PH-responsive antibacterial multifunctional hydrogel dressing as well as preparation method and application thereof

Abstract

The invention provides a pH-responsive antibacterial multifunctional hydrogel dressing and a preparation method thereof, and belongs to the technical field of hydrogel. The preparation method comprises the following steps: (1) mixing a diacrylate monomer and a diamine monomer according to a molar ratio of 1.1: 1-2: 1 for reaction, and purifying to obtain poly (beta-amino ester); and (2) mixing hyaluronic acid with epsilon-poly-L-lysine, adding a poly (beta-amino ester) solution dissolved in deionized water, repeatedly sucking and extruding, defoaming, and standing to form the hydrogel. The collagen hydrogel has rapid self-repairing performance, good pH intelligent responsiveness and good antibacterial property, the application range of the collagen hydrogel can be widened, and the service life of the collagen hydrogel can be prolonged.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogels, and particularly to a preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing, a pH-responsive antibacterial multifunctional hydrogel dressing prepared by using the preparation method, and an application as an inflammatory wound dressing. Background Art

[0002] The skin, as the first line of defense of the human immune system, is crucial for maintaining normal metabolism and information exchange. In daily life, open wounds formed due to injuries, burns, scratches or surgical incisions inevitably damage the integrity of the skin. Without proper treatment, skin injuries may be infected by microorganisms, leading to chronically non-healing wounds and even tissue necrosis. In recent years, a great deal of work has been done in developing various types of wound dressings to accelerate the wound healing process. Among them, hydrogel dressings are considered an ideal choice for wound healing dressings due to their advantages in maintaining a moist wound environment, absorbing excess exudate and allowing oxygen penetration.

[0003] Self-healing hydrogels are a class of hydrogels that can autonomously restore their structure and function after injury, which can be autonomous or rely on external stimuli. There are various self-healing mechanisms of hydrogels, which can be classified into two major categories according to the formation of their internal networks: dynamic chemical covalent bond crosslinking and physical non-self-healing. The main common dynamic covalent bonds are imine bonds, Diels-Alder (DA) reactions, borate ester bonds and disulfide bonds, while the main common physical non-covalent interactions are hydrogen bonds, hydrophobic interactions and host-guest interactions. The main advantages of physically crosslinked hydrogels lie in their biomedical safety, easy manufacturability and excellent biocompatibility. Physically crosslinked hydrogels are usually formed by reversible intermolecular interactions and weak secondary forces, such as ion / electrostatic interactions, hydrogen bonds, hydrophobic / hydrophilic interactions, crystallization / stereocomplex formation, etc., avoiding the use of toxic initiators or chemical catalysts.

[0004] Among antibacterial agents, ε-poly-L-lysine (ε-PL) is a hydrophilic cationic homopolyamide based on L-lysine, characterized by biocompatibility, biodegradability, excellent tissue adhesion properties, anti-infection and anti-cancer activities, and has been approved as a commercial food preservative by the food and drug administrations of multiple countries. According to recently reported studies, ε-PL-based biomaterials or hydrogels have shown great potential for numerous biomedical applications, including antibacterial agents, targeted drug and gene delivery systems, bioadhesives, and wound healing membranes. In the past decade, hydrogels with anti-inflammatory and antibacterial functions have been a research hotspot in the biomedical field. ε-PL has high antibacterial activity against Gram-negative bacteria (such as Escherichia coli) and Gram-positive bacteria (such as Staphylococcus aureus), as well as certain types of fungi and yeasts. In addition, ε-PL has strong polycationic properties and allows complexation or complementary stacking through electrostatic interactions with anionic polyelectrolytes or polymers. However, the long-term sudden release of high concentrations of ε-PL can cause wound bacteria to exhibit drug resistance, thus affecting the later wound healing effect, and can cause severe cytotoxicity, affecting cell healing.

[0005] Poly(β-amino esters) (PBAEs) have recently attracted extensive attention due to their inherent biocompatibility, biodegradability, and responsiveness, and are a polymer library for various biomedical applications, such as anti-cancer drugs, antibacterial agents, protein delivery, and tissue repair. PBAEs are synthesized by a one-pot Michael addition of amines to acrylates without generating any by-products. The hydrolyzable ester bonds provide excellent biodegradability for PBAEs, thus reducing cytotoxicity caused by necrosis and apoptosis. The tertiary amine groups can electrostatically interact with negatively charged genes or therapeutic agents to form nanocomposites. In addition, the amino groups undergo a phase change under the action of the surrounding pH value, with pH-responsive and charge-reversible characteristics, which make PBAEs potential candidate polymers for controlled and programmable release.

[0006] Therefore, three problems need to be solved, namely, the hydrogel can achieve intelligent and continuous release of an appropriate dose of ε-PL according to the wound inflammation situation, and how the hydrogel adheres to irregular wounds and can adapt to frequent body movements, and no by-products and monomers harmful to cells are generated during the synthesis of the hydrogel. Summary of the Invention

[0007] In view of this, to solve the technical problems in the prior art, such as the potential risk of monomers such as hydrogel crosslinkers exacerbating wound inflammation, excessive release of antibacterial drugs from hydrogel dressings, resulting in an increase in bacterial drug resistance in wound inflammation, as well as insufficient adhesion to skin wounds, and the rupture and shedding of hydrogels caused by physiological activities of the body, affecting the healing effect. For this reason, on the one hand, the present invention provides a preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing, which has rapid self-repair performance, good pH intelligent responsiveness, good antibacterial properties, and can broaden the application range and service life of collagen hydrogels.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] A preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing, comprising the following steps:

[0010] Step (1): Mix and react a diacrylate monomer and a diamine monomer in a molar ratio of 1.1:1 to 2:1, and purify to obtain poly(β-amino ester);

[0011] Step (2): Mix hyaluronic acid and ε-poly-L-lysine, add a poly(β-amino ester) solution dissolved in deionized water, repeatedly suck and extrude, and after defoaming, let it stand to form a hydrogel.

[0012] Preferably, in step (1), by weight, the diacrylate monomer is 1.237 to 3.373 parts, and the diamine monomer is 0.5 part.

[0013] Preferably, in step (2), by weight, hyaluronic acid is 0.4 to 0.6 part, ε-poly-L-lysine is 0.4 to 0.6 part, and the poly(β-amino ester) solution is 0.01 part.

[0014] Preferably, the diacrylate monomer is 1,4-butanediol diacrylate, and the diamine monomer is primary diamine (N,N-dimethylethylenediamine).

[0015] Preferably, step (2) is specifically:

[0016] Mix hyaluronic acid powder and ε-poly-L-lysine powder and shake well to obtain a mixed powder. Dissolve poly(β-amino ester) in deionized water and inject it into the mixed powder to obtain a hydrogel mixture. Continuously suck and extrude the hydrogel mixture using a syringe and a three-way valve, stir, perform vacuum defoaming and ultrasonic treatment, and then let it stand to obtain a pH-responsive antibacterial multifunctional hydrogel dressing.

[0017] Preferably, vacuum defoaming is carried out for 5 to 10 minutes, and ultrasonic treatment is carried out for 1 to 3 minutes.

[0018] Preferably, the reaction temperature in step (1) is 50 °C and the time is 48 hours.

[0019] On the other hand, the present invention also provides a pH-responsive antibacterial multifunctional hydrogel dressing prepared by the above preparation method.

[0020] On yet another aspect, the present invention provides the use of the above pH-responsive antibacterial multifunctional hydrogel dressing as an inflammatory wound dressing.

[0021] The pH-responsive antibacterial multifunctional hydrogel dressing and its preparation method provided by the present invention have the following beneficial effects compared with the prior art:

[0022] (1) In this invention, ε-poly-L-lysine (ε-PL) with antibacterial properties is innovatively dissolved in the solution of hyaluronic acid hydrogel. As a substance with significant polycationic properties, ε-PL can form a complex or complementary stacking structure through electrostatic interaction with the negatively charged anionic polyelectrolyte hyaluronic acid. The formation of this structure depends on the intermolecular interaction between reversible amino groups and carboxylic acid groups, as well as weak secondary forces, enabling the prepared hydrogel to not only possess antibacterial properties but also achieve rapid self-healing function. In this process, ε-PL not only serves as a component of the hydrogel structure but also, under specific pH conditions, can degrade responsively and release antibacterial agents, thus endowing the hydrogel structure with the "dual" identity of structure and responsive antibacterial.

[0023] (2) The hydrogel involved in the present invention exhibits excellent broad-spectrum antibacterial properties. Its core component ε-PL (ε-polylysine) shows significant antibacterial activity against a variety of microorganisms, including Gram-negative bacteria (such as Escherichia coli) and Gram-positive bacteria (such as Staphylococcus aureus), as well as specific types of fungi and yeasts. The development of this hydrogel provides new solutions for medical treatment, food preservation, and other fields requiring antibacterial protection.

[0024] (3) The hydrogel product involved in the present invention has remarkable properties. It can effectively adhere to a variety of different object surfaces, including but not limited to the human skin, various rubber products, transparent glass materials, metal surfaces, and common plastic items. The uniqueness of this hydrogel lies in the synergistic effect between its positive charge and fluidity, which endows it with extraordinary adhesion ability. Through a series of rheological tests and adhesion tests, it has been clearly confirmed that the hydrogel has excellent performance in soft tissue adhesion, making it a material with broad application potential in multiple fields such as medical dressing, personal care, and industrial applications.

[0025] (4) The present invention relates to a physically cross-linked hydrogel formed by static stirring. By introducing poly(β-amino ester) (PBAE) as a functional material, the hydrogel is endowed with the ability to release antibacterial agents in a pH-responsive manner. The preparation process of this gel is simple and fast, the reaction conditions are mild, it is environmentally friendly and non-toxic, and it also has a fast self-healing ability. In addition, the gel exhibits excellent pH-intelligent responsiveness and good antibacterial properties. These characteristics enable it to significantly expand the application fields of collagen hydrogels and extend their service life. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Self-healing behavior of PHAE55 hydrogel.

[0027] Figure 2 Bacteriostatic effect diagrams of the hydrogels prepared in Examples 1-3 at different pH values.

[0028] Figure 3 Antibacterial activity evaluation of PHAEs hydrogels against Escherichia coli and Staphylococcus aureus.

[0029] Figure 4 Rheological characterization of the destruction and structural recovery of PHAE55 hydrogel in strain mode.

[0030] Figure 5 Morphology and density of L929 cells co-cultured with PHAEs hydrogel extracts for 1 day and 3 days.

[0031] Figure 6 Proliferation rate of L929 cells co-cultured with PHAEs hydrogel extracts for 1 day and 3 days. DETAILED DESCRIPTION OF THE INVENTION

[0032] The present invention provides a preparation method for a pH-responsive antibacterial multifunctional hydrogel dressing, which includes the following steps:

[0033] Step (1): In step (1) of synthesizing poly(β-amino ester), first, a diacrylate monomer and a diamine monomer need to be mixed and reacted in a certain molar ratio. Specifically, this ratio should be controlled between 1.1:1 and 2:1 to ensure the smooth progress of the reaction. After the mixing reaction, the product needs to be purified to obtain pure poly(β-amino ester).

[0034] When selecting the diacrylate monomer, it is recommended to use 1,4-butanediol diacrylate because it shows good reactivity and product performance during the synthesis process. For the diamine monomer, primary diamine (N,N-dimethylethylenediamine) is a preferred choice because it can provide the required amino groups to participate in the formation of the poly(β-amino ester) structure.

[0035] In terms of reaction conditions, the recommended reaction temperature is 50 °C. Such a temperature can ensure that the reaction proceeds under relatively mild conditions, avoiding side reactions or product decomposition that may be caused by high temperatures. At the same time, the reaction time is set to 48 hours. Such a time length can ensure sufficient reaction between monomers, thereby improving the conversion rate and purity of the product.

[0036] Finally, calculated by weight parts, the dosage of the diacrylate monomer should be between 1.237 parts and 3.373 parts, while the recommended dosage of the diamine monomer is 0.5 parts. Such a dosage ratio and monomer selection, combined with the above reaction conditions, can effectively synthesize the required poly(β - amino ester).

[0037] Step (2): By mixing hyaluronic acid and ε - poly - L - lysine, and adding a poly(β - amino ester) solution dissolved in deionized water, through repeated suction and extrusion operations, as well as degassing treatment, and finally allowing it to stand to form a hydrogel. In this process, calculated by weight parts, the optimal dosage range of hyaluronic acid is 0.4 - 0.6 parts, and the dosage of ε - poly - L - lysine is also within this range, which is 0.4 - 0.6 parts. As for the poly(β - amino ester) solution, its dosage is 0.01 part.

[0038] In the implementation process of the present invention, the preferred method for step (2) is as follows:

[0039] First, mix hyaluronic acid powder and ε - poly - L - lysine powder, and shake well to ensure uniformity to obtain a mixed powder. Then, use deionized water to dissolve poly(β - amino ester), and inject the dissolved solution into the previously obtained mixed powder. Subsequently, use a syringe and three - way valve to perform repeated suction and extrusion operations on the hydrogel mixture, further mix by stirring, then perform vacuum degassing treatment, and use ultrasonic waves for treatment, and finally let it stand. In this way, a hydrogel with pH responsiveness, antibacterial properties, adhesiveness, and rapid self - repair ability can be obtained. For specific parameter conditions, the preferred method is:

[0040] First, weigh 0.4 - 0.6 parts of hyaluronic acid and 0.4 - 0.6 parts of ε-poly-L-lysine, mix and shake these two powders. Then, dissolve 0.01 part of PBAE (i.e., the poly(β-amino ester) prepared in step (1)) using 2.5 mL of deionized water, and inject the dissolved solution into the previously mixed powders. Next, use two syringes and a three-way valve to perform at least 30 inhalation and extrusion operations on the hydrogel mixture, then stir, followed by 5 - 10 minutes of vacuum degassing treatment, and ultrasonic treatment for 1 - 3 minutes. Finally, let it stand still, and thus the pH-responsive antibacterial multifunctional hydrogel dressing PHAE can be obtained.

[0041] On the other hand, the present invention further provides an antibacterial hydrogel with pH-responsive properties. This hydrogel not only has adhesiveness but also can achieve a rapid self-healing function. This hydrogel is obtained through the preparation method described above. It exhibits excellent rapid self-repair performance and good pH intelligent responsiveness, which means it can adjust its properties according to changes in the environmental pH value. In addition, this hydrogel also has significant antibacterial properties and can effectively inhibit the growth and reproduction of bacteria. Therefore, this pH-responsive antibacterial multifunctional hydrogel dressing can significantly broaden the application scope of traditional collagen hydrogels and extend their service life, making it have a broader application prospect in the fields of medicine, bioengineering, and other related fields.

[0042] The technical solutions of the present invention will be clearly and detailedly described below in combination with specific embodiments.

[0043] Example 1

[0044] Weigh 1.687 g of 1,4-butanediol diacrylate and 0.5 g of primary diamine (N,N-dimethylethylenediamine), and the molar ratio of the two is 1.5:1;

[0045] After mixing the required amount of diacrylate with DCM (dichloromethane), mix the diamine monomer with this solution and mix at 50 °C for 48 hours. At this time, a viscous yellow solution is obtained. Precipitate the solution into ether to remove unreacted monomers, such as residual amines;

[0046] After preparation, store PBAE at 4 °C until the next experiment, named PBAE2;

[0047] Weigh 0.4 g of hyaluronic acid and 0.6 g of ε-PL. Mix the two powders and shake well. Dissolve 10 mg of PBAE2 in 2.5 mL of deionized water and inject it into the powder. Continuously suck and extrude the hydrogel mixture using two syringes and a three-way valve. After 30 operations, stir, perform vacuum degassing for 8 min and ultrasonic treatment for 2 min, and then let it stand to obtain the pH-responsive antibacterial multifunctional hydrogel dressing PHAE46.

[0048] Example 2

[0049] Weigh 1.687 g of 1,4-butanediol diacrylate and 0.5 g of primary diamine (N,N-dimethylethylenediamine), and the molar ratio of the two is 1.5:1;

[0050] After mixing the required amount of diacrylate with DCM, mix the diamine monomer with this solution and mix at 50 °C for 48 h. At this time, a viscous yellow solution is obtained. Precipitate the solution into ether to remove unreacted monomers, such as residual amines;

[0051] After preparation, store PBAE at 4 °C until the next experiment and name it PBAE2;

[0052] Weigh 0.5 g of hyaluronic acid and 0.5 g of ε-PL. Mix the two powders and shake well. Dissolve 10 mg of PBAE2 in 2.5 mL of deionized water and inject it into the powder. Continuously suck and extrude the hydrogel mixture using two syringes and a three-way valve. After 30 operations, stir, perform vacuum degassing for 8 min and ultrasonic treatment for 2 min, and then let it stand to obtain the pH-responsive antibacterial multifunctional hydrogel dressing PHAE55.

[0053] Example 3

[0054] Weigh 1.687 g of 1,4-butanediol diacrylate and 0.5 g of primary diamine (N,N-dimethylethylenediamine), and the molar ratio of the two is 1.5:1;

[0055] After mixing the required amount of diacrylate with DCM, mix the diamine monomer with this solution and mix at 50 °C for 48 h. At this time, a viscous yellow solution is obtained. Precipitate the solution into ether to remove unreacted monomers, such as residual amines;

[0056] After preparation, store PBAE at 4 °C until the next experiment and name it PBAE2;

[0057] Weigh 0.6 g of hyaluronic acid and 0.4 g of ε-PL. Mix the two powders and shake well. Dissolve 10 mg of PBAE2 in 2.5 mL of deionized water and inject it into the powder. Use two syringes and a three-way valve to continuously aspirate and extrude the hydrogel mixture. After operating 30 times, stir, perform vacuum degassing for 8 min, and ultrasonically treat for 2 min, then let it stand to obtain the pH-responsive antibacterial multifunctional hydrogel dressing PHAE64.

[0058] Test Example 1

[0059] In a mixed solution of pullulan / polyvinyl alcohol, load Congo red (red) and fast green (blue) into the mixed solution respectively. After adding borax solution, pour it into a mold to make the hydrogel show red and green. Cut the red and green hydrogels of the same shape into two equal halves respectively. At room temperature, bring the cut surfaces of the hydrogels of different colors into contact with each other without applying any external intervention, and observe the self-healing phenomenon of the hydrogel. Take pictures of the self-healed hydrogel and its stretching situation for record.

[0060] Test Example 2

[0061] In this experiment, we first used the macroscopic observation method to evaluate the injectability and self-repair performance of the hydrogel. Taking the PHAE55 hydrogel as an example, at 25 °C, squeeze the hydrogel in the syringe onto the back of the index finger of a latex glove. After the hydrogel is flattened and stable, bend the finger by 90°. Use a scalpel to cut the hydrogel into two equal parts at the joint. Then straighten the finger and let the cut surfaces contact each other. After 10 s, bend the finger by 90° again and observe the repair situation of the hydrogel, as Figure 1 shown.

[0062] As Figure 4 shown, a rheometer was used to quantitatively test the self-healing test of the hydrogel. The experiment was carried out by performing a time sweep test at a frequency of 1 rad / s at 37 °C. Switch the parameters from small strain (γ = 5.0%, every interval of 120 s) to large strain (γ = 500%, every interval of 120 s), and perform 3 cycles.

[0063] Test Example 3

[0064] Cultivation of bacteria

[0065] Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli were selected to test the antibacterial performance of the hydrogel.

[0066] Streak the indicator bacteria on the LB plate medium and culture at 37°C for 1 day. Use a sterile inoculation loop to pick a small amount of bacteria from the activated LB medium and inoculate it into 5 mL of LB liquid medium. Incubate at 37°C and 180 rpm for 8 - 16 h. Determine the concentration of the bacterial solution to be 0.8 - 1 by measuring the absorbance value (OD600) of the bacterial solution at 600 nm using an ultraviolet spectrophotometer for standby.

[0067] Antibacterial experiment

[0068] Select the method of pouring the plate with pre - added bacterial solution to prepare the experimental plate: Pour 200 μL of the indicator bacteria solution into 50 mL of 1% agar LB plate medium that has cooled to about 25°C. Use a spreading rod to spread it evenly. Weigh 0.2 g of the PHAE46, PHAE55, and PHAE64 hydrogels prepared according to the preparation methods of Examples 1, 2, and 3, sterilize them under ultraviolet light in the ultra - clean bench for 2 hours, then put them into 2 mL of 0.9% physiological saline, soak for 24 h, coat them on the experimental plate inoculated with the bacterial solution, and place the plate upright in an incubator at 37°C for 24 h. Take pictures to observe the growth of colonies on the experimental plate, and take samples of the liquid. Determine the antibacterial rates of PHAE46, PHAE55, and PHAE64 by measuring the absorbance value (OD600) of the bacterial solution at 600 nm using an ultraviolet spectrophotometer, as Figures 2-3 shown.

[0069] Test Example 4

[0070] Cytotoxicity experiment

[0071] (1) Observation of cell morphology and density

[0072] Inoculate L929 cells into a 12 - well plate at a cell density of 1×10 5 and culture in a cell incubator at 37°C and 5% CO2 for 24 h to allow the cells to adhere and grow. Remove the old medium, replace it with 500 μL of the hydrogel extract. Use DMEM medium as the blank group. After culturing in a cell incubator at 37°C and 5% CO2 for 1 and 3 days, remove the hydrogel extract in the well plate. After washing with sterile normal saline, stain with a double - staining agent of calcein and propidium iodide (Calcein / PI) for 30 min, and take pictures and observe the cell morphology under a fluorescence microscope.

[0073] (2) Use the CCK - 8 test method to determine the cytotoxicity of the PHAE46, PHAE55, and PHAE64 hydrogel extracts on L929 cells to evaluate the cell compatibility of the materials. Inoculate L929 cells at a density of 1×10 per well 5Cells were seeded in 12-well plates and cultured in a cell incubator at 37 °C and 5% CO2 for 24 h to allow the cells to adhere and grow. In the experimental group, the culture medium was replaced with 500 μL of hydrogel extract, and in the negative control group, normal culture medium was added. On the 1st and 3rd days after culture, the old culture medium was removed, and the cells were washed 3 times with sterile normal saline. Then, 300 μL of fresh culture medium containing 10% (v / v) CCK-8 reagent was added. Fresh culture medium with 10% CCK-8 reagent was used as the blank control. The samples were incubated for 2 h in the dark. 100 μL of the supernatant from each well was transferred to a 96-well plate, and the absorbance was measured at 450 nm using a microplate reader. As Figure 6 shown, the detection on the 1st day showed that the PHAE46 activity was the lowest among the four groups (75.5% ± 6.4%), while the cell activities of the PHAE55 group and the PHAE64 group were 87.1% ± 5.2% and 82.1% ± 9.7% respectively. The cell activities of the three hydrogels were all >75%. After 3 days of culture, the cell activities were increased to 153.6% ± 11.7%, 178.4% ± 10.4% and 174.0% ± 6.4% respectively. The above results indicate that PHAEs hydrogels are non-toxic in the cytotoxicity experiment. The live / dead cell double staining experiment further verified this conclusion ( Figure 5 ): Fluorescence microscopy observation showed that the samples in each group were mainly live cells (green fluorescence), and only sporadic dead cells (red fluorescence) appeared in the late stage of culture, presumably related to the nutrient competition caused by excessive cell density. The results show that the introduction of PHAEs did not cause cytotoxicity, and the sustained-release effect of the hydrogel significantly activated the metabolic activity of fibroblasts. This finding provides crucial safety evidence for the application of antibacterial materials in wound repair and confirms the biocompatibility advantage of the composite hydrogel system at the cellular level.

Claims

1. A preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing, characterized in that It includes the following steps: Step (1): Mix a diacrylate monomer and a diamine monomer in a molar ratio of 1.1:1 to 2:1 and react, and obtain poly(β-amino ester) after purification; Step (2): Mix hyaluronic acid and ε-poly-L-lysine, add the poly(β-amino ester) solution dissolved in deionized water, suck and extrude repeatedly, and stand after defoaming to form a hydrogel.

2. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to claim 1, characterized in that, In step (1), by weight, the diacrylate monomer is 1.237 to 3.373 parts, and the diamine monomer is 0.5 part.

3. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to claim 1, characterized in that, In step (2), by weight, hyaluronic acid is 0.4 to 0.6 part, ε-poly-L-lysine is 0.4 to 0.6 part, and the poly(β-amino ester) solution is 0.01 part.

4. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to claim 1, characterized in that, The diacrylate monomer is 1,4-butanediol diacrylate, and the diamine monomer is primary diamine (N,N-dimethylethylenediamine).

5. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to claim 1, characterized in that, Step (2) specifically is: Mix hyaluronic acid powder and ε-poly-L-lysine powder and shake well to obtain a mixed powder, dissolve poly(β-amino ester) with deionized water, and inject it into the mixed powder to obtain a hydrogel mixture. Use a syringe and a three-way valve to continuously suck and extrude the hydrogel mixture, stir, perform vacuum defoaming and ultrasonic treatment, and then stand to obtain a pH-responsive antibacterial multifunctional hydrogel dressing.

6. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to claim 5, characterized in that, Perform vacuum defoaming for 5 to 10 min and ultrasonic treatment for 1 to 3 min.

7. The preparation method of a pH-responsive antibacterial multifunctional hydrogel dressing according to any one of claims 1-6, characterized in that, The reaction temperature of step (1) is 50 °C and the time is 48 hours.

8. A pH-responsive antibacterial multifunctional hydrogel dressing, characterized in that, It is prepared by the preparation method described in any one of claims 1-7.

9. Use of the pH-responsive antibacterial multifunctional hydrogel dressing described in claim 8 as an inflammatory wound dressing.

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