hydroxyl groups in oxidized hyaluronic acid and hydroxyl groups in carboxymethyl chitosan, and the antibacterial hydrogel is obtained in a Schiff base bond-hydrogen bond synergistic dual-network crosslinking form. According to the invention, a synergistic mechanism of Schiff base bonds and hydrogen bonds is introduced, so that the hydrogel has excellent mechanical properties, antibacterial properties and wet surface adhesion at the same time.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, in particular to an antibacterial hydrogel with wet surface adhesion. Background Art

[0002] As a water-based material with significant antibacterial activity, antibacterial hydrogel has received extensive attention in the biomedical field in recent years. Hydrogels have a hydrated structure similar to biological tissues and can maintain a high water content under physiological conditions, thereby simulating the properties of tissues in the body. They are usually formed by cross-linking of natural or synthetic polymers and have good biocompatibility, flexibility, biodegradability and high hydrophilicity. These properties make them have important application potential in wound dressings, drug delivery systems, tissue engineering and cell culture. Antibacterial hydrogels are not only used in traditional medical fields for wound repair and tissue engineering, but also play a key role in modern antibacterial treatment, especially in the face of the increasingly severe global problem of antibiotic resistance, as an alternative material has attracted much attention.

[0003] As the problem of antibiotic resistance becomes increasingly serious, traditional antimicrobial treatments face increasing challenges. The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria (MDR), which are not only resistant to traditional antibiotics but can also cause serious hospital-acquired infections. According to the World Health Organization (WHO), antibiotic resistance causes millions of deaths worldwide each year, and this number is expected to continue to rise. In response to this problem, researchers have made a lot of efforts to develop materials that replace antibiotics. As a new type of therapeutic material, antimicrobial hydrogels have become an important means to deal with antibiotic resistance because they can release antimicrobial agents locally through physical or chemical means, enhance local immune responses, and directly inhibit bacterial growth.

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

[0005] The water solubility and biocompatibility of CMC make it an important material for the preparation of antibacterial hydrogels. In the preparation process of hydrogels, CMC can interact with other materials through physical or chemical crosslinking to enhance the mechanical properties and antibacterial activity of hydrogels. The carboxyl group (-COOH) of CMC can not only provide strong hydrophilicity, but also form crosslinking reactions with other molecules with active groups (such as amino groups, aldehyde groups, etc.) to enhance the stability of hydrogels. In addition, CMC itself has certain natural antibacterial properties and 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 process of antibacterial hydrogels, commonly used crosslinkers, such as glutaraldehyde (GA) or ultraviolet light crosslinking, can effectively crosslink hydrogels and enhance their mechanical properties, but these crosslinkers are usually toxic and may cause the performance of hydrogels to deteriorate after long-term use. Glutaraldehyde, as a traditional crosslinker, is known to have certain cytotoxicity, which may have adverse effects on organisms. In order to overcome these problems, in recent years, more and more studies have begun to focus on natural crosslinkers that are non-toxic, low-cost and environmentally friendly. For example, by introducing Schiff base reactions (such as the reaction of aldehyde groups with amino groups), a new crosslinking strategy has been developed. This method can not only avoid the toxicity problems caused by traditional chemical crosslinkers, 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 made in the antibacterial properties 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 usually has a wet environment such as bleeding and exudate. 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, can temporarily cover the wound, but they often lack good adhesion to the wet surface 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 prone to swelling or hydration in these wet environments, causing changes in the surface tension of the hydrogel, thereby losing effective adhesion. Summary of the invention

[0008] In view of the above-mentioned shortcomings, the present invention proposes an antibacterial hydrogel with wet surface adhesion. By introducing the 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 invention provides the following technical solution: an antibacterial hydrogel with wet surface adhesion, comprising oxidized hyaluronic acid, carboxymethyl chitosan and polyvinyl pyrrolidone, wherein the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan undergo cross-linking reaction to form a Schiff base bond, and the carbonyl group in the polyvinyl pyrrolidone molecule forms 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 cross-linking form, and its general structural formula is: Among them, 60<n 1 <300,20<n 2 <110,100<n 3 <1500.

[0010] As an improvement, the preparation of the antibacterial hydrogel includes the following steps: S1: dissolving hyaluronic acid in water to prepare a hyaluronic acid aqueous solution, adding sodium periodate and stirring to form oxidized hyaluronic acid, and purifying by dialysis to obtain an oxidized hyaluronic acid solution; S2: adding carboxymethyl chitosan to deionized water or hydrochloric acid solution and stirring until completely dissolved to form a carboxymethyl chitosan solution; S3: adding polyvinyl pyrrolidone into deionized water and stirring until completely dissolved to form a polyvinyl pyrrolidone solution; S4: mixing the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution and the polyvinyl pyrrolidone solution in proportion; S5: Pour the uniformly stirred mixed solution into a mold to carry out a cross-linking reaction so that the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan form a Schiff base bond, and the carbonyl group in the polyvinyl pyrrolidone molecule forms hydrogen bonds with the hydroxyl groups in the oxidized hyaluronic acid and carboxymethyl chitosan respectively, and then take the molded hydrogel out of the mold to obtain the final antibacterial hydrogel product.

[0011] 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%, the stirring time is 6-12 hours, and the stirring temperature is 20-50°C.

[0012] As an improvement, in step S1, dialysis purification is performed through a molecular weight cutoff membrane, and the molecular weight cutoff membrane has a molecular weight of 3500-5000 Da.

[0013] As an improvement, the mass concentration of carboxymethyl chitosan in step S2 is 3-7%, the concentration of the hydrochloric acid solution is 0.1-0.5 mol / L, the stirring time is 2-4 hours, and the stirring temperature is room temperature.

[0014] As an improvement, the mass concentration of polyvinyl pyrrolidone in step S3 is 10-30%, the stirring time is 2-3 hours, and the stirring temperature is room temperature.

[0015] As an improvement, the ratio of oxidized hyaluronic acid solution: carboxymethyl chitosan solution: polyvinyl pyrrolidone solution in step S4 is 1:1:1 to 1:3:4.

[0016] As an improvement, the molding temperature in step S5 is 25-55°C, the molding humidity is 40-60%RH, and the molding time is 24-48 hours.

[0017] Compared with the prior art, the advantages of the present invention are: The present invention has developed a low-toxic, degradable, antibacterial hydrogel suitable for wet surfaces based on oxidized hyaluronic acid (OHA), carboxymethyl chitosan (CMC) and polyvinyl pyrrolidone (PVP). The hydrogel has good biocompatibility and is suitable for medical treatment and drug delivery. In this hydrogel system, the aldehyde groups in oxidized hyaluronic acid and the amino groups in carboxymethyl chitosan can form Schiff base bonds to build a stable covalent cross-linked network, enhancing the mechanical strength and structural integrity of the hydrogel. At the same time, the polyvinyl pyrrolidone 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, thus forming a "Schiff base bond-hydrogen bond synergy" dual network system. This synergistic cross-linking mechanism effectively improves the strength, flexibility and durability of the hydrogel; When the mass ratio of oxidized hyaluronic acid solution: carboxymethyl chitosan solution: polyvinyl pyrrolidone solution is within the range of 1:1:1 to 1:3:4, the aldehyde residues in the Schiff base bonds and the active structure of the oxidized hyaluronic acid itself can better react covalently with the amine groups in the bacterial cell wall, destroy the cell membrane structure, and hinder its metabolic process, thereby achieving an excellent antibacterial effect. At the same time, the polar structure of polyvinyl pyrrolidone can also better maintain the hydration state of the hydrogel surface to enhance its adhesion to the wet tissue surface, avoid the hydrogel from falling off due to friction or body fluid scouring, extend the use period, and prevent infection. In summary, by introducing the synergistic mechanism of Schiff base bonds and hydrogen bonds, the hydrogel has excellent mechanical properties, antibacterial properties and wet surface adhesion, showing broad potential for clinical application. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments: Figure 1 This is a schematic diagram of the general structure of the antibacterial hydrogel of the invention; Figure 2 Schematic diagram of the process of forming Schiff base bonds by cross-linking reaction between aldehyde groups in oxidized hyaluronic acid and amino groups in carboxymethyl chitosan; Figure 3 Schematic diagram of the general structure of the carbonyl group in polyvinyl pyrrolidone forming hydrogen bonds with the hydroxyl groups in oxidized hyaluronic acid (left) and carboxymethyl chitosan (right); Figure 4 This is a comparison diagram of the antibacterial hydrogel inoculated with Staphylococcus aureus and Escherichia coli in Example 1 and the control group; Figure 5 This is a diagram of the mechanical properties of the antibacterial hydrogel in Example 1; Figure 6 This is a comparison diagram of the antibacterial hydrogel inoculated with Staphylococcus aureus and Escherichia coli in Example 2 and the control group; Figure 7 This is a diagram of the mechanical properties of the antibacterial hydrogel of Example 2; Figure 8 This is a comparison diagram of the antibacterial hydrogel inoculated with Staphylococcus aureus and Escherichia coli in Example 3 and the control group; Fig. 9 This is a diagram of the mechanical properties of the antibacterial hydrogel of Example 3; Fig.10 This is a graph showing the change in storage modulus of the hydrogel at different cross-linking temperatures in Example 4; Fig.11 This is a comparison diagram of the antibacterial hydrogel of Example 4 after inoculation with Staphylococcus aureus and Escherichia coli and the control group; Fig.12 This is a diagram of the mechanical properties of the antibacterial hydrogel of Example 4; Fig.13 This is a comparison diagram of the antibacterial hydrogel inoculated with Staphylococcus aureus and Escherichia coli when the mass concentration of polyvinyl pyrrolidone is 22% in Example 5; Fig.14 This is a graph showing the mechanical properties of the antibacterial hydrogel when the mass concentration of polyvinyl pyrrolidone is 22% in Example 5; Fig.15 This is a comparison diagram of the antibacterial hydrogels containing different mass concentrations of polyvinyl pyrrolidone in Example 5 after being inoculated with Staphylococcus aureus and Escherichia coli; Fig.16 Schematic diagram of antibacterial hydrogel before gelation, where Fig.16 (a) is a schematic diagram of the antibacterial hydrogel before gelation under normal container placement. Fig.16 (b) is a schematic diagram of the antibacterial hydrogel before gelation when the container is inverted; Fig.17 This is a summary diagram of the mechanical properties of the antibacterial hydrogels of Examples 1 to 5; Fig.18 This is a diagram showing the adhesion effect of antibacterial hydrogel on biological tissues (different mouse organs). Fig.18 (a) shows the adhesion effect of antibacterial hydrogel on the heart of mice. Fig.18 (b) is a diagram showing the adhesion effect of antibacterial hydrogel on the liver of mice. Fig.18 (c) is a diagram showing the adhesion effect of antibacterial hydrogel on the spleen of mice. Fig.18 (d) is the adhesion effect of antibacterial hydrogel on the kidney of mice. Fig.18 (e) is a diagram showing the adhesion effect of antibacterial hydrogel on the lungs of mice. Fig.18 (f) shows the adhesion effect of antibacterial hydrogel on the gastric tract of mice. DETAILED DESCRIPTION

[0019] Embodiment 1 S1: Dissolve 1g of hyaluronic acid in 100mL of water to prepare a hyaluronic acid aqueous solution with a mass concentration of 1%, add 1.8g of sodium periodate so that the mass ratio of the hyaluronic acid aqueous solution to the sodium periodate is 1:1.8, react at 35°C with stirring for 6 hours and a stirring speed of 250rpm / min to introduce aldehyde functional groups into the molecular structure of the hyaluronic acid to form oxidized hyaluronic acid, dialysis and purification through a molecular weight cutoff membrane with a molecular weight cutoff of 4500 Da, remove by-products and unreacted sodium periodate in the reaction, and finally freeze-dry to obtain oxidized hyaluronic acid powder, add 0.2g of oxidized hyaluronic acid powder into 10ml of deionized water to completely dissolve it into a transparent oxidized hyaluronic acid solution with a mass concentration of 2%; S2: Add 0.5 g of carboxymethyl chitosan into 10 mL of deionized water and stir at room temperature for 4 hours until completely dissolved to form a light yellow carboxymethyl chitosan solution with a mass concentration of 5%; S3: Add 2 g of polyvinyl pyrrolidone into 10 mL of deionized water and stir at room temperature for 3 hours until it is completely dissolved to form a colorless, transparent polyvinyl pyrrolidone solution with a mass concentration of 20%; S4: mixing the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution, and the polyvinyl pyrrolidone solution in a weight ratio of 1:1:2; S5: Pour the evenly stirred mixed solution into a mold, and carry out a cross-linking reaction at a temperature of 30°C and a humidity of 40-60%RH for 24 hours, so that the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan form a Schiff base bond, and the carbonyl group in the polyvinyl pyrrolidone molecule forms hydrogen bonds with the hydroxyl groups in the oxidized hyaluronic acid and carboxymethyl chitosan, respectively. Then, the molded hydrogel is taken out of the mold to obtain the final antibacterial hydrogel product.

[0020] like Figures 1 to 5 , Figures 16 to 18As shown in the figure, 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, improved cross-linking performance, and enhanced antibacterial properties. The advantage of the compound is that the oxidized hyaluronic acid forms a stable cross-linked structure through the reaction of aldehyde groups with the amino groups of carboxymethyl chitosan. Carboxymethyl chitosan provides antibacterial properties and biocompatibility, and polyvinyl pyrrolidone improves the toughness and stability of the gel. After the improvement, the plate count method antibacterial test was carried out, and Staphylococcus aureus and Escherichia coli were inoculated respectively. Compared with the control group, the colony counts of the sample group decreased by 68% and 65%.

[0021] Embodiment 2 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. with a stirring time of 9 hours and a stirring speed of 350 rpm / min.

[0022] The remaining steps are consistent with those in the first embodiment and are not described in detail.

[0023] like Figure 6 , Figure 7 , Figures 16 to 18 As shown, under this condition, the oxidation rate of oxidized hyaluronic acid is improved, and the antibacterial performance is enhanced by synergistic action with carboxymethyl chitosan and polyvinyl pyrrolidone. Carboxymethyl chitosan provides strong antibacterial properties, and polyvinyl pyrrolidone increases flexibility and elasticity. After the improvement, the antibacterial effect was detected by plate counting method, and the colony counts of Staphylococcus aureus and Escherichia coli were reduced by 80% and 78% respectively, and the antibacterial effect was significantly better than that of Example 1.

[0024] Embodiment 3 In the adjustment step S4, the oxidized hyaluronic acid solution, the carboxymethyl chitosan solution, and the polyvinyl pyrrolidone solution are mixed in a weight ratio of 1:2.5:3.5; In the adjustment step S5, the uniformly stirred mixed solution is poured into a mold, and the cross-linking reaction is carried out for 48 hours at a temperature of 37° C. and a humidity of 40-60% RH, so that the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan form a Schiff base bond, and the formed hydrogel is taken out of the mold to obtain the final antibacterial hydrogel product.

[0025] The remaining steps are consistent with those in the first embodiment and are not described in detail.

[0026] like Figure 8 , Fig. 9 , Figures 16 to 18As shown, by optimizing the ratio of oxidized hyaluronic acid solution: carboxymethyl chitosan solution: polyvinyl pyrrolidone solution to 1:2.5:3.5, and the cross-linking temperature in step S5 is 37 ° C, the reaction time is 48 hours, the cross-linking density and mechanical properties of the hydrogel are enhanced, and the flexibility test shows that the compressive strength is 0.8 MPa, which is 30% higher than that of Example 1. The antibacterial properties were detected by the plate counting method, and the colony counts of the sample group in the Staphylococcus aureus and Escherichia coli experiments were reduced by 87% and 85%, respectively. After the improvement, significant antibacterial properties were shown, and the flexibility and pressure resistance of the material were enhanced.

[0027] Embodiment 4 This example tests the effect of different cross-linking temperatures on the antibacterial properties of the hydrogel.

[0028] In step S5, a cross-linking reaction is performed at different temperatures: Group 1: cross-linking reaction temperature was 25°C and reaction time was 24 h; Group 2: cross-linking reaction temperature was 35°C and reaction time was 24 h; Group 3: cross-linking reaction temperature was 45°C and reaction time was 24 hours; Group 4: cross-linking reaction temperature was 50°C and reaction time was 24 hours; Group 5: The cross-linking reaction temperature was 55°C and the reaction time was 24 hours.

[0029] The remaining steps are consistent with those in the first embodiment and are not described in detail.

[0030] like Figures 10 to 12 , Figures 16 to 18 As shown in Figure 2, the higher the storage modulus (G' value) of the hydrogel, the more stable the hydrogel is. Fig.10 The storage modulus change diagram of the hydrogel under different cross-linking temperatures shows that the optimal cross-linking temperature is determined to be 45 ° C. Under this condition, oxidized hyaluronic acid and carboxymethyl chitosan react fully, and polyvinyl pyrrolidone is evenly dispersed and further optimized for stability. Antibacterial performance is detected by plate counting method. The hydrogel prepared under 45 ° C conditions reduces the colony count of Staphylococcus aureus and Escherichia coli by 91% and 89%, respectively, and the antibacterial performance is significantly better than Example 3. Meanwhile, although 50 ° C cross-linking conditions slightly improve antibacterial performance, mechanical properties are slightly reduced. As the temperature rises, the activation energy of the cross-linking reaction decreases, and the chemical reaction rate increases, thereby promoting the formation of chemical bonds between oxidized hyaluronic acid and carboxymethyl chitosan, and improving the degree of cross-linking.

[0031] When the temperature is low (such as 25°C), the reaction is slow and incomplete, resulting in a loose cross-linking network and poor mechanical strength and antibacterial properties of the material. When the temperature gradually rises to 45°C, oxidized hyaluronic acid and carboxymethyl chitosan can fully react, the cross-linking network is denser and more stable, and polyvinyl pyrrolidone can be evenly dispersed in the network, further improving the stability and antibacterial properties of the material. However, when the temperature continues to rise to 50°C or 55°C, it may cause excessive cross-linking or material degradation, resulting in network embrittlement, decreased mechanical properties, or the formation of locally uneven microstructures. Therefore, 45°C was determined to be the optimal cross-linking temperature, which can balance the structural stability, composition uniformity and antibacterial properties of the material while ensuring sufficient cross-linking.

[0032] Embodiment 5 This example discusses the effect of polyvinyl pyrrolidone solutions of different mass concentrations on the antibacterial properties of hydrogels.

[0033] In step S3, the mass concentrations of the polyvinyl pyrrolidone solution are adjusted to 10%, 15%, 20%, 22%, 25%, 27% and 30% respectively.

[0034] The remaining steps are consistent with those in the first embodiment and are not described in detail.

[0035] like Figures 13 to 18 As shown in the figure, the optimal concentration was determined to be 22% through experiments, when the antibacterial property and flexibility were balanced. The plate count experiment showed that under this condition, the colony counts of Staphylococcus aureus and Escherichia coli were reduced by 94% and 92%. At the same time, the sample maintained good flexibility and transparency, and was suitable for antibacterial dressings or drug carriers.

[0036] As the mass concentration of polyvinyl pyrrolidone solution increases from 10% to 30%, it has a significant difference in the mechanical properties, antibacterial effect, swelling performance and biocompatibility of the hydrogel. In the low concentration range (10%-15%), the distribution of polyvinyl pyrrolidone solution is relatively uniform, which helps to form a stable cross-linked network, but due to the low mass concentration of polyvinyl pyrrolidone solution, it cannot significantly improve the water retention and antibacterial ability of the hydrogel. As the concentration increases to 20%-25%, the polyvinyl pyrrolidone solution further penetrates into the cross-linked network to form a more uniform and dense three-dimensional structure, which can significantly enhance the mechanical strength, swelling ability and antibacterial properties of the hydrogel. This is because the polyvinyl pyrrolidone solution can absorb more water molecules through chelation and act as a hydrophilic carrier to further improve the release efficiency of the antibacterial agent. However, when the mass concentration of the polyvinyl pyrrolidone solution continues to increase to 27%-30%, the opposite effect may occur: too high a mass concentration of the polyvinyl pyrrolidone solution may lead to excessive distribution of cross-linking points or the formation of an uneven microstructure, thereby weakening the mechanical properties of the hydrogel and causing an excessively high swelling rate, which in turn triggers the risk of material degradation. In addition, excessive mass concentration of the polyvinyl pyrrolidone solution may dilute the effective concentration of the antibacterial component (CMCS), thereby reducing the antibacterial effect. Therefore, a polyvinyl pyrrolidone solution with a mass concentration in the range of 22% is considered to be the optimal choice, which can provide good antibacterial properties and biocompatibility while maintaining the structural stability of the material.

[0037] The above description is only for the best embodiment of the present invention, but it should not be understood as limiting the claims. The present invention is not limited to the above embodiments, and its specific structure is allowed to be changed. All changes made within the scope of protection of the independent claims of the present invention are within the scope of protection of the present invention.

Claims

1. An antibacterial hydrogel with wet surface adhesion, characterized in that The invention comprises oxidized hyaluronic acid, carboxymethyl chitosan and polyvinyl pyrrolidone. The aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan undergo cross-linking reaction to form a Schiff base bond, and the carbonyl group in the polyvinyl pyrrolidone molecule forms hydrogen bonds with the hydroxyl groups in the oxidized hyaluronic acid and the carboxymethyl chitosan, respectively, so as to obtain the antibacterial hydrogel in the form of Schiff base bond-hydrogen bond synergistic double network cross-linking. The general structural formula is: Among them, 60<n1<300, 20<n2<110, 100<n3<1500.

2. The antibacterial hydrogel with wet surface adhesion according to claim 1, characterized in that: 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 and stirring to form oxidized hyaluronic acid, and purifying by dialysis to obtain an oxidized hyaluronic acid solution; S2: adding carboxymethyl chitosan to deionized water or hydrochloric acid solution and stirring until completely dissolved to form a carboxymethyl chitosan solution; S3: adding polyvinyl pyrrolidone into deionized water and stirring until completely dissolved to form a polyvinyl pyrrolidone solution; S4: mixing the oxidized hyaluronic acid solution, carboxymethyl chitosan solution, and polyvinyl pyrrolidone solution according to a certain proportion; S5: Pour the uniformly stirred mixed solution into a mold, perform a cross-linking reaction so that the aldehyde group in the oxidized hyaluronic acid and the amino group in the carboxymethyl chitosan form a Schiff base bond, and the carbonyl group in the polyvinyl pyrrolidone molecule forms a hydrogen bond with the hydroxyl groups in the oxidized hyaluronic acid and carboxymethyl chitosan, respectively, and then take the molded hydrogel out of the mold to obtain the final antibacterial hydrogel product.

3. The antibacterial hydrogel with wet surface adhesion according to claim 2, characterized in that: 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%, the stirring time is 6-12 hours, and the stirring temperature is 20-50°C.

4. The antibacterial hydrogel with wet surface adhesion according to claim 2, characterized in that: In step S1, the dialysis purification is performed through a molecular weight cut-off membrane, and the molecular weight cut-off membrane has a molecular weight of 3500-5000 Da.

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

6. The antibacterial hydrogel with wet surface adhesion according to claim 2, characterized in that: The mass concentration of polyvinyl pyrrolidone in step S3 is 10-30%, the stirring time is 2-3 hours, and the stirring temperature is room temperature.

7. The antibacterial hydrogel with wet surface adhesion according to claim 2, characterized in that: The ratio of the oxidized hyaluronic acid solution: the carboxymethyl chitosan solution: the polyvinyl pyrrolidone solution in step S4 is 1:1:1 to 1:3:

4.

8. The antibacterial hydrogel with wet surface adhesion according to claim 2, characterized in that: The molding temperature in step S5 is 25-55° C., the molding humidity is 40-60% RH, and the molding time is 24-48 hours.

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