Antibacterial and antioxidant hydrogel wound dressing as well as preparation method and application thereof

Abstract

The invention belongs to the field of preparation of hydrogel dressings, and particularly relates to an antibacterial and antioxidant hydrogel wound dressing as well as a preparation method and application thereof. The preparation method comprises the following steps: mixing TEMPO oxidized cellulose with a zinc salt to coordinate and chelate zinc ions and carboxyl groups of the TEMPO oxidized cellulose, then adding tannic acid to coordinate phenolic hydroxyl groups of the tannic acid with the zinc ions, then adding an organic ligand, and mixing to obtain a metal organic framework-cellulose compound loaded with the tannic acid; a cross-linking agent and an initiator are sequentially added into the metal organic framework-cellulose compound loaded with the tannic acid, and the antibacterial and antioxidant hydrogel wound dressing of a three-dimensional hydrogel structure is obtained through a cross-linking reaction. The antibacterial and antioxidant hydrogel wound dressing provided by the invention has a long-acting slow-release effect, antibacterial property, oxidation resistance and good mechanical properties.

Description

Technical Field

[0001] The present invention belongs to the field of preparation of hydrogel dressings, and particularly relates to an antibacterial and antioxidant hydrogel wound dressing, a preparation method thereof and an application thereof. Background Art

[0002] A chronic wound refers to a wound that fails to heal within the normal healing time, usually manifested as not healing for more than 1 month. The healing of chronic wounds is affected by bacterial infection, oxidative stress and vascular damage, resulting in delayed healing and potential complications. Chronic wounds do not heal for a long time, and patients will continuously and repeatedly experience problems such as pain, exudate, and odor. Chronic wounds are prone to secondary infection, which may lead to aggravated local infection and even systemic infection such as sepsis. In addition, non-healing wounds for a long time may also increase the risk of canceration. Therefore, selecting a suitable dressing for the wound is beneficial to accelerating wound healing and alleviating the pain of patients.

[0003] Currently developed wound dressings include traditional wound dressings (such as gauze, cotton pads, bandages, etc.) and moist wound dressings (such as hydrogel wound dressings). Traditional wound dressings have poor adhesion, need to be changed frequently, increasing the pain of patients and the nursing burden; in addition, once the dressing is soaked, bacteria are easy to invade, increasing the risk of wound infection; there are many deficiencies in wound care. Compared with traditional wound dressings, moist wound dressings can maintain a moist environment around the wound and its surrounding area, which is beneficial to the migration of epithelial cells and the growth of granulation tissue, thereby accelerating wound healing; and moist wound dressings have a high water content, can reduce the temperature around the wound, slow down pain, and have low adhesion, and will not cause secondary damage to the newly formed tissue when replaced. Therefore, compared with traditional wound dressings, moist wound dressings have significant advantages in promoting healing, reducing pain and infection risk.

[0004] Cellulose-based hydrogel wound dressings have good biocompatibility, degradability and various functional characteristics, and have received extensive attention and research in the field of wound care in recent years. Preparing a hydrogel wound dressing by compounding cellulose with metal-organic frameworks is an emerging preparation method for cellulose-based hydrogel wound dressings. Cellulose-based hydrogels have good biocompatibility and the function of maintaining a wet wound environment. After introducing metal-organic frameworks, the prepared dressings have additional functions such as drug slow release, antibacterial and loading of bioactive components on the original basis. However, when cellulose is combined with metal-organic frameworks, due to poor dispersibility, uneven reaction and insufficient combination, this limits the development and application of the functionalization of cellulose-based hydrogel wound dressings. Summary of the Invention

[0005] In order to solve the above problems, the present invention provides an antibacterial and antioxidant hydrogel wound dressing, a preparation method thereof and an application thereof. The antibacterial and antioxidant hydrogel wound dressing provided by the present invention improves the stability of cellulose-based hydrogel wound dressings and accelerates the healing of chronic wounds.

[0006] In the first aspect of the present invention, a method for preparing an antibacterial and antioxidant hydrogel wound dressing is provided, comprising the following steps: Mix TEMPO-oxidized cellulose with a zinc salt to chelate zinc ions with the carboxyl groups of TEMPO-oxidized cellulose, obtaining a TEMPO-oxidized cellulose-zinc ion coordination complex; Mix the TEMPO-oxidized cellulose-zinc ion coordination complex with tannic acid to coordinate the phenolic hydroxyl groups of tannic acid with zinc ions, obtaining a TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex; Mix the TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex with an organic ligand to obtain a metal-organic framework-cellulose complex loaded with tannic acid; After mixing the metal-organic framework-cellulose complex loaded with tannic acid with a crosslinking agent, then add an initiator to react, obtaining an antibacterial and antioxidant hydrogel wound dressing with a three-dimensional network structure.

[0007] TEMPO-oxidized cellulose has abundant carboxyl and hydroxyl groups on its surface, which can improve the stability of its combination with the metal-organic framework, making the zinc ions of the metal-organic framework disperse evenly in the cellulose hydrogel. On the one hand, it improves the antibacterial performance and mechanical properties of the hydrogel wound dressing, and on the other hand, it reduces the large amount of zinc ions dissolved at one time; adding tannic acid with high antioxidant properties can simultaneously improve the stability and antibacterial properties of tannic acid and the metal-organic framework in the hydrogel wound dressing.

[0008] Further, the TEMPO-oxidized cellulose is a TEMPO-oxidized cellulose suspension gel, and the dry matter content of the TEMPO-oxidized cellulose suspension gel is 1.0 wt% - 1.2 wt%; the organic ligand is 2-methylimidazole; the zinc salt is zinc nitrate or zinc acetate.

[0009] Further, the dry matter content of the TEMPO-oxidized cellulose suspension gel is 1.14 wt%.

[0010] Further, the mass ratio of the TEMPO-oxidized cellulose suspension gel, tannic acid, and the metal-organic framework in the antibacterial and antioxidant hydrogel wound dressing is 100:10 - 40:74 - 100; the molar ratio of zinc nitrate and 2-methylimidazole is 1:60 - 70.

[0011] Further, the mixing time of the TEMPO-oxidized cellulose suspension gel and zinc nitrate is 4 h - 6 h; the mixing time of the TEMPO-oxidized cellulose-zinc ion coordination complex and tannic acid is 3 h - 5 h; the mixing time of the TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex and the organic ligand is 7 h - 9 h.

[0012] Furthermore, the mixing time of the tannic acid-loaded metal-organic framework-cellulose composite and the crosslinking agent is 7 h to 9 h; the reaction with the initiator added is 6.5 h to 8 h; the crosslinking agent is polyvinyl alcohol, N,N'-methylenebisacrylamide, paraformaldehyde alcohol or glutaraldehyde; the initiator is borax, ammonium persulfate or potassium hydroxide.

[0013] Furthermore, the mass ratio of the crosslinking agent to TEMPO-oxidized cellulose is 4 to 4.5:1.

[0014] Furthermore, the mass ratio of the crosslinking agent to the initiator is 3 to 5:1.

[0015] In a second aspect of the present invention, there is provided an antibacterial and antioxidant hydrogel wound dressing prepared by the above-described preparation method.

[0016] In a third aspect of the present invention, there is provided an application of the antibacterial and antioxidant hydrogel wound dressing in the preparation of a product for promoting skin wound healing.

[0017] Furthermore, the skin wounds include abrasions, skin breaks, burns, skin wound infections and chronic non-healing wound injuries.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention provides a preparation method of an antibacterial and antioxidant hydrogel wound dressing. First, the carboxyl group of TEMPO-oxidized cellulose is coordinated with metal ions, and then the phenolic hydroxyl group of tannic acid is introduced, realizing the orderly utilization of multiple coordination sites, avoiding the problem of poor homogeneity caused by competitive coordination, and ensuring the high loading and uniform distribution of tannic acid. During the formation of the metal-organic framework, tannic acid is embedded in the pores, and tannic acid is "anchored" inside the metal-organic framework through metal coordination, while retaining the phenolic hydroxyl group of tannic acid, combining high loading and functionality. Through coordination chemistry, TEMPO-oxidized cellulose (mechanical support), metal-organic framework (antibacterial / carrier), and tannic acid (antioxidant) are chemically bonded to endow the hydrogel with a more stable multi-level structure.

[0019] This antibacterial and antioxidant hydrogel wound dressing exerts its effects through multiple mechanisms working in synergy. In terms of the physical barrier, the nano-scale network of TEMPO-oxidized cellulose forms a physical barrier with pore sizes smaller than the size of bacteria (micrometer scale), effectively blocking the invasion of bacteria. In terms of antibacterial activity, the metal-organic framework destroys the bacterial cell wall and inhibits metabolic activities by slowly releasing zinc ions, and its porous structure can also adsorb bacteria. Moreover, the polyphenol groups of tannic acid further damage the bacterial cell membrane, forming a dual antibacterial pathway to avoid the generation of drug resistance. In terms of antioxidant activity, the antioxidant properties of tannic acid can scavenge free radicals and reduce the level of oxidative stress. In terms of promoting wound healing, zinc ions can promote angiogenesis, and in combination with the hydrophilicity of TEMPO-oxidized cellulose to absorb exudate and maintain a moist microenvironment, jointly accelerating epithelial regeneration and wound healing.

[0020] The coordination bonds between the carboxyl / hydroxyl groups of TEMPO-oxidized cellulose and the metal-organic framework significantly enhance the mechanical stability of the hydrogel. The catechol groups on tannic acid enhance the local adhesiveness, and the in-situ aqueous synthesis of the metal-organic framework avoids the residue of organic solvents. The controlled release of zinc ions reduces the potential risks to the environment. In addition, TEMPO-oxidized cellulose, the metal-organic framework, and tannic acid all possess excellent biocompatibility and biodegradability, and trace amounts of zinc ions, as essential elements for the human body, also have the function of promoting wound healing. Through the multi-functional synergy of "physical barrier - chemical antibacterial - antioxidant - promoting wound healing", it significantly overcomes the problems of insufficient antibacterial properties of traditional cellulose hydrogels and poor stability of tannic acid, is suitable for the treatment of chronic wounds, and can reduce the frequency of dressing changes and nursing costs. Brief Description of the Drawings

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1 SEM image of the hydrogel wound dressing prepared in Example 1.

[0023] Figure 2 FTIR spectra of the hydrogel wound dressings prepared in Example 1 and Comparative Examples 1 - 3.

[0024] Figure 3 FTIR spectra of TA, ZIF-8, and TA@ZIF-8 powders.

[0025] Figure 4 Adhesion strength diagrams of the hydrogel wound dressings prepared in Example 1 and Comparative Examples 1 - 3.

[0026] Figure 5 The curve graph of the influence of the hydrogel wound dressings prepared in Examples 1 to 6 on the growth of Escherichia coli.

[0027] Figure 6 The curve graph of the influence of the hydrogel wound dressings prepared in Examples 1 to 6 on the growth of Staphylococcus aureus.

[0028] Figure 7 The results graph of the plate antibacterial experiment of the hydrogel wound dressings prepared in Example 1, Comparative Examples 1 to 3; among them, the pictures in row A are all the plate pictures of the antibacterial test against Escherichia coli, and the pictures in row B are all the plate pictures of the antibacterial test against Staphylococcus aureus. From left to right in each row of pictures are the antibacterial results graphs of the hydrogel wound dressings prepared in Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 3.

[0029] Figure 8 The curve graph of the influence of the hydrogel wound dressings prepared in Example 1 of the present invention, Comparative Examples 1 to 3 on the growth of Escherichia coli.

[0030] Figure 9 The curve graph of the influence of the hydrogel wound dressings prepared in Example 1 of the present invention, Comparative Examples 1 to 3 on the growth of Staphylococcus aureus. Detailed Description of the Invention

[0031] The following is a detailed description of the specific embodiments of the present invention, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the protection scope of the present invention. The experimental methods described in the embodiments of the present invention are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following embodiments can be obtained from commercial channels unless otherwise specified.

[0032] The TOCNF suspension gel in the present invention is purchased from Tianjin Mujingling Biotechnology Company, and the solid content of the TOCNF suspension gel is 1.14 wt%.

[0033] Cellulose-based hydrogel wound dressings have good biocompatibility, degradability and various functional characteristics, and have received extensive attention and research in the field of wound care in recent years. Preparing hydrogel wound dressings by compounding cellulose with metal-organic frameworks is a new preparation method for cellulose-based hydrogel wound dressings. Cellulose-based hydrogels have good biocompatibility and the function of maintaining a moist wound environment. After introducing metal-organic frameworks, the prepared dressings have additional functions such as drug slow release, antibacterial and loading of bioactive components on the original basis. However, when cellulose combines with metal-organic frameworks, due to poor dispersibility, uneven reaction, and insufficient combination, this limits the development and application of the functionalization of cellulose-based hydrogel wound dressings.

[0034] The present invention provides an antibacterial and antioxidant hydrogel wound dressing, which uses TEMPO-oxidized cellulose with carboxyl and hydroxyl groups on the surface as the matrix. In the present invention, TEMPO-oxidized cellulose is mixed with a zinc salt to chelate zinc ions with the carboxyl groups of TEMPO-oxidized cellulose, and then tannic acid is added to coordinate the phenolic hydroxyl groups of tannic acid with zinc ions. Then, an organic ligand is added, and after mixing, a metal-organic framework-cellulose composite loaded with tannic acid is obtained; a crosslinking agent and an initiator are sequentially added to the metal-organic framework-cellulose composite loaded with tannic acid, and an antibacterial and antioxidant hydrogel wound dressing with a three-dimensional hydrogel structure is obtained through a crosslinking reaction. The antibacterial and antioxidant hydrogel wound dressing provided by the present invention not only reduces the secondary damage caused by frequent replacement of traditional wound dressings, but also improves the antibacterial property, antioxidant ability and stability of cellulose-based hydrogel wound dressings, and accelerates the healing of chronic wounds.

[0035] Example 1: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method has the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension, ultrasonically treat the suspension for 20 min, and then stir it at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel to obtain a TOCNF aqueous solution. Then, add 0.2205 g of zinc nitrate hexahydrate to the TOCNF aqueous solution and stir it at a speed of 400 rpm for 4 h to obtain Solution 1.

[0036] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1, stir it at a speed of 600 rpm for 1 h, then add 0.0456 g of tannic acid, and stir it at a speed of 600 rpm for 4 h to obtain Solution 2.

[0037] (3) Add 4.2585 g of 2-methylimidazole to Solution 2 and stir it at a speed of 600 rpm for 8 h to obtain Solution 3.

[0038] (4) Add an aqueous solution containing 0.98 g of polyvinyl alcohol (PVA) to Solution 3, ultrasonically stir for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue to stir for 7 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0039] Example 2: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method has the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension. Sonicate the suspension for 20 min, then stir it at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel and obtain an aqueous TOCNF solution. Then add 0.2205 g of zinc nitrate hexahydrate to the aqueous TOCNF solution and stir at a speed of 400 rpm for 5 h to obtain Solution 1.

[0040] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1 and stir at a speed of 600 rpm for 1 h. Then add 0.0228 g of tannic acid and stir at a speed of 600 rpm for 5 h to obtain Solution 2.

[0041] (3) Add 4.2585 g of 2-methylimidazole to Solution 2 and stir at a speed of 600 rpm for 7 h to obtain Solution 3.

[0042] (4) Add an aqueous solution containing 0.912 g of polyvinyl alcohol (PVA) to Solution 3. After sonication and stirring for 20 min, stir at 800 rpm for 40 min, then add an aqueous solution containing 0.304 g of borax and continue stirring for 8 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0043] Example 3: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension. Sonicate the suspension for 20 min, then stir it at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel and obtain an aqueous TOCNF solution. Then add 0.2205 g of zinc nitrate hexahydrate to the aqueous TOCNF solution and stir at a speed of 400 rpm for 6 h to obtain Solution 1.

[0044] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1 and stir at a speed of 600 rpm for 1 h. Then add 0.0912 g of tannic acid and stir at a speed of 600 rpm for 3 h to obtain Solution 2.

[0045] (3) Add 4.2585 g of 2-methylimidazole to Solution 2 and stir at a speed of 600 rpm for 9 h to obtain Solution 3.

[0046] (4) Add an aqueous solution containing 1.026 g of polyvinyl alcohol to Solution 3. After ultrasonic stirring for 10 min, stir at 800 rpm for 20 min, then add an aqueous solution containing 0.245 g of borax and continue stirring for 6.5 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0047] Example 4: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension. Ultrasonically treat the suspension for 20 min, then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel, obtaining a TOCNF aqueous solution. Then add 0.298 g of zinc nitrate hexahydrate to the TOCNF aqueous solution and stir at 400 rpm for 4 h to obtain Solution 1.

[0048] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1 and stir at 600 rpm for 1 h. Then add 0.0228 g of tannic acid and stir at 600 rpm for 4 h to obtain Solution 2.

[0049] (3) Add 5.7576 g of 2-methylimidazole to Solution 2 and stir at 600 rpm for 8 h to obtain Solution 3.

[0050] (4) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to Solution 3. After ultrasonic stirring for 10 min, stir at 800 rpm for 30 min, then add an aqueous solution containing 0.196 g of borax and continue stirring for 7 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0051] Example 5: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension. Ultrasonically treat the suspension for 20 min, then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel, obtaining a TOCNF aqueous solution. Then add 0.298 g of zinc nitrate hexahydrate to the TOCNF aqueous solution and stir at 400 rpm for 4 h to obtain Solution 1.

[0052] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1 and stir at 600 rpm for 1 h. Then add 0.0456 g of tannic acid and stir at 600 rpm for 4 h to obtain Solution 2.

[0053] (3) Add 5.7576 g of 2-methylimidazole to Solution 2 and stir at a speed of 600 rpm for 8 h to obtain Solution 3.

[0054] (4) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to Solution 3, stir ultrasonically for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue stirring for 7 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0055] Example 6: An antibacterial and antioxidant hydrogel wound dressing (TA-ZIF-8@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension, ultrasonically treat the suspension for 20 min, and then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel to obtain a TOCNF aqueous solution. Then add 0.298 g of zinc nitrate hexahydrate to the TOCNF aqueous solution and stir at a speed of 400 rpm for 4 h to obtain Solution 1.

[0056] (2) Add 0.1388 g of polyvinylpyrrolidone to Solution 1 and stir at a speed of 600 rpm for 1 h, then add 0.0912 g of tannic acid and stir at a speed of 600 rpm for 4 h to obtain Solution 2.

[0057] (3) Add 5.7576 g of 2-methylimidazole to Solution 2 and stir at a speed of 600 rpm for 8 h to obtain Solution 3.

[0058] (4) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to Solution 3, stir ultrasonically for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue stirring for 7 h to obtain the TA-ZIF-8@TOCNF hydrogel wound dressing.

[0059] Comparative Example 1: A hydrogel wound dressing (ZIF-8@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a 0.8 mg / mL TOCNF suspension, ultrasonically treat the suspension for 20 min, and then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel to obtain a TOCNF aqueous solution. Then add 0.2205 g of zinc nitrate hexahydrate to the TOCNF aqueous solution and stir at a speed of 400 rpm for 4 h to obtain Solution 1.

[0060] (2) Add 4.2585 g of 2-methylimidazole to Solution 1 and stir at a speed of 600 rpm for 8 h to obtain Solution 2.

[0061] (3) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to Solution 2, stir ultrasonically for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue stirring for 7 h to obtain the ZIF-8@TOCNF hydrogel.

[0062] Comparative Example 2: A hydrogel wound dressing (TA@TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a TOCNF suspension of 0.8 mg / mL, ultrasonically treat the suspension for 20 min, and then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel to obtain a TOCNF aqueous solution; (2) Add 0.0456 g of tannic acid to the TOCNF aqueous solution and stir at a speed of 600 rpm for 4 h to obtain a tannic acid-TOCNF mixed solution.

[0063] (3) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to the tannic acid-TOCNF mixed solution, stir ultrasonically for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue stirring for 7 h to obtain the TA@TOCNF hydrogel.

[0064] Comparative Example 3: A hydrogel wound dressing (TOCNF), and its preparation method comprises the following steps: (1) Dilute 20.00 g of TOCNF suspension gel with deionized water to a TOCNF suspension of 0.8 mg / mL, ultrasonically treat the suspension for 20 min, and then stir at a speed of 400 rpm for 18 h to uniformly disperse the TOCNF suspension gel to obtain a TOCNF aqueous solution; (2) Add an aqueous solution containing 0.98 g of polyvinyl alcohol to the TOCNF aqueous solution, stir ultrasonically for 10 min, then stir at 800 rpm for 30 min, and then add an aqueous solution containing 0.245 g of borax and continue stirring for 7 h to obtain the TOCNF hydrogel.

[0065] The present invention first successfully prepared a TA-ZIF-8@TOCNF hydrogel containing tannic acid and ZIF-8 by an in-situ plus non-in-situ method, and then quenched and freeze-dried the hydrogel with liquid nitrogen for a series of characterizations. Examples 1-3 have similar effects. For the convenience of subsequent discussion and reference, the test results of Example 1 are taken as an example. The following are the test results of Example 1.

[0066] Experimental Example 1: Characterization Test First, the hydrogel wound dressing prepared in Example 1 was lyophilized and then cut, and its surface morphology was observed using a scanning electron microscope.

[0067] As Figure 1 shown, it can be observed that the hydrogel wound dressing prepared in Example 1 has uniformly dense pore sizes.

[0068] Experimental Example 2: Infrared Spectroscopy Analysis Test The lyophilized hydrogel wound dressing was subjected to infrared detection using an infrared spectrometer, and the molecular structure and chemical composition of the hydrogel wound dressing were analyzed based on the detection results. The infrared spectra are as Figure 2 and Figure 3 shown. According to Figure 2 and Figure 3 , the analysis results are as follows.

[0069] The preparation method of TA@ZIF-8 is as follows: Dissolve 0.2205 g of zinc nitrate hexahydrate in 10 mL of water to obtain an aqueous solution of zinc nitrate hexahydrate; dissolve 0.0456 g of tannic acid in 10 mL of water to obtain an aqueous solution of tannic acid; dissolve 4.2585 g of dimethylimidazole in 40 mL of water to obtain an aqueous solution of dimethylimidazole; then add the aqueous solution of tannic acid to the aqueous solution of zinc nitrate hexahydrate and stir for 6 h, then add the dimethylimidazole solution and stir for 2 h, place it in a centrifuge at 4000 rpm for 15 min, and wash the centrifuged precipitate 3 times with deionized water. Put the washed centrifuged product into a vacuum drying oven at 45 °C and dry for 16 h to obtain TA@ZIF-8.

[0070] 1. Analysis of TOCNF Characteristic Peaks O-H stretching vibration: A broad peak appears at approximately 3200 cm -1 -3600 cm -1 , originating from the hydroxyl groups (-OH) in the TOCNF cellulose molecular chain and adsorbed water.

[0071] C-H stretching vibration: A weak peak is located at 2800 cm -1 3000 cm -1 , corresponding to the vibration of C-H in TOCNF cellulose.

[0072] C-O vibration: A strong absorption peak in the fingerprint region (1000 cm -1 -1200 cm -1 ) is attributed to the stretching vibrations of C-O-C (glycosidic bond) and C-O in TOCNF cellulose.

[0073] 2. Analysis of TA@TOCNF Characteristic Peaks Peaks introduced by tannic acid: C=O stretching vibration of ester group: A new peak appears near 1714 cm -1 , indicating the successful loading of the ester group in tannic acid.

[0074] C=C vibration of aromatic ring: Absorption peaks appear in the range of 1500 cm -1 -1600 cm -1 , from the benzene ring structure of tannic acid.

[0075] O-H vibration of phenolic hydroxyl group: The O-H peak (3200 cm -1 -3600 cm -1 ) of the original CNF becomes broader and its intensity increases because there are a large number of phenolic hydroxyl groups in tannic acid.

[0076] Retention of cellulose characteristic peaks: The C-H (2800cm -1 -3000 cm -1 ) and C-O (1000cm -1 -1200 cm -1 ) peaks still exist.

[0077] 3. Analysis of ZIF-8 characteristic peaks Vibration of imidazole ring: C=N stretching vibration: Strong peaks appear in the range of 1450cm -1 -1580 cm -1 .

[0078] C-N stretching vibration: A peak near about 1250 cm -1 .

[0079] C-H vibration of methyl group: A weak peak at 2800cm -1 -3000 cm -1 , from the methyl group in 2-methylimidazole.

[0080] Zn-N vibration: A low-frequency vibration peak appears in the range of 422 cm -1 .

[0081] 4. Analysis of TA@ZIF-8 characteristic peaks Characteristic peaks of tannic acid: O-H vibration of phenolic hydroxyl group: The peak in the range of 3200cm -1 -3500 cm -1 becomes enhanced or broader.

[0082] C=O vibration of ester group: A new peak appears near 1700 cm -1 as tannic acid binds to ZIF-8 through the ester group.

[0083] Retention of characteristic peaks of ZIF-8: 1450 cm -1 -1580 cm -1 (C=N / C=C) and 1250 cm -1 The (C-N) peaks still exist, but the peak shape changes or shifts due to the loading of tannic acid, indicating the existence of interactions between the two (such as hydrogen bonds or coordination).

[0084] In summary, according to the infrared spectra of TA@TOCNF and TOCNF, it can be found that a new peak appears at 1714 cm -1 confirming the successful introduction of tannic acid; the broadening or displacement of the O-H peak indicates the formation of hydrogen bonds between TOCNF cellulose and tannic acid. According to the infrared spectra of TA@ZIF-8 and ZIF-8, it can be found that phenolic hydroxyl groups (3200 cm -1 -3500 cm -1 ) and ester groups (1700 cm -1 ) appear, indicating the successful modification of ZIF-8 by tannic acid; the displacement of the characteristic peaks of ZIF-8 may be due to the coordination or hydrogen bond interaction between tannic acid and the imidazole ring. The phenolic hydroxyl groups in tannic acid may bind to TOCNF cellulose or ZIF-8 through hydrogen bond or coordination interactions, forming TA@ZIF-8 or TA@ZIF-8, resulting in changes in the position or intensity of the characteristic peaks.

[0085] Therefore, infrared spectroscopy analysis shows that tannic acid is successfully loaded into TOCNF and ZIF-8, and there are chemical or physical interactions.

[0086] Experimental Example 3: Determination of the adhesion strength of hydrogel wound dressings The tensile adhesion test was used to evaluate the adhesion strength of the hydrogel. First, the prepared hydrogel was cut into samples with dimensions of 25 mm × 25 mm and a thickness of 1 mm. Then, the hydrogel samples were adhered to the flat surface of porcine skin, and each specimen was uniformly compressed with a force of 3 N and maintained for 1 min to ensure good adhesion contact. Next, a gradually increasing tensile force was applied to the samples through a uniaxial tensile testing machine until the adhesion force between the hydrogel and the porcine skin could not be maintained, resulting in the detachment of the hydrogel from the porcine skin surface. This state was defined as the "failure state". Each group of tests included 5 parallel specimens to ensure the reliability and repeatability of the experimental results.

[0087] The formula for determining the bonding strength (P) is: P = F / S; In the formula, F is the maximum tensile load and S is the bonding area.

[0088] The results are as Figure 4As shown, the adhesion strength of TOCNF is 9.33 KPa, the adhesion strength of TA@TOCNF is 19.4 KPa, the adhesion strength of ZIF-8@TOCNF is 7.33 KPa, and the adhesion strength of TA-ZIF-8@TOCNF is 15.07 KPa. The adhesion strength of TA@TOCNF is the highest, significantly higher than the other three materials, while the adhesion strength of ZIF-8@TOCNF is the lowest, indicating that the addition of tannic acid can significantly improve the adhesion performance of the TA-ZIF-8@TOCNF hydrogel product. Excessive addition of ZIF-8 will affect the adhesion of the TA-ZIF-8@TOCNF hydrogel product.

[0089] Experimental Example 4: Antibacterial Test The present invention first detected the antibacterial properties of the hydrogel wound dressings prepared in Examples 1 to 6. Gram-negative bacterium Escherichia coli and Gram-positive bacterium Staphylococcus aureus were respectively selected as representative strains for the antibacterial activity experiment. The results are as shown in Figure 6 As shown, it can be seen from the figure that the hydrogel wound dressings prepared in Examples 1 to 6 have strong antibacterial activity and durability against Escherichia coli and Staphylococcus aureus, and the addition of ZIF-8 is more effective in inhibiting Escherichia coli, while the addition of tannic acid is more effective in inhibiting Staphylococcus aureus.

[0090] Then the present invention explored the antibacterial properties of the TA-ZIF-8@TOCNF hydrogel wound dressing prepared in Example 1 and the dressings prepared in Comparative Examples 1 to 3. The results are as shown in Figures 7 - 9 As shown.

[0091] Figure 7 The results of the plate antibacterial test after culturing at 37°C for 16 h are shown in Figure 8 and Figure 9 are the antibacterial growth curves. It can be seen from Figures 7 - 9 that the TOCNF hydrogel wound dressing prepared in Comparative Example 3 has no antibacterial activity, which is consistent with the plate culture results. The TA@TOCNF hydrogel wound dressing prepared in Comparative Example 2 has antibacterial activity but poor durability. In contrast, the TA-ZIF-8@TOCNF hydrogel wound dressing prepared in Example 1 has strong antibacterial activity and durability against both Escherichia coli and Staphylococcus aureus.

[0092] It should be noted that when the present invention involves numerical ranges, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the step methods adopted are the same as those in the embodiments, in order to avoid redundancy, the present invention describes preferred embodiments. Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications to these embodiments once they know the basic creative concept. Therefore, the appended claims are intended to be construed as including the preferred embodiments and all changes and modifications falling within the scope of the present invention.

[0093] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these changes and modifications.

Claims

1. A preparation method of an antibacterial and antioxidant hydrogel wound dressing, characterized in that, It includes the following steps: Mix TEMPO-oxidized cellulose with a zinc salt to chelate zinc ions with the carboxyl groups of TEMPO-oxidized cellulose, obtaining a TEMPO-oxidized cellulose-zinc ion coordination complex; Mix the TEMPO-oxidized cellulose-zinc ion coordination complex with tannic acid to coordinate the phenolic hydroxyl groups of tannic acid with zinc ions, obtaining a TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex; Mix the TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex with an organic ligand to obtain a metal-organic framework-cellulose complex loaded with tannic acid; After mixing the metal-organic framework-cellulose complex loaded with tannic acid with a crosslinking agent, then add an initiator to react, obtaining an antibacterial and antioxidant hydrogel wound dressing with a three-dimensional network structure.

2. The preparation method according to claim 1, characterized in that, The TEMPO-oxidized cellulose is a TEMPO-oxidized cellulose suspension gel, and the dry matter content of the TEMPO-oxidized cellulose suspension gel is 1.0 wt% to 1.2 wt%; the organic ligand is 2-methylimidazole.

3. The preparation method according to claim 2, characterized in that, The zinc salt is zinc nitrate or zinc acetate.

4. The preparation method according to claim 3, wherein In the antibacterial and antioxidant hydrogel wound dressing, the mass ratio of the TEMPO-oxidized cellulose suspension gel, tannic acid, and metal-organic framework is 100:10-40:74-100; the molar ratio of zinc nitrate and 2-methylimidazole is 1:60-70.

5. The preparation method according to claim 4, characterized in that, The mixing time of the TEMPO-oxidized cellulose suspension gel and zinc nitrate is 4 h to 6 h; the mixing time of the TEMPO-oxidized cellulose-zinc ion coordination complex and tannic acid is 3 h to 5 h; the mixing time of the TEMPO-oxidized cellulose-zinc ion-tannic acid coordination complex and the organic ligand is 7 h to 9 h.

6. The preparation method according to claim 1, wherein The mixing time of the metal-organic framework-cellulose complex loaded with tannic acid and the crosslinking agent is 7 h to 9 h; the reaction time for adding the initiator is 6.5 h to 8 h; the crosslinking agent is polyvinyl alcohol, N,N′-methylenebisacrylamide, paraformaldehyde alcohol or glutaraldehyde; the initiator is borax, ammonium persulfate or potassium hydroxide.

7. The preparation method according to claim 6, characterized in that, The mass ratio of the crosslinking agent to TEMPO-oxidized cellulose is 4-4.5:1; the mass ratio of the crosslinking agent to the initiator is 3-5:

1.

8. An antibacterial and antioxidant hydrogel wound dressing prepared by the preparation method according to any one of claims 1 to 7.

9. Use of the antibacterial and antioxidant hydrogel wound dressing according to claim 8 in the preparation of a product for promoting skin wound healing.

10. The application according to claim 9, characterized in that, The skin wounds include abrasions, skin breaks, burns, skin wound infections and chronic non-healing wound injuries.

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