Preparation and application of antibacterial and anti-inflammatory multifunctional hydrogel

Abstract

The present application relates to the technical field of biomaterial preparation, and particularly relates to preparation and application of an antibacterial and anti-inflammatory multifunctional hydrogel, the present application uses aldehyde-based glucomannan grafted polyarginine and polyacrylamide grafted glycyrrhizic acid-phenylboronic acid complex as a double network, and the hydrogel prepared by dynamic borate ester bond crosslinking has excellent mechanical properties, self-healing and tissue adhesion properties. It can break the membrane and resist bacteria under external ultrasound, respond to the high-sugar and low-pH microenvironment of diabetic wound surface to release glycyrrhizic acid, and regulate M2 polarization of macrophages to relieve excessive inflammation. The hydrogel obtained by the present application solves the problems of poor mechanical properties, lack of self-healing and adhesion properties of current diabetic wound dressings, and the present application is not limited by the precision of processing conditions, has a simple preparation method, mild process conditions, safety and reliability, better biocompatibility and economy.

Description

Technical Field

[0001] This invention relates to the field of biomaterial preparation technology, and in particular to the preparation and application of an antibacterial and anti-inflammatory multifunctional hydrogel. Background Technology

[0002] Diabetes mellitus is a prevalent chronic metabolic disease worldwide, with its incidence rate increasing year by year, becoming a public health problem threatening human health. Among the various complications of diabetes, impaired wound healing is a common clinical challenge. Long-term hyperglycemia in diabetic patients can induce dysfunction in multiple bodily systems, hindering the wound healing process and ultimately leading to the formation of chronic wounds. High blood sugar can trigger microvascular complications, leading to narrowing of blood vessels in the wound area. This prevents oxygen, nutrients, and repair cells from effectively reaching the wound site, hindering the normal wound repair process. Simultaneously, high blood sugar can damage peripheral nerves, causing sensory disturbances and making patients less sensitive to minor injuries. This can result in hidden injuries that are difficult to detect and treat promptly, further exacerbating wound damage. Furthermore, a high-glycemic environment inhibits the activity of immune cells, leading to weakened immune function, dysregulation of the local inflammatory response at the wound site, and the accumulation and persistence of inflammatory factors. This causes the wound healing process to stagnate in the inflammatory phase, preventing the transition to the proliferative and remodeling phases. Additionally, high blood sugar significantly reduces the proliferative capacity of fibroblasts and inhibits collagen synthesis and orderly arrangement, resulting in slow granulation tissue growth, insufficient tensile strength of the wound, and difficulty in achieving effective healing.

[0003] Currently, clinical treatments for chronic diabetic wounds still have many limitations and cannot meet clinical needs. Blood glucose regulation is fundamental to diabetic wound treatment, but blood glucose levels are easily affected by various factors such as diet, exercise, individual metabolic differences, and medication adherence, making it difficult to maintain the stable internal environment required for wound repair, thus affecting wound healing outcomes. Debridement is an important means of removing necrotic tissue and promoting healing, but traditional debridement methods easily damage the normal granulation tissue around the wound, and the exposed wound after debridement increases the risk of bacterial infection. Antibiotics can control wound infection to some extent, but long-term overuse of antibiotics can lead to increased bacterial resistance, resulting in persistently high bacterial infection rates in chronic wounds, further exacerbating the difficulty in wound healing. Exogenous growth factors can promote the proliferation of repair cells and collagen synthesis, but their local administration suffers from poor biostability, short in vivo half-life, and susceptibility to enzymatic degradation, and their insufficient targeting can easily trigger immune rejection reactions, making it difficult to achieve precise and long-term drug release, thus limiting therapeutic effects.

[0004] The unique pathological characteristics of diabetic wounds, such as the high-glucose microenvironment, chronic inflammation, and vascular damage, lead to slow healing and frequent recurrence. Conventional wound dressings, such as gauze and non-woven fabrics, only provide simple coverage and absorption, failing to address the core issues in the wound healing process and thus unable to meet the personalized repair requirements of diabetic wounds. Hydrogels, as a type of polymer material with a three-dimensional network structure, possess excellent biocompatibility and moisture retention. Their porous structure facilitates drug loading and sustained release, effectively maintaining stable local drug concentrations and prolonging the duration of drug action. Furthermore, the mechanical properties and degradation rate of hydrogels can be optimized by controlling material composition and preparation processes to adapt to diabetic wounds of different sizes and depths. In addition, by altering the composition of hydrogels, they can be endowed with intelligent responsive properties such as pH and glucose responses, enabling on-demand drug release, precise regulation of wound inflammation, and promotion of repair cell proliferation.

[0005] Therefore, in order to address the existing problems, designing a smart hydrogel-based diabetic wound dressing that combines stretchability, adhesion, self-healing, and antibacterial and anti-inflammatory functions is an urgent problem to be solved in this field. This can effectively solve the shortcomings of existing treatment methods and improve the healing effect of chronic diabetic wounds. Summary of the Invention

[0006] Therefore, the purpose of this invention is to overcome the shortcomings of the prior art and provide a multifunctional antibacterial and anti-inflammatory hydrogel for the repair of diabetic wounds. This multifunctional antibacterial and anti-inflammatory hydrogel is made by oxidizing the ortho-hydroxyl groups on the konjac sugar molecular chain with sodium periodate to generate oxidized konjac sugar GM-CHO. Subsequently, polyarginine PArg is grafted onto GM-CHO through Schiff base bonds to obtain GM-PArg, which constitutes the first network layer in the hydrogel. The GM-PArg hydrogel system, as an antibacterial material, can achieve efficient biofilm disruption and antibacterial effects through synergistic action with ultrasound. In addition, glycyrrhizic acid GA is formed into a dynamic borate ester complex with 3-acryloylphenylboronic acid APBA to obtain the APBA-GA complex. The APBA-GA complex undergoes free radical polymerization with acryloylamine AM to form the second network layer PPAM-GA in the hydrogel. The two networks form a GM-PArg / PPAM-GA hydrogel through dynamic borate ester bonds. This antibacterial and anti-inflammatory hydrogel solves the problems of poor mechanical properties, lack of adhesion, and low self-healing efficiency of current wound dressings. Furthermore, this invention is not limited by the precision of processing conditions, has a simple preparation method, mild process conditions, is safe and reliable, and has better biocompatibility and economy.

[0007] On the one hand, the present invention proposes an antibacterial and anti-inflammatory multifunctional hydrogel, which constructs a dual-network system, including a first network formed by grafting polyarginine with aldehyde-modified glucomannan as the basic skeleton substrate, and a second network constructed by grafting modified polyacrylamide with phenylboronic acid to construct a polymer-reinforced network. The polyarginine is fixed on the first network backbone through covalent grafting, and the glycyrrhizic acid and the phenylboronic acid groups on the second network are complexed together through dynamic borate ester bonds. In the formed hydrogel, the concentration of polyarginine in the hydrogel is 0.5~2.5 mg / mL, and the concentration of glycyrrhizic acid in the hydrogel is 25~35 mg / mL; Polyarginine imparts antibacterial properties to the hydrogel, while complexed glycyrrhizic acid provides anti-inflammatory activity.

[0008] On the other hand, the present invention also proposes a method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel, comprising the following steps: S1. Add glycyrrhizic acid to sodium hydroxide solution and stir at room temperature to dissolve it to obtain glycyrrhizic acid stock solution; S2. Add 3-acryloylaminophenylboronic acid to ultrapure water and stir at room temperature until completely dissolved to obtain a stock solution of 3-acryloylaminophenylboronic acid. S3. Add glycyrrhizic acid stock solution dropwise to 3-acrylamidophenylboronic acid stock solution and stir continuously to ensure that the two solutions are fully mixed and allowed to stand at room temperature to obtain 3-acrylamidophenylboronic acid-glycyrrhizic acid complex. The formation of the complex is driven by the borate ester bond between GA and APBA. S4. Add sodium periodate aqueous solution dropwise to glucomannan aqueous solution and stir at room temperature in the dark. Observe the system state every 30 minutes to ensure no precipitation or layering. After adding ethylene glycol and stirring, the oxidation reaction is terminated by the reaction of ethylene glycol with the remaining sodium periodate. Transfer the mixed solution after the reaction is terminated to a dialysis bag. Seal both ends of the dialysis bag with dialysis clips and place it in a dialysis tank filled with deionized water for dialysis purification. Change the deionized water 3 times a day during dialysis to ensure thorough removal of small molecule impurities such as unreacted sodium periodate, ethylene glycol, and reaction byproducts. After freeze-drying, obtain white, loose solid oxidized konjac sugar (the aldehyde degree of konjac sugar was titrated, and the results showed that the degree of aldehyde was about 27%, and the two networks of the hydrogel were connected by unoxidized hydroxyl groups and phenylboronic acid bonds, which did not affect the cross-linking). S5. Add acrylamide and 3-acrylamidophenylboronic acid-glycyrrhizic acid complex to the dressing solvent, then add 3-acrylamidophenylboronic acid, stir and mix, purge with nitrogen, and then add oxidized konjac sugar and polyarginine in sequence. After stirring thoroughly, a homogeneous mixture without particles or precipitates is obtained. S6. Add the crosslinking agent N-methylenebisacrylamide, the initiator ammonium persulfate, and the accelerator tetramethylethylenediamine to the mixture in sequence. After magnetic stirring, ensure that the reagents are evenly dispersed in the mixture to avoid excessive local concentration affecting the polymerization reaction. Quickly pour the mixture into a pre-cleaned and dried polytetrafluoroethylene mold, and place it at a constant temperature to obtain a hydrogel. Store it in a sterile environment for later use.

[0009] Preferably, in S1, the room temperature is 24~26℃; The concentration of the glycyrrhizic acid stock solution is 25-35 mg / mL, preferably 30 mg / mL; The concentration of the sodium hydroxide solution is 0.03~0.1 mol / L, preferably 0.1 mol / L; The stirring speed is 2000~2500 r / min, preferably 2000 r / min.

[0010] Preferably, in S2, the concentration of the 3-acrylamidophenylboronic acid stock solution is 10-20 mg / mL, more preferably 15.2 mg / mL; The stirring speed is 2000~2500 r / min, preferably 2000 r / min.

[0011] Preferably, in S3, the molar ratio of the glycyrrhizic acid stock solution to the 3-acrylamidophenylboronic acid stock solution is 2:1 to 2.5:1, preferably 2:1; The stirring speed is 2000~2500 r / min, preferably 2000 r / min, and the stirring time is 20~40 s, preferably 30 s; The settling time is 10-20 minutes, preferably 15 minutes.

[0012] Preferably, in S4, the mass-volume concentration of the sodium periodate aqueous solution is 10%, and the preparation process involves adding sodium periodate to ultrapure water and stirring at room temperature until completely dissolved. The stirring speed is 2000~2500 r / min, preferably 2000 r / min; The glucomannan aqueous solution has a mass-volume concentration of 2%, and the preparation process involves adding glucomannan to ultrapure water and stirring at room temperature until completely dissolved to obtain a homogeneous and transparent glucomannan aqueous solution. The glucomannan has a molecular weight of 50,000~100,000 Da; The stirring speed is 500~600 r / min, preferably 550 r / min.

[0013] Preferably, in step S4, the sodium periodate aqueous solution is added dropwise to the glucomannan aqueous solution at a stirring speed of 1000~1300 rpm / min, preferably 1200 rpm / min, for a time of 1~3 h, preferably 2 h; The amount of ethylene glycol added is 0.8~1.5mL, preferably 1mL, the stirring speed is 2000~2500r / min, preferably 2000r / min, and the time is 5~20min, preferably 10min; The molecular weight cutoff of the dialysis bag is 4000~8000 Da; The continuous dialysis period is 3 days; The freeze-drying conditions are: pre-freezing temperature -80℃, pre-freezing time 12h, vacuum degree 10~20Pa, and freeze-drying time 24h.

[0014] Preferably, in step S5, the dressing solvent is ultrapure water; The concentration of the acrylamide is 223 mg / mL; The concentration of the 3-acrylamidophenylboronic acid-glycyrrhizic acid complex is 10 mg / mL; The concentration of the added 3-acrylamide phenylboronic acid was 7.6 mg / mL; The nitrogen purging time is 5-15 minutes; The concentration of the oxidized konjac sugar is 20 mg / mL; The molecular weight of the polyarginine is 1000~2000 Da; The stirring speed is 600~800 r / min, preferably 800 r / min, and the stirring time is 30~40 min, preferably 30 min.

[0015] Preferably, in S6, the concentration of N,N-methylenebisacrylamide is 30-35 mg / mL, more preferably 32 mg / mL; The concentration of the ammonium persulfate is 100-150 mg / mL, preferably 120 mg / mL; The volume of tetramethylethylenediamine used is 8~12 μL / mL, preferably 10 μL; The stirring speed is 2000~2500 r / min, preferably 2000 r / min, and the stirring time is 5~10 min, preferably 10 min; The constant temperature is 20~30℃, preferably 25℃, and the time is 100~400s, preferably 300s.

[0016] Finally, this invention proposes the application of an antibacterial and anti-inflammatory multifunctional hydrogel in wound healing dressings, antibacterial and anti-inflammatory dressings, medical adhesives, and artificial tissue skin.

[0017] Compared with the prior art, the present invention has achieved the following beneficial effects: 1. It has mechanical properties that match the skin, making it easy to fix and change as a dressing for diabetic wounds. It also has excellent adhesion properties, allowing it to adhere tightly to the skin surface and solve problems such as difficulty in fixing to tissues and incomplete coverage. 2. It has excellent self-healing properties, and can autonomously repair its structural and mechanical integrity after damage, thus extending its service life. At the same time, it can maintain the barrier function and drug delivery efficiency of wound dressings, improve cell compatibility, and has good biocompatibility and hemostatic properties. In vitro cytotoxicity experiments and fluorescence staining have confirmed that this hydrogel has good cell compatibility and is non-irritating to human skin tissue. Tail-cutting experiments have shown that its hemostatic performance is superior to gauze. 3. Exhibits excellent antibacterial properties. Under US irradiation, it can generate ROS, which have high oxidizing power. These ROS can oxidize polylysine molecules to generate NO, which then destroys the bacterial cell wall and interferes with DNA synthesis, thus killing bacteria. In vitro antibacterial experiments have verified that it has significant antibacterial effects (>99%) against both MRSA and E. coli. 4. It has excellent anti-inflammatory ability by regulating the macrophage phenotype polarization from M1 to M2, thereby regulating macrophage recruitment behavior; 5. The preparation method of the multifunctional antibacterial and anti-inflammatory hydrogel of this invention is simple, not easily restricted by precise operation, and suitable for dressings for diabetic wounds and tissue regeneration aids. Animal experiments have confirmed that it can significantly accelerate the healing of diabetic wounds in the absence of drug or cytokine delivery. Attached Figure Description

[0018] Figure 1 A schematic diagram of the structure of an antibacterial and anti-inflammatory multifunctional hydrogel; Figure 2 This is a schematic diagram of the phase transition from solution to gel. Figure 3 The ultraviolet spectrum of APBA-GA; Figure 4 Infrared spectrum of GM-CHO; Figure 5 Infrared spectra of PAM, PPAM-GA, and GM-PArg / PPAM-GA hydrogels; Figure 6 This is a scanning electron microscope image of the lyophilized GM-PArg / PPAM-GA hydrogel. Figure 7 The image shows the tensile properties of the GM-PArg / PPAM-GA hydrogel. Figure 7(a) shows the uniaxial tensile test results of PAM, PPAM-GA, and GM-PArg / PPAM-GA hydrogels. Figure 7 (b) shows the elongation at break of the hydrogel. Figure 7 (c) shows the tensile strength diagram of the hydrogel. Figure 7 In the middle (d), the modulus diagram of the hydrogel is shown. Figure 8 The graph shows the compression properties of the GM-PArg / PPAM-GA hydrogel. Figure 8 (a) shows the stress-strain diagram of 70% cyclic compression of the GM-PArg / PPAM-GA hydrogel. Figure 8 (b) shows the modulus loss of GM-PArg / PPAM-GA hydrogel under 70% cyclic compression. Figure 9 The graph shows the adhesion properties of the GM-PArg / PPAM-GA hydrogel. Figure 9 (a) shows the stress-strain diagram of the GM-PArg / PPAM-GA hydrogel overlap shear test. Figure 9 (b) is a stress statistics diagram of the GM-PArg / PPAM-GA hydrogel overlap shear test; Figure 10 The graph shows the characterization of the self-healing properties of GM-PArg / PPAM-GA hydrogel. Figure 10 (a) shows the self-healing effect of GM-PArg / PPAM-GA hydrogel. Figure 10 (b) shows the alternating rheological characterization of the GM-PArg / PPAM-GA hydrogel; Figure 11 The graph shows the characterization of the antibacterial properties of GM-PArg / PPAM-GA hydrogel. Figure 11 (a) shows the antibacterial properties of GM-PArg / PPAM-GA hydrogel. Figure 11 (b) shows the mortality rates of E. coli and MRSA bacteria. Figure 12 A diagram illustrating how GM-PArg / PPAM-GA hydrogel promotes macrophage polarization towards M2. Figure 12 (a) is a confocal image showing how GM-PArg / PPAM-GA hydrogel promotes macrophage polarization toward M2. Figure 12 (b) shows the CD86 / CD206 values ​​in the GM-PArg / PPAM-GA hydrogel image; Figure 13 Images of GM-PArg / PPAM-GA hydrogel used to repair diabetic wounds in mice. Figure 13 (a) shows typical photographs of wound healing on days 0, 3, 7, and 14. Figure 13 (b) shows the wound contraction area of ​​each group. Detailed Implementation

[0019] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments. It should be noted that, unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps described in these embodiments do not limit the scope of this application.

[0020] The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the scope of this application and its application or use.

[0021] Techniques, methods, and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, they should be considered part of the specification.

[0022] In all the examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values.

[0023] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0024] The antibacterial and anti-inflammatory multifunctional hydrogel constructed in this invention comprises a first network layer grafted with polyarginine via aldehyde-modified glucomannan, and a second network layer grafted with a glycyrrhizic acid-acrylamidophenylboronic acid complex via polyacrylamide. The two networks are connected by dynamic borate ester bonds. Polyacrylamide imparts good mechanical strength to the hydrogel system, the dynamic borate ester bonds between the two networks impart good self-healing properties, and the o-dihydroxy group of glycyrrhizic acid, the phenylboronic acid bond of 3-acrylamidophenylboronic acid, and the guanidinyl group of polyarginine impart good adhesion properties, enabling the hydrogel to adapt to wound mechanical changes during skin movement.

[0025] In vitro experiments showed that the hydrogel could disrupt the biomembrane using external ultrasound at a power of 1.0 W and a duty cycle of 20%, converting hydrogen peroxide into highly oxidizing reactive oxygen species (ROS), which oxidized polyarginine to generate nitric oxide (NO), achieving highly efficient membrane-breaking and antibacterial effects. The high-glucose and low-pH diabetic microenvironment allowed the hydrogel to release glycyrrhizic acid, promoting macrophage polarization towards the anti-inflammatory and pro-repair M2 type, reducing excessive inflammatory responses in macrophages, and reshaping the immune microenvironment towards anti-inflammatory and pro-repair. The hydrogel was used to construct a three-dimensional microenvironment with a biomimetic extracellular matrix (ECM) nanofiber structure, endothelial glycocalyx, and NO-releasing activity, replacing the lost ECM in the wound area to provide mechanical support. This synergistically promoted wound re-epithelialization, angiogenesis, collagen deposition, and skin appendage formation. After 14 days of treatment, the hydrogel-treated wound healing rate approached 100%, reaching 90%. Histological analysis showed that the repaired wound had intact epidermis, abundant collagen deposition, and angiogenesis. The hydrogel synergistically promoted diabetic wound repair by exerting immunomodulatory, bioactive, and mechanical support functions in situ on the diabetic wound.

[0026] This invention provides an antibacterial and anti-inflammatory multifunctional hydrogel, comprising a first network formed by grafting polyarginine with aldehyde-modified glucomannan as a basic skeleton substrate, and a second network formed by grafting glycyrrhizic acid-phenylboronic acid complex with polyacrylamide as a polymeric reinforcing network. Polyarginine is anchored to the basic matrix, while glycyrrhizic acid is complexed with the polymer reinforcement network through dynamic borate ester bonds. The concentration of polyarginine in the hydrogel is 0.5~2.5 mg / mL, preferably 0.5 mg / mL, and the concentration of glycyrrhizic acid in the hydrogel is 25~35 mg / mL, preferably 30 mg / mL.

[0027] This invention also provides a method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel, comprising the following steps: S1. Add glycyrrhizic acid to sodium hydroxide solution and stir at room temperature to dissolve it to obtain glycyrrhizic acid stock solution; S2. Add 3-acrylamidophenylboronic acid to ultrapure water and stir at room temperature until completely dissolved to obtain a 3-acrylamidophenylboronic acid stock solution. S3. Add glycyrrhizic acid stock solution dropwise to 3-acrylamidophenylboronic acid stock solution and stir continuously to ensure that the two solutions are fully mixed and allowed to stand at room temperature to obtain 3-acrylamidophenylboronic acid-glycyrrhizic acid complex. The formation of the complex is driven by the borate ester bond between GA and APBA. S4. Add sodium periodate aqueous solution dropwise to glucomannan aqueous solution and stir at room temperature in the dark. Observe the state of the system every 30 minutes to ensure that there is no precipitation or layering. After adding ethylene glycol and stirring, the oxidation reaction is terminated by the reaction of ethylene glycol with the remaining sodium periodate. Transfer the mixed solution after the reaction is terminated to a dialysis bag. Seal both ends of the dialysis bag with dialysis clips and place it in a dialysis tank containing deionized water for dialysis purification. Change the deionized water 3 times a day during dialysis to ensure that small molecule impurities such as unreacted sodium periodate, ethylene glycol and reaction byproducts are fully removed from the system. After freeze-drying, white, loose solid oxidized konjac sugar is obtained. S5. Add acrylamide and 3-acrylamidophenylboronic acid-glycyrrhizic acid complex to the dressing solvent, then add 3-acrylamidophenylboronic acid, stir and mix, purge with nitrogen, and then add oxidized konjac sugar and polyarginine in sequence. After stirring thoroughly, a homogeneous mixture without particles or precipitates is obtained. S6. Add the crosslinking agent N-methylenebisacrylamide, the initiator ammonium persulfate, and the accelerator tetramethylethylenediamine to the mixture in sequence. After magnetic stirring, ensure that the reagents are evenly dispersed in the mixture to avoid excessive local concentration affecting the polymerization reaction. Quickly pour the mixture into a pre-cleaned and dried polytetrafluoroethylene mold, and place it at a constant temperature to obtain a hydrogel. Store it in a sterile environment for later use.

[0028] In this invention, the concentration of glycyrrhizic acid stock solution in S1 is preferably 25-35 mg / mL, more preferably 30 mg / mL; The concentration of the sodium hydroxide solution is preferably 0.03~0.1 mol / L, more preferably 0.1 mol / L; The stirring speed is preferably 2000~2500 r / min, more preferably 2000 r / min.

[0029] In this invention, the concentration of the 3-acrylamidophenylboronic acid stock solution in S2 is preferably 10-20 mg / mL, more preferably 15.2 mg / mL; The stirring speed is preferably 2000~2500 r / min, more preferably 2000 r / min.

[0030] In this invention, in S3, the molar ratio of glycyrrhizic acid stock solution to 3-acrylamidophenylboronic acid stock solution is preferably 2:1 to 2.5:1, more preferably 2:1; The stirring speed is preferably 2000~2500 r / min, more preferably 2000 r / min, and the stirring time is preferably 20~40 s, more preferably 30 s; The settling time is preferably 10-20 minutes, more preferably 15 minutes.

[0031] In this invention, in S4, the mass-volume concentration of the sodium periodate aqueous solution is 10%, and the preparation process is to add sodium periodate to ultrapure water and stir at room temperature until completely dissolved; The stirring speed is preferably 2000~2500 r / min, more preferably 2000 r / min; The glucomannan aqueous solution has a mass-volume concentration of 2%. The preparation process involves adding glucomannan to ultrapure water and stirring at room temperature until completely dissolved to obtain a homogeneous and transparent glucomannan aqueous solution. Glucomannan has a molecular weight of 50,000~100,000 Da; The stirring speed is preferably 500~600 r / min, more preferably 550 r / min.

[0032] In this invention, in step S4, the stirring speed of adding sodium periodate aqueous solution to glucomannan aqueous solution is preferably 1000~1300 rpm / min, more preferably 1200 rpm / min, and the time is preferably 1~3h, more preferably 2h; The preferred amount of ethylene glycol added is 0.8~1.5 mL, more preferably 1 mL; the stirring speed is 2000~2500 r / min, more preferably 2000 r / min; and the stirring time is preferably 5~20 min, more preferably 10 min. The molecular weight cutoff of the dialysis bag is 4000~8000 Da; The continuous dialysis period is 3 days; The freeze-drying conditions were: pre-freezing temperature -80℃, pre-freezing time 12h, vacuum degree 10~20Pa, and freeze-drying time 24h.

[0033] In this invention, in step S5, the dressing solvent is ultrapure water; The concentration of acrylamide was 223 mg / mL; The concentration of the 3-acrylamidophenylboronic acid-glycyrrhizic acid complex was 10 mg / mL; The concentration of 3-acrylamide phenylboronic acid to be supplemented was 7.6 mg / mL; The nitrogen purging time is preferably 5 to 15 minutes, more preferably 5 minutes; The concentration of oxidized konjac sugar was 20 mg / mL; Polyarginine has a molecular weight of 1000~2000 Da; The stirring speed is preferably 600~800 r / min, more preferably 800 r / min, and the stirring time is preferably 30~40 min, more preferably 30 min.

[0034] In this invention, the concentration of N,N-methylenebisacrylamide in S6 is preferably 30-35 mg / mL, more preferably 32 mg; The concentration of ammonium persulfate is preferably 100-150 mg / mL, more preferably 120 mg; The preferred volumetric volume of tetramethylethylenediamine is 8-12 μL / mL, more preferably 10 μL; The stirring speed is preferably 2000~2500 r / min, more preferably 2000 r / min, and the stirring time is preferably 5~10 min, more preferably 10 min; The constant temperature is 20~30℃, preferably 25℃, and the time is 100~400s, preferably 300s.

[0035] Finally, this invention proposes the application of an antibacterial and anti-inflammatory multifunctional hydrogel in wound healing dressings, antibacterial and anti-inflammatory dressings, medical adhesives, and artificial tissue skin.

[0036] Example 1 This embodiment provides a method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel, and performs material-based characterization, functional performance characterization, and bio-pharmacological characterization of the hydrogel.

[0037] The preparation steps in this embodiment are as follows: (1) Preparation of acryloylaminophenylboronic acid-glycyrrhizic acid complex APBA-GA.

[0038] Accurately weigh 15 mg of glycyrrhizic acid and slowly add it to 500 μL of 0.1 mol / L sodium hydroxide solution. Stir with a vortex stirrer at 2000 r / min until the GA is completely dissolved to prepare a GA stock solution with a concentration of 30 mg / mL, i.e., 36 mM. Accurately weigh 7.6 mg of 3-acrylamidophenylboronic acid and add it to 500 μL of ultrapure water with a resistivity ≥18.2 MΩ·cm at 25 °C. Stir the solution with a vortex stirrer at 2000 r / min until completely dissolved to prepare an APBA stock solution with a concentration of 15.2 mg / mL, or 72 mM. The prepared GA stock solution was slowly added dropwise to the APBA stock solution. During the addition, the mixture was continuously stirred with a vortex stirrer at a speed of 2000 r / min. After the addition was completed, the mixture was stirred for 30 seconds to ensure that the two solutions were fully mixed. The mixture was then placed at room temperature and allowed to stand for 15 minutes. After the reaction was completed, the acryloylaminophenylboronic acid-glycyrrhizic acid complex was obtained.

[0039] (2) Preparation of aldehyde-modified glucomannan.

[0040] Accurately weigh 1.00 g glucomannan with a molecular weight of 50,000 to 100,000 Da, add it to 50 mL of ultrapure water, and stir magnetically at 550 r / min at room temperature until completely dissolved to obtain a homogeneous and transparent 2% (w / v) GM aqueous solution. Accurately weigh 0.22 g of sodium periodate and add it to 2.2 mL of ultrapure water. Stir at 2000 rpm until completely dissolved to obtain a 10% (w / v) NaIO4 aqueous solution. Slowly add the prepared NaIO4 aqueous solution dropwise to the GM aqueous solution. After the addition is complete, place the reaction system at room temperature and in the dark, i.e., wrap the reaction vessel with aluminum foil and continuously stir magnetically at 1200 rpm for 2 hours to ensure that the oxidation reaction proceeds fully. During this period, observe the state of the system every 30 minutes to ensure that there is no precipitation or layering. After the oxidation reaction proceeded for 2 hours, 1 mL of analytical grade ethylene glycol (≥99.5%) was slowly added to the reaction system. The mixture was stirred continuously at 2000 r / min for 10 min. The resulting solution was then transferred to a dialysis bag with a molecular weight cutoff of 4000~8000 Da. The dialysis bag was sealed at both ends with dialysis clips and placed in a dialysis tank containing sufficient deionized water for dialysis purification. The deionized water was changed 3 times a day during dialysis to ensure thorough removal of small molecule impurities from the system. Dialysis was continued for 3 days. The solution in the dialysis bag was transferred to a freeze dryer, and the freeze drying conditions were set as follows: pre-freezing temperature -80℃, pre-freezing time 2h, vacuum degree 10Pa, freeze drying time 24h. After the sample was completely freeze-dried, a white, loose solid GM-CHO was obtained.

[0041] (3) Preparation of GM-PArg / PPAM-GA multifunctional hydrogel.

[0042] Beforehand, equilibrate 1 mL of ultrapure water dressing solvent to room temperature. Weigh 446 mg of acrylamide AM monomer (analytical grade, purity ≥99.0%) and mix it with 1 mL of APBA-GA complex solution. Then weigh 15.2 mg of APBA and add it to the mixture, stirring until homogeneous. After purging with N2 for 5 min, add 40 mg of GM-CHO and 1 mg of polyarginine PArg (molecular weight 1000~2000 Da). Place the mixture on a magnetic stirrer and stir at 800 r / min for 30 min until all components are completely dissolved, resulting in a homogeneous mixture free of particles and precipitates. Add 32 mg N,N-methylenebisacrylamide (BIS, analytical grade, purity ≥99.0%), 120 mg ammonium persulfate (APS, analytical grade, purity ≥98.0%), and 10 μL tetramethylethylenediamine (TMEDA, analytical grade, purity ≥99.0%) sequentially to the above mixture. Stir with a magnetic stirrer at 2000 r / min for 10 min to ensure that the reagents are evenly dispersed in the mixture and to avoid excessively high local concentrations that could affect the polymerization reaction.

[0043] The mixture was quickly poured into a pre-cleaned and dried polytetrafluoroethylene mold. The mold was placed in a constant temperature water bath at 25°C and reacted for 300 seconds. A three-dimensional network structure was formed through free radical polymerization and cross-linking reactions. After the reaction was completed, the product was removed from the mold, yielding a product 1 that is uniform in appearance, soft in texture, and has good elasticity. The schematic diagram of the solution-gel phase transition is shown below. Figure 2 As shown.

[0044] Example 2 The preparation method of this embodiment is the same as that of Example 1, except that oxidized glucomannan and polyarginine are not added, resulting in product 2.

[0045] Example 3 The preparation method of this embodiment is the same as that of Example 2, except that glycyrrhizic acid was not added to obtain the final product 3.

[0046] Example 4 15 mg of glycyrrhizic acid was dissolved in 500 μL of sodium hydroxide solution, resulting in a concentration of 30 mg / mL (36 mM). Then, 7.6 mg of 3-acrylamidophenylboronic acid was added to 500 μL of ultrapure water, resulting in a concentration of 15.2 mg / mL (72 mM). After adding the glycyrrhizic acid solution to the 3-acrylamidophenylboronic acid solution, the mixture was stirred with a vortex stirrer for 30 s and allowed to stand for 15 min to drive the formation of the complex. Then, an excess of 5 mg of alizarin red S was added to obtain product 6.

[0047] Example 5 The preparation method of this embodiment is the same as that of Example 4, except that glycyrrhizic acid was not added to obtain the final product 7.

[0048] Example 6 The preparation method of this embodiment is the same as that of Example 5, except that 3-acrylamidophenylboronic acid was not added to obtain the final product 8.

[0049] Characterization results: like Figure 1As shown, an antibacterial and anti-inflammatory multifunctional hydrogel is characterized by comprising a first network formed by grafting polyarginine with aldehyde-modified glucomannan as a basic skeleton substrate, and a second network formed by grafting glycyrrhizic acid-phenylboronic acid complex with polyacrylamide as a polymeric reinforcing network, the two networks together constituting a hydrogel network.

[0050] UV-vis characterization of APBA-GA and its results.

[0051] Test solutions containing ARS, ARS-APBA, and ARS-APBA-GA from Examples 4-6 were prepared at a concentration of 0.1 mmol / mL and subjected to spectral scanning using a UV spectrometer. The scanning results are as follows: Figure 3 As shown, UV-vis spectroscopy reveals that the binding of GA with the diol competitively binds to benzoic acid, disrupting the balance between ARS and boric acid, leading to a decrease in the fluorescence intensity of ARS-APBA. The redshift from the 480 nm ARS-APBA peak to the 515 nm ARS-APBA-GA peak further demonstrates the formation of the APBA-GA complex, as the color changes from red to blue.

[0052] Characterization of product 1 from Example 1 and its results.

[0053] (1) FT-IR characterization of GM-CHO and GM-PArg / PPAM-GA hydrogels.

[0054] Infrared spectra of the lyophilized CM-CHO and the obtained polyacrylamide (PAM), PPAM-GA, and GM-PArg / PPAM-GA hydrogels were measured. Figure 4 As shown, the infrared spectrum indicates that GM-CHO is at 1735 cm⁻¹ -1 The presence of a distinct aldehyde peak demonstrates the successful preparation of GM-CHO, such as... Figure 5 As shown, at 1654cm -1 The absorption peak at this point corresponds to the C=O stretching vibration of the amide group and is the most typical characteristic peak of PAM. When PAM forms a hydrogel with the AG complex, intermolecular hydrogen bonds or functional group grafting cause a shift in the characteristic peak, with the amide band wavenumber decreasing to 1632 cm⁻¹. -1 Meanwhile, in the hydrogel system at 3269cm... -1 A broad absorption peak corresponding to the hydroxyl group of GA appeared at 1699 cm⁻¹. The last component, GM-PArg / PPAM-GA, showed an absorption peak at 1699 cm⁻¹. -1 There is a distinct carboxylic acid peak at 1182 cm⁻¹. -1 The presence of a guanidinyl peak at 773 cm⁻¹ confirms the presence of PArg. Furthermore, the glycosidic bond of GM is observed at 773 cm⁻¹. -1 A significant peak was observed at the point, proving that the hydrogel and the final component were successfully synthesized.

[0055] (2) SEM characterization of GM-PArg / PPAM-GA hydrogel.

[0056] The porous structure was determined by observing the microstructure of the PAM, PPAM-GA, and GM-PArg / PPAM-GA hydrogels prepared in Examples 1-3 using transmission electron microscopy. Figure 6 As shown in the SEM results, all hydrogel samples exhibited an irregular porous network structure, but the GM-PArg / PPAM-GA hydrogel had the smallest pore size of about 100 μm and a uniform and dense pore structure, which could facilitate the delivery of growth factors or nutrients during wound healing.

[0057] (3) Characterization of the mechanical properties of GM-PArg / PPAM-GA hydrogel.

[0058] Using a computer-controlled electronic universal testing machine, uniaxial tensile and compression tests demonstrated that the prepared hydrogel possesses good tensile properties and stress recovery properties. Figure 7 It can be observed that these hydrogels have excellent extensibility (>500%), which is 60-75% better than that of human skin. Their mechanical strength reaches 137 kPa, and their maximum strain, maximum stress, and modulus reach 796.02%, 136.99 kPa, and 521.1 kJ / m, respectively. 3 . Figure 8 b shows that multi-cycle loading-unloading cyclic testing was conducted on the hydrogel under 70% compressive strain. The cyclic compressive stress-strain curves and energy loss evolution patterns confirm that the dynamic cross-linked network can dissipate energy through the sliding effect. The hydrogel exhibits low mechanical property degradation after multiple cycles, demonstrating good fatigue stability. A p-value > 0.05 is considered statistically insignificant between groups. p ≤ 0.05, p ≤ 0.01, and p ≤ 0.001 correspond to significant, highly significant, and extremely significant differences, respectively. A p-value > 0.05 does not prove that the two groups are completely identical; it only indicates that the existing data are insufficient to confirm a statistical difference.

[0059] (4) Characterization of the adhesion properties of GM-PArg / PPAM-GA hydrogel.

[0060] Using a microcomputer-controlled electronic universal testing machine, the lap tensile test demonstrated that the prepared hydrogel has adjustable adhesive properties. Figure 9 The results showed that the adhesion strength reached 17.8 kPa, higher than the 11.69 kPa of commercially available PVA adhesive. The total dissipated energy during the failure process was obtained by integrating the force-displacement curve. Dividing the total dissipated energy by the volume of the hydrogel adhesive layer, the calculated overlap adhesion energy reached 386.84 kJ / m. 3 The edge-to-edge adhesive bonding energy reaches 337.81 kJ / m. 3180° peel adhesion energy reaches 192.53 kJ / m 3 This adhesive property ensures that the hydrogel dressing adheres closely to the tissue during application, achieving complete wound coverage.

[0061] (5) Characterization of the self-healing properties of GM-PArg / PPAM-GA hydrogel.

[0062] Through intuitive healing stretching Figure 10 (a) shows that the hydrogel has good self-healing properties; in addition, the prepared hydrogel has self-healing properties through cyclic testing experiments using a rotational rheometer with a small strain of 1% and a strain of 1500%. Figure 10 (b) shows that under large strain, the storage modulus (G') of the hydrogel decreases significantly and is lower than the loss modulus (G''), indicating that its three-dimensional network structure dissociates. However, when the strain is 1%, G' and G'' can quickly recover to their initial levels, indicating that the network structure has been reconstructed. Even after 5 cycles of loading, the modulus did not show significant decay. This result fully confirms that the GM-PArg / PPAM-GA hydrogel has excellent dynamic self-healing properties, with a self-healing efficiency of up to 82%.

[0063] (6) Characterization of the antibacterial properties of GM-PArg / PPAM-GA hydrogel.

[0064] MRSA~10 6 CFU / mL and E. coli ~10 6 The CFU / mL solution was co-cultured with the prepared hydrogel at 37°C for 6 h, and then the treated bacterial culture was plated on agar plates and incubated for 12 h. Colony-forming units (CFU) were photographed on the culture dishes to evaluate the antibacterial activity of the hydrogel. Figure 11 Representative images from each group in (a) show a synergistic antibacterial effect. Quantitative statistical analysis... Figure 11 (b) The bacterial survival rate can be reduced to 5% by calculating the colony count and the proportion of the control group, and the sterilization effect is significantly better than other groups (P*<0.05).

[0065] (7) Characterization of the macrophage polarization-promoting properties of hydrogels.

[0066] The polarization state of GM-PArg / PPAM-GA hydrogels on macrophages was observed by immunofluorescence staining to identify CD206 (M2 marker), green, and CD86 (M1 marker), with red indicating M1. Figure 12 (a) It can be seen that, compared with the GM-PArg / PPAM-GA, PPAM-GA and LPS groups, the US+GM-PArg / PPAM-GA group showed more green CD206 staining and less red CD86 staining. Figure 12(b) It can be seen that the CD86 / CD206 values ​​are 0.24 for US+GM-PArg / PPAM-GA, 0.73 for GM-PArg / PPAM-GA, 1.17 for PPAM-GA, and 11.21 for LPS, indicating that GA and NO synergistically promote M2 polarization of macrophages in the hydrogel. These findings suggest that the GM-PArg / PPAM-GA hydrogel can transform the immune microenvironment from an inflammatory state to a pro-repair state, which has advantages for the regeneration and repair of diabetic wounds.

[0067] (8) Characterization of the anti-diabetic wound repair performance of GM-PArg / PPAM-GA hydrogel.

[0068] A full-skin lesion MRSA bacterial infection model was established on the back of mice, and the prepared hydrogel was applied to the wound. The wound was compared with that of untreated mice, and the healing process was photographed and the wound contraction rate was calculated. Figure 13 (a) shows gross wound healing photographs and corresponding quantitative statistical results of wound healing rate on days 0, 3, 7, and 14 in a rat full-thickness skin defect model, for the control group, the membrane group, and the US+GM-PArg / PPAM-GA hydrogel group. From the gross wound photographs, it can be visually observed that the wound area in all three groups gradually decreased with prolonged healing time. 13(b) shows that at days 3, 7, and 14, the wound contraction degree in the US+GM-PArg / PPAM-GA group was significantly better than that in the control group and the membrane material group alone. By day 14, this group had the smallest wound area and the best wound closure effect. Quantitative statistical analysis of wound healing rates further validated the general observations: on days 3 and 7, the wound healing rate in the US+GM-PArg / PPAM-GA group was significantly higher than the other two groups (P≤0.001); on day 14, the healing rate in this group was still significantly higher than the control group and the membrane group (P≤0.01). These statistical differences indicate that US combined with GM-PArg / PPAM-GA hydrogel can effectively accelerate the closure of skin wounds and has excellent wound healing capabilities. It is evident that the hydrogel dressing can shorten the wound healing cycle to 14 days without significant infection during this process. Calculations showed that the healing area reached over 90% on day 14, with a significant difference compared to the control group.

[0069] The above characterization results demonstrate that the APBA-GA complex and GM-CHO were successfully prepared and characterized, and the UV test confirmed the successful preparation. Subsequently, GM-PArg / PPAM-GA hydrogel was prepared by covalent and non-covalent interactions. This hydrogel possesses good mechanical properties, excellent self-healing ability, and outstanding tissue adhesion properties, which can effectively meet the skin adaptation needs of dynamic wounds.

[0070] Experiments such as bacterial plating showed that GM-PArg / PPAM-GA hydrogel can disrupt biofilms through ultrasound and convert H2O2 into strong oxidizing ROS, which oxidizes PArg to generate NO, thus achieving highly efficient antibacterial activity.

[0071] Cellular experiments showed that GM-PArg / PPAM-GA hydrogel can regulate macrophage polarization towards M2, reduce excessive inflammatory response in macrophages, and reshape the immune microenvironment towards anti-inflammatory and repair-promoting transformation.

[0072] In vivo diabetic wound repair experiments showed that GM-PArg / PPAM-GA hydrogel can accelerate the healing of diabetic wounds in mice by inhibiting bacterial proliferation, reducing excessive inflammatory response in the wound, and thus promoting wound re-epithelialization, collagen deposition and angiogenesis.

[0073] In summary, GM-PArg / PPAM-GA hydrogel has the potential to be a more effective antibacterial and anti-inflammatory biomaterial to promote the repair of diabetic wounds.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical methods of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical methods of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical methods to deviate from the spirit and scope of the technical methods of the present invention.

Claims

1. An antibacterial and anti-inflammatory multifunctional hydrogel, characterized in that, The hydrogel constructs a dual-network system, including a first network formed by grafting polyarginine with aldehyde-modified glucomannan as the basic skeleton substrate, and a second network constructed by grafting phenylboronic acid with modified polyacrylamide to form a polymer-reinforced structure. The polyarginine is fixed on the first network backbone through covalent grafting, and the glycyrrhizic acid and the phenylboronic acid groups on the second network are complexed together through dynamic borate ester bonds. In the formed hydrogel, the concentration of polyarginine in the hydrogel is 0.5~2.5 mg / mL, and the concentration of glycyrrhizic acid in the hydrogel is 25~35 mg / mL; Polyarginine imparts antibacterial properties to the hydrogel, while complexed glycyrrhizic acid provides anti-inflammatory activity.

2. A method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel, used to prepare the antibacterial and anti-inflammatory multifunctional hydrogel as described in claim 1, characterized in that, Includes the following steps: S1. Add glycyrrhizic acid to sodium hydroxide solution and stir at room temperature to dissolve it to obtain glycyrrhizic acid stock solution; S2. Add 3-acrylamidophenylboronic acid to ultrapure water and stir at room temperature until completely dissolved to obtain a 3-acrylamidophenylboronic acid stock solution. S3. Add glycyrrhizic acid stock solution dropwise to 3-acryloylaminophenylboronic acid stock solution, stir continuously, and let stand at room temperature to obtain 3-acrylamidophenylboronic acid-glycyrrhizic acid complex. S4. Add sodium periodate aqueous solution dropwise to glucomannan aqueous solution, stir at room temperature in the dark, add ethylene glycol and continue stirring, then transfer to dialysis bag, place in dialysis tank containing deionized water, perform continuous dialysis, and freeze dry to obtain oxidized konjac sugar. S5. Add acrylamide and 3-acrylamidophenylboronic acid-glycyrrhizic acid complex to the dressing solvent, then add 3-acrylamidophenylboronic acid, stir and mix, purge with nitrogen, and then add oxidized konjac sugar and polyarginine in sequence. After stirring thoroughly, a mixture is obtained. S6. Add N-methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine to the mixture in sequence. After magnetic stirring, place it in a polytetrafluoroethylene mold and keep it at a constant temperature to obtain a hydrogel.

3. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S1, the room temperature is 24~26℃; The concentration of the glycyrrhizic acid stock solution is 25-35 mg / mL; The concentration of the sodium hydroxide solution is 0.03~0.1 mol / L; The stirring speed is 2000~2500 r / min.

4. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S2, the concentration of the 3-acryloylaminophenylboronic acid stock solution is 10~20 mg / mL; The stirring speed is 2000~2500 r / min.

5. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S3, the molar ratio of the glycyrrhizic acid stock solution to the 3-acryloylaminophenylboronic acid stock solution is 2:1 to 2.5:1; The stirring speed is 2000~2500 r / min, and the time is 20~40 s; The settling time is 10-20 minutes.

6. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S4, the mass-volume concentration of the sodium periodate aqueous solution is 10%, and the preparation process is to add sodium periodate to ultrapure water and stir at room temperature until completely dissolved; The stirring speed is 2000~2500 r / min; The glucomannan aqueous solution has a mass-volume concentration of 2%, and the preparation process involves adding glucomannan to ultrapure water and stirring at room temperature until completely dissolved. The glucomannan has a molecular weight of 50,000~100,000 Da; The stirring speed is 500~600 r / min.

7. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S4, the sodium periodate aqueous solution is added dropwise to the glucomannan aqueous solution at a stirring speed of 1000~1300 rpm / min for 1~3 h. The amount of ethylene glycol added is 0.8~1.5 mL, the stirring speed is 2000~2500 r / min, and the time is 5~20 min; The molecular weight cutoff of the dialysis bag is 4000~8000 Da; The continuous dialysis period is 3 days; The freeze-drying conditions are: pre-freezing temperature -80℃, pre-freezing time 12h, vacuum degree 10~20Pa, and freeze-drying time 24h.

8. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S5, the dressing solvent is purified water; The concentration of the acrylamide is 223 mg / mL; The concentration of the 3-acrylamidophenylboronic acid-glycyrrhizic acid complex is 10 mg / mL; The concentration of the added 3-acrylamide phenylboronic acid was 7.6 mg / mL; The nitrogen purging time is 5-15 minutes; The concentration of the oxidized konjac sugar is 20 mg / mL; The molecular weight of the polyarginine is 1000~2000 Da; The stirring speed is 600~800 r / min, and the stirring time is 30~40 min.

9. The method for preparing an antibacterial and anti-inflammatory multifunctional hydrogel according to claim 2, characterized in that, In S6, the concentration of N,N-methylenebisacrylamide is 30-35 mg / mL; The concentration of the ammonium persulfate is 100-150 mg / mL; The volume of tetramethylethylenediamine used is 8~12 μL / mL; The stirring speed is 600~800 r / min, and the time is 5~10 min; The constant temperature is 20~30℃, and the time is 100~400s.

10. An application of an antibacterial and anti-inflammatory multifunctional hydrogel, characterized in that, The application of the antibacterial and anti-inflammatory multifunctional hydrogel according to any one of claims 2-9 in wound healing dressings, antibacterial and anti-inflammatory dressings, medical adhesives, and artificial tissue skin.

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