Preparation method and application of multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and promoting diabetic wound healing

Abstract

The application relates to a preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promotion functions. First, silver-doped carbon quantum dots (AgCD) are synthesized through a one-step hydrothermal method. Second, sodium hyaluronate (HA) is oxidized into oxidized sodium hyaluronate (OHA) by taking sodium periodate as an oxidant, and then AgCD and metformin (Met) are encapsulated into a hydrogel formed through a Schiff base reaction between carboxymethyl chitosan (CMCS) and OHA. The hydrogel provided by the application has certain adhesion, suitable absorption of wound exudate and good biocompatibility. In addition, the addition of AgCD enables the hydrogel to have excellent antibacterial property, and metformin can promote angiogenesis at a wound site, so that the hydrogel can better promote diabetic wound healing. The preparation method of the hydrogel is simple and fast, the hydrogel has low biological toxicity and antibacterial property, and the hydrogel provides a strategic choice for promoting diabetic wound healing.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical materials for promoting wound healing, and particularly relates to a preparation method and application of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promotion. BACKGROUND

[0002] Diabetes is the first chronic disease in the world, which is divided into type I diabetes and type II diabetes. Type I diabetes is caused by insufficient insulin secretion, and type II diabetes is caused by insulin resistance and high blood sugar. With the development of the disease, diabetic patients usually have multiple system damage and some complications. Chronic non-healing wounds are one of the common complications of diabetic patients, and chronic non-healing wounds include various ulcer types, such as diabetic foot ulcers, lower extremity venous ulcers and pressure ulcers. About 15%-20% of patients with diabetic foot ulcers have lower extremity amputation, and the mortality rate of patients with diabetic foot ulcers is about 30%. Because the diabetic wound is in a high-sugar environment for a long time, it is more susceptible to bacterial infection, and the macrophage response at the diabetic wound site is disordered, making it difficult to kill invading bacteria, which causes the diabetic wound to be in a long-term inflammation and high ROS level, which is one of the reasons for the slow healing of the diabetic wound. High blood sugar also causes hardening of cell membranes and vasoconstriction, leading to insufficient blood supply to the wound, which also hinders wound healing.

[0003] So far, various methods have been used to treat diabetic wounds, such as debridement, surgical angiogenesis, hyperbaric oxygen therapy and wound dressings. Among them, the dressing treatment has low cost, is easy to make and simple to operate, and is more suitable for most people. However, the barrier property of traditional dressings (such as gauze, bandage, transparent film, etc.) is poor, the risk of bacterial infection is high, and the newly formed tissue in the wound is easily infected, which will cause secondary damage to the newly formed tissue when changing the dressing and will not promote wound healing. A moist skin environment is more conducive to wound healing, and a hydrogel dressing can provide a moist environment for the wound, which is conducive to tissue growth and epithelial cell migration, and promotes wound recovery. Due to the special environment of diabetic wounds, a single-function hydrogel cannot meet the rapid healing of the wound, 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 natural polysaccharide with positive charge, which is obtained by deacetylation of chitin. It is widely used in biomedical and pharmaceutical fields due to its wide source, low cost, biodegradability, excellent biocompatibility and hemostatic property. However, its insolubility in water greatly limits its practical application. Carboxymethyl chitosan is a derivative of chitosan obtained by chemical modification of active groups in chitosan. It can overcome the insolubility barrier of chitosan, while maintaining the excellent properties of chitosan. In addition, it can promote cell proliferation and migration, and is a good hydrogel raw material.

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

[0006] Metformin is a biguanide molecule, which is a first-line drug for treating type II diabetes. It has relative safety, low cost, beneficial effects on cardiovascular and blood glucose reduction, and also has anti-inflammatory and anti-aging effects. Previous studies have shown that metformin has oral hypoglycemic and anticancer effects. However, some studies have shown that metformin also plays a certain role in promoting the healing of diabetic wounds. Metformin can reduce blood glucose at the site of diabetic wound and promote the growth of new blood vessels.

[0007] Bacterial infection is still a difficult problem today, and bacterial infection often occurs at the site of diabetic wound. Therefore, to cure diabetic wound, it is important to eliminate bacteria at the wound site. However, due to the abuse of antibiotics, bacteria have developed drug resistance, so there is an urgent need for a new material to replace antibiotics for sterilization. Carbon quantum dots are carbon-containing quantum dots, usually only a few nanometers in size. The unique antibacterial properties of carbon quantum dots are due to their small size. They can bypass the antibiotic resistance mechanism of bacteria, and have high stability, low toxicity, biocompatibility and easy surface chemical properties, making them an excellent antibiotic substitute. In addition, the synthesis method of carbon quantum dots is simple, fast, low cost and versatile, making it have a wide application prospect. SUMMARY

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

[0009] To achieve the above object and other related objects, the technical scheme provided by the present application is as follows: a preparation method of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promotion, comprising the following steps:

[0010] Step 1: polyethyleneimine and silver nitrate AgNO3 are added to deionized water, stirred at room temperature, and then citric acid and water are added; the mixed solution is transferred to a hydrothermal reaction kettle, and then reacted at 160-200 DEG C for 0.5-2h, and the obtained reaction solution is filtered and freeze-dried to obtain silver-doped carbon quantum dots;

[0011] Step 2: sodium periodate solution is added to sodium hyaluronate solution, the pH value is adjusted to 3.0-3.5, stirred at room temperature in the dark, then glycol is added to quench the unreacted sodium periodate, and then stirred, and then the reaction solution is transferred into a dialysis bag and dialyzed in deionized water, and then freeze-dried to obtain oxidized sodium hyaluronate;

[0012] Step 3: metformin is dispersed into a carboxymethyl chitosan aqueous solution to obtain a first raw material solution, and silver-doped carbon quantum dots are dispersed into an oxidized sodium hyaluronate aqueous solution to obtain a second raw material solution, and the first raw material solution and the second raw material solution are mixed uniformly, and then reacted to obtain a hydrogel.

[0013] Preferably, the concentration of the first raw material solution is 2-8wt%, the concentration of the second raw material solution is 2-8wt%, and the volume ratio of the first raw material solution to the second raw material solution is 0.8-1.2:1.

[0014] Preferably, in the mixed solution composed 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 object and other related objects, the technical scheme provided by the present application is as follows: the hydrogel is applied to the preparation of a biomedical material.

[0016] Preferably, the hydrogel is applied to the preparation of a diabetic wound healing promotion hydrogel wound dressing.

[0017] Thanks to the above technical scheme, the present application has the following advantages compared with the prior art:

[0018] The multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and diabetic wound healing promotion provided by the present application 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 show a synergistic therapeutic effect in promoting diabetic wound healing. BRIEF DESCRIPTION OF DRAWINGS

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

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

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

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

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

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

[0025] Figure 7 is the test results of the antibacterial performance of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and promoting diabetic wound healing in Example 3.

[0026] Figure 8 is the cell compatibility performance test results of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and promoting diabetic wound healing in Example 4.

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

[0028] Figure 10 is the test results of the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and promoting diabetic wound healing in Example 6 on diabetic mouse wound healing. DETAILED DESCRIPTION

[0029] The following specific embodiments illustrate the embodiments of the present application, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in the specification.

[0030] Please refer to​Figures 1-10 It is to be understood that the structures, proportions, sizes, etc. shown in the drawings accompanying the present specification are shown by way of illustration only and are not intended as limitations of the present application. Therefore, any modification, change, or variation that does not depart from the scope of the present application should still be considered to fall within the scope of the present application. Meanwhile, the terms such as "upper", "lower", "left", "right", "middle", and "one" used in the present specification are only for the convenience of clear description and are not intended to limit the scope of the present application. Any change in relative relationship without substantial change in technical content is also considered to fall within the scope of the present application.

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

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

[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, 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 up to 25 mL. The mixture was transferred to a hydrothermal reactor, then placed in an oven at 180°C for 1 h. Finally, the obtained solution was filtered with a 0.22 μm filter, and then freeze-dried to obtain AgCD powder.

[0035] AgCD was synthesized by one-step hydrothermal method using silver nitrate and citric acid as raw materials and polyethyleneimine as reducing agent, as shown in Figure 1 TEM was used to evaluate the morphology and dispersity of the prepared AgCD. AgCD was regular spherical, uniformly dispersed, had good dispersity Figure 1 ) and its particle size was relatively small, the particle distribution was relatively uniform, and the average diameter was 3.89 nm ± 1.91 nm. The solution of AgCD was light yellow under sunlight, and emitted blue fluorescence under ultraviolet light. Fourier infrared spectroscopy was used to characterize it Figure 1 ). A typical band representing the stretching vibration of secondary amino groups was observed near 3454 cm -1 . In addition, the absorption band of O-H group almost disappeared, and the peak at 1701 cm -1 was related to the stretching vibration of C=O / C=C group. The peak at 1642 cm -1The peak at 1289 cm⁻¹ represents the stretching vibration of the -CONH- group. -1 A strong absorption band with CH bending appears at the location, which may belong to a redox aldehyde group.

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

[0037] Dissolve 2g of HA in 200mL of deionized water (concentration 10mg / mL) and stir until completely dissolved. Add 5mL of 0.5M sodium periodate solution dropwise to the HA solution. Adjust the pH of the solution to between 3.0 and 3.5 by adding 1M H2SO4 solution. Stir for 3 hours at room temperature in the dark. Then add 1mL of ethylene glycol to quench unreacted sodium periodate and stir for another 1 hour. Transfer the reaction solution to a dialysis bag and dialyze in deionized water for 3 days. Change the dialysate every 12 hours. Freeze dry to obtain white spongy OHA.

[0038] OHA is synthesized by oxidatively cleaving 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 1H NMR spectroscopy confirmed the formation of aldehydes in OHA. Figure 2 The appearance of new peaks at 4.92 ppm, 5.01 ppm, and 5.11 ppm indicates the formation of a hemiacetal proton between the aldehyde and hydroxyl groups, as well as the presence of an ortho-hydroxyl group in the system. These results confirm the successful synthesis of OHA. The synthesized aldehyde group after oxidation provides a reaction site for the subsequent Schiff base reaction.

[0039] 3. Preparation of hydrogels

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

[0041] The repairable hydrogel based on Met and AgCD dual drug delivery is formed through a Schiff base reaction between -NH2 of CMCS and -CHO of OHA. Figure 3 The gelation time of the hydrogel was determined by the inverted vial method. Equal volumes of CMCS and OHA formed a gel within 2-4 minutes. Figure 3 As shown.

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

[0043] 1. The microstructure of the formed hydrogel and its bacterial morphology were studied using a hot field emission scanning electron microscope (Gemini 500). The hydrogel was prepared by freeze-drying. Before observation, all samples were sputter-coated with gold. The pore size and shape of the hydrogel were observed and recorded. The hydrogel sample showed a typical three-dimensional network with a pore size of about 20-60 pm.

[0044] 2. The self-healing ability of the hydrogel was evaluated by direct visual method. The self-repairing performance of the hydrogel was studied on a plastic surface. Two circular hydrogels of different colors were prepared respectively. Subsequently, the two groups of hydrogels were cut into two halves, and two hydrogels of different colors were placed together to observe their self-repairing behavior. In addition, the adhesion of the hydrogel to the skin, plastic and glass was tested. As shown in Figure 5 , the hydrogel reconnected and completed the "healing" within 2 minutes. The adhesion of the hydrogel was tested using different materials Figure 5 . The results showed that the hydrogel could tightly adhere to the 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 rate (%) = (W t -W0) / W t x 100%.

[0047] An ideal wound dressing should have the ability to absorb wound exudate, while providing a moist environment for the wound, promoting wound cell hydration to promote wound recovery. Therefore, the hydrogel needs to have certain swelling properties. 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 20000, indicating that the hydrogel has excellent ability to absorb wound exudate Figure 6 .

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

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

[0050] 2. Results analysis: An ideal adjuvant should have excellent antibacterial activity and will not cause bacterial resistance. Plate counting method was used to evaluate the antibacterial ability of the hydrogel to each group of bacteria. First, we studied the ability of the hydrogel to capture bacteria within 3 hours (we counted the ability of the hydrogel to capture bacteria as the antibacterial ability of the material). As shown in Figure 7 , the hydrogel showed significant antibacterial performance, and 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 results of a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory and promoting diabetic wound healing

[0052] 1. Experimental method: Gel liquid was prepared under sterile conditions and placed in a 37°C incubator. According to the material weight to extraction medium volume ratio of 10 mg / mL, 10% serum containing DMEM medium was added, and the extraction was carried out at 37°C for 24 h. The extraction liquid was collected by filtering with a 0.2 μm filter membrane. Mouse preadipocytes (3T3-L1 cells) were suspended in DMEM complete medium containing 10% fetal bovine serum and 1% double antibody, and cultured at 37°C in a cell incubator with a CO2 concentration of 5% for 24 h. Then the culture medium was removed, and PBS and hydrogel extract were added for further culture for 24 h. 96-well plates were used for cytotoxicity test. After co-culturing with drugs for 24 h, MTT solution was added, and DMSO was added after incubation in the incubator for 4 h. Finally, the absorbance value of each well at 490 nm was detected by an enzyme marker, and the cell viability was calculated using the following formula:

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

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

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

[0056] 1. Experimental method: The hydrogel was placed in 5 mL PBS (pH = 7) and shaken in a shaking bed at 37°C (150 rpm). 2 mL of old PBS release medium was taken out and 2 mL of new PBS medium was added regularly. The release amount of metformin was measured by ultraviolet spectrophotometer at 232 nm. The cumulative release amount (CR) of metformin was calculated by the equation

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

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

[0059] 2. Result analysis: The results are shown in Figure 9 . Within the first 24 hours, Met was released rapidly and linearly from the hydrogel, with a cumulative release of up to 72%. The cumulative release gradually increased thereafter, with a maximum release of 80%. A sudden release of metformin was measured at the beginning, which could be due to the rapid penetration of PBS into the hydrogel when the hydrogel was first contacted with the release medium solvent PBS, causing the molecular chains inside the hydrogel to relax and trigger a state mutation, resulting in a sudden release of the drug. The burst release of Met from the hydrogel can have a positive therapeutic effect on alleviating the persistent inflammatory response.

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

[0061] 1. Experimental method: Male KM mice were randomly divided into two groups, with 8 mice in one group. Before modeling, normal water supply was maintained, and after fasting for 6 h, a single intraperitoneal injection of streptozotocin (STZ) solution (dissolved in 1% and pH = 4.5 sodium citrate buffer) was performed at 180 mg / kg. Food was added promptly after injection. After one week, the fasting blood glucose level of the mice was detected by blood glucose meter, and if the blood glucose was ≥16.65 mM, the diabetic model was successful. The diabetic mice were anesthetized, shaved, and a full-thickness wound about 10 mm in diameter was created on the central dorsal skin of each mouse. Then the wound was covered with hydrogel dressing, and the control group was only covered with PBS, and the covered dressing was replaced every 1 day, while the wound was photographed and measured.

[0062] 2. Results Analysis: For example... Figure 10 As shown, the wound area gradually decreased in each group with increasing treatment time. However, the wound healing in the experimental group was significantly better than that in the control group at all time points. On the second day of treatment, the wound area in the control group was significantly larger than the initial wound area. This wound expansion phenomenon is consistent with the clinical fact that diabetic wounds are difficult to heal 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, with almost zero remaining wound area, while the remaining wound area in the control group was 0.42 mm.

[0063] In summary, the multifunctional self-healing hydrogel material provided by this invention, possessing antibacterial, anti-inflammatory, and wound-healing properties for diabetic patients, exhibits good adhesion, self-healing ability, suitable swelling ratio, excellent biocompatibility, and antibacterial properties, effectively promoting wound healing in diabetic patients. This demonstrates 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 with antibacterial, anti-inflammatory, and diabetic wound-healing properties includes the following steps:

[0066] Step 1: Add polyethyleneimine and silver nitrate AgNO3 to deionized water and stir at room temperature. Then add citric acid and water. Transfer the mixture to a hydrothermal reactor and react at 160°C for 2 hours. Filter the resulting reaction solution and freeze-dry it to obtain silver-doped carbon quantum dots.

[0067] Step 2: Add sodium periodate solution to sodium hyaluronate solution one by one, adjust the pH value to 3.0, stir at room temperature and in the dark, then add ethylene glycol to quench 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: Metformin is dispersed in an aqueous solution of carboxymethyl chitosan to obtain the first raw material solution, and silver-doped carbon quantum dots are dispersed in an aqueous solution of sodium hyaluronate oxide to obtain the second raw material solution. The first and second raw material solutions are mixed evenly, and a hydrogel is obtained after the reaction.

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

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

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

[0072] The application of the hydrogel in the preparation of a hydrogel wound dressing for promoting the healing of diabetic wounds.

[0073] The above description is only intended to explain the preferred embodiments of the present application and is not intended to limit the present application in any form. Any modification or change made to the present application in the same spirit should be included in the scope intended to be protected by the present application.

Claims

1. A method for preparing a multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory, and wound-healing properties for diabetic patients, characterized in that: Includes the following steps: Step 1: Add polyethyleneimine and silver nitrate AgNO3 to deionized water and stir at room temperature. Then add citric acid and water. Transfer the mixture to a hydrothermal reactor and react at 160-200°C for 0.5-2 hours. Filter the resulting reaction solution and freeze-dry it to obtain silver-doped carbon quantum dots. Step 2: Add sodium periodate solution to sodium hyaluronate solution one by one, adjust the pH value to 3.0-3.5, stir at room temperature and in the dark, then add ethylene glycol to quench 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: Metformin is dispersed in an aqueous solution of carboxymethyl chitosan to obtain the first raw material solution, and silver-doped carbon quantum dots are dispersed in an aqueous solution of sodium hyaluronate oxide to obtain the second raw material solution. The first and second raw material solutions are mixed evenly, and a hydrogel is obtained after the reaction. The concentration of the first feed solution is 2-8 wt%, and the concentration of the second feed solution is 2-8 wt%; the volume ratio of the first feed solution to the second feed solution is 0.8-1.2:

1.

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

3. The application of the hydrogel material prepared by the method of claim 1 or 2, which has antibacterial, anti-inflammatory and promotes the healing of diabetic wounds, in the preparation of biomedical materials.

4. The application of the hydrogel material prepared by the method for preparing the multifunctional self-healing hydrogel material with antibacterial, anti-inflammatory, and diabetic wound-healing properties according to claim 3 in the preparation of biomedical materials is characterized by: The application of the hydrogel material in the preparation of hydrogel wound dressings that promote the healing of diabetic wounds.

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