WO2023231051A1 - Antibacterial, antioxidant hydrogel dressing for treating diabetic wounds and preparation method therefor - Google Patents

Abstract

The present invention relates to an antibacterial, antioxidant hydrogel dressing for treating diabetic wounds and a preparation method therefor. The dressing is obtained by cross-linking epoxy groups in a gel-forming framework polymer containing glycidyl methacrylate with amino groups in an electrostatic complex of hyperbranched polylysines and a manganese dioxide nanosheet by means of a ring-opening reaction. A multifunctional injectable hydrogel with antibacterial activity, active oxygen removal, oxygen supply and drug release can be prepared by combining a drug promoting nitric oxide synthesis. By means of electrostatic compounding of hyperbranched polylysines and the manganese dioxide nanosheet, the problem that manganese dioxide has poor stability in physiological environments is solved. The in-vitro characterization of the hydrogel confirms its good antibacterial performance and excellent performance in removing active oxygen or free radicals such as diphenyl picrylhydrazyl radicals, hydrogen peroxide, hydroxyl radicals and superoxide anions. The hydrogel dressing can be used for treating wounds in patients with type II diabetes. The hydrogel dressing can help diabetic infection wounds transition steadily from an inflammatory phase to a proliferative phase, accelerating the organized repair of wounds.

Description

An antibacterial and antioxidant hydrogel dressing for treating diabetic wounds and preparation method thereof Technical field

The invention relates to the technical field of medical hydrogel dressings, and in particular to an antibacterial and antioxidant hydrogel dressing used to treat wounds of diabetic patients and a preparation method thereof.

Background technique

With the extension of human life span and the improvement of living standards, the incidence of diabetes is increasing year by year, and the incidence of type II diabetes is trending younger. Clinically, diabetic patients have weakened ability to resist bacterial infections due to immune system disorders, and are more susceptible to infection in various damaged areas. Because the skin wounds of diabetic patients are characterized by moisture and high sugar content, they provide a good place for the growth of bacteria. Skin wound infection is the most serious problem and is one of the important factors inducing diabetic foot. Neutrophils are one of the most important immune cells in fighting infection during the early stages of inflammation. However, due to long-term systemic chronic inflammation induced by hyperglycemia in diabetic patients, neutrophils are under long-term pressure and often have major functional defects and are unable to exert their proper immune function. Compared with ordinary infected wounds, the microenvironment of diabetic infected wounds is more complex. In addition to oxidative stress caused by high levels of reactive oxygen species, it is also accompanied by diabetes-specific highly expressed pro-inflammatory factors (such as tumor necrosis factor-α, leukocyte-mediated inflammatory factors). factor-1β, interleukin-6, etc.), hypoxia, nutritional deficiencies, blocked nitric oxide synthesis, etc. The healing of skin wounds includes four processes: hemostasis, inflammation, proliferation, and remodeling. The slow inflammatory process hinders the normal transition from the inflammatory phase to the subsequent proliferation and remodeling phases, further inducing the generation of chronic wounds that are difficult to heal.

More and more studies have proven that antioxidant hydrogel can alleviate the development of inflammation by regulating the level of reactive oxygen species in the wound. It is the most ideal and most potential dressing for caring for wounds in diabetic patients. Water with both antibacterial and antioxidant functions The gel is effective in preventing excessive inflammation caused by infection. Antioxidant enzymes are required to eliminate reactive oxygen species, but enzymes are very easy to inactivate and require strict preparation and application conditions. The inorganic material manganese dioxide nanozyme can simulate the functions of a variety of antioxidant enzymes, such as catalase and superoxide dismutase, and is an ideal antioxidant enzyme substitute. Manganese dioxide can be made into various nanoscale forms, such as nanorods, nanosheets, nanospheres, nanoparticles, etc. Among them, ultra-thin two-dimensional nanosheets are easy to prepare, have large specific surface area, strong redox ability, and are environmentally friendly. It has good biocompatibility and has attracted widespread attention.

Currently, some hydrogel dressings used on wounds of diabetic patients can achieve both antibacterial and antioxidant properties, but there is still no solution to the problems of hypoxia and obstruction of nitric oxide synthesis in the wounds of diabetic patients. If functional substances that promote the production of oxygen are added to the hydrogel dressing, dissolved oxygen can be effectively delivered to diabetic wounds, and local hypoxia caused by the mismatch between the synthesis rate of antioxidant enzymes and the production rate of reactive oxygen species can be further promoted. Orderly healing of skin wounds. Manganese dioxide nanozymes can achieve this function because manganese dioxide nanozymes can generate oxygen while scavenging reactive oxygen species. However, nanoscale manganese dioxide has poor stability in physiological environments and is prone to aggregation under the action of ions. And when the dosage of manganese dioxide is inappropriate, it can easily cause cytotoxicity. Increasing manganese dioxide stability and avoiding toxicity are issues that continue to be addressed in the nanozyme field.

Similarly, the problem of blocked nitric oxide synthesis in wounds of diabetic patients can also be solved by adding drugs that can promote nitric oxide synthesis into hydrogel dressings. However, existing hydrogel dressings lack the exploration of this method. .

In addition, the wounds of diabetic patients often have complex shapes, and if the infection is not treated promptly in the early stage, it is easy to spread to deep tissues and even penetrate into the bones. This puts forward higher requirements for the application form of hydrogel dressings, that is, it needs to be spreadable. sex. However, most hydrogel dressings that can achieve antibacterial and antioxidant properties are in the form of blocks and cannot adapt to the complex shape and depth of wounds in diabetic patients, and cannot effectively cover and protect the entire wound.

Contents of the invention

In view of the above problems, the object of the present invention is to provide an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds and a preparation method thereof. The hydrogel dressing consists of a ring-opening reaction between epoxy groups in a gel-forming backbone polymer containing glycidyl methacrylate and amino groups in an electrostatic complex of hyperbranched polylysine and manganese dioxide nanosheets. It is cross-linked and has the characteristics of high-efficiency broad-spectrum antibacterial, elimination of reactive oxygen species, oxygen supply, drug release to promote nitric oxide synthesis, and smearability to cope with the complex tissue microenvironment of diabetic infected wounds and promote wound healing in diabetic patients.

In order to achieve the above objects, the present invention provides the following technical solution, an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds and a preparation method thereof, which includes the following steps:

1) Dissolve glycidyl methacrylate and other gel-forming skeleton monomers in methanol, bubble with nitrogen to remove oxygen, add azobisisobutyronitrile initiator, and heat to reflux at 50-80°C for 8-24 hours. . After the reaction was completed, the crude product was obtained by precipitating with glacial ether and centrifuging. The crude product was repeatedly dissolved and precipitated in a methanol-glacial ether system to remove impurities. Finally, the solvent is fully removed by rotary evaporation and vacuum drying to obtain a gel-forming skeleton polymer.

2) Add sodium lauryl sulfate and sulfuric acid to the water, stir and heat to 95°C. After heating for 10-20 minutes, add potassium permanganate dropwise to the reaction solution and continue heating for about 1 hour. Stop the reaction when the reaction system changes from purple to colorless and brown precipitate particles are produced. The manganese dioxide precipitate was collected by centrifugation and washed repeatedly with water. Manganese dioxide powder is dispersed by ultrasound. Add manganese dioxide powder to water and ultrasonic for 3-6 hours to obtain a brown suspension, which is manganese dioxide nanosheet dispersion.

3) Mix equal volumes of the hyperbranched polylysine solution and the manganese dioxide nanosheet dispersion prepared in step 2) and sonicate for 20-60 minutes. The mixed solution was centrifuged, the bottom precipitate was discarded, and the upper liquid was collected and further centrifuged to obtain a hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution.

4) Mix the drug to be loaded into the hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution prepared in step 3), and then add the gel-forming skeleton polymer prepared in step 1) and make it fully Dissolve and then react at 37°C for 10-24 hours to obtain an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds.

Further, the other gel-forming skeleton monomer in step 1) is at least one of polyethylene glycol methyl ether methacrylate, acrylamide, and acrylic acid.

Further, in step 1), the molar ratio of glycidyl methacrylate and other gel-forming skeleton monomers is 1:1-1:3, and the total monomer concentration is 5-10 mg/mL; the initiator The molar amount of azobisisobutyronitrile accounts for 1 to 15% of the total molar amount of monomers.

Further, the concentrations of sodium lauryl sulfate, sulfuric acid and potassium permanganate in step 2) are 5-20mmol/L, 1-10mmol/L and 0.1-1mmol/L respectively.

Further, the concentration of the manganese dioxide nanosheet dispersion in step 2) is 0.5-10 mg/mL.

Further, the molecular weight of hyperbranched polylysine in step 3) is 2-10kDa, the solution concentration is 20-200mg/mL, and the concentrations of hyperbranched polylysine and manganese dioxide nanosheets after mixing are 10-100mg respectively. /mL, 0.25-5mg/mL.

Further, the drug to be loaded in step 4) is at least one of pravastatin sodium, madecassoside, epicatechin and other tea polyphenols, with a concentration of 0.5-5 mg/mL.

Further, the concentration of the gel-forming skeleton solution in step 4) is 0.01-0.5 mg/mL.

Furthermore, the antibacterial and antioxidant hydrogel dressing prepared by the method of the present invention can be directly used as a wound treatment drug for diabetic patients or mixed with pharmaceutically acceptable auxiliary materials and then applied to the wound.

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

1. The invention provides an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds. It is loaded with hyperbranched polylysine and contains a large amount of amino groups. It can achieve this by destroying bacterial cell membranes and DNA and increasing the level of active oxygen in the bacteria. Antibacterial and bactericidal effects. And hyperbranched polylysine is safe and non-toxic.

2. The invention provides an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds. Through the loaded manganese dioxide nanosheets, it can eliminate hydrogen peroxide, superoxide anions, hydroxyl radicals and other active oxygen species. Oxygen is released at the same time, and the negatively charged oxygen atoms in the manganese dioxide nanosheets are electrostatically combined with the positively charged amino groups in the hyperbranched polylysine to achieve the effect of stabilizing the nanomanganese dioxide in a physiological environment.

3. The invention provides an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds, which can realize drug loading and can transport pravastatin sodium, a drug that promotes nitric oxide synthesis, to the wounds of diabetic patients and release it to improve diabetes. The problem of nitric oxide synthesis in the patient's wound is blocked.

4. The present invention provides an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds. It is a spreadable ointment and can therefore effectively protect various wounds of diabetic patients with complex shapes and depths.

Description of the drawings

Figure 1 is a synthesis route diagram of hydrogel in Example 1, (a) is the synthesis route of poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylamide), (b) ) is the synthesis of hydrogel obtained by reacting the epoxy group in poly(ethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylamide) and the amino group in hyperbranched polylysine route;

Figure 2 is the Fourier transform infrared spectrum of the hydrogel and each main component in Example 1;

Figure 3 is a schematic diagram of the spreadability of the hydrogel in Example 1;

Figure 4 shows the scavenging capabilities of hydrogels H and HM in Example 2 for (a) hydrogen peroxide, (b) superoxide anion, (c) diphenylpicrylhydrazyl radical and (d) hydroxyl radical;

Figure 5 is a graph showing oxygen release from hydrogel HM (a) in the presence of 10mM hydrogen peroxide in Example 2 and (b) oxygen bubbles observed after 30 minutes of reaction;

Figure 6 shows the in vitro antibacterial properties of hydrogels H and HM in Example 2;

Figure 7 shows the therapeutic effect of the hydrogel in Example 2 on full-thickness skin defects infected by methicillin-resistant Staphylococcus aureus in diabetic rats.

Detailed ways

The technical solutions of the present invention will be further described below with reference to examples, but these examples are not intended to limit the present invention.

Example 1:

1) Dissolve 18.0g polyethylene glycol methacrylate, 2.84g glycidyl methacrylate and 2.84g acrylamide in 250mL methanol, remove oxygen by bubbling with nitrogen, and add 2.56g azobisisobutyronitrile. The mixture was heated to reflux at 70°C for 10 hours. The reaction product was separated by sedimentation in glacial ether, and the crude product was obtained after centrifugation (×5,000 rpm, 10 min). Repeat the dissolution-sedimentation process of the crude product in a methanol-glacial ether system more than two times to remove impurities. Finally, the solvent was completely removed by rotary evaporation and vacuum drying. The obtained product poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylamide) is a white transparent viscous liquid.

2) Add 30 mL of 0.1 mol/L sodium lauryl sulfate and 1.5 mL of 0.1 mol/L sulfuric acid to 265.5 mL of water, stir and heat to 95°C, and after heating for 15 minutes, add 3 mL of 50 mM potassium permanganate. Add dropwise to the reaction solution. Continue heating for about 1 hour, stop the reaction when the reaction system changes from purple to colorless, and brown precipitate particles are produced. The manganese dioxide precipitate was collected by centrifugation (×8000 rpm, 5 min) and washed repeatedly with water. Manganese dioxide powder is dispersed by ultrasound. Add 3 mg of manganese dioxide to 3 mL of water and ultrasonic for 4 hours to obtain a brown suspension, which is the manganese dioxide nanosheet dispersion.

3) Mix the hyperbranched polylysine solution (45.36mg/mL, 3kDa) and the manganese dioxide nanosheet dispersion prepared in the second step at a volume ratio of 1:1 and sonicate for 30 minutes. The final concentrations of hyperbranched polylysine and manganese dioxide were 22.68 mg/mL and 0.5 mg/mL respectively. Centrifuge the mixed solution at 1000 rpm for 5 minutes, discard the bottom precipitate, and collect the upper liquid. The upper liquid was further centrifuged at 10,000 rpm for 10 minutes to obtain a hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution.

4) Fully dissolve 0.07 mg of poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylamide) in 1 mL of hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution and reacted at 37°C for 12 hours to obtain a hyperbranched polylysine cross-linked hydrogel (hydrogel HM) containing manganese dioxide nanosheets. As a reference, 0.07 mg of poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylamide) was dissolved in 1 mL, 22.68 mg/mL, 3 kDa hyperbranched polylysine solution , reacted at 37°C for 12 hours to obtain hyperbranched polylysine cross-linked hydrogel (hydrogel H).

The synthetic route for preparing hydrogel in this embodiment is shown in Figure 1. The Fourier transform infrared spectrum of the hydrogel and each main component is shown in Figure 2. The spreadability of the hydrogel is shown in Figure 3. , in the form of an ointment, can be easily squeezed out from a 0.45 mm diameter syringe needle for easy application.

Example 2:

1) Dissolve 18.0g polyethylene glycol methacrylate, 2.84g glycidyl methacrylate and 2.88g acrylic acid in 250mL methanol. After bubbling with nitrogen to remove oxygen, add 2.56g azobisisobutyronitrile to the mixture. medium, and heated to reflux at 70°C for 10 hours. The reaction product was separated by sedimentation in glacial ether, and the crude product was obtained after centrifugation (×5,000 rpm, 10 min). Repeat the dissolution-sedimentation process of the crude product in a methanol-glacial ether system more than two times to remove impurities. Finally, the solvent was completely removed by rotary evaporation and vacuum drying. The obtained product poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylic acid) is a white transparent viscous liquid.

2) Add 30 mL of 0.1 mol/L sodium lauryl sulfate and 1.5 mL of 0.1 mol/L sulfuric acid to 265.5 mL of water, stir and heat to 95°C, and after heating for 15 minutes, add 3 mL of 50 mM potassium permanganate. Add dropwise to the reaction solution. Continue heating for about 1 hour, stop the reaction when the reaction system changes from purple to colorless, and brown precipitate particles are produced. The manganese dioxide precipitate was collected by centrifugation (×8000 rpm, 5 min) and washed repeatedly with water. Manganese dioxide powder is dispersed by ultrasound. Add 3 mg of manganese dioxide to 3 mL of water and ultrasonic for 4 hours to obtain a brown suspension, which is the manganese dioxide nanosheet dispersion.

3) Mix the hyperbranched polylysine solution (45.36mg/mL, 5kDa) and the manganese dioxide nanosheet dispersion prepared in the second step at a volume ratio of 1:1 and sonicate for 30 minutes. The final concentrations of hyperbranched polylysine and manganese dioxide were 22.68 mg/mL and 0.5 mg/mL respectively. Centrifuge the mixed solution at 1000 rpm for 5 minutes, discard the bottom precipitate, and collect the upper liquid. The upper liquid was further centrifuged at 10,000 rpm for 10 minutes to obtain a hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution.

4) Fully dissolve 0.07 mg of poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylic acid) in 1 mL of hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution and reacted at 37°C for 12 hours to obtain a hyperbranched polylysine cross-linked hydrogel (hydrogel HM) containing manganese dioxide nanosheets. As a reference, 0.07 mg of poly(polyethylene glycol methacrylate-co-glycidyl methacrylate-co-acrylic acid) was dissolved in 1 mL, 22.68 mg/mL, 5 kDa hyperbranched polylysine solution, The reaction was carried out at 37°C for 12 hours to obtain a hyperbranched polylysine cross-linked hydrogel (hydrogel H). For drug-loaded hydrogels, 1 mg/mL pravastatin sodium was mixed into the pre-gelling solutions of HM and H and then the gelling reaction was performed to obtain hydrogels HMP and HP respectively.

The following is a test of the antioxidant properties of the above hydrogels. The antioxidant properties of hydrogels H and HM were evaluated through the scavenging capabilities of hydrogels H and HM on hydrogen peroxide, superoxide anions, diphenylpicrylhydrazyl radicals and hydroxyl radicals, and the results are shown in Figure 4. Figure 4a shows that H cannot react with 10 mM hydrogen peroxide, while HM can completely remove hydrogen peroxide within 4 hours. Similar results were observed for superoxide anion scavenging in Figure 4b, where manganese dioxide in HM contributes to efficient scavenging of superoxide anion, while H has no scavenging ability. H and HM show almost the same curves in scavenging diphenylhydrazyl radicals (Figure 4c), indicating that it is mainly the amino groups of hyperbranched polylysine in H and HM that scavenge diphenylhydrazyl radicals. plays a major role in. Both hydrogels H and HM showed strong hydroxyl radical scavenging ability, and this result can also be attributed to the reaction of amino groups with hydroxyl radicals. In summary, the hyperbranched polylysine in the hydrogels HM and H helped to scavenge diphenyl hydrazyl radicals and hydroxyl radicals, while the HM loaded with manganese dioxide nanosheets could further scavenge hydrogen peroxide and hyper oxygen anion.

The following is a test of the oxygen supply performance of the above hydrogel. As a nanoenzyme that can simulate catalase, manganese dioxide can produce oxygen while helping to remove hydrogen peroxide. As shown in Figure 5, after adding hydrogel HM to a 10mM hydrogen peroxide solution, The oxygen content in the solution increased greatly (Figure 5a), and obvious oxygen bubbles were produced (Figure 5b). However, when H is added to hydrogen peroxide, or H or HM is added to PBS, no change in oxygen content in the solution can be observed.

The following is an in vitro antibacterial performance test of the above hydrogels. As one of the main components of hydrogels H and HM, hyperbranched polylysine will provide a positively charged antibacterial surface interface for the hydrogels. The antibacterial efficiency of the hydrogel was studied by immersing the hydrogel in a suspension of methicillin-resistant Staphylococcus aureus bacteria, and analyzing the changes in the number of bacteria before and after adding the hydrogel. The results are shown in Figure 6. When the initial bacterial density was 1.8×10 ⁹ CFU/mL (OD ₆₀₀ =1), compared with the control group, H and HM killed 94.1% and 95.5% of methicillin-resistant Staphylococcus aureus, respectively. When the bacterial density was 4.0×10 ⁸ CFU/mL (OD ₆₀₀ =0.5), both H and HM killed more than 99.9% of the bacteria.

The following is an animal experiment on the above hydrogel. Goto-kakisaki spontaneous type II diabetic rats (GK rats) were selected as the diabetes model. High-fat feed was fed continuously for 7 days to induce hyperglycemia. If the fasting blood glucose value was greater than 11.1mmol/L twice in a row, type II diabetes was considered Modeling successful. Create a full-thickness skin defect model on the back of GK rats: First, shave the back hair of the diabetic rats, make 4 circular full-thickness skin defect wounds with a diameter of 10 mm on their backs, and inoculate each wound with 10 ⁷ CFU Oxycillin Staphylococcus aureus (5×10 ⁸ CFU/mL, 20 μL). After the bacterial solution is completely absorbed by the wound, the wound is randomly divided into 5 groups (n=6), and the corresponding materials are added: Ctrl group (100 μL PBS), H group (100 μL hydrogel H), HP group (100 μL water Gel HP), HM group (100 μL hydrogel HM) and HMP group (100 μL hydrogel HMP), and were covered with 3M Tegaderm film to fix the material and maintain the moisture of the hydrogel. The day of modeling is the 0th day, and new materials are used or replaced on the 0th, 1st, and 2nd days respectively. Starting on day 0, the wounds were photographed every 3 days, and the wound area was measured and analyzed. Photos of the wound during treatment are shown in Figure 7. For wounds treated with antibacterial hydrogels H, HP, HM and HMP, the wound healing rates observed on the third day were 21.4%, 27.8%, 23.5% and 32.2% respectively, which were significantly higher than Ctrl group (8.5%). After stopping hydrogel treatment from day 3 onwards, the difference in wound healing rates between groups gradually decreased. These results indicate that hydrogel HMP treatment during the inflammatory phase can greatly promote wound healing, and after stopping treatment, the accumulation in the early stage can provide a good start for self-healing in the later stage.

Claims (10)

A method for preparing an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds, which is characterized in that the epoxy group in the gel-forming skeleton polymer containing glycidyl methacrylate is combined with hyperbranched polylysine and It is obtained by the ring-opening reaction and cross-linking of the amino groups in the electrostatic complex of manganese dioxide nanosheets. A method for preparing an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 1, characterized in that the preparation method includes the following steps: 1) Dissolve glycidyl methacrylate and gel-forming skeleton monomers in methanol, remove oxygen by bubbling with nitrogen, add initiator azobisisobutyronitrile to the mixture, and heat to reflux at 50-80°C for 8- 24 hours, after the reaction is completed, use glacial ether to precipitate and centrifuge to obtain the crude product. The crude product is repeatedly dissolved and precipitated in a methanol-glacial ether system to remove impurities. Finally, the solvent is fully removed by rotary evaporation and vacuum drying to obtain the final product. Colloidal skeleton polymer; 2) Add sodium lauryl sulfate and sulfuric acid to the water, stir and heat to 95°C. After heating for 10-20 minutes, add potassium permanganate dropwise into the reaction solution and continue heating. When the reaction system changes from purple to purple, When it is colorless and brown precipitate particles are produced, stop the reaction; collect the manganese dioxide precipitate by centrifugation and wash it repeatedly with water; disperse the manganese dioxide powder by ultrasonic, add the manganese dioxide powder to the water, and ultrasonic for 3- After 6 hours, a brown suspension is obtained, which is the manganese dioxide nanosheet dispersion; 3) Mix equal volumes of the hyperbranched polylysine solution and the manganese dioxide nanosheet dispersion prepared in step 2) and sonicate for 20-60 minutes; centrifuge the mixed solution, discard the bottom precipitate, collect the upper liquid and further centrifuge To obtain a hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution; 4) Mix the drug to be loaded into the hyperbranched polylysine-manganese dioxide nanosheet electrostatic complex solution prepared in step 3), and then add the gel-forming skeleton polymer prepared in step 1) and make it fully Dissolve and then react at 37°C for 10-24 hours to obtain an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds. A method for preparing an antibacterial and antioxidant hydrogel dressing for treating wounds of diabetic patients according to claim 2, wherein the gel-forming skeleton monomer in step 1) is polyethylene glycol methyl ether methacrylic acid. At least one of ester, acrylamide, and acrylic acid. The preparation method of an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, characterized in that the moles of glycidyl methacrylate and gel-forming skeleton monomers described in step 1) are The ratio is 1:1-1:3, and the total monomer concentration is 5-10 mg/mL; the molar amount of the initiator azobisisobutyronitrile accounts for 1-15% of the total molar amount of monomers. The preparation method of an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, wherein the concentrations of sodium lauryl sulfate, sulfuric acid and potassium permanganate in step 2) are respectively It is 5-20mmol/L, 1-10mmol/L, 0.1-1mmol/L. The method for preparing an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, wherein the concentration of the manganese dioxide nanosheet dispersion in step 2) is 0.5-10 mg/mL. A method for preparing an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, characterized in that the molecular weight of the hyperbranched polylysine in step 3) is 2-10kDa, and the solution concentration is 20 -200mg/mL. After mixing, the concentrations of hyperbranched polylysine and manganese dioxide nanosheets are 10-100mg/mL and 0.25-5mg/mL respectively. The preparation method of an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, wherein the drugs to be loaded in step 4) are pravastatin sodium, madecassoside, and At least one of catechins and other tea polyphenols, with a concentration of 0.5-5 mg/mL. The preparation method of an antibacterial and antioxidant hydrogel dressing for treating diabetic wounds according to claim 2, wherein the concentration of the gel-forming skeleton polymer solution in step 4) is 0.01-0.5 mg/mL. An antibacterial and antioxidant hydrogel dressing for treating diabetic wounds, characterized in that it contains an antibacterial and antioxidant hydrogel dressing prepared by the method of any one of claims 1 to 9, and can be used in various shapes, Deep wounds in diabetic patients.

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