Preparation method and application of multifunctional self-healing hydrogel material capable of resisting bacteria and inflammation and promoting healing of diabetic wounds

Abstract

The invention discloses a preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promotion functions. The preparation method comprises the following steps: firstly, synthesizing silver-doped carbon quantum dots (AgCD) in one step through a hydrothermal method; the preparation method comprises the following steps: firstly, preparing sodium hyaluronate (HA), secondly, oxidizing the sodium hyaluronate (HA) into oxidized hyaluronic acid (OHA) by taking sodium periodate as an oxidizing agent, and then encapsulating AgCD and metformin (Met) into hydrogel formed by Schiff base reaction between carboxymethyl chitosan (CMCS) and the oxidized hyaluronic acid (OHA). The hydrogel provided by the invention has certain adhesion, suitable capacity of absorbing wound exudate and good biocompatibility, meanwhile, due to the addition of AgCD, the hydrogel has excellent antibacterial property, and the metformin can promote angiogenesis of a wound part, so that the hydrogel can better promote healing of a diabetic wound. The hydrogel is simple and rapid in preparation method, has low biotoxicity and antibacterial property, and provides a strategic choice for promoting healing of diabetic wounds.

Description

Technical Field

[0001] The invention belongs to the technical field of medical materials for promoting wound healing, and specifically relates to a preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promoting properties. Background Art

[0002] Diabetes is the world's largest chronic disease, divided into type 1 diabetes and type 2 diabetes. Type 1 diabetes is caused by insufficient insulin secretion, and type 2 diabetes is caused by insulin resistance, which causes hyperglycemia. As the disease progresses, diabetic patients usually suffer from multi-system damage and some complications. Chronic non-healing wounds are one of the common complications of diabetic patients. Chronic non-healing wounds include various types of ulcers, such as diabetic foot ulcers, lower limb venous ulcers and pressure sores. Among them, about 15%-20% of diabetic foot ulcer patients have lower limb amputations, and the mortality rate of diabetic foot ulcer patients is about 30%. Because diabetic wounds are in a high-sugar environment for a long time, their wounds are more susceptible to bacterial infection, and the dysregulated response of macrophages in diabetic wounds makes it difficult to kill the bacteria that invade the wound, which causes diabetic wounds to be in a long-term inflammatory and high ROS level, which is one of the reasons why diabetic wounds heal slowly. High blood sugar can also cause human cell membrane hardening and vasoconstriction, resulting in insufficient blood supply to the wound, which can also hinder wound healing.

[0003] So far, people have adopted a variety of methods to treat diabetic wounds, such as debridement, surgical angiogenesis, hyperbaric oxygen therapy and wound dressings, among which dressings have low treatment costs, are easy to make, and are simple to operate, making them more suitable for most people. However, traditional dressings (such as gauze, bandages, transparent films, etc.) have poor barrier properties, a high risk of bacterial infection, and are easy to grow into the new tissue of the wound. When changing the dressing, they will damage the new tissue and cause secondary damage to the wound, and they will not promote wound healing. A moist skin environment is more conducive to wound healing, and hydrogel dressings can provide a moist environment for the wound, which is conducive to tissue growth and migration of epithelial cells, and promotes wound recovery. Due to the special environment of diabetic wounds, single-function hydrogels cannot meet the needs of rapid wound healing. Therefore, it is particularly important to find a multifunctional hydrogel that can adapt to the shape of the wound and accelerate wound healing.

[0004] Chitosan is a positively charged natural polysaccharide obtained by deacetylation of chitin. It is widely used in biomedicine and pharmaceutical fields due to its wide source, low cost, biodegradability, excellent biocompatibility and hemostasis. However, due to its insolubility in water, it has great limitations in practical applications. Carboxymethyl chitosan is a derivative obtained by chemical modification of the active groups in chitosan. It can overcome the insoluble barrier of chitosan while maintaining the original excellent properties of chitosan, and can also promote cell proliferation and migration. It is a good raw material for hydrogels.

[0005] Hyaluronic acid (HA) is a natural linear glycosaminoglycan that mainly exists in the extracellular matrix of human tissues. It has anti-wrinkle, anti-wrinkle, beauty and health care, and skin physiological restoration functions, and is commonly found in women's cosmetics. However, it also has excellent moisturizing properties, can regulate the permeability of blood vessel walls, promote angiogenesis and epidermal regeneration, which plays an important role in wound healing. The ortho-hydroxyl group of hyaluronic acid is oxidized to an aldehyde group, which can directly react with the amino group on carboxymethyl chitosan at room temperature to form a dynamic imine bond. This reaction is also called the Schiff base reaction.

[0006] Metformin is a biguanide molecule and a first-line drug for the treatment of type 2 diabetes. It is relatively safe, low-cost, has beneficial effects on cardiovascular and blood sugar, and also has anti-inflammatory and anti-aging effects. In the past, there have been many studies on its oral hypoglycemic and anti-cancer effects. However, some studies have shown that metformin also plays a certain role in promoting diabetic wound healing. Metformin can reduce blood sugar in diabetic wounds and promote the growth of new blood vessels in the wound.

[0007] Bacterial infection is still the most difficult problem today, and bacterial infection occurs more frequently in diabetic wounds. Therefore, to heal diabetic wounds, it is important to eliminate the bacteria in the wounds. However, due to the abuse of antibiotics, bacteria have become resistant, so there is an urgent need for a new material that can replace antibiotics for sterilization. Carbon quantum dots are a type of carbon-containing quantum dots, usually only a few nanometers in size. Their extremely small size gives them unique antibacterial properties. They can not only bypass the bacterial resistance mechanism to antibiotics, but also have high stability, low toxicity, biocompatibility and easy surface chemical properties, making them an outstanding antibiotic substitute. In addition, the synthesis method of carbon quantum dots is simple and fast, low cost, and diverse performance, which makes them have broad application prospects. Summary of the invention

[0008] The purpose of the present invention is to provide a preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties.

[0009] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: a method for preparing a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties, comprising the following steps:

[0010] Step 1: Add polyethyleneimine and silver nitrate AgNO3 to deionized water, stir at room temperature, and then add citric acid and water; transfer the mixture to a hydrothermal reactor, and then react at 160-200°C for 0.5-2h, filter the obtained reaction solution and freeze-dry it to obtain silver-doped carbon quantum dots;

[0011] Step 2: Add the sodium periodate solution to the sodium hyaluronate solution, adjust the pH value to 3.0-3.5, stir at room temperature in the dark, then add ethylene glycol to quench the unreacted sodium periodate, stir again, then transfer the reaction solution to a dialysis bag, dialyze in deionized water, and freeze-dry to obtain oxidized sodium hyaluronate;

[0012] Step 3: Disperse metformin in an aqueous solution of carboxymethyl chitosan to obtain a first raw material solution, disperse silver-doped carbon quantum dots in an aqueous solution of oxidized sodium hyaluronate to obtain a second raw material solution, mix the first raw material solution and the second raw material solution evenly, and obtain a hydrogel after reaction.

[0013] The preferred technical solution is: the concentration of the first raw material liquid is 2-8wt%, the concentration of the second raw material liquid is 2-8wt%; the volume ratio of the first raw material liquid to the second raw material liquid is 0.8-1.2:1.

[0014] The preferred technical solution is: in the mixed solution consisting of the first raw material solution and the second raw material solution, the final concentration of metformin is 15-25mM, and the final concentration of silver-doped carbon quantum dots is 100-300μg / mL.

[0015] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: application of the hydrogel in the preparation of biomedical materials.

[0016] The preferred technical solution is: use of the hydrogel in preparing a hydrogel wound dressing for promoting diabetic wound healing.

[0017] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0018] The multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties provided by the present invention has adhesion, self-healing, suitable swelling rate and good cell compatibility. The hydrogel can release metformin and AgCD to have bactericidal, anti-inflammatory and angiogenic properties, and shows a synergistic therapeutic effect in promoting diabetic wound healing. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is the field emission transmission electron microscope (TEM) image and infrared spectrum of the AgCD suspension obtained by dispersion in aqueous solution in Example 1.

[0020] Figure 2 is the nuclear magnetic resonance hydrogen spectrum image of HA oxidized OHA in Example 1 ( 1 1H NMR).

[0021] Figure 3 It is a schematic diagram of the synthesis of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 1 and an image of the finished hydrogel product.

[0022] Figure 4 This is a thermal field emission scanning electron microscope (SEM) image of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 2.

[0023] Figure 5 These are the self-healing and adhesion test results of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 2.

[0024] Figure 6 This is the test result of the swelling performance of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 2.

[0025] Figure 7 These are the test results of the antibacterial properties of the multifunctional self-healing hydrogel material having antibacterial, anti-inflammatory and diabetic wound healing properties in Example 3.

[0026] Figure 8 These are the results of testing the cell compatibility of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 4.

[0027] Fig. 9 This is a test of the release results of metformin from the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 5.

[0028] Fig.10 The test results of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties in Example 6 on the wound healing of diabetic mice. DETAILED DESCRIPTION

[0029] The following is a description of the implementation of the present invention by means of specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.

[0030] See also Figure 1-10 . It should be noted that the structures, proportions, sizes, etc. illustrated in the drawings in this specification are only used to match the contents disclosed in the specification for people familiar with this technology to understand and read, and are not used to limit the limiting conditions for the implementation of the present invention, so they have no substantial technical significance. Any modification of the structure, change in the proportional relationship, or adjustment of the size should still fall within the scope of the technical content disclosed by the present invention without affecting the effects and purposes that can be achieved by the present invention. At the same time, the terms such as "upper", "lower", "left", "right", "middle" and "one" quoted in this specification are only for the convenience of description, and are not used to limit the scope of the implementation of the present invention. Changes or adjustments in their relative relationships should also be regarded as the scope of the implementation of the present invention without substantially changing the technical content.

[0031] Unless otherwise specified, the reagents or materials described in the following examples are commercially available.

[0032] Example 1: Preparation of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0033] 1. Preparation of silver-doped carbon quantum dots (AgCD)

[0034] 0.15 g of polyethyleneimine (PEI) and 0.2 g of silver nitrate (AgNO3) were added to 5 mL of deionized water and stirred at room temperature for 1 h. Then 0.25 g of citric acid (CA) was added to the above solution, and water was added to make the volume to 25 mL. The mixed solution was transferred to a hydrothermal reactor and then added to an oven at 180°C for reaction for 1 h. Finally, the obtained solution was filtered with a 0.22 μm filter head and freeze-dried to obtain AgCD powder.

[0035] AgCD is synthesized by a one-step hydrothermal method using silver nitrate and citric acid as raw materials and polyethyleneimine as a reducing agent. Figure 1 As shown in Figure 2, the morphology and dispersibility of the prepared AgCD were evaluated using TEM. AgCD is regular spherical, uniformly dispersed, and has good dispersibility ( Figure 1 ) and its particle size is relatively small, the particle distribution is relatively uniform, and the average diameter is 3.89nm±1.91nm. Under sunlight, the AgCD solution is light yellow, and under ultraviolet light, it emits blue fluorescence. It was characterized by Fourier infrared spectroscopy ( Figure 1 ). At 3454cm -1 The typical band representing the stretching vibration of secondary amino groups was observed near 1701 cm -1 The peak at 1642 cm is related to the stretching vibration of the C=O / C=C group. -1The peak at 1289 cm represents the stretching vibration of the -CONH- group. -1 A strong absorption band of CH bending appeared at , which may belong to the redox aldehyde group.

[0036] 2. Sodium hyaluronate (HA) is oxidized to oxidized hyaluronic acid (OHA)

[0037] Dissolve 2 g HA in 200 mL of deionized water (concentration of 10 mg / mL), and stir to completely dissolve; add 5 mL of 0.5 M sodium periodate solution dropwise to the above HA solution, adjust the solution pH to between 3.0 and 3.5 by adding 1 M H2SO4 solution, stir for 3 hours at room temperature in the dark, then add 1 mL of ethylene glycol to quench the unreacted sodium periodate, and stir for another 1 hour. Then, transfer the reaction solution to a dialysis bag, dialyze in deionized water for 3 days, replace the dialysate every 12 hours, and freeze-dry to obtain white sponge-like OHA.

[0038] OHA is synthesized by oxidative cleavage of the hydroxyl groups on the second and third carbon atoms of the HA chain repeating unit with sodium periodate to form aldehyde groups ( Figure 2 ).pass 1 H NMR spectroscopy confirmed the formation of aldehydes in OHA ( Figure 2 ). The new peaks at 4.92ppm, 5.01ppm and 5.11ppm indicate the formation of hemiacetal protons between the aldehyde group and the hydroxyl group and the presence of ortho-hydroxyl groups in the system, which confirm the successful synthesis of OHA. The aldehyde group synthesized after oxidation provides a reaction site for the subsequent Schiff base reaction.

[0039] 3. Preparation of hydrogel

[0040] Carboxymethyl chitosan (CMCS) and OHA were dissolved in deionized water to form 4 wt% aqueous solutions. Metformin (Met) was dissolved in the CMCS aqueous solution, while AgCD was dispersed in the OHA aqueous solution. Then, the two mixtures were mixed in equal volumes to obtain a multifunctional self-healing hydrogel with antibacterial, anti-inflammatory and diabetic wound healing properties. The final concentrations of Met and AgCD in the hydrogel matrix were 20 mM and 200 μg / mL, respectively.

[0041] The healable hydrogel based on Met and AgCD dual-drug loading was formed by the Schiff base reaction between -NH2 of CMCS and -CHO of OHA ( Figure 3 The gelation time of the hydrogel was determined by the vial inversion method. Equal volumes of CMCS and OHA were mixed to form a gel within 2-4 min. Figure 3 shown.

[0042] Example 2: Performance test of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0043] 1. The microstructure of the formed hydrogels and their bacterial morphology were studied using a thermal field emission scanning electron microscope (Gemini 500). The hydrogels were prepared by freeze drying. All samples were sputter-coated with gold before observation. The pore size and shape of the hydrogels were observed and recorded. The hydrogel samples showed a typical three-dimensional network with pore sizes of about 20-60 μm.

[0044] 2. Evaluate the self-healing ability of the hydrogel by direct visual inspection. The self-healing properties of the hydrogel were studied on plastic surfaces. Two circular hydrogels of different colors were prepared separately. Subsequently, the two groups of hydrogels were cut in half and the two hydrogels of different colors were put together to observe their self-healing behavior. In addition, the hydrogels were adhered to the skin, plastic, and glass to test the adhesion of the hydrogels. Figure 5 As shown, the hydrogel reattached and "healed" within 2 minutes. The adhesion of the hydrogel was tested using different materials ( Figure 5 ). The results showed that the hydrogel could adhere tightly to skin, plastic and glass, and had good adhesion.

[0045] 3. The hydrogel was freeze-dried and weighed to obtain its initial weight (W0). Then, the hydrogel was immersed in PBS. When the preset time interval was reached, the hydrogel was weighed (Wt), and all experiments were repeated five times. The swelling percentage was calculated according to the following formula:

[0046] Swelling ratio (%) = (W t -W0) / W t ×100%.

[0047] An ideal wound dressing should have the ability to absorb wound exudate while providing a moist environment for the wound to promote wound cell hydration and promote wound recovery. Therefore, the hydrogel needs to have a certain swelling capacity. The swelling capacity of the hydrogel was measured by immersing the hydrogel in PBS (pH = 7.4). The hydrogel can reach swelling equilibrium within 7 hours, and the swelling rate of the hydrogel is about 20,000, indicating that the hydrogel has excellent ability to absorb wound exudate ( Figure 6 ).

[0048] Example 3: Antibacterial test of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0049] 1. Experimental method: Pick single colonies of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa respectively, and culture them in beef extract-peptone broth at 37°C and 220rpm overnight to obtain bacterial suspension. Place the ultraviolet sterilized hydrogel at the bottom of a sterilized 24-well plate. Then dilute the bacteria to 10 with PBS. 7 CFU / mL, and finally, the bacterial suspension was added to the hydrogel surface. Bacteria cultured with PBS (pH = 7.4) were set as controls. After incubation at 37°C for 3 hours, 100.0 μL of the diluted bacterial suspension was evenly spread on a beef extract-peptone agar plate. After incubation at 37°C for 24 hours, the colonies on the agar plate were photographed.

[0050] 2. Result analysis: The ideal excipient should have excellent antibacterial activity and will not cause bacterial resistance. The plate count method was used to evaluate the antibacterial ability of the hydrogel against each group of bacteria. First, we studied the ability of the hydrogel to capture bacteria within 3 hours (we counted the ability to capture bacteria as the antibacterial ability of the material). Figure 7 As shown, the hydrogel exhibited significant antibacterial properties. The antibacterial effect of the hydrogel on Escherichia coli was the same as that on Pseudomonas aeruginosa, and the antibacterial effect on Staphylococcus aureus was also strong.

[0051] Example 4: Cytotoxicity test of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0052] 1. Experimental method: Prepare the gel solution under sterile conditions and place it in a 37°C incubator to form a gel. Add DMEM culture medium containing 10% serum at a ratio of 10 mg / mL of material weight to extraction medium volume, extract at 37°C for 24 hours, and collect the extract with a 0.2μm filter membrane. Suspend mouse preadipocytes (3T3-L1 cells) in DMEM complete culture medium containing 10% fetal bovine serum and 1% double antibody, and culture in a cell culture incubator at 37°C and a CO2 concentration of 5% for 24 hours. Then remove the culture medium, add PBS and hydrogel extract and continue to culture for 24 hours. Use a 96-well plate for cytotoxicity experiments. After co-culture with the drug for 24 hours, add MTT solution. After culturing in the incubator for 4 hours, add DMSO. Finally, use an enzyme marker to detect the absorbance value of each well at 490nm, and use the following formula to calculate cell viability:

[0053] Cell viability (%)=(ODsamples-ODzero) / (ODcontrol-ODzero)×100%.

[0054] 2. Result analysis: In this experiment, the MTT method was used to evaluate the cytotoxicity of hydrogels. Mouse preadipocytes 3T3-L1 were cultured with PBS and hydrogel extract for 24 hours to evaluate cytotoxicity. Figure 8As shown, after 24 h of co-culture, the cell viability in the hydrogel group was 89.7%, and the cell viability was >85%, indicating that the hydrogel had good cell compatibility.

[0055] Example 5: Release result test of metformin from a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties.

[0056] 1. Experimental method: Place the hydrogel in 5 mL PBS (PH = 7), shake it in a shaker at 37 ° C (150 rpm), take out 2 mL of old PBS release medium, and regularly add 2 mL of new PBS medium. The release of metformin is measured by UV spectrophotometer at 232 nm. The cumulative release of metformin (CR) is calculated by the equation

[0057] CR(%)=(5C i +2ΣC i-1 ) / M0*100%

[0058] C i : The concentration of metformin released at each sampling time point; M0: The initial mass of metformin loaded into the gel.

[0059] 2. Result analysis: The results are as follows Fig. 9 As shown. In the first 24 hours, Met was rapidly released linearly from the hydrogel, with a cumulative release of up to 72%. The cumulative release then gradually increased, with the highest release reaching 80%. The sudden release of metformin was measured at the beginning. This may be because when the hydrogel first came into contact with the release medium solvent PBS, PBS quickly penetrated into the hydrogel, causing the molecular chains inside the hydrogel to relax and trigger a state mutation, resulting in a sudden release of the drug. The hydrogel can achieve a positive therapeutic effect on alleviating persistent inflammatory responses through the burst release of Met.

[0060] Example 6: Test results of wound healing of diabetic mice using a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0061] 1. Experimental method: Male KM mice were randomly divided into two groups, each with 8 mice. Normal water supply was maintained before modeling. After fasting for 6 hours, a single intraperitoneal injection of 180 mg / kg streptozotocin (STZ) solution (dissolved in 1% sodium citrate buffer with pH = 4.5) was given, and feed was added in time after injection. One week later, the blood glucose level of fasting mice was tested with a blood glucose meter. If the blood glucose was ≥16.65 mM, the diabetes model was successfully established. The diabetic mice were anesthetized and shaved, and a full-thickness wound with a diameter of about 10 mm was created on the central dorsal skin of each mouse. The wound was then covered with a hydrogel dressing, and the control group was covered with PBS only. The covering dressing was changed every 1 day, and the wound was photographed and measured.

[0062] 2. Result analysis: Fig.10 As shown, as the treatment time increased, the wound area of ​​each group gradually decreased. However, the wound healing of the experimental group at each time point was significantly better than that of the control group. On the second day of treatment, the wound area of ​​the control group was significantly larger than the initial wound area. This phenomenon of wound expansion is consistent with the fact that diabetic wounds are difficult to heal clinically and often continue to expand due to excessive inflammation. However, this phenomenon did not occur in the hydrogel group, and there was a significant difference in wound area between the hydrogel group and the control group. After an 8-day healing period, the wounds in the hydrogel group had completely healed, and the remaining wound area was almost 0, while the remaining wound area in the control group was 0.42.

[0063] In summary, the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties provided by the present invention exhibits good adhesion, self-healing, suitable swelling rate, excellent biocompatibility and antibacterial properties, and can effectively promote diabetic wound healing, showing its application potential as a biomedical material.

[0064] Example 7: Preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties

[0065] A method for preparing a multifunctional self-healing hydrogel material having antibacterial, anti-inflammatory and diabetic wound healing properties, comprising the following steps:

[0066] Step 1: Add polyethyleneimine and silver nitrate AgNO3 to deionized water, stir at room temperature, and then add citric acid and water; transfer the mixture to a hydrothermal reactor, and then react at 160°C for 2h. The obtained reaction solution is filtered and freeze-dried to obtain silver-doped carbon quantum dots;

[0067] Step 2: Add the sodium periodate solution to the sodium hyaluronate solution, adjust the pH value to 3.0, stir at room temperature in the dark, then add ethylene glycol to quench the unreacted sodium periodate, stir again, then transfer the reaction solution to a dialysis bag, dialyze in deionized water, and freeze-dry to obtain oxidized sodium hyaluronate;

[0068] Step 3: Disperse metformin in an aqueous solution of carboxymethyl chitosan to obtain a first raw material solution, disperse silver-doped carbon quantum dots in an aqueous solution of oxidized sodium hyaluronate to obtain a second raw material solution, mix the first raw material solution and the second raw material solution evenly, and obtain a hydrogel after reaction.

[0069] The preferred technical solution is: the concentration of the first raw material liquid is 2wt%, the concentration of the second raw material liquid is 2wt%; the volume ratio of the first raw material liquid to the second raw material liquid is 0.8:1.

[0070] The preferred technical solution is: in the mixed solution consisting of the first raw material solution and the second raw material solution, the final concentration of metformin is 15 mM, and the final concentration of silver-doped carbon quantum dots is 100 μg / mL.

[0071] The application of the hydrogel in preparing biomedical materials.

[0072] The hydrogel is used in preparing a hydrogel wound dressing for promoting diabetic wound healing.

[0073] The above description is only used to explain the preferred embodiments of the present invention, and is not intended to limit the present invention in any form. Therefore, any modifications or changes made to the present invention under the same inventive spirit should still be included in the scope of protection intended by the present invention.

Claims

1. A method for preparing a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing properties, characterized in that: The following steps are involved: Step 1: Add polyethyleneimine and silver nitrate AgNO3 to deionized water, stir at room temperature, and then add citric acid and water; transfer the mixture to a hydrothermal reactor, and then react at 160-200°C for 0.5-2h, filter the obtained reaction solution and freeze-dry it to obtain silver-doped carbon quantum dots; Step 2: Add the sodium periodate solution to the sodium hyaluronate solution, adjust the pH value to 3.0-3.5, stir at room temperature in the dark, then add ethylene glycol to quench the unreacted sodium periodate, stir again, then transfer the reaction solution to a dialysis bag, dialyze in deionized water, and freeze-dry to obtain oxidized sodium hyaluronate; Step 3: Disperse metformin in an aqueous solution of carboxymethyl chitosan to obtain a first raw material solution, disperse silver-doped carbon quantum dots in an aqueous solution of oxidized sodium hyaluronate to obtain a second raw material solution, mix the first raw material solution and the second raw material solution evenly, and obtain a hydrogel after reaction.

2. The method for preparing the multifunctional self-healing hydrogel material having antibacterial, anti-inflammatory and diabetic wound healing properties according to claim 1, characterized in that: The concentration of the first raw material liquid is 2-8wt%, and the concentration of the second raw material liquid is 2-8wt%; the volume ratio of the first raw material liquid to the second raw material liquid is 0.8-1.2:

1.

3. The method for preparing the multifunctional self-healing hydrogel material having antibacterial, anti-inflammatory and diabetic wound healing properties according to claim 1, characterized in that: In the mixed solution consisting of the first raw material solution and the second raw material solution, the final concentration of metformin is 15-25 mM, and the final concentration of silver-doped carbon quantum dots is 100-300 μg / mL.

4. Use of the hydrogel according to any one of claims 1 to 3 in the preparation of biomedical materials.

5. Use of the hydrogel according to claim 2 in the preparation of biomedical materials, characterized in that: The hydrogel is used in preparing a hydrogel wound dressing for promoting diabetic wound healing.

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