Antibacterial and antioxidant bionic hydrogel as well as preparation method and application thereof

Abstract

The invention discloses antibacterial and antioxidant bionic hydrogel as well as a preparation method and application thereof. The antibacterial and antioxidant bionic hydrogel disclosed by the invention comprises a hydrogel bracket, wherein the hydrogel bracket is prepared from methacrylated quaternized chitosan, acrylated cyclodextrin, methacrylated gelatin and dopamine grafted methacrylated hyaluronic acid according to the mass ratio of (2 to 4) to (1 to 3) to (5 to 7) to (0.5 to 1.5). The antibacterial and antioxidant bionic hydrogel disclosed by the invention has a porous intercommunication structure, relatively large porosity and water absorption rate, and excellent hydrophilicity, electroactivity, antibacterial property, oxidation resistance and biocompatibility. The antibacterial and antioxidant bionic hydrogel disclosed by the invention can be used as an antibacterial material, especially used as a dressing for treating chronic infection wound surfaces.

Description

Technical Field

[0001] This application belongs to the technical field of biomedical tissue engineering, and particularly relates to an antibacterial and antioxidant bionic hydrogel, a preparation method and an application thereof. Background Art

[0002] When the skin is externally stimulated, it will lose its barrier function due to injury, and can be divided into acute wounds and chronic wounds according to the healing situation. Acute wounds generally refer to wounds with relatively fast healing. Chronic wounds are wounds formed due to reasons such as bacterial infection, venous ulcers, diabetic ulcers and tumors, and the healing period usually exceeds 12 weeks. Wound healing is a dynamic physiological process, including four stages, namely the hemostasis stage, the inflammation stage, the proliferation stage and the remodeling stage. If abnormalities occur in these stages, such as bacterial infection or persistent inflammation, it will cause delayed wound healing.

[0003] Traditional wound dressings are mostly dry materials such as bandages, sponges, films and gauzes, which cannot provide a moist healing environment for the wound surface and will cause secondary damage during the replacement process. Therefore, the idea of using hydrogel as a wound dressing was proposed. The porous network structure of the hydrogel makes it highly water-absorbent. When used as a wound dressing, it can absorb the exudate at the wound surface, keep the wound surface moist, and prevent the invasion of external bacteria. Therefore, as a wound dressing, the hydrogel must meet the requirements of clinical applications: 1) Biocompatibility. It has no cytotoxicity during use, does not cause tissue-specific immunogenicity, and has an appropriate host response ability; 2) Shape adaptability. In real life, the shape of the wound is not always regular, and the hydrogel has good shape adaptability to completely cover the wound surface; 3) Antibacterial and antioxidant properties. The antibacterial and antioxidant properties of the hydrogel can protect the wound from the invasion of external microorganisms and can effectively eliminate the free radicals generated on the wound surface. However, at present, how to effectively solve the interfacial water on the surface of biological tissues, achieve effective binding between the adhesive and the surface of biological tissues, quickly form a barrier during the healing process of infected wounds to resist the invasion of external microorganisms, inhibit the reproduction of bacteria in the wound area, and reduce the inflammatory response, and realize the repair and construction of damaged tissues are important scientific issues guiding new medical wound dressings. Summary of the Invention

[0004] Object of the Invention: This application provides an antibacterial and antioxidant bionic hydrogel, a preparation method and an application thereof. The antibacterial and antioxidant bionic hydrogel of this application has a porous interconnected structure, a large porosity and water absorption rate, excellent hydrophilicity, electroactivity, antibacterial properties, antioxidant properties and biocompatibility. The antibacterial and antioxidant bionic hydrogel of this application can be used as an antibacterial material, especially as a dressing for treating chronic infected wounds.

[0005] Technical solution: An antibacterial and antioxidant biomimetic hydrogel is provided in an embodiment of the present application. The antibacterial and antioxidant biomimetic hydrogel includes a hydrogel scaffold, and the hydrogel scaffold includes methacryloylated quaternized chitosan, acryloylated cyclodextrin, methacryloylated gelatin, and dopamine-grafted methacryloylated hyaluronic acid with a mass ratio of (2-4):(1-3):(5-7):(0.5-1.5).

[0006] In some embodiments, the antibacterial and antioxidant biomimetic hydrogel further includes a dopamine adhesion layer, and the dopamine adhesion layer is located on the surface layer of the hydrogel scaffold.

[0007] In some embodiments, the dopamine adhesion layer is prepared by the following method: The hydrogel scaffold is immersed in a dopamine solution and incubated in the dark to prepare a dopamine adhesion layer on the surface layer of the hydrogel scaffold.

[0008] In some embodiments, the antibacterial and antioxidant biomimetic hydrogel further includes basic fibroblast growth factor.

[0009] In some embodiments, the basic fibroblast growth factor is loaded by the following method: The hydrogel scaffold is immersed in a solution containing basic fibroblast growth factor to obtain the antibacterial and antioxidant biomimetic hydrogel.

[0010] In some embodiments, the hydrogel scaffold is crosslinked by a photoinitiator.

[0011] The embodiment of the present application further provides a preparation method of the antibacterial and antioxidant biomimetic hydrogel, including the following steps:

[0012] (1) In the order of methacryloylated quaternized chitosan, acryloylated cyclodextrin, methacryloylated gelatin, and dopamine-grafted methacryloylated hyaluronic acid, they are successively dissolved in ultrapure water to form a homogeneous solution;

[0013] (2) A photoinitiator is added to the solution prepared in step (1), and ultraviolet light is irradiated to initiate polymerization to obtain a hydrogel scaffold;

[0014] (3) A dopamine adhesion layer and basic fibroblast growth factor are loaded on the outer layer of the hydrogel scaffold to obtain the antibacterial and antioxidant biomimetic hydrogel.

[0015] In some embodiments, the dopamine adsorption layer is prepared by the following method: The hydrogel scaffold is immersed in a dopamine solution and incubated in the dark to prepare a dopamine adsorption layer.

[0016] In some embodiments, the basic fibroblast growth factor is loaded in the following manner: a hydrogel scaffold with a dopamine adhesion layer is immersed in a basic fibroblast growth factor solution to load the basic fibroblast growth factor, and after washing with PBS, an antibacterial and antioxidant biomimetic hydrogel is obtained.

[0017] The embodiments of the present application further provide the application of the antibacterial and antioxidant biomimetic hydrogel or the antibacterial and antioxidant biomimetic hydrogel prepared by the preparation method of the antibacterial and antioxidant biomimetic hydrogel in wound healing materials, biomedical repair materials, medical device materials, and tissue engineering repair materials. In particular, it is applied in the preparation of dressing materials for treating chronic infected wounds.

[0018] Beneficial effects: The present application provides an antibacterial and antioxidant biomimetic hydrogel, a preparation method, and an application. The antibacterial and antioxidant biomimetic hydrogel of the present application includes a hydrogel scaffold, and the hydrogel scaffold includes methacryloylated quaternized chitosan, acryloylated cyclodextrin, methacryloylated gelatin, and dopamine-grafted methacryloylated hyaluronic acid with a mass ratio of (2-4):(1-3):(5-7):(0.5-1.5). The antibacterial and antioxidant biomimetic hydrogel of the present application has a porous interconnected structure, a large porosity and water absorption rate, excellent hydrophilicity, electroactivity, antibacterial performance, antioxidant property, and biocompatibility. The antibacterial and antioxidant biomimetic hydrogel of the present application can be used as an antibacterial material, especially as a dressing for treating chronic infected wounds. Description of the Drawings

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present application. For those skilled in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0020] Figure 1 It is the nuclear magnetic resonance hydrogen spectrum of dopamine-grafted methacryloylated hyaluronic acid prepared in Example 1 of the present application. Among them, (a) is the nuclear magnetic resonance hydrogen spectrum of hyaluronic acid, (b) is the nuclear magnetic resonance hydrogen spectrum of methacryloylated hyaluronic acid, (c) is the nuclear magnetic resonance hydrogen spectrum of dopamine-grafted methacryloylated hyaluronic acid, and (d) is the comparison diagram of the characteristic peaks of the nuclear magnetic resonance hydrogen spectra of hyaluronic acid, methacryloylated hyaluronic acid, and dopamine-grafted methacryloylated hyaluronic acid;

[0021] Figure 2 It is the infrared spectrum of dopamine-grafted methacryloylated hyaluronic acid prepared in Example 1 of the present application;

[0022] Figure 31H NMR spectrum of methacryloylated quaternized chitosan prepared in Example 1 of this application. Among them, (a) is the 1H NMR spectrum of chitosan, (b) is the 1H NMR spectrum of quaternized chitosan, (c) is the 1H NMR spectrum of methacryloylated quaternized chitosan, and (d) is the comparison chart of characteristic peaks of 1H NMR spectra of chitosan, quaternized chitosan, and methacryloylated quaternized chitosan;

[0023] Figure 4 Infrared spectrum of methacryloylated quaternized chitosan prepared in the examples of this application;

[0024] Figure 5 Morphology observation diagram of the hydrogel scaffold material prepared in the examples of this application, where Figure 5 The upper part is the appearance of the hydrogel, Figure 5 The lower part is the scanning electron microscope photograph of the hydrogel;

[0025] Figure 6 TGA curve of the hydrogel scaffold material prepared in the examples of this application;

[0026] Figure 7 Cyclic voltammogram of the hydrogel scaffold material prepared in the examples of this application. Among them, (a) is the cyclic voltammogram of GelMA hydrogel, (b) is the cyclic voltammogram of GC hydrogel, (c) is the cyclic voltammogram of HH6 hydrogel, and (d) is the position of oxidation-reduction peaks of HH6 hydrogel and D@HH6 hydrogel;

[0027] Figure 8 Contact angle test results of the hydrogel scaffold material prepared in the examples of this application;

[0028] Figure 9 Antioxidant test results of the hydrogel scaffold material prepared in the examples of this application. Among them, (a) is the absorption peak of the hydrogel scaffold material, and (b) is the scavenging efficiency of the hydrogel scaffold material for free radical ABTS;

[0029] Figure 10 Changes in the moduli (G′ and G″) of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel when the external strain is enhanced and fixed at 1% strain for 600 s for the hydrogel scaffold material prepared in the examples of this application;

[0030] Figure 11 Antibacterial performance test results of the hydrogel scaffold material prepared in the examples of this application. Among them, (a) is the colony picture of the co-culture of bacteria and four hydrogels, and (b) is the test result of the antibacterial rate of the hydrogel scaffold material;

[0031] Figure 12Test results of the cell viability of the hydrogel scaffold material prepared in the embodiment of the present application cultured in the L929 cell extract for 24 h;

[0032] Figure 13 Test results of the in vitro immunomodulatory properties of the Raw 264.7 macrophages of the hydrogel scaffold material prepared in the embodiment of the present application. Among them, in Figure (a), after LPS stimulates macrophages, fluorescence staining is used to evaluate the intracellular ROS scavenging performance of the photocrosslinked antibacterial and antioxidant bionic evaluation. Figures (b)-(d) are the cell percentage and quantitative statistical results of the expression of DCFH-DA (ROS, FITC-A), CD86 (M1, PE), IL-4 (M2, FITC-A), and F4 / 80 (M0, PE) in macrophages analyzed by flow cytometry. Figure (e) is the quantitative statistical result of the fluorescence intensity of ROS fluorescence staining; Figures (f)-(g) are the test results of the production of NO and the expression levels of IL-6 and IL-10 in the supernatant;

[0033] Figure 14 Test results of the in vivo wound healing of the hydrogel scaffold material prepared in the embodiment of the present application. Among them, Figure (a) is the image of the wound healing process of the mouse infected wound model, and Figure (b) is the wound healing rate at each time point. Detailed implementation manners

[0034] Next, the technical solutions in the embodiments of the present application will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative efforts belong to the scope of protection of the present application. In addition, in the description of the present application, the term "including" means "including but not limited to". The terms first, second, third, etc. are only used as labels and do not impose numerical requirements or establish an order. The various embodiments of the present application may exist in a range form; it should be understood that the description in a range form is only for convenience and brevity and should not be construed as a rigid limitation on the scope of the present application; therefore, it should be considered that the described range description has specifically disclosed all possible sub-ranges and single values within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers within the counted range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. In addition, whenever a numerical range is indicated herein, it means including any cited number (fraction or integer) within the indicated range.

[0035] Natural polymers have characteristics such as biocompatibility, high hydrophilicity, degradability, and easy gelation. They are commonly used as the backbone materials of hydrogels, which can reduce infections, relieve local inflammation, and improve the wound microenvironment. The natural polymer backbone contains a large number of groups such as amino, hydroxyl, and carboxyl groups. By modifying these groups, it can be made to have additional functionality. Based on this, in the embodiments of the present application, an antibacterial and antioxidant biomimetic hydrogel is provided. The antibacterial and antioxidant biomimetic hydrogel includes a hydrogel scaffold, and the hydrogel scaffold includes methacryloylated quaternized chitosan, acryloylated cyclodextrin, methacryloylated gelatin, and dopamine-grafted methacryloylated hyaluronic acid with a mass ratio of (2-4):(1-3):(5-7):(0.5-1.5). A key component of 3,4-dihydroxy-L-phenylalanine (DOPA) is the catechol group (catechol), which imparts unique cell affinity and tissue adhesion to the hydrogel. In the present application, electrostatic attraction is generated between a large number of positively charged amino groups on quaternized chitosan and negatively charged bacteria to capture the bacteria, which can effectively prevent the bacteria from falling off and spreading, and also has a bactericidal ability. At the same time, DOPA is embedded in the hydrogel voids to provide free catechol groups for a long time, playing a synergistic bactericidal role, and can inactivate the bacteria at the chronic infection wound site in a short time. In addition, in the embodiments of the present application, embedding DOPA in the hydrogel voids can provide long-term adhesion, antibacterial and antioxidant properties.

[0036] In some embodiments, the hydrogel scaffold includes methacryloylated quaternized chitosan, acryloylated cyclodextrin, methacryloylated gelatin, and dopamine-grafted methacryloylated hyaluronic acid with a mass ratio of 3:1.6:6.4:1.

[0037] In some embodiments, based on the total mass of the antibacterial and antioxidant biomimetic hydrogel, the mass percentage content of methacryloylated quaternized chitosan is 2% - 4%, such as any value or the range composed of any two values among 2%, 3%, and 4% of the mass percentage content of methacryloylated quaternized chitosan.

[0038] In some embodiments, based on the total mass of the antibacterial and antioxidant biomimetic hydrogel, the mass percentage content of acryloylated cyclodextrin is 1% - 3%, such as any value or the range composed of any two values among 1%, 1.5%, 1.6%, 2.0%, and 3.0% of the mass percentage content of acryloylated cyclodextrin.

[0039] In some embodiments, based on the total mass of the antibacterial and antioxidant biomimetic hydrogel, the mass percentage content of methacryloylated gelatin is 5% - 7%, such as any value or the range composed of any two values among 5%, 6%, 6.4%, and 7% of the mass percentage content of methacryloylated gelatin.

[0040] In some embodiments, based on the total mass of the antibacterial and antioxidant bionic hydrogel, the mass percentage content of dopamine-grafted methacryloylated hyaluronic acid is 0.5% to 1.5%, such as any value or the range composed of any two values among 0.5%, 1%, and 1.5% of the mass percentage content of dopamine-grafted methacryloylated hyaluronic acid.

[0041] In some embodiments, the methacryloylated quaternized chitosan of the present application is prepared by the following method: after the quaternization modification of chitosan, it is grafted with methacrylic anhydride to obtain methacryloylated quaternized chitosan.

[0042] In some embodiments, the dopamine-grafted methacryloylated hyaluronic acid of the present application is prepared by the following method: after grafting hyaluronic acid with methacrylic anhydride, it is further grafted with dopamine hydrochloride to obtain dopamine-grafted methacryloylated hyaluronic acid.

[0043] In some embodiments, the antibacterial and antioxidant bionic hydrogel further includes a dopamine adhesion layer, and the dopamine adhesion layer is located on the surface layer of the hydrogel scaffold.

[0044] In some embodiments, the dopamine adhesion layer is prepared by the following method: the hydrogel scaffold is immersed in a dopamine solution and incubated in the dark to prepare a dopamine adhesion layer on the surface layer of the hydrogel scaffold.

[0045] In some embodiments, the concentration of the dopamine solution is 1 mg / mL to 5 mg / mL, such as any value or the range composed of any two values among 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, and 5 mg / mL of the concentration of the dopamine solution.

[0046] In some embodiments, the dopamine adhesion layer is prepared by the following method: the hydrogel scaffold is immersed in a dopamine solution and incubated in the dark at a temperature of 35°C to 38°C, and the incubation time in the dark is 20 min to 60 min. Such as any value or the range composed of any two values among 35°C, 36°C, 37°C, and 38°C of the incubation temperature in the dark; such as any value or the range composed of any two values among 20 min, 30 min, 40 min, 50 min, and 60 min of the incubation time in the dark.

[0047] In some embodiments, the antibacterial and antioxidant bionic hydrogel further includes basic fibroblast growth factor (bFGF).

[0048] In some embodiments, the basic fibroblast growth factor is coated by the following method: the hydrogel scaffold is immersed in a solution containing basic fibroblast growth factor to obtain the antibacterial and antioxidant bionic hydrogel.

[0049] In some embodiments, after the dopamine adhesion layer is prepared, the hydrogel scaffold with the dopamine adhesion layer is sterilized, and then immersed in a bFGF solution at 4°C. After washing with PBS, an antibacterial and antioxidant biomimetic hydrogel is prepared.

[0050] In some embodiments, the concentration of the bFGF solution is 50 ng / mL to 150 ng / mL, such as any value or the range composed of any two values among 50 ng / mL, 60 ng / mL, 70 ng / mL, 80 ng / mL, 90 ng / mL, 100 ng / mL, 110 ng / mL, 120 ng / mL, 130 ng / mL, 140 ng / mL, and 150 ng / mL.

[0051] In some embodiments, the soaking time of the hydrogel scaffold in the bFGF solution is 10 h to 20 h, such as any value or the range composed of any two values among 10 h, 11 h, 12 h, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, 19 h, and 20 h.

[0052] In this application, basic fibroblast growth factor (bFGF) is loaded into the hydrogel. On the one hand, due to the high water content of the hydrogel prepared in the embodiments of this application, bFGF can be better stored in the hydrogel to maintain the activity of the growth factor. On the other hand, DOPA has bioadhesion, which further enhances the stability of the growth factor in the hydrogel, prolongs the retention time of the hydrogel at the wound site, provides conditions for the specific release of the growth factor, and better exerts its effect of promoting chronic wound healing. In addition, a growth factor is a type of cytokine, which is a class of polypeptide substances that regulate cell growth by binding to specific and highly affinity cell membrane receptors. The growth factor will transmit signals into the cell through specific receptors on the plasma membrane and act on genes related to cell proliferation to affect cell growth or differentiation. This hydrogel can closely contact the wound site to maintain the moist environment required for wound healing. In addition, its three-dimensional porous structure is conducive to gas exchange and nutrient transport between the wound site and the outside, absorbs a large amount of exudate from the wound tissue, physically isolates the invasion of microorganisms, and promotes cell migration and skin regeneration.

[0053] In some embodiments, the hydrogel scaffold is crosslinked by a photoinitiator. Specifically, the antibacterial and antioxidant biomimetic hydrogel of this application is prepared by ultraviolet crosslinking method. Using methacrylated gelatin (GelMA), acrylated cyclodextrin (CD), dopamine-grafted methacrylated sodium hyaluronate (HAMA-DA), and methacrylated quaternized chitosan (HTCCMA) as raw materials, a hydrogel is prepared by ultraviolet crosslinking, then dopamine is embedded and adhered to the surface, and finally bFGF (basic fibroblast growth factor) is loaded.

[0054] In some embodiments, the mass percentage concentration of the photoinitiator is 0.1% - 0.5%, such as any value among 0.1%, 0.2%, 0.3%, 0.4%, 0.5% or the range composed of any two values of the mass percentage concentration of the photoinitiator.

[0055] In some embodiments, the photoinitiator is LAP (Lithiumphenyl-2,4,6-trimethylbenzoylphosphinate). In the embodiments of the present application, methacrylated gelatin (GelMA), acrylated cyclodextrin (CD), dopamine-grafted methacrylated sodium hyaluronate (HAMA-DA), and methacrylated quaternized chitosan (HTCCMA) are crosslinked by a photocrosslinking method to prepare a bionic composite hydrogel. The preparation method of this hydrogel is simple, has good biocompatibility, stable structure, fast gelation speed, and high controllability. Therefore, photocrosslinking can improve the mechanical properties and achieve in-situ gelation while ensuring the injectability of the hydrogel.

[0056] In some embodiments, the room temperature in the present application refers to the temperature range of 25°C ± 5°C.

[0057] Example 1: Preparation of antibacterial and antioxidant bionic hydrogel

[0058] Preparation of dopamine-grafted methacrylated hyaluronic acid (HAMA-DA): Take hyaluronic acid (HA, 2 g) and dissolve it in a mixed solution of N,N-dimethylformamide (DMF, 67 mL) and deionized water (135 mL). Dropwise add methacrylic anhydride (15 mL) in an ice-water bath, adjust the pH to 8 - 9, and react in the ice-water bath for 12 h. Precipitate the crude product in ethanol. Add it to an appropriate amount of ultrapure water, heat and dissolve it at 40°C, then dialyze for 5 days, changing the water 3 times a day, and freeze-dry to obtain methacrylated hyaluronic acid (HAMA). Dissolve 2 g of HAMA at 1% w / v in ultrapure water. In a nitrogen environment, add EDC and NHS to the solution (the molar ratio of HAMA: EDC: NHS = 1:3:3), maintain the pH stable at 5.5, and continuously stir for 30 min. Then, add 1.2 g of dopamine hydrochloride to the reaction system and stir at room temperature for 12 h. Place the reaction solution in a dialysis bag and dialyze in ultrapure water for 5 days, changing the water 3 times a day. After freeze-drying, obtain HAMA-DA and store it in a -20°C environment for later use.

[0059] The nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) of dopamine-grafted methacrylated hyaluronic acid is as Figure 1 shown, Figure 1 and the (a) figure in 1The HNMR spectrum showed peaks at 3.10 ppm, 3.26 ppm, 3.83 ppm, 3.89 ppm, and 4.38 ppm, which were respectively assigned to H-2, H-4, H-5, H-7, and H-8 in the six-membered ring skeleton, and the characteristic peaks at 4.47 ppm and 3.93 ppm were respectively assigned to -OH connected to the six-membered ring skeleton; Figure 1 Figure (b) shows that the double bond characteristic peaks (Ha) of HAMA appear at 5.68 ppm and 6.12 ppm, confirming the successful synthesis of HAMA; Figure 1 Figures (c) and (d) show that after HAMA was grafted with dopamine, the characteristic peak of the dopamine benzene ring appeared at 6.97 ppm. The above data confirmed the successful synthesis of HAMA-DA.

[0060] like Figure 2 As shown, HAMA is at 3350 cm -1 、2890cm -1 、1715cm -1 and 1650cm -1 The -OH, -CH 3 , ester bond carbonyl -C=O and -CHR=CH 2 The characteristic absorption peak of HAMA-DA is 2930cm -1 and 2740cm -1 -CH 2 - Characteristic peak: 1450cm -1 It is the characteristic peak of the benzene ring in the dopamine chain segment. The results prove that HAMA-DA has been successfully synthesized.

[0061] Preparation of methacryloyl quaternary ammonium chitosan (HTCCMA): Chitosan (3.6 g), deionized water (150 mL), and acetic acid (0.75 mL) were added to a round-bottom flask, stirred for 30 min, and then dehydrated glyceryl trimethyl ammonium chloride (GTMAC, 6.92 mL, density 1.13 g / mL) was added dropwise to the reaction solution, reacted at 55 ° C for 24 h, the reaction solution was dialyzed for 7 days, and quaternary ammonium chitosan (HTCC) was obtained after filtration and freeze-drying. HTCC (2 g) was dissolved in ultrapure water (200 mL), and methacrylic anhydride (1.2 mL) was added dropwise. The mixed solution was reacted at room temperature for 12 h, and the filtered product solution was placed in a dialysis bag for 7 days. After freeze-drying, a light yellow product, methacryloyl quaternary ammonium chitosan (HTCCMA), was obtained.

[0062] like Figure 3 As shown in Figure (a), the CS 1The \(^1H\) NMR spectrum showed peaks at 3.84 ppm, 3.77 ppm, 3.62 ppm and 2.63 ppm, which were attributed to H-2, H-3, H-6 and H-7 in the six-membered ring skeleton, respectively; Figure 3 As shown in Figure (b) of 2 , after CS was modified by GTMAC, its characteristic peak (H-a) appeared at 3.27 ppm, while the peak of -NH-CH Figure 3 - protons in the quaternary ammonium salt structure appeared at 3.37 ppm. The above data confirmed the successful synthesis of HTCC;

[0063] As Figure 4 shown, in the infrared spectrum of HTCC, the characteristic absorption peaks of C-N and -CH -1 on GTMAC appeared at 1635 \(cm^{-1}\) and 1484 \(cm^{-1}\) respectively. In the infrared spectrum of HTCCMA, the characteristic absorption peaks of C=C and C-H in the methacryloyl group appeared at 1635 \(cm^{-1}\) and 1540 \(cm^{-1}\) respectively. The results proved the successful synthesis of HTCCMA. -1 3 -1 -1

[0064] HH6 hydrogel: Weigh the masses of the raw materials required to prepare the photo-crosslinked antibacterial and antioxidant bionic hydrogel. In the order of methacryloylated quaternized chitosan (HTCCMA), acryloylated cyclodextrin (Ac-β-CD), methacryloylated gelatin (GelMA) and dopamine-grafted methacryloylated hyaluronic acid (HAMA-DA), dissolve them in ultrapure water in sequence, and stir by ultrasound until completely dissolved to make a homogeneous solution. After adding the photoinitiator LAP (Lithium phenyl-2,4,6-trimethylbenzoylphosphinate), irradiate with ultraviolet light to initiate polymerization to prepare the HH6 hydrogel. See Table 1 for details.

[0065] D@HH6 hydrogel: The HH6 hydrogel prepared according to the components and dosages in Table 1 was soaked in 5 mL of dopamine solution (2 mg / mL), incubated at 37 °C in the dark for 30 min, the dopamine solution was aspirated, and washed 3 times with PBS to prepare the D@HH6 hydrogel.

[0066] ​​​​BD@HH6 hydrogel: The D@HH6 hydrogel prepared by the above method was sterilized, adhered to bFGF (100 ng / mL) at 4°C for 12 h, and after washing with PBS, the BD@HH6 hydrogel was prepared.

[0067] GelMA hydrogel: The preparation method was the same as that of the HH6 hydrogel. The difference was that HTCCMA, Ac-β-CD, and HAMA-DA were not added to the hydrogel, and only GelMA was added. For details, see Table 1, and the GelMA hydrogel was obtained.

[0068] GC hydrogel: The preparation method was the same as that of the HH6 hydrogel. The difference was that HTCCMA and HAMA-DA were not added to the hydrogel, and only Ac-β-CD and GelMA were added. For details, see Table 1, and the GC hydrogel was obtained.

[0069] Table 1 Component contents of hydrogels

[0070]

[0071] Example 2: Performance test of photo-crosslinked antibacterial and antioxidant biomimetic hydrogels

[0072] 1. The general view and cross-sectional scanning microscope photos of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogels are as Figure 5 shown. From the general view of the appearance, it can be seen that the photo-crosslinked antibacterial and antioxidant biomimetic hydrogels are all uniform and complete circular structures with a smooth and flat surface. From the SEM photos, it can be seen that the hydrogels with four different components all have excellent three-dimensional porous interconnected structures. As Ac-β-CD, HTCCMA, and HAMA-DA are gradually introduced, the pores of the hydrogel gradually become larger. The pore size of the D@HH6 hydrogel is about 100 μm, which is beneficial for the hydrogel to absorb tissue exudate and provide space for the extension of fibroblasts and the transport of nutrients, metabolites, etc. In addition, polydopamine particles are observed inside the D@HH6 hydrogel under a high-power microscope, indicating that polydopamine has been successfully and uniformly embedded in the hydrogel voids, providing conditions for the loading and specific release of growth factors.

[0073] 2. Test of the water absorption rate of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0074] As shown in Table 2, at 30 h, the water absorption rate of the GelMA hydrogel was 479.48 ± 25.66%, and the water absorption rate of the GC hydrogel increased to 622.65 ± 8.08%. This was because the introduction of Ac-β-CD enlarged the pores of the hydrogel. Compared with the GC hydrogel, with the introduction of HTCCMA and HAMA-DA, the water absorption rate of the HH6 hydrogel increased to 680.81 ± 94.78%, and the swelling property improved. After further introducing the dopamine component, the water absorption rate and swelling rate of the D@HH6 hydrogel increased significantly, and the swelling rate reached 834.16 ± 38.72%. The research in the examples of this application shows that the water absorption and swelling properties of the hydrogel are positively correlated with the complexity of the cross-linked structure of the hydrogel.

[0075] Table 2 Water absorption rate of hydrogels at different time points

[0076]

[0077] 3. Thermal property analysis of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0078] The thermal properties of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6) were analyzed by TGA ( Figure 6 ). When the mass loss of the hydrogel was 5%, the thermal decomposition temperatures of the GelMA hydrogel, GC hydrogel, HH6 hydrogel, and D@HH6 hydrogel were 137 °C, 139.83 °C, 108.5 °C, and 123.67 °C, respectively. When the mass loss of the hydrogel was 10%, the thermal decomposition temperatures of the GelMA hydrogel, GC hydrogel, HH6 hydrogel, and D@HH6 hydrogel were 187 °C, 196.67 °C, 178.5 °C, and 142.5 °C, respectively. Generally speaking, T 95％ was all higher than 123 °C, and T 90％ was all higher than 142 °C, indicating that the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel prepared in the examples of this application has good thermal stability while having injectability and can remain stable at the body temperature (about 37 °).

[0079] Table 3 Thermal decomposition temperature of hydrogels

[0080]

[0081] 4. Electrochemical properties of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0082] Electroactive biomaterials have the ability to promote intracellular and intercellular electrical signal conduction, which is beneficial to cell proliferation and differentiation at chronic wound sites. In the examples of this application, the electroactivity of the scaffold material was characterized by testing the cyclic voltammetry curve, and the results are as Figure 7As shown, no redox peaks appeared in the cyclic voltammograms of the GelMA hydrogel and the GC hydrogel materials, indicating that they are not electroactive. A pair of reversible redox peaks appeared on the cyclic voltammogram of the HH6 hydrogel, with relatively weak peak positions; while a pair of reversible redox peaks appeared on the D@HH6 hydrogel, with relatively strong peak positions, indicating excellent electroactivity. With the introduction of DOPA, the area of the closed curve increased, indicating that its redox ability gradually increased.

[0083] 5. Conductivity of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0084] When skin defects occur, the negative charges around the skin and the positive charges in the wound combine to form an endogenous electric field, which plays an important role in maintaining cell function and influencing cell behavior. The photocrosslinked antibacterial and antioxidant biomimetic hydrogel prepared in the embodiments of the present application is a water-rich 3D structure and has a conductive function. In the embodiments of the present application, the conductivity of the hydrogel was measured by the four-probe method. As shown in Table 4, all four hydrogels have conductivity. After the introduction of Ac-β-CD, the conductivity of GC decreased, but the analysis showed that there was no significant difference between the GelMA hydrogel and the GC hydrogel. Compared with the GelMA hydrogel and the GC hydrogel, after the introduction of HTCCMA, HAMA-DA, and DOPA, the conductivity of the HH6 hydrogel and the D@HH6 hydrogel increased, but not significantly, because ionic conductivity dominates in wet hydrogels. Among them, the conductivity of D@HH6 was (2.94 ± 0.11)×10 -4 S / m, which is close to the conductivity of human epidermis (0.26 mS / cm), and will help transmit electrical signals in skin tissues and promote wound healing.

[0085] Table 4 Conductivity of the hydrogels

[0086]

[0087]

[0088] 6. Hydrophilicity of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0089] The hydrophobicity / hydrophilicity of biomaterials will significantly affect biocompatibility and thus affect wound healing. The hydrophilicity / hydrophobicity is characterized by measuring the contact angle values at different time points after a water droplet contacts the material. Figure 8The results showed that the water droplet contact angles of different hydrogels at 0 s were all 0°, indicating that the hydrogels had excellent hydrophilicity. After the water droplets contacted the hydrogel surface, they quickly penetrated into the hydrogel. This was due to the three-dimensional porous structure of the hydrogel, which could quickly absorb and store water, facilitating the absorption of tissue exudate, keeping the chronic infection wound site moist, and promoting cell ingrowth and proliferation. In addition, the adhesion ability of proteins was affected by the surface hydrophilicity and hydrophobicity of biomaterials. The good hydrophilicity of the hydrogel was conducive to the stable attachment of growth factors inside the hydrogel and maintaining their activity.

[0090] 7. Antioxidant property of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0091] The presence of free radicals at the wound site can lead to oxidative stress, which in turn causes lipid peroxidation, DNA damage, and enzyme inactivation. Studies on the topical application of materials with free radical scavenging properties in patients or animals have been shown to significantly improve wound healing. The antioxidant ability of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel was evaluated by detecting the efficiency of scavenging the stable free radical ABTS. The results were as Figure 9 shown. The GelMA hydrogel and the GC hydrogel had poor antioxidant ability. However, due to the introduction of Ac-β-CD, the free radical scavenging rate of the GC hydrogel increased after 30 min, indicating an improvement in the antioxidant property of the GC hydrogel. The scavenging rate reached 76.8% at 1 h and was completely scavenged at 4 h. After the introduction of HAMA-DA and DOPA into the hydrogel, the antioxidant property of the HH6 hydrogel was significantly improved, and the HH6 hydrogel could completely scavenge free radicals at 1 h. The scavenging rate of the D@HH6 hydrogel reached 96.99% at 10 min. It can be seen from this that the D@HH6 hydrogel has excellent antioxidant property, increasing its potential application in skin wound dressings, enabling it to quickly scavenge reactive oxygen free radicals during the wound healing process, reducing the oxidative stress response, and promoting the healing of chronic infection wounds.

[0092] 8. Rheological properties of the photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0093] In the embodiments of this application, the mechanical properties of the photo-crosslinked antioxidant hydrogel were deeply studied through rheological tests. Rheological strain sweep measurements were carried out to quantitatively study the response behavior to external strain ( Figure 10)。As the applied strain increases, the storage modulus (G′) and loss modulus (G″) of the hydrogel remain highly consistent from 0.1% to 25%. When the strain of GelMA and GC hydrogels increases to 63%, the storage modulus (G′) decreases and the loss modulus (G″) increases. Crossings are found when the strains reach 277.81% and 182.58% respectively. When the strain of HH6 hydrogel and D@HH6 hydrogel increases to 63%, the storage modulus (G′) decreases and the loss modulus (G″) increases. Crossings are found when the strains reach 244.29% and 254.99% respectively. At this time, the hydrogel network has broken. The results show that the decrease in hydrogel concentration reduces the maximum external strain that the hydrogel can withstand, while the introduction of HTCCMA makes the inside of the hydrogel more stable and increases the maximum external strain that the hydrogel can withstand. In addition, the storage modulus (G′) and loss modulus (G″) of the hydrogel prepared in the embodiment of the present application can be stably maintained for 600 s under a strain of 1%.

[0094] 9. Antibacterial Properties of Photo-Crosslinked Antibacterial and Antioxidant Bionic Hydrogel (D@HH6)

[0095] An ideal wound dressing should have antibacterial properties against infection. Bacterial infection can increase the formation of exudate and delay the wound healing process. In addition, antibacterial wound dressings can promote the wound healing process by reducing the number of pathogens and the inflammatory response at the wound site. The antibacterial activity of the hydrogel against Escherichia coli (Gram-negative bacterium) and Staphylococcus aureus (Gram-positive bacterium) was evaluated using the surface antibacterial activity test. HTCCMA has certain antibacterial properties against both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), such as Figure 11As shown, the antibacterial rates of GelMA hydrogel, GC hydrogel, HH6 hydrogel, and D@HH6 hydrogel against Staphylococcus aureus were 57.75%, 63.52%, 86.18%, and 99.61% respectively, and the antibacterial rates against Escherichia coli were 49.28%, 72.88%, 84.02%, and 98.44% respectively. It can be seen from this that the antibacterial rates of the four hydrogels against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) gradually increased, and the antibacterial performance gradually enhanced. The antibacterial rates of HH6 hydrogel against Staphylococcus aureus and Escherichia coli were both above 80%. This is because quaternized chitosan has antibacterial properties. The positive charge carried by the amino group in its molecule interacts with the negative charge on the surface of bacteria, causing the bacteria to flow out of the substance. And the quaternary ammonium salt has a flexible long-chain carbon, which can enter the interior of bacteria and inhibit the synthesis of enzymes required by bacteria. Therefore, it has good antibacterial properties. And D@HH6 hydrogel introduces dopamine component on the basis of HH6 hydrogel. Dopamine has good antibacterial properties, so the antibacterial property is further improved, and the antibacterial rate reaches 95%. The results show that the prepared photo-crosslinked antibacterial and antioxidant biomimetic hydrogel has excellent antibacterial properties and can effectively prevent and treat wound bacterial infections.

[0096] 10. Biocompatibility evaluation of photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0097] In the examples of this application, the stent material extraction solution culture method was used to test its in vitro toxicity, and then its biocompatibility was evaluated. The hydrogel prepared in the examples of this application was soaked in HG-DMEM medium at a standard of 6 cm 2 / mL, and shaken at 130 rpm for 24 h to obtain the extraction solution. L929 cells were cultured with the extraction stock solution and gradient dilution solutions (1 / 2, 1 / 4, 1 / 8, 1 / 16) respectively. The results are as Figure 12 shown. The cell survival rates of the extraction solutions of GelMA hydrogel, GC hydrogel, HH6 hydrogel, and D@HH6 hydrogel were 99.42±5.92%, 112.37±8.27%, 101.68±2.52%, and 97.14±6.19% respectively, indicating that their cytotoxicity can be ignored, and they all have excellent cell compatibility. And the cell survival rates of the extraction solutions after gradient dilution of all hydrogels reached more than 95%. The above experiments confirmed that these hydrogels have good biocompatibility and broad application prospects as hemostatic and wound healing materials.

[0098] 11. Anti-inflammatory properties of photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6)

[0099] In the examples of this application, fluorescence staining was further used to evaluate the intracellular ROS scavenging performance of the photo-crosslinked antibacterial and antioxidant biomimetic evaluation. As Figure 13 shown, Figure 13Figures (b)-(d) show the results of cell percentage and quantitative statistics of the expression of macrophage DCFH-DA (ROS, FITC-A), CD86 (M1, PE), IL-4 (M2, FITC-A), and F4 / 80 (M0, PE) analyzed by flow cytometry. Figure (e) shows the quantitative statistics results of the fluorescence intensity of ROS fluorescence staining. Figures (f)-(g) show the test results of the production of NO and the expression levels of IL-6 and IL-10 in the supernatant.

[0100] Imbalance of inflammatory response is one of the main reasons affecting the healing of chronic infected wounds, and reactive oxygen species (ROS) produced by wound or bacterial infection will further hinder wound healing. Macrophages are important inflammatory cells that play roles in many aspects, including mediating innate immune processes, phagocytosing apoptotic cells, and secreting cytokines or growth factors during wound healing. The dynamic plasticity of macrophages enables them to regulate tissue destruction and repair. M1 macrophages can secrete pro-inflammatory cytokines, while M2 macrophages can regulate inflammation, angiogenesis, and induce tissue regeneration by secreting anti-inflammatory cytokines and growth factors. Previous studies have shown that both chitosan and DOPA components have anti-inflammatory effects. Therefore, RAW264.7 was selected to study the effects of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel on scavenging ROS and promoting macrophage phenotype polarization.

[0101] The excellent antioxidant performance of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel scaffold protects cells from ROS-induced damage. In the examples of this application, the content of ROS in cells stimulated by LPS was detected by fluorescence staining and flow cytometry respectively as Figure 13 shown in Figures (a), (b), and (e). The fluorescence intensities of GelMA hydrogel and GC hydrogel were similar to those of the LPS group. In sharp contrast, with the introduction of HAMA-DA and HTCCMA, the fluorescence intensity of HH6 hydrogel decreased significantly. After DOPA was embedded in the hydrogel, the fluorescence intensity of D@HH6 hydrogel further decreased, and the fluorescence intensity was only 1.35 ± 0.5. This result corresponded to the antioxidant results of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel, indicating the effectiveness of D@HH6 in scavenging ROS in vivo and reducing oxidative stress response.

[0102] Oxidative stress response is closely related to the inflammatory process. Macrophages affect the inflammatory response and wound healing by polarizing into two phenotypes. However, it is difficult for macrophages to polarize into the M2 phenotype in chronic infected wounds. To explore the effect of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel on the inflammatory response, RAW264.7 was co-cultured with hydrogels of each group, and CD86 (M1 macrophage marker) and IL-4 (M2 macrophage marker) were selected for flow cytometry. As Figure 12As shown in Figures (c) and (d), compared with GelMA hydrogel (52.77±6.46%), GC hydrogel (44±3.46%), and HH6 hydrogel (43.3±3.17%), although the percentage of M1 macrophages in each group of hydrogels decreased, there was no significant difference. However, the M1 macrophages in D@HH6 hydrogel decreased to 33.83±3.56%, which was significantly lower than that of other groups. F4 / 80 / IL-4 showed the opposite trend. To further confirm the polarized macrophage phenotype, the expression of NO, inflammatory factor IL-6, and anti-inflammatory factor IL-10 in RAW264.7 macrophages co-cultured with hydrogels was detected using Griss reagent and ELISA kit, as Figure 13 shown in Figures (f) and (g). After treatment with HH6 hydrogel, the production and expression of NO (65.92±16.06%) and IL-6 (7.17±0.17 pg / mL) were significantly reduced. After the introduction of DOPA, the production and expression of NO (36.13±16.13%) and IL-6 (5.31±0.17) in D@HH6 hydrogel were further reduced, and the expression of IL-10 (411.83±0.96 pg / mL) was significantly increased. In summary, after the introduction of HAMA-DA and HTCCMA, the M1 polarization of RAW264.7 cells stimulated by LPS was significantly reduced. After the embedding of DOPA, the M1 polarization was further inhibited, promoting macrophages to tend to M2 polarization, reducing the inflammatory response, regulating the inflammatory microenvironment of chronic wounds, and being beneficial to wound healing.

[0103] 12. Photo-crosslinked antibacterial and antioxidant biomimetic hydrogel (BD@HH6) accelerates the in vivo wound healing process

[0104] As can be seen from Figure 14 the infected full-thickness skin wound model, the wound areas of mice in all hydrogel groups closed and became smaller on the 3rd to 7th day of healing. At 14 days, the healing rate of BD@HH6 hydrogel reached over 90%, showing the best repair effect. At 21 days, the wound healing rates of D@HH6 and BD@HH6 groups were close to 100%. Clinically, it is stipulated that a wound healing rate reaching 95% can be considered complete healing. Therefore, the wounds in D@HH6 and BD@HH6 groups can be considered completely healed. Therefore, the wound healing promotion effects of the hydrogel dressings prepared in the embodiments of this application are all better than those of the blank group, and the BD@HH6 hydrogel dressing group has the best wound healing effect. This is because the hydrogel can absorb tissue exudate, keep the wound moist, act as a physical barrier to block the invasion of foreign bacteria. In addition, the excellent antibacterial properties of quaternary ammonium chitosan and DOPA inhibit the proliferation of bacteria at the infected wound, scavenge reactive oxygen free radicals in the wound area, and promote the M2 polarization of macrophages, providing a suitable regeneration microenvironment for the proliferation and differentiation of fibroblasts, which is beneficial to wound healing and skin regeneration.

[0105] The application of the photocrosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6) of the present application can be used in the preparation of materials for treating chronic infected wounds. The photocrosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6) of the present application can also be used in the fields of biomedical repair materials or medical devices. The photocrosslinked antibacterial and antioxidant biomimetic hydrogel (D@HH6) of the present application can also be used for the preparation of tissue engineering repair materials.

[0106] An embodiment of the present application provides an antibacterial and antioxidant biomimetic hydrogel, which uses methacrylated gelatin (GelMA), acrylated cyclodextrin (CD), methacrylated sodium hyaluronate grafted with dopamine (HAMA-DA), and methacrylated quaternized chitosan (HTCCMA) as raw materials, and is prepared into a hydrogel by ultraviolet photocrosslinking, then embedded and surface-adhered with dopamine, and finally loaded with bFGF (basic fibroblast growth factor). As the complexity of the crosslinked network increases, the porosity of the hydrogel increases, the pore size becomes larger, and the water absorption capacity is enhanced. In addition, the hydrogel also has good hydrophilicity, conductivity, electroactivity, antibacterial properties, antioxidant properties, and biocompatibility, and can effectively promote the healing of chronic wounds. The novel photocrosslinked antibacterial hydrogel wound dressing provided by the present invention can adhere to skin tissues, absorb tissue exudate, act as a physical barrier to block the invasion of foreign bacteria, inhibit the reproduction of bacteria in the wound area, and at the same time provide hydrogen ions to free radicals, inhibit the activity of free radicals, reduce oxidative stress response, reduce inflammatory response, and promote the healing of chronic wounds, and has great potential in the biomedical field.

[0107] The above has introduced in detail an antibacterial and antioxidant biomimetic hydrogel, its preparation method and application provided by the embodiments of the present application. Specific examples are used in this article to elaborate on the principle and implementation manner of the present application. The description of the above embodiments is only used to help understand the method and its core idea of the present application; at the same time, for those skilled in the art, according to the idea of the present application, there will be changes in the specific implementation manner and application scope. In summary, the content of this specification should not be construed as a limitation to the present application.

Claims

1. An antibacterial and antioxidant bionic hydrogel, characterized in that: The antibacterial and antioxidant bionic hydrogel comprises a hydrogel scaffold, which comprises methacryloyl quaternary ammonium chitosan, acrylated cyclodextrin, methacryloyl gelatin and dopamine-grafted methacryloyl hyaluronic acid in a mass ratio of (2-4):(1-3):(5-7):(0.5-1.5).

2. The antibacterial and antioxidant bionic hydrogel according to claim 1, characterized in that: The antibacterial and antioxidant bionic hydrogel further comprises a dopamine adhesion layer, and the dopamine adhesion layer is located on the surface of the hydrogel support.

3. The antibacterial and antioxidant bionic hydrogel according to claim 2, characterized in that: The dopamine adhesion layer is prepared by the following method: immersing the hydrogel scaffold in a dopamine solution, incubating in the dark, and preparing the dopamine adhesion layer on the surface of the hydrogel scaffold.

4. The antibacterial and antioxidant bionic hydrogel according to claim 3, characterized in that: The antibacterial and antioxidant bionic hydrogel also includes basic fibroblast growth factor.

5. The antibacterial and antioxidant bionic hydrogel according to claim 4, characterized in that: The basic fibroblast growth factor is loaded by the following method: the hydrogel scaffold is immersed in a solution containing the basic fibroblast growth factor to obtain an antibacterial and antioxidative bionic hydrogel.

6. The antibacterial and antioxidant bionic hydrogel according to claim 1, characterized in that: The hydrogel scaffold is cross-linked by a photoinitiator.

7. A method for preparing the antibacterial and antioxidant bionic hydrogel according to claim 1, characterized in that: The following steps are involved: (1) dissolving methacryloyl quaternary ammonium chitosan, acrylated cyclodextrin, methacryloyl gelatin and dopamine-grafted methacryloyl hyaluronic acid in ultrapure water in this order to prepare a uniform solution; (2) adding a photoinitiator to the solution prepared in step (1), irradiating with ultraviolet light, and initiating polymerization to obtain a hydrogel scaffold; (3) A dopamine adhesion layer and basic fibroblast growth factor were prepared on the outer layer of the hydrogel scaffold to obtain an antibacterial and antioxidant biomimetic hydrogel.

8. The method for preparing the antibacterial and antioxidant bionic hydrogel according to claim 7, characterized in that: The dopamine adsorption layer is prepared by the following method: immersing the hydrogel scaffold in a dopamine solution and incubating the solution in the dark to prepare the dopamine adsorption layer.

9. The method for preparing the antibacterial and antioxidant bionic hydrogel according to claim 7, characterized in that: The basic fibroblast growth factor is loaded in the following manner: the hydrogel scaffold with the dopamine adhesion layer is immersed in a basic fibroblast growth factor solution, the basic fibroblast growth factor is loaded, and after washing with PBS, an antibacterial and antioxidative bionic hydrogel is obtained.

10. Use of the antibacterial and antioxidant bionic hydrogel as described in any one of claims 1 to 6 or the antibacterial and antioxidant bionic hydrogel prepared by the preparation method of the antibacterial and antioxidant bionic hydrogel as described in any one of claims 7 to 9 in the preparation of wound healing materials, biomedical repair materials, medical device materials, and tissue engineering repair materials.

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