Antibacterial hydrogel and its preparation method and application

Abstract

The present invention relates to an antibacterial hydrogel and its preparation method and application. The antibacterial hydrogel is obtained by in-situ self-crosslinking using organic acid modified gelatin quaternary ammonium salt as a base material and oxidized alginate, borax and CuS@TA-Fe NPs as crosslinking agents. The mass ratio of organic acid modified gelatin quaternary ammonium salt, oxidized alginate, borax and CuS@TA-Fe NPs is (5-30): (2.5-15): (0.1-10): (0.01-5). The present invention uses organic acid modified gelatin quaternary ammonium salt as a raw material, adopts oxidized alginate and borax to carry out chemical crosslinking to form a stable network structure, has good swelling performance, has good self-healing effect and shape adaptability, can be used as a wound dressing, and has antioxidant capacity and anti-inflammatory effects.

Description

Technical Field

[0001] The present invention belongs to the field of biomaterials, and in particular relates to an antibacterial hydrogel and a preparation method and application thereof. Background Art

[0002] Hydrogel is a three-dimensional network polymer formed by cross-linking of macromolecules. Because of the presence of hydrophilic groups (such as hydroxyl, ether, amino or carboxyl groups) in the skeleton of its macromolecular polymer, it can bind a large amount of water and has good biocompatibility and softness. In surgical operations, the repair of infectious wounds is a difficult problem in current clinical operations. Traditional antibacterial methods have many disadvantages, such as narrow application areas, poor antibacterial properties, lack of durability and continuous use that increases bacterial resistance. Therefore, antibacterial and anti-inflammatory hydrogels are used to replace traditional antibacterial methods. At present, commonly used natural polymer hydrogels or loaded metal ions (Ag, Ni, Sr, etc.) are antibacterial, but the antibacterial effect is still poor and there is also a certain degree of cytotoxicity. Summary of the Invention

[0003] The purpose of the present invention is to overcome the above technical deficiencies, provide an antibacterial hydrogel and its preparation method and application, and solve the technical problem of poor antibacterial effect of hydrogel in the prior art.

[0004] In order to achieve the above technical objectives, the technical solution of the present invention provides a method for preparing an antibacterial hydrogel:

[0005] Using organic acid-modified gelatin quaternary ammonium salt as the matrix, oxidized alginate, borax and CuS@TA-Fe NPs as cross-linking agents, antibacterial hydrogels were obtained through in situ self-crosslinking.

[0006] Among them, the mass ratio of organic acid modified gelatin quaternary ammonium salt, oxidized alginate, borax and CuS@TA-Fe NPs is (5-30): (2.5-15): (0.1-10): (0.01-5).

[0007] Furthermore, the preparation steps of the organic acid modified gelatin quaternary ammonium salt include:

[0008] S11, mixing a gelatin aqueous solution having a pH value of 2 to 3 and a 2,3-epoxypropyltrimethylammonium chloride solution, and reacting for 6 to 12 hours to obtain an oxygen-substituted gelatin quaternary ammonium salt; the mass ratio of gelatin to 2,3-epoxypropyltrimethylammonium chloride is 10:(1 to 10);

[0009] S12. Prepare an aqueous solution of oxygen-substituted gelatin quaternary ammonium salt, add an organic acid and react for 8 to 12 hours, dialyze and dry to obtain an organic acid-modified gelatin quaternary ammonium salt; wherein the mass ratio of the oxygen-substituted gelatin quaternary ammonium salt to the organic acid is 5:(8 to 12).

[0010] Furthermore, in step S11, the concentration of the gelatin aqueous solution is 0.1 g / mL, and the concentration of the 2,3-epoxypropyltrimethylammonium chloride solution is 0.01-0.1 g / mL; in step S12, the concentration of the oxygen-substituted gelatin quaternary ammonium salt aqueous solution is 0.05 g / mL.

[0011] Furthermore, the organic acid is gallic acid.

[0012] Furthermore, the preparation steps of CuS@TA-Fe NPs include:

[0013] S21, adding TA solution to the CuS dispersion and mixing uniformly to obtain a mixed solution A;

[0014] S22. Add FeCl3-6H2O solution to mixed solution A to obtain mixed solution B, adjust the pH value of mixed solution B to weak alkalinity, collect the precipitate by centrifugation, and obtain CuS@TA-Fe NPs; wherein the mass ratio of CuS, TA and FeCl3-6H2O is 100:(70~90):(18~25).

[0015] Furthermore, in step S21, CuS is prepared as CuS nanospheres, and the specific preparation steps include: adding a CuCl2 solution to a PVP-K30 aqueous solution, then adding a NaOH solution and a N2H4-H2O solution, adding a Na2S aqueous solution after 10 to 15 minutes, centrifuging, washing and drying to obtain CuS nanospheres;

[0016] The ratio of PVP-K30, CuCl2, NaOH solution, N2H4-H2O solution and Na2S is (11-14) g: (2-3) mmol: (1200-1300) mL: (300-350) mL: (3-3.5) g; the pH value of the NaOH solution is 10, and the mass concentration of the N2H4-H2O solution is 50%.

[0017] Furthermore, in step S21, the concentration of the CuS dispersion is 2-3 mg / mL, and the concentration of the TA solution is 35-45 mg / mL; in step S22, the concentration of the FeCl3-6H2O solution is 10-12 mg / mL; and the pH value of the mixed solution B is adjusted to 7.2-7.8.

[0018] Furthermore, the specific preparation steps include:

[0019] Dissolve the organic acid-modified gelatin quaternary ammonium salt in deionized water to obtain solution A;

[0020] Dissolve oxidized alginate in deionized water to obtain solution B, and add borax to solution B to obtain solution C;

[0021] Mix equal volumes of solution A and solution C to obtain a hydrogel precursor solution;

[0022] Add the hydrogel precursor solution to the hydrogel precursor solution, disperse it evenly, and let it stand for 10 to 30 minutes to obtain the antibacterial hydrogel.

[0023] The present invention provides an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0024] The present invention provides an application of an antibacterial hydrogel in preparing an infectious wound repair medicine.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The present invention uses organic acid-modified gelatin quaternary ammonium salt as raw material, and uses oxidized alginate and borax for chemical crosslinking to form a stable network structure. The hydrogel has certain adhesion properties. The organic acid-modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel of the present invention also has good swelling properties. The swelling properties of the gel are significantly improved by the addition of CuS@TA-Fe NPs. The hydrogel has good self-healing effect and shape adaptability, and can be used as a wound dressing. Since gelatin itself is a product of natural collagen hydrolysis, the hydrogel prepared by the present invention has in vitro degradability. The CuS@TA-Fe NPs used in the present invention have peroxidase (POD)- and catalase (CAT)-like activities, and also give the hydrogel excellent antioxidant capacity. In addition, TA can also exert anti-inflammatory effects and inhibit the release of inflammatory factors. The preparation method of the present invention is low-cost, simple and easy to operate, and is expected to be industrialized. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the infrared spectrum of the synthesis of oxidized alginate (Figure A) and organic acid modified gelatin quaternary ammonium salt (Figure B) of the present invention.

[0028] Figure 2 X-ray photoelectron energy (Figure A), X-ray diffraction (Figure B), scanning electron microscopy (Figure C) and transmission electron microscopy (Figure D) of the CuS@TA-Fe NPs material of the present invention.

[0029] Figure 3 Schematic diagram of the preparation of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel of the present invention.

[0030] Figure 4 Scanning electron micrograph of organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0031] Figure 5 This is a diagram showing the self-healing effect of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel of the present invention.

[0032] Figure 6 This is a graph showing the adhesion performance results of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-FeNPs antibacterial hydrogel prepared in the present invention.

[0033] Figure 7 This is the photothermal result of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-FeNPs antibacterial hydrogel prepared in the present invention.

[0034] Figure 8 This is a diagram showing the effect of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-FeNPs antibacterial hydrogel prepared by the present invention on the repair of infected wounds in rats. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0036] The present invention provides a preparation method of an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel. The method comprises the following steps: using the organic acid modified gelatin quaternary ammonium salt as a base material, adding a chemical crosslinking agent, oxidized alginate, borax and CuS@TA-Fe NPs, and performing in-situ self-crosslinking. The added sodium tetraborate (borax) can accelerate the in-situ self-crosslinking and achieve rapid gelation. The CuS@TA-Fe NPs also serve as a physical crosslinking agent to form a three-dimensional network structure. The added CuS@TA-Fe NPs also provide the hydrogel with a photothermal effect.

[0037] The mass ratio of organic acid modified gelatin quaternary ammonium salt: oxidized alginate: borax: CuS@TA-Fe NPs is (5~30): (2.5~15): (0.1~10): (0.01~5).

[0038] The main mechanism of this invention is that traditional gelatin hydrogels have virtually no antibacterial properties. This invention improves the hydrogel's antibacterial properties by modifying gelatin into a quaternary ammonium salt. Secondly, by grafting gallic acid, the hydrogel acquires antioxidant properties. Finally, the addition of CuS@TA-Fe NPs imparts photothermal properties to the hydrogel, enabling photothermal therapy (PTT) and photodynamic therapy (PDT). This not only provides excellent antibacterial properties, but also prevents the development of drug resistance, while simultaneously enhancing the hydrogel's antibacterial and antioxidant properties. Furthermore, the hydrogel's adhesion and mechanical properties are significantly improved.

[0039] The preparation method of the present invention specifically comprises the following steps:

[0040] (1) Preparation of gelatin quaternary ammonium salt: Weigh gelatin and dissolve it in deionized water. Stir at 40-50°C until it is completely dissolved. Adjust the pH value to about 2-3 with 1% (v:v) dilute hydrochloric acid and stir evenly. Add 2,3-epoxypropyltrimethylammonium chloride dissolved in deionized water to the fully dispersed gelatin and react for 6-12 hours. After adding a certain amount of deionized water to dilute it, the product is dialyzed in distilled water, most of the water is removed by rotary evaporation, and lyophilized to obtain oxygen-substituted gelatin quaternary ammonium salt (O-Gel). The mass ratio of gelatin to 2,3-epoxypropyltrimethylammonium chloride is 10: (1-10); the concentration of the gelatin aqueous solution is 0.1 g / mL, and the concentration of the 2,3-epoxypropyltrimethylammonium chloride solution is 0.01-0.1 g / mL;

[0041] (2) Preparation of organic acid-modified gelatin quaternary ammonium salt: Weigh the prepared oxygen-substituted gelatin quaternary ammonium salt and dissolve it in deionized water. Stir at 40-50°C until it is completely dissolved. Add gallic acid at a final concentration of 8-12% (w:v) and react for 8-12 hours to obtain a gelatin quaternary ammonium salt-gallic acid solution. Dialyze in distilled water, remove most of the water using a rotary evaporator, and dry to obtain an organic acid-modified gelatin quaternary ammonium salt (O-Gel-Ga). The mass ratio of the oxygen-substituted gelatin quaternary ammonium salt to the organic acid is 5:(8-12), and the concentration of the oxygen-substituted gelatin quaternary ammonium salt aqueous solution is 0.05 g / mL.

[0042] (3) Weighing a proportion of organic acid-modified gelatin quaternary ammonium salt and dissolving it in deionized water to obtain solution A; dissolving oxidized alginate in deionized water to obtain solution B; adding a certain proportion of borax to solution B to obtain solution C; then mixing equal volumes of solution A and solution C, stirring them magnetically at room temperature, and uniformly mixing to obtain a hydrogel precursor solution. The concentrations of the crosslinking agents oxidized alginate and borax in solution C are preferably 4% and 2%, respectively.

[0043] (4) The hydrogel precursor solution was taken into a beaker, and a certain amount of CuS@TA-Fe NPs was added and magnetically stirred. After uniform dispersion, the solution was allowed to stand for 10 to 30 minutes to obtain an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0044] Preferably, the preparation steps of CuS@TA-Fe NPs include:

[0045] (a) Synthesis of CuS hollow nanospheres: 12.4 g of PVP-K30 was dissolved in 1250 ml of deionized water, followed by the addition of 5 ml of CuCl2 solution (0.5 M) and magnetic stirring at 30°C. 1250 ml of NaOH solution (pH = 10.0) and 320 μl of N2H4-H2O (50%) were then added to the suspension. 10 ml of Na2S aqueous solution (320 mg / ml) was added to the suspension after 10 minutes. The CuS nanospheres were centrifuged at 8,000 rpm for 10 minutes and washed several times with deionized water and ethanol. Finally, the CuS nanospheres were dried at 60°C to obtain the obtained CuS nanospheres.

[0046] (b) Obtaining CuS@TA-Fe NPs: 100 mg of CuS was dispersed in 40 mL of deionized water and stirred for 10 minutes. Then, 2 mL of TA solution (40 mg / mL) was added and stirred for 30 minutes. Subsequently, 2 mL of FeCl₃-6H₂O solution (10.6 mg / mL) was added, and the pH of the solution was adjusted to 7.4 with 1 M NaOH. The precipitate was collected through three centrifugation cycles at 8000 rpm for 10 minutes to obtain CuS@TA-Fe NPs.

[0047] The organic acid-modified gelatin quaternary ammonium salt of the present invention not only retains the characteristics of natural gelatin, but also has good water solubility, immunopotentiating activity and good antibacterial properties. The organic acid-modified gelatin quaternary ammonium salt (O-Gel-Ga) has a simple preparation method and low cost. Since gelatin is the product of natural collagen hydrolysis, it has good biocompatibility and can be absorbed by the skin after degradation. The organic acid-modified gelatin has good free radical scavenging ability, destroying bacterial growth and thus playing an antibacterial role.

[0048] NPs (nanoparticle) materials have great application value. The CuS@TA-Fe NPs used in this invention are nanoparticles composed of tannic acid-iron (TA-Fe) coated on the surface of hollow copper sulfide (CuS). CuS@TA-Fe NPs have both peroxidase (POD)-like and catalase (CAT)-like activities. Under acidic conditions, H2O2 can be catalyzed into ·OH; under neutral conditions, H2O2 can be decomposed into O2 to alleviate hypoxia and provide sufficient O2. The POD-like activity is mainly attributed to the CuS NPs, while the CAT-like activity is mainly attributed to the TA-Fe complex. In addition, the CuS@TA-Fe NPs endow the hydrogel with excellent antioxidant capacity, scavenging excess reactive oxygen species (ROS) in a neutral environment to maintain the balance of the antioxidant system and prevent inflammation. In addition, the hydrogel can also exert an anti-inflammatory effect by releasing TA.

[0049] The obtained organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel is used in the preparation of infectious wound repair drugs.

[0050] The present invention is further described in detail below through specific examples.

[0051] Example 1

[0052] An application of an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel is prepared by the following method;

[0053] (1) Preparation of gelatin quaternary ammonium salt: Weigh 10 g of gelatin and dissolve it in 100 mL of deionized water. Stir at 45°C until it is completely dissolved. Adjust the pH value to about 2-3 with 1% (v:v) dilute hydrochloric acid and stir evenly. Dissolve 2 g of 2,3-epoxypropyltrimethylammonium chloride in deionized water and add it to the fully dispersed gelatin solution. React for 6 hours to obtain crude oxygen-substituted gelatin quaternary ammonium salt. After adding a certain amount of deionized water for dilution, the product is then dialyzed in distilled water, most of the water is removed by rotary evaporation, and lyophilized to obtain oxygen-substituted gelatin quaternary ammonium salt (O-Gel).

[0054] (2) Preparation of organic acid-modified gelatin quaternary ammonium salt: 5 g of the prepared oxygen-substituted gelatin quaternary ammonium salt was weighed and dissolved in 100 mL of deionized water. The mixture was stirred at 45°C for 30 min. After complete dissolution, gallic acid was added at a weight volume ratio (w:v) of 10%. The mixture was reacted for 8 hours to obtain a gelatin quaternary ammonium salt-gallic acid solution. The solution was dialyzed against distilled water, most of the water was removed using a rotary evaporator, and the solution was dried to obtain the organic acid-modified gelatin quaternary ammonium salt (O-Gel-Ga).

[0055] (3) Weigh 8 g of organic acid-modified gelatin quaternary ammonium salt according to the ratio to prepare an organic acid-modified gelatin quaternary ammonium salt solution with a mass volume percentage of 8%, which is recorded as solution A;

[0056] Take oxidized alginate and water to prepare solution B, then add borax to solution B to prepare solution C, wherein the mass volume percentages of oxidized alginate and borax in solution C are 4% and 2% respectively;

[0057] Equal volumes of solution A and solution C were mixed, and magnetic stirring was performed at room temperature to uniformly mix to obtain a hydrogel precursor solution (at this time, the amounts of oxidized alginate and borax used as cross-linking agents accounted for 2% and 1% of the total volume of the hydrogel precursor solution, respectively).

[0058] (4) The hydrogel precursor solution was taken into a beaker, 0.25 g of CuS@TA-Fe NPs was added and magnetically stirred. After uniform dispersion, it was allowed to stand for 30 min to obtain an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0059] Figure 1 The infrared spectra of oxidized alginate and organic acid modified gelatin quaternary ammonium salt in this embodiment are shown in FIG. Figure 1 As shown in A, compared with SA, the -1 The new peak at confirms the structure of ADA, which is caused by the CH and C=O stretching vibrations on the aldehyde group in ADA. Figure 1 As shown in B, compared with Gel, 1464 and 1357 cm -1 The absorption peaks at 980cm and 980cm are attributed to the stretching vibrations of (CH) on the trimethylammonium group and (CN) in the tertiary amine. -1 The stretching vibration of the ether bond (COC) appears at 1604cm -1 The characteristic peaks at 1569 and 748 cm-1 of O-Gel-Ga indicate that -NH2 is retained, proving that the quaternary ammonium group is successfully introduced into the oxygen position. -1 The benzene ring shows strong stretching vibration at 1405cm -1 The bending vibration of phenolic hydroxyl (OH) appeared, and the 1464 and 1357 cm -1 The absorption peak at still exists, confirming the successful coupling of gallic acid and O-Gel.

[0060] Figure 2 Characterization was performed to verify the successful preparation of CuS@TA-Fe NPs used in this example.

[0061] Figure 3Schematic diagram of the preparation of the CuS@TA-Fe NPs-coated antibacterial hydrogel using organic acid-modified gelatin quaternary ammonium salts and oxidized alginate in this example. Oxidized alginate and organic acid-modified gelatin quaternary ammonium salts undergo a Schiff base reaction (i.e., a reaction between amino groups and aldehyde groups, removing a water molecule) to form a cross-linked network. Borax and CuS@TA-Fe NPs are then added to form another cross-linked network, resulting in the photothermal antibacterial hydrogel.

[0062] Example 2

[0063] The difference from Example 1 is that the amount of raw materials in step (3) is changed, and the other conditions are the same as those in Example 1. Specifically:

[0064] (3) Weigh 10 g of organic acid-modified gelatin quaternary ammonium salt according to the ratio to prepare a 10% by weight volume solution of organic acid-modified gelatin quaternary ammonium salt, which is referred to as solution A;

[0065] Take oxidized alginate and water to prepare solution B, then add borax to solution B to prepare solution C, wherein the mass volume percentages of oxidized alginate and borax in solution C are 6% and 3% respectively;

[0066] Equal volumes of solution A and solution C were mixed, and magnetic stirring was performed at room temperature to uniformly mix to obtain a hydrogel precursor solution (at this time, the amounts of oxidized alginate and borax used as cross-linking agents accounted for 3% and 1.5% of the total volume of the hydrogel precursor solution, respectively).

[0067] Figure 4 This is a scanning electron micrograph of the CuS@TA-Fe NPs antibacterial hydrogel coated with organic acid modified gelatin quaternary ammonium salt-oxidized alginate in this example. Figure 4 As can be seen, the surface is densely populated with pores, demonstrating the gel's ability to store large amounts of water while maintaining a stable shape. The pore walls are intact and thick, smooth, and strong, demonstrating the gel's excellent mechanical properties.

[0068] Example 3

[0069] The difference from Example 1 is that the amount of raw materials in steps (3) and (4) is changed, and the other conditions are the same as those in Example 1. Specifically:

[0070] (3) Weigh 12 g of organic acid-modified gelatin quaternary ammonium salt according to the ratio to prepare a 12% by weight volume organic acid-modified gelatin quaternary ammonium salt solution, which is referred to as solution A;

[0071] Take oxidized alginate and water to prepare solution B, then add borax to solution B to prepare solution C, wherein the mass volume percentages of oxidized alginate and borax in solution C are 8% and 4% respectively;

[0072] Equal volumes of solution A and solution C were mixed, and magnetic stirring was performed at room temperature to uniformly mix to obtain a hydrogel precursor solution (at this time, the amounts of oxidized alginate and borax used as cross-linking agents accounted for 4% and 2% of the total volume of the hydrogel precursor solution, respectively).

[0073] (4) The hydrogel precursor solution was taken into a beaker, 0.6 g of CuS@TA-Fe NPs was added and magnetically stirred. After uniform dispersion, it was allowed to stand for 30 min to obtain an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0074] Figure 5 This is the self-healing effect of the organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel in this example. Figure 5 It can be seen that the hydrogel has good shape stability, and the cracks at the joints of the two gels are clearly blurred, indicating that the hydrogel has good self-healing properties.

[0075] Example 4

[0076] The difference from Example 1 is that the amount of raw materials in steps (3) and (4) is changed, and the other conditions are the same as those in Example 1. Specifically:

[0077] (3) Weigh 16 g of organic acid-modified gelatin quaternary ammonium salt according to the ratio to prepare a 16% by weight volume organic acid-modified gelatin quaternary ammonium salt solution, which is referred to as solution A;

[0078] Take oxidized alginate and water to prepare solution B, then add borax to solution B to prepare solution C, wherein the mass volume percentages of oxidized alginate and borax in solution C are 12% and 6% respectively;

[0079] Equal volumes of solution A and solution C were mixed, magnetically stirred at room temperature, and mixed evenly to obtain a hydrogel precursor solution (at this time, the amounts of oxidized alginate and borax used as cross-linking agents accounted for 6% and 3% of the total volume of the hydrogel precursor solution, respectively).

[0080] (4) The hydrogel precursor solution was taken into a beaker, 0.75 g of CuS@TA-Fe NPs was added and magnetically stirred. After uniform dispersion, it was allowed to stand for 30 min to obtain an organic acid modified gelatin quaternary ammonium salt-oxidized alginate coated CuS@TA-Fe NPs antibacterial hydrogel.

[0081] Figure 6This figure shows the adhesion performance of the CuS@TA-Fe NPs antibacterial hydrogel coated with organic acid-modified gelatin quaternary ammonium salt and oxidized alginate in this example. The figure demonstrates the hydrogel's ability to adhere to a variety of materials and maintain firm adhesion to tissue surfaces, demonstrating excellent adhesion. Furthermore, a lap shear test on pigskin demonstrated the hydrogel's adhesion strength, reaching up to 30 kPa.

[0082] Figure 7 The photothermal temperature rise diagram of CuS@TA-Fe NPs antibacterial hydrogel coated with organic acid modified gelatin quaternary ammonium salt-oxidized alginate in this embodiment (808nm, 1W / cm 2 irradiation for 3 min).

[0083] It can be seen from the figure that the CuS@TA-Fe NPs-coated hydrogel (sample group) has a faster heating rate, reaching 61.7°C in 3 minutes, indicating better antibacterial properties.

[0084] Figure 8 The following is a photograph of the experimental results of the hydrogel prepared in Example 4 on the repair of infected wounds in rats. Specifically, a circular wound with a diameter of about 10 nm was created on the back of the rat, and the wound was used as a bacterial infection model. The blank group was not treated, while the sample group was injected with the hydrogel of the present invention and evenly spread on the wound site, and the 808 nm (1 W / cm 2 ) NIR irradiation was performed for 10 minutes on the first day. Wounds were photographed on days 0, 2, 4, 8, 12, and 14. After 2 days, all wound surfaces began to shrink, and the area of infected wounds gradually decreased with prolonged healing time. Compared with the blank group, the wound area in the sample group healed more significantly within the same healing time. This indicates that the photothermal antibacterial effect provided by the CuS@TA-Fe NPs hydrogel of the present invention contributes to wound repair.

[0085] Comparative Example 1

[0086] If the amount of organic acid-modified gelatin quaternary ammonium salt is too small and the ratio with oxidized alginate is inconsistent, the prepared hydrogel's three-dimensional network structure will be incomplete and the cross-linking density will be low, resulting in poor mechanical strength. Furthermore, if the amount of CuS@TA-Fe NPs added is too small, the antibacterial effect will not be achieved, while too much will lead to excessive toxicity. Therefore, precise control of the amount and ratio of each raw material is crucial for experimental success.

[0087] The present invention presents an organic acid-modified gelatin quaternary ammonium salt-oxidized alginate-coated CuS@TA-Fe NPs antibacterial hydrogel. Using an organic acid-modified gelatin quaternary ammonium salt as a base material, the oxidized alginate is cross-linked and coated with CuS@TA-Fe NPs for photothermal antibacterial and antioxidant properties. The process specifically comprises the following steps: dissolving the gelatin in deionized water at 45°C. After complete dissolution, the pH is adjusted to approximately 2-3 with 1% (v:v) dilute hydrochloric acid. 2,3-Epoxypropyltrimethylammonium chloride is then added to the solution to react and produce an oxygen-substituted gelatin quaternary ammonium salt solution. Dissolved gallic acid is then added to the solution to produce an organic acid-modified gelatin quaternary ammonium salt solution. Oxidized alginate and borax are added to the organic acid-modified gelatin quaternary ammonium salt solution and stirred to obtain a hydrogel precursor solution. Finally, CuS@TA-Fe NPs are added to the hydrogel precursor solution to produce the antibacterial hydrogel. The present antibacterial hydrogel can be used in the repair of infected wounds. The hydrogel has excellent photothermal effect and antioxidant capacity, and has a good healing effect on infectious wounds in mice; and the adhesion and mechanical strength of the hydrogel are significantly improved.

[0088] The specific advantages of the present invention are as follows:

[0089] 1. The present invention uses organic acid modified gelatin quaternary ammonium salt as the base material, which has excellent biocompatibility and good antibacterial properties.

[0090] 2. The present invention uses oxidized alginate and borax as cross-linking agents, which are safe and environmentally friendly and can also accelerate gelation.

[0091] 3. The CuS@TA-Fe NPs prepared in this invention exhibit excellent photothermal therapy (PTT) and photodynamic therapy (PDT), as well as peroxidase (POD)- and catalase (CAT)-like activities, exerting antibacterial, antioxidant, and anti-inflammatory effects. They demonstrated an antibacterial rate of 98.7% against Escherichia coli and 99.5% against Staphylococcus aureus. Their antioxidant capacity (free radical scavenging rate) reached approximately 85%.

[0092] 4. Pass 808nm, 1W / cm 2 The temperature can rise to above 55°C after irradiation for 3 minutes, and it has a broad-spectrum antibacterial effect.

[0093] The specific embodiments of the present invention described above do not limit the scope of protection of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. A method for preparing an antibacterial hydrogel, characterized in that: The following steps are involved: An antibacterial hydrogel was prepared by in situ self-crosslinking using organic acid-modified gelatin quaternary ammonium salt as the base material and oxidized alginate, borax and CuS@TA-Fe NPs as crosslinkers. TA is tannic acid, and the oxidized alginate is oxidized sodium alginate ADA. Among them, the mass ratios of organic acid-modified gelatin quaternary ammonium salt, oxidized alginate, borax, and CuS@TA-Fe NPs are (5-30): (2.5-15): (0.1-10): (0.01-5); The preparation steps of the organic acid modified gelatin quaternary ammonium salt include: S11, mixing a gelatin aqueous solution having a pH value of 2 to 3 and a 2,3-epoxypropyltrimethylammonium chloride solution, and reacting for 6 to 12 hours to obtain an oxygen-substituted gelatin quaternary ammonium salt; the mass ratio of gelatin to 2,3-epoxypropyltrimethylammonium chloride is 10:(1 to 10); S12, preparing an aqueous solution of an oxygen-substituted gelatin quaternary ammonium salt, adding an organic acid and reacting for 8 to 12 hours, dialyzing and drying to obtain an organic acid-modified gelatin quaternary ammonium salt; wherein the mass ratio of the oxygen-substituted gelatin quaternary ammonium salt to the organic acid is 5:(8 to 12); the organic acid is gallic acid; The preparation steps of the CuS@TA-Fe NPs include: S21, adding TA solution to the CuS dispersion and mixing uniformly to obtain a mixed solution A; S22. Add FeCl3·6H2O solution to mixed solution A to obtain mixed solution B, adjust the pH value of mixed solution B to weak alkalinity, collect the precipitate by centrifugation, and obtain CuS@TA-Fe NPs; wherein the mass ratio of CuS, TA, and FeCl3·6H2O is 100:(70-90):(18-25).

2. The method for preparing the antibacterial hydrogel according to claim 1, wherein: In step S11, the concentration of the gelatin aqueous solution is 0.1 g / mL, and the concentration of the 2,3-epoxypropyltrimethylammonium chloride solution is 0.01-0.1 g / mL; in step S12, the concentration of the oxygen-substituted gelatin quaternary ammonium salt aqueous solution is 0.05 g / mL.

3. The method for preparing the antibacterial hydrogel according to claim 1, wherein: In step S21, CuS is prepared as CuS nanospheres, and the specific preparation steps include: adding CuCl2 solution to PVP-K30 aqueous solution, then adding NaOH solution and N2H4·H2O solution, adding Na2S aqueous solution after 10-15 minutes, centrifuging, washing and drying to obtain CuS nanospheres; The ratio of PVP-K30, CuCl2, NaOH solution, N2H4·H2O solution and Na2S is (11-14) g: (2-3) mmol: (1200-1300) mL: (300-350) mL: (3-3.5) g; the pH value of the NaOH solution is 10, and the mass concentration of the N2H4·H2O solution is 50%.

4. The method for preparing the antibacterial hydrogel according to claim 1, wherein: In step S21, the concentration of the CuS dispersion is 2-3 mg / mL, and the concentration of the TA solution is 35-45 mg / mL; in step S22, the concentration of the FeCl3·6H2O solution is 10-12 mg / mL; and the pH value of the mixed solution B is adjusted to 7.2-7.

8.

5. The method for preparing the antibacterial hydrogel according to claim 1, wherein: The specific preparation steps include: Dissolve the organic acid-modified gelatin quaternary ammonium salt in deionized water to obtain solution A; Dissolve oxidized alginate in deionized water to obtain solution B, and add borax to solution B to obtain solution C; Mix equal volumes of solution A and solution C to obtain a hydrogel precursor solution; CuS@TA-Fe NPs were added to the hydrogel precursor solution and dispersed evenly, and the solution was allowed to stand for 10 to 30 minutes to obtain the antibacterial hydrogel.

6. The antibacterial hydrogel prepared by the preparation method according to any one of claims 1 to 5.

7. Use of the antibacterial hydrogel according to claim 6 in preparing a drug for repairing infectious wounds.

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