Multi-responsive synergistic antibacterial gel and applications thereof

Abstract

This invention discloses a multi-responsive synergistic antibacterial gel and its applications, relating to the field of biomedical materials technology. The multi-responsive synergistic antibacterial gel comprises a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix. The metal polyphenol core-shell nanoparticles include a core and a core-shell encapsulating the core. The core comprises a natural antibacterial active molecule and a first metal ion. The core-shell is composed of a network formed by the self-assembly of tannic acid and a second metal ion through coordination. The first metal ion and the second metal ion may be the same or different, and are independently selected from Fe. 3+ and Cu 2+ At least one of the following; the gel matrix is ​​composed of a cross-linked network containing dynamic covalent bonds formed by cross-linking of aldehyde-containing polysaccharides, amino-containing cationic polysaccharides, and polyguanidine polymers.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and more specifically, to a multi-responsive synergistic antibacterial gel and its application. Background Technology

[0002] The skin is the body's primary barrier against invading pathogens, and once damaged by trauma or surgery, it is highly susceptible to bacterial infection. Clinically, existing antibacterial strategies are often relatively simple in their mechanisms. Long-term use of chemical drugs such as antibiotics can easily induce bacterial resistance; the antibacterial efficacy, persistence, or stability of inorganic antibacterial agents (such as silver and copper ions) or natural extracts are often insufficient; physical sterilization methods (such as photothermal and electrotherapy) usually require external equipment and may damage normal tissue due to thermal effects.

[0003] In recent years, gels have received widespread attention as a medical dressing. However, existing gel dressing technologies still have the following defects, which restrict their efficacy: (1) Drug-loaded gels often have significant initial burst release problems, and it is difficult to maintain a long-lasting antibacterial concentration in the later stages of release, resulting in a short treatment window and the need for frequent dressing changes. (2) The drug release of gels mostly depends on passive diffusion or material degradation, and cannot recognize and respond to signals such as the unique slightly acidic environment and high reactive oxygen species levels of the infection site, thus failing to achieve on-demand drug release. (3) Existing technologies mostly focus on the physical blending of different antibacterial components, which has limited improvement in overall antibacterial efficiency and is difficult to deal with existing bacterial biofilms. Summary of the Invention

[0004] The purpose of this invention is to overcome the above-mentioned defects in the prior art and provide a multi-responsive synergistic antibacterial gel and its application.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows:

[0006] A multi-responsive synergistic antibacterial gel comprises a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix: the metal polyphenol core-shell nanoparticles include a core and a core-shell encapsulating the core; the core comprises a natural antibacterial active molecule and a first metal ion; the core-shell is composed of a network formed by the self-assembly of tannic acid and a second metal ion through coordination; the first metal ion may be the same as or different from the second metal ion, and is independently selected from Fe. 3+ and Cu 2+ At least one of the following; the gel matrix is ​​composed of a cross-linked network containing dynamic covalent bonds formed by cross-linking of aldehyde-containing polysaccharides, amino-containing cationic polysaccharides, and polyguanidine polymers; The preparation method of the multi-responsive synergistic antibacterial gel includes the following steps: S1. The natural antibacterial active molecule and the first metal salt are added to a buffer solution with a pH of 5.0-6.0, and stirred for 10-30 min at 25-35°C in the dark to obtain a core precursor solution. Under continuous stirring, an aqueous solution of tannic acid is added dropwise to the core precursor solution. After the addition is complete, stirring is continued for 10-20 min. Subsequently, an aqueous solution of the second metal salt is added dropwise to the resulting mixture. After the addition is complete, the reaction is continued for 1-3 h at 25-37°C in the dark to obtain a crude dispersion. The crude dispersion is purified by centrifugation to obtain a nanoparticle dispersion. S2. Add the aldehyde-containing polysaccharide to the phosphate buffer solution and mix and stir to prepare solution A; add the amino-containing cationic polysaccharide and the polyguanidine polymer to the solvent and mix and stir to prepare solution B; add solution B to solution A and mix and stir to obtain precursor solution C; S3. Add the nanoparticle dispersion to the precursor solution C and mix and stir. Then let the resulting mixture stand and crosslink at 25~37℃ for 1~10 min. After that, place it in a 4℃ environment to cure for 1~2 h to obtain the multi-responsive synergistic antibacterial gel.

[0007] Optionally, the mass percentage of the metal polyphenol core-shell nanoparticles in the gel is 0.1% to 5%.

[0008] Optionally, the core comprises 5% to 40% of the mass percentage of the metal polyphenol core-shell nanoparticles.

[0009] Optionally, in the core, the mass ratio of the natural antibacterial active molecule to the first metal ion is (1:2) to (2:1).

[0010] Optionally, in the core-shell structure, the molar ratio of the second metal ion to the catechol group in the tannic acid is 1:(2~4).

[0011] Optionally, in the gel matrix, the mass ratio of the aldehyde-containing polysaccharide, the amino-containing cationic polysaccharide, and the polyguanidine polymer is (1~10):(1~10):(0.5~5).

[0012] Optionally, the natural antibacterial active molecule is selected from at least one of curcumin, baicalin, notoginsenoside R1, and gallocatechin gallate.

[0013] Optionally, the first metal ion is Cu. 2+ The second metal ion is Fe. 3+ .

[0014] Optionally, the aldehyde-containing polysaccharide is oxidized dextran or oxidized hyaluronic acid.

[0015] Optionally, the amino-containing cationic polysaccharide is chitosan.

[0016] Optionally, the polyguanidine polymer is polyhexamethylene biguanide.

[0017] Optionally, the dynamic covalent bond is a Schiff base bond.

[0018] Optionally, in step S1, the buffer solution is 2-(N-morpholine)ethanesulfonic acid buffer; the dropping rate is 0.5~2 mL / min.

[0019] Optionally, the first metal salt is selected from metal chlorides, nitrates, or sulfates; the metal salt in the second metal salt aqueous solution is selected from metal chlorides, nitrates, or sulfates.

[0020] Optionally, the first metal salt is copper chloride or copper nitrate; the metal salt in the second metal salt aqueous solution is ferric chloride or ferric nitrate.

[0021] Optionally, in step S2, the solvent is a 0.1% acetic acid solution; and the pH of the phosphate buffer solution is 7.0~7.4.

[0022] The present invention also discloses the application of the above-described multi-responsive synergistic antibacterial gel in the preparation of antibacterial materials or medical dressings.

[0023] Optional, the pathogenic bacterium is Staphylococcus aureus.

[0024] The present invention also discloses the application of the above-described multi-responsive synergistic antibacterial gel in the preparation of products for treating bacterial infections caused by Staphylococcus aureus.

[0025] Optionally, the multi-responsive synergistic antibacterial gel has an inhibition rate of 99.1% to 99.9% against Staphylococcus aureus.

[0026] Implementing the embodiments of the present invention will have the following beneficial effects: The multi-responsive synergistic antibacterial gel provided by this invention comprises a gel matrix and metal polyphenol core-shell nanoparticles dispersed therein. The metal polyphenol core-shell nanoparticles contain natural antibacterial active molecules and Cu... 2+ With metal ions at the core, the reaction occurs through the catechol groups of tannic acid and Fe. 3+ Metal ions undergo coordination complexation to form a shell on the core surface. The nanoparticles are encapsulated in a dynamic covalently bonded gel network formed by cross-linking of aldehyde-containing polysaccharides, amino-containing cationic polysaccharides, and polyguanidine polymers via Schiff base reaction.

[0027] When applied to infected wounds, the multi-responsive synergistic antibacterial gel of this invention achieves synergistic antibacterial action through a multi-level structure and responsive design. First, the amino-containing cationic polysaccharides and polyguanidine polymers in the gel matrix, with their positive charge, can disrupt the negatively charged bacterial (Staphylococcus aureus) cell membranes through electrostatic interactions, facilitating initial physical sterilization and reducing the bacterial load on the wound. Subsequently, the unique slightly acidic microenvironment of the infected site triggers the gel's intelligent response. On one hand, the dynamic Schiff base bonds constituting the gel network can undergo reversible breakage under slightly acidic conditions, facilitating the diffusion and release of the encapsulated metal polyphenol core-shell nanoparticles into the wound environment. On the other hand, the metal-polyphenol shell of the nanoparticles becomes less stable in this microenvironment, undergoing responsive dissociation, thereby controllably releasing the natural antibacterial active molecules and Cu from its core. 2+ This helps overcome the problems of sudden release and uncontrollable release in traditional drug delivery systems, and the released Cu 2+ It can interfere with bacterial metabolism; natural antibacterial molecules can disrupt biofilms and synergize with metal ions, thereby continuously clearing residual bacteria and early biofilms, thus producing a highly effective antibacterial effect against Staphylococcus aureus. Furthermore, this invention uses natural polysaccharides and biodegradable polymers as base materials, exhibiting good biocompatibility. The preparation method involved is reliable and highly reproducible, possessing promising prospects for industrial application. Detailed Implementation

[0028] The present invention will be further described below with reference to specific embodiments, but this does not limit the present invention in any way.

[0029] Example 1 The multi-responsive synergistic antibacterial gel of this embodiment includes a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix, wherein the mass percentage of the metal polyphenol core-shell nanoparticles in the gel is 2%.

[0030] The metal polyphenol core-shell nanoparticles consist of a core and a core-shell coating the core; the core accounts for 20% of the mass of the metal polyphenol core-shell nanoparticles.

[0031] The core contains curcumin and Cu 2+ The core and shell are composed of tannic acid and Fe. 3+ The network is formed through self-assembly via coordination; in the core, curcumin and Cu... 2+ The mass ratio is 1:1. In the core and shell, Fe... 3+ The molar ratio of the catechol group in tannic acid to the catechol group is 1:3.

[0032] The gel matrix is ​​composed of a cross-linked network containing Schiff base bonds formed by cross-linking oxidized hyaluronic acid, chitosan and polyhexamethylene biguanide; the mass ratio of oxidized hyaluronic acid, chitosan and polyhexamethylene biguanide in the gel matrix is ​​5:5:1.

[0033] The preparation method of the multi-responsive synergistic antibacterial gel in this embodiment includes the following steps: S1. Curcumin and copper nitrate were added to a 2-(N-morpholine)ethanesulfonic acid buffer solution with a pH of 5.5 and stirred for 20 min at 30°C in the dark to obtain a core precursor solution. Under continuous stirring, an aqueous solution of tannic acid was added dropwise to the core precursor solution at a rate of 1 mL / min. After the addition was complete, stirring was continued for 15 min. Subsequently, an aqueous solution of ferric chloride was added dropwise to the resulting mixture at the same rate. After the addition was complete, the reaction was continued for 2 h at 30°C in the dark to obtain a crude dispersion. The crude dispersion was purified by centrifugation to obtain a nanoparticle dispersion.

[0034] S2. Add oxidized hyaluronic acid to a phosphate buffer solution with a pH of 7.2 and mix to prepare solution A; add chitosan and polyhexamethylene biguanide to a 0.1% acetic acid solution and mix to prepare solution B; add solution B to solution A and mix to obtain precursor solution C.

[0035] S3. Add the nanoparticle dispersion to the precursor solution C and mix and stir. Then let the resulting mixture stand and crosslink at 37°C for 5 min. After that, place it in an environment of 4°C to cure for 1.5 h to obtain a multi-responsive synergistic antibacterial gel.

[0036] Example 2 The multi-responsive synergistic antibacterial gel of this embodiment includes a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix: the mass percentage of metal polyphenol core-shell nanoparticles in the gel is 0.5%.

[0037] The metal polyphenol core-shell nanoparticles consist of a core and a core-shell coating the core; the core accounts for 10% of the mass of the metal polyphenol core-shell nanoparticles.

[0038] The core contains baicalin and Cu. 2+ The core and shell are composed of tannic acid and Fe. 3+ The network is formed through self-assembly via coordination; in the core, baicalin and Cu... 2+ The mass ratio is 1:2. In the core and shell, Fe... 3+ The molar ratio of the catechol group in tannic acid to the catechol group is 1:2.

[0039] The gel matrix consists of a cross-linked network containing Schiff base bonds, formed by cross-linking oxidized dextran, chitosan, and polyhexamethylene biguanide. The mass ratio of oxidized dextran, chitosan, and polyhexamethylene biguanide in the gel matrix is ​​2:2:0.5.

[0040] The preparation method of the multi-responsive synergistic antibacterial gel in this embodiment includes the following steps: S1. Baicalin and copper chloride were added to a 2-(N-morpholine)ethanesulfonic acid buffer solution with a pH of 5.0 and stirred for 30 min at 25°C in the dark to obtain a core precursor solution. Under continuous stirring, an aqueous solution of tannic acid was added dropwise to the core precursor solution at a rate of 0.5 mL / min. After the addition was complete, stirring was continued for 20 min. Subsequently, an aqueous solution of ferric nitrate was added dropwise to the resulting mixture at the same rate. After the addition was complete, the reaction was continued for 1 h at 25°C in the dark to obtain a crude dispersion. The crude dispersion was purified by centrifugation to obtain a nanoparticle dispersion.

[0041] S2. Add oxidized dextran to phosphate buffer solution with pH 7.0 and mix to prepare solution A; add chitosan and polyhexamethylene biguanide to 0.1% acetic acid solution and mix to prepare solution B; add solution B to solution A and mix to obtain precursor solution C.

[0042] S3. Add the nanoparticle dispersion to the precursor solution C and mix and stir. Then let the resulting mixture stand and crosslink at 25°C for 10 min. After that, place it in a 4°C environment to cure for 2 h to obtain a multi-responsive synergistic antibacterial gel.

[0043] Example 3 The multi-responsive synergistic antibacterial gel of this embodiment includes a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix: the mass percentage of metal polyphenol core-shell nanoparticles in the gel is 5%.

[0044] The metal polyphenol core-shell nanoparticles consist of a core and a core-shell coating the core; the core accounts for 30% of the mass of the metal polyphenol core-shell nanoparticles.

[0045] The core contains curcumin and Cu 2+ The core and shell are composed of tannic acid and Fe. 3+ The network is formed through self-assembly via coordination; in the core, curcumin and Cu... 2+ The mass ratio is 2:1. In the core and shell, Fe... 3+ The molar ratio of the catechol group in tannic acid to the catechol group is 1:4.

[0046] The gel matrix consists of a cross-linked network containing Schiff base bonds, formed by cross-linking oxidized hyaluronic acid, chitosan, and polyhexamethylene biguanide. The mass ratio of oxidized hyaluronic acid, chitosan, and polyhexamethylene biguanide in the gel matrix is ​​8:8:3.

[0047] The preparation method of the multi-responsive synergistic antibacterial gel in this embodiment includes the following steps: S1. Curcumin and copper nitrate were added to a 2-(N-morpholine)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred for 10 min at 35°C in the dark to obtain a core precursor solution. Under continuous stirring, an aqueous solution of tannic acid was added dropwise to the core precursor solution at a rate of 2 mL / min. After the addition was complete, stirring was continued for 10 min. Subsequently, an aqueous solution of ferric nitrate was added dropwise to the resulting mixture at the same rate. After the addition was complete, the reaction was continued for 3 h at 37°C in the dark to obtain a crude dispersion. The crude dispersion was purified by centrifugation to obtain a nanoparticle dispersion.

[0048] S2. Add oxidized hyaluronic acid to a phosphate buffer solution with a pH of 7.4 and mix to prepare solution A; add chitosan and polyhexamethylene biguanide to a 0.1% acetic acid solution and mix to prepare solution B; add solution B to solution A and mix to obtain precursor solution C.

[0049] S3. Add the nanoparticle dispersion to the precursor solution C and mix and stir. Then let the resulting mixture stand and crosslink at 30°C for 3 min. After that, place it in an environment of 4°C for 1 h to cure and obtain a multi-responsive synergistic antibacterial gel.

[0050] Comparative Example 1 The only difference between this comparative example and Example 1 is that no metal polyphenol core-shell nanoparticles were added.

[0051] The preparation method of this comparative example includes the following steps: oxidized hyaluronic acid is added to a phosphate buffer solution with a pH of 7.2 and mixed and stirred to prepare solution A; chitosan and polyhexamethylene biguanide are added to a 0.1% acetic acid solution and mixed and stirred to prepare solution B; solution B is added to solution A and mixed and stirred to obtain precursor solution C. Precursor solution C is then allowed to stand and crosslinked at 37°C for 5 min, followed by curing at 4°C for 1.5 h to obtain the gel of this comparative example.

[0052] Comparative Example 2 The only difference between this comparative example and Example 1 is that polyhexamethylene biguanide is not added.

[0053] Comparative Example 3 The only difference between this comparative example and Example 1 is that step S1 involves a one-step mixing process.

[0054] The preparation method of this comparative example includes the following steps: Curcumin, copper nitrate, aqueous solutions of tannic acid, and ferric chloride are simultaneously added to a 2-(N-morpholine)ethanesulfonic acid buffer solution with a pH of 5.5. The mixture is stirred at 30°C under light-protected conditions for 2 hours to obtain a crude dispersion. The crude dispersion is then purified by centrifugation to obtain a final dispersion. Then, the gel of this comparative example is prepared according to the preparation methods S2 and S3 of Example 1.

[0055] Test Example 1 Weigh 100.0 mg of the gel samples from the examples and comparative examples into sterile 1.5 mL centrifuge tubes. Inoculate Staphylococcus aureus into liquid culture medium and culture at 37°C and 150 rpm with shaking until the logarithmic growth phase. Adjust the bacterial concentration to approximately 1 × 10⁻⁶ using sterile phosphate-buffered saline (PBS, pH 7.4). 6 CFU / mL. A blank control group was set up, in which no gel sample was added to the centrifuge tubes. 1.0 mL of the prepared bacterial suspension was added to all centrifuge tubes (including the sample group and the blank control group). All centrifuge tubes were incubated at 37°C in a shaker at 100 rpm for 4 h. After incubation, the bacterial suspension was aspirated from each centrifuge tube and serially diluted 10-fold using sterile PBS. 100 μL of the appropriately diluted bacterial suspension was evenly spread onto nutrient agar plates. All plates were incubated at 37°C for 24 h, after which the colonies on the plates were counted (CFU). The inhibition rate of each sample was calculated. The test results are shown in Table 1.

[0056] Antibacterial rate = (AB) / A × 100%, where A is the number of colonies after the blank sample is cultured and B is the number of colonies after the test sample is cultured.

[0057] Table 1

[0058] Test Example 2 Two 5 mL portions of the gels prepared in Example 1 and Comparative Example 3 were transferred and placed in dialysis bags with a molecular weight cutoff of 3.5 kDa. The two dialysis bags were then placed in two stoppered conical flasks containing 200 mL of PBS buffer solution (pH = 5.5 and pH = 7.4, respectively), and the mixture was subjected to in vitro release in a constant-temperature shaker at 37°C and 120 rpm. 1 mL samples were taken at predetermined time points and measured using ultraviolet spectrophotometry. An equal volume of fresh PBS buffer solution was added to each sample. Three replicates were prepared for each sample group, and the concentration of curcumin was calculated to determine the release rate. Release rate = cumulative release amount / drug loading × 100%. Data from four time points (1 h, 4 h, 24 h, and 72 h) were analyzed and compared. The results are shown in Table 2.

[0059] Table 2

[0060] As shown in Table 2, the gel of Example 1 exhibited pH-responsive release behavior. Under physiological conditions (pH=7.4), a total of 32.4% was released by 72 hours. However, in a simulated slightly acidic infection environment (pH=5.5), the release rate of curcumin increased significantly, reaching 89.5% within 72 hours. Comparative Example 3 showed a rapid burst release within 24 hours under both pH conditions, with no difference in pH response. These results demonstrate that the gel structure constructed through stepwise self-assembly in this invention can achieve controlled drug release.

[0061] Test Example 3 The gel samples from Example 1 and Comparative Example 3 were sealed and aliquoted, and stored at 25°C in the dark for 6 months. After treatment, the antibacterial activity retention rate of the samples was tested: the antibacterial rate of the samples before and after treatment was determined according to the antibacterial test method for Staphylococcus aureus in Test Example 1, and the activity retention rate (%) was calculated as (antibacterial rate of treated sample / antibacterial rate of fresh sample) × 100%. The test results are shown in Table 3.

[0062] Table 3

[0063] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A multi-responsive synergistic antibacterial gel, characterized in that, Includes a gel matrix and metal polyphenol core-shell nanoparticles dispersed in the gel matrix: The metal polyphenol core-shell nanoparticles include a core and a core-shell covering the core; The core comprises a natural antibacterial active molecule and a first metal ion; the natural antibacterial active molecule is selected from at least one of curcumin, baicalin, notoginsenoside R1 and gallic catechin gallate; The core-shell structure is composed of a network formed by the self-assembly of tannic acid and a second metal ion through coordination; the first metal ion may be the same as or different from the second metal ion, and is independently selected from Fe. 3+ and Cu 2+ At least one of them; The gel matrix is ​​composed of a cross-linked network containing dynamic covalent bonds, formed by cross-linking aldehyde-containing polysaccharides, amino-containing cationic polysaccharides, and polyguanidine polymers. The preparation method of the multi-responsive synergistic antibacterial gel includes the following steps: S1. The natural antibacterial active molecule and the first metal salt are added to a buffer solution with a pH of 5.0-6.0, and stirred for 10-30 min at 25-35°C in the dark to obtain a core precursor solution. Under continuous stirring, an aqueous solution of tannic acid is added dropwise to the core precursor solution. After the addition is complete, stirring is continued for 10-20 min. Subsequently, an aqueous solution of the second metal salt is added dropwise to the resulting mixture. After the addition is complete, the reaction is continued for 1-3 h at 25-37°C in the dark to obtain a crude dispersion. The crude dispersion is purified by centrifugation to obtain a nanoparticle dispersion. S2. Add the aldehyde-containing polysaccharide to the phosphate buffer solution and mix and stir to prepare solution A; add the amino-containing cationic polysaccharide and the polyguanidine polymer to the solvent and mix and stir to prepare solution B; add solution B to solution A and mix and stir to obtain precursor solution C; S3. Add the nanoparticle dispersion to the precursor solution C and mix and stir. Then let the resulting mixture stand and crosslink at 25~37℃ for 1~10 min. After that, place it in a 4℃ environment to cure for 1~2 h to obtain the multi-responsive synergistic antibacterial gel.

2. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, The mass percentage of the metal polyphenol core-shell nanoparticles in the gel is 0.1% to 5%. The core contains 5% to 40% by mass of the metal polyphenol core-shell nanoparticles. In the core, the mass ratio of the natural antibacterial active molecule to the first metal ion is (1:2) to (2:1). In the core-shell structure, the molar ratio of the second metal ion to the catechol group in the tannic acid is 1:(2~4). In the gel matrix, the mass ratio of the aldehyde-containing polysaccharide, the amino-containing cationic polysaccharide, and the polyguanidine polymer is (1~10):(1~10):(0.5~5).

3. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, The first metal ion is Cu 2+ The second metal ion is Fe. 3+ ; The polysaccharide containing aldehyde groups is oxidized dextran or oxidized hyaluronic acid; The amino-containing cationic polysaccharide is chitosan; The polyguanidine polymer is polyhexamethylene biguanide.

4. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, The dynamic covalent bond is a Schiff base bond.

5. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, In step S1, the buffer solution is 2-(N-morpholine)ethanesulfonic acid buffer; the dropping rate is 0.5~2 mL / min; the first metal salt is selected from metal chloride, nitrate or sulfate; the metal salt in the second metal salt aqueous solution is selected from metal chloride, nitrate or sulfate.

6. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, The first metal salt is copper chloride or copper nitrate; the metal salt in the aqueous solution of the second metal salt is ferric chloride or ferric nitrate.

7. The multi-responsive synergistic antibacterial gel according to claim 1, characterized in that, In step S2, the solvent is a 0.1% acetic acid solution; the pH of the phosphate buffer solution is 7.0~7.

4.

8. The use of a multi-responsive synergistic antibacterial gel as described in any one of claims 1-7 in the preparation of antibacterial materials or medical dressings.

9. The use of a multi-responsive synergistic antimicrobial gel as described in any one of claims 1-7 in the preparation of a product for treating bacterial infections caused by Staphylococcus aureus.

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