Hydrogel dressing for packaging multifunctional nano-enzyme for healing diabetic wound and preparation method of hydrogel dressing

A nanoscale enzyme-embedded water gel dressing addresses the limitations of traditional dressings by mimicking enzymatic functions to clear reactive oxygen species and prevent infection, promoting diabetic ulcer healing through enhanced absorption and mechanical support.

CN120305448APending Publication Date: 2025-07-15ZHEJIANG UNIV OF TECH
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
CN202510379004.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-03-28
Publication Date
2025-07-15

AI Technical Summary

Technical Problem

Existing wound dressings are difficult to effectively absorb exudate, keep moisturized, prevent infection, promote diabetic wound healing, and lack immune regulation functions.

Method used

The hydrogel dressing that encapsulates multifunctional nanoenzymes is used to generate hydroxyl radicals for bactericidal use of the Fenton reaction of Ce3+ and Mn2+. Ce3+ and Ce4+, Mn2+ and Mn3+ simulate the SOD and CAT self-cascade reaction to eliminate reactive oxygen, and combine the hydration ability and photothermal properties of zwitterionic polymers to prepare a simple and efficient hydrogel dressing.

Benefits of technology

It has achieved efficient absorption of exudate, prevent infection, and promote wound healing, and has good mechanical properties, antibacterial properties, antioxidant properties and biocompatibility, simplifying the preparation process.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN120305448A_ABST
    Figure CN120305448A_ABST
Patent Text Reader

Abstract

The invention relates to the technical field of polymer hydrogel, in particular to a hydrogel dressing for packaging multifunctional nano-enzyme and used for diabetes wound healing and a preparation method of the hydrogel dressing, the hydrogel dressing contains the nano-enzyme, and the hydrogel dressing is a zwitterionic polymer. The preparation method disclosed by the invention is simple, efficient and environment-friendly; nano-enzyme in the hydrogel dressing simulates peroxidase activity to cooperate with photo-thermal performance for sterilization, and simulates superoxide dismutase activity and catalase activity to remove redundant active oxygen in a wound microenvironment; and the prepared material has proper mechanical properties, antibacterial properties, oxidation resistance, biocompatibility and excellent in-vivo wound healing promoting effect, and has wide application prospects in the field of biomedical materials, especially in the aspects of wound dressing for promoting wound healing and the like.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the technical field of polymer hydrogels, and particularly relates to a hydrogel dressing encapsulating multifunctional nanozymes for diabetic wound healing and a preparation method thereof. Background Art

[0002] Diabetic wounds are common complications of diabetic patients and have a relatively high incidence rate. Diabetic wounds are prone to persistent infection and poor healing, and even amputation may occur if the treatment is not timely or appropriate. Diabetic wounds seriously affect the quality of life and health of patients and significantly increase social medical costs. Persistent bacterial infection, impaired trophoblast angiogenesis, local immune environment disorder, excessive wound exudate, and improper wound treatment all lead to persistent non-healing of diabetic wounds. The early treatment of diabetic wounds includes disinfection, exudate control, immune environment improvement, angiogenesis promotion, infection control, blood glucose control, and surgical debridement. The difficult problem in the treatment of diabetic wounds is the wound microenvironment with bacterial infection, oxidative imbalance, hypoxia, excessive inflammation, and vascular network disruption. Therefore, developing multifunctional materials and improving the above complex microenvironment are the keys to diabetic wound healing. Traditional wound dressings, such as iodophor gauze, hydrocolloid, foam dressing, and silver-containing dressing, cannot fully meet the requirements of diabetic wounds for absorbing exudate, keeping the wound moist, preventing infection, and being breathable. In addition, the lack of immune regulation function makes them insufficient for the entire healing process of diabetic wounds. Wu et al. prepared a nanozyme catalytic system by immobilizing CeO x nanoclusters on a Mn3O4 nanoscaffold through an alkali precipitation and annealing strategy (CeO x / (Mn3O4). This nanozyme exhibits excellent CAT and SOD activities in both chemical and cellular environments (WU Y, ZHANG J, WANG Z. Mn-Ce Symbiosis: Nanozymes with Multiple Active Sites Facilitate Scavenging of Reactive Oxygen Species (ROS) Based on Electron Transfer and Confinement Anchoring[J]. Angew. Chem. Int. Ed. 2024, e202416686.). Cao et al. designed a hydrogel encapsulating a bioactive glass-based nanozyme, which can scavenge free radicals and reduce oxidative stress by mimicking multiple enzyme activities, ultimately effectively promoting wound healing. (CAO X, ZHU S, LI M. Bioactive Glasses-Based Nanozymes Composite Macroporous Cryogel with Antioxidative, Antibacterial, and Pro-Healing Properties for Diabetic Infected Wound Repair[J]. Adv. Healthc. Mater. 2023, 202302073.)

[0003] Nanozymes can exhibit biocatalytic activities similar to natural enzymes in harsh biological environments and have stronger stability and controllability, being widely used in the biomedical field. Zwitterionic materials have strong hydration ability, anti-nonspecific protein adhesion, and excellent biocompatibility, being widely used in the biomedical field and being a potential material for wound dressings. Considering that nanozymes need to be immobilized and concentrated in the wound area to play their role, it is necessary to design a hydrogel dressing to encapsulate nanozymes to achieve tissue repair and thus promote wound healing. Summary of the Invention

[0004] The object of the present invention is to overcome the disadvantages of complex preparation process and poor enzyme-like activity in the prior art, and provide a hydrogel dressing encapsulating multifunctional nanozymes for diabetic wound healing and its preparation method, so as to achieve the following objects: First, explore nanozymes with high-efficiency peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities; Second, the hydrogel dressing can absorb wound exudate, keep the wound moist, prevent infection, and maintain ventilation; Third, the hydrogel dressing has appropriate mechanical properties, antibacterial properties, antioxidant properties, antibacterial adhesion ability, biocompatibility, and excellent in vivo wound healing effect; Fourth, simplify the preparation.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] A hydrogel dressing encapsulating multifunctional nanozymes for diabetic wound healing, the hydrogel dressing contains nanozymes, and the hydrogel dressing is an amphoteric ion polymer.

[0007] The nanozymes in the hydrogel dressing have good photothermal properties with rapid temperature rise under near-infrared irradiation. The nanozymes contain Ce 3+ and Mn 2+ which can generate antibacterial hydroxyl radicals (·OH) through the Fenton reaction. The nanozymes contain Ce 3+ and Ce 4+ as well as Mn 2+ and Mn 3+ which can scavenge excessive reactive oxygen species through the self-cascade reaction of mimicking SOD and CAT. The hydrogel dressing is an amphoteric ion polymer, and the polymer molecular chain has both anionic and cationic groups, which can strongly bind water molecules through solvation, generate repulsive forces, and can effectively resist the adhesion of proteins.

[0008] A preparation method of a hydrogel dressing encapsulating multifunctional nanozymes for diabetic wound healing, the preparation method includes the following preparation steps:

[0009] 1) Using cerium nitrate hexahydrate, manganese acetate tetrahydrate, and trimesic acid as raw materials to obtain a cerium-manganese mixed metal-organic framework (Ce x Mn y -BTC);

[0010] 2) Annealing Ce x Mn y -BTC to obtain a cerium-manganese mixed metal oxide nanocomposite (Ce x Mn y -MMON);

[0011] 3) Prepare an amphoteric ion monomer, a crosslinking agent, Ce x Mny -MMON and initiator mixed solution;

[0012] 4) Deoxygenate the mixed solution and remove the bubbles in the mixed solution to obtain a pre-solution;

[0013] 5) Uniformly inject the pre-solution into a transparent mold and polymerize it under ultraviolet light. After the reaction, a uniform hydrogel dressing encapsulated with multifunctional nanozymes for diabetic wound healing is obtained.

[0014] In the present invention, a cerium-manganese mixed metal oxide nanocomposite with enzyme-like activity is first synthesized. An amphoteric ion monomer, a nanozyme, and a cross-linking agent react under the action of an initiator under certain conditions to obtain a hydrogel. The nanozyme in the hydrogel dressing has good photothermal performance with rapid temperature rise under near-infrared irradiation. The nanozyme contains Ce 3+ and Mn 2+ and can generate antibacterial hydroxyl radicals (·OH) through the Fenton reaction. The nanozyme contains Ce 3+ and Ce 4+ as well as Mn 2+ and Mn 3+ and can scavenge excessive reactive oxygen species through a simulated SOD and CAT self-cascade reaction. Specifically, the amphoteric ion hydrogel dressing prepared in the present invention has a compressive strength of 0.14 MPa; a relatively high water retention rate and swelling rate; excellent photothermal conversion performance; good antioxidant effect; good antibacterial adhesion resistance; excellent biocompatibility and in vivo wound healing promotion effect.

[0015] Preferably, in the step 1): the molar ratio of cerium nitrate hexahydrate to manganese acetate tetrahydrate is 1:(1-20); and / or the molar ratio of cerium nitrate hexahydrate and manganese acetate tetrahydrate to trimesic acid is 1:1.

[0016] Preferably, in the step 2): the annealing environment is air; the annealing temperature is 350 °C; and / or the annealing time is 2 h.

[0017] Preferably, in the mixed solution of the step 3): the concentration of the amphoteric ion monomer is 0.5-1.0 mol / L; the concentration of the cross-linking agent is 0.0005-0.002 mol% relative to the amphoteric ion monomer; the dosage of the initiator is 0.004 mol% relative to the amphoteric ion monomer; the preparation process is to dissolve the amphoteric ion monomer, the cross-linking agent, Ce x Mn y -MMON and the initiator in a solvent and then stir evenly.

[0018] Preferably, the solvent is water.

[0019] Preferably, in the step 3): the zwitterionic monomer is carboxybetaine acrylamide; the crosslinking agent is N,N'-methylenebisacrylamide; Ce x Mn y -MMON is Ce 0.1 Mn 0.9 -MMON, with a concentration of 100 - 500 μg / mL; the initiator is I2959.

[0020] Preferably, in the step 4): deoxygenation is carried out by introducing nitrogen or an inert gas to reduce the solubility of oxygen; the method for removing bubbles in the mixed solution is centrifugation.

[0021] Preferably, in the step 5): the transparent mold includes a glass mold; the ultraviolet light wavelength is 350 - 380 nm; the ultraviolet light irradiation time is 6 h.

[0022] In summary, the present invention has the following beneficial effects: the preparation method is simple, efficient and environmentally friendly, being friendly to the environment; the hydrogel dressing is made of zwitterions and N,N'-methylenebisacrylamide; the nanozyme in the hydrogel dressing sterilizes by simulating peroxidase activity and synergistic photothermal performance, and simulates superoxide dismutase activity and catalase activity to scavenge excessive reactive oxygen species in the wound microenvironment; the present invention has appropriate mechanical properties, antibacterial properties, antioxidant properties, anti-bacterial adhesion ability, biocompatibility and excellent in vivo promoting effect on diabetic wound healing. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is the scanning electron microscope image of the hydrogel dressing prepared in Example 5 of the present invention.

[0024] Figure 2 It is the swelling ratio of the hydrogel dressing prepared in Example 5 of the present invention in H2O or PBS.

[0025] Figure 3 It is the polarization level of M1 macrophages after co-incubation with the hydrogel dressing prepared in Example 5 of the present invention.

[0026] Figure 4 It is the schematic diagram of the plate colonies after 1-day co-culture of the hydrogel dressing prepared in Example 5 of the present invention with Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) bacterial solutions.

[0027] Figure 5 It is the fluorescence microscope image of bacterial adhesion in the hydrogel dressing after 1-day co-culture of the hydrogel dressing prepared in Example 5 of the present invention with Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) bacterial solutions.

[0028] Figure 6Digital photograph of the hydrogel dressing prepared in Example 5 of the present invention for promoting wound healing in a diabetic rat infected wound model. Detailed implementation manners

[0029] The following provides a detailed introduction to the implementation manners of the present invention in conjunction with the accompanying drawings of the specification, but the protection scope of the present invention is not limited thereto.

[0030] Unless otherwise specified, the raw materials used in the embodiments of the present invention are all commercially available or raw materials that can be obtained by those skilled in the art; unless otherwise specified, the methods used in the embodiments of the present invention are all methods mastered by those skilled in the art.

[0031] Examples 1-9

[0032] 1) Cerium-manganese mixed metal-organic framework (Ce x Mn y -BTC) was obtained using cerium nitrate hexahydrate, manganese acetate tetrahydrate and trimesic acid as raw materials. The molar ratio of cerium nitrate hexahydrate and manganese acetate tetrahydrate to trimesic acid was 1:1, and the specific addition amounts are shown in Table 1.

[0033] 2) Annealing treatment was performed on Ce x Mn y -BTC to obtain a cerium-manganese mixed metal oxide nanocomposite (Ce x Mn y -MMON). The annealing environment was air, the annealing temperature was 350 °C, and the annealing time was 2 h. 3) The zwitterionic monomer, crosslinking agent, Ce x Mn y -MMON and I2959 were dissolved in deionized water and stirred evenly to form a mixed solution. The zwitterionic monomer was carboxybetaine acrylamide with a concentration of 0.5-1.0 mol / L, the concentration of N,N-methylenebisacrylamide was 0.0005-0.002 mol% relative to the zwitterionic monomer, and the dosage of I2959 was 0.004 mol% relative to the zwitterionic monomer. The specific dosages are shown in Table 1;

[0034] 4) The mixed solution was purged with nitrogen to remove oxygen, and the bubbles in the mixed solution were removed by centrifugation to obtain a pre-liquid;

[0035] 5) The pre-liquid was uniformly injected into a light-transmitting mold and polymerized under ultraviolet light at 365 nm for 6 h. After the reaction, a uniform encapsulated multifunctional nanozyme hydrogel dressing for diabetic wound healing was obtained.

[0036] Table 1 Summary of raw material dosages in the preparation process of Examples 1-9

[0037]

[0038]

[0039] After the preparation, the nanozymes and hydrogel dressings prepared in Examples 1-9 were subjected to performance tests. The performance tests included the following aspects:

[0040] (1) POD-like enzyme activity test: Different samples were added to 1 mL of PBS (pH = 6.5), 1 mM OPD and 1 mM H2O2 were added, and the mixture was shaken at 37 °C for 5 min. After centrifugation, the OD value of the supernatant was measured at a wavelength of 420 nm.

[0041] (2) SOD-like enzyme activity test: The SOD-like enzyme activity of Ce x Mn y -MMON was determined by measuring the inhibition rate of photoreduction of NBT. Different samples were incubated with a mixed solution containing riboflavin (20 μM), methionine (13 mM) and NBT (75 μM) under a constant light intensity for 30 minutes, and the OD value of the supernatant was measured at 560 nm. The sample containing riboflavin, methionine and NBT after illumination was defined as the positive control, and the inhibition rate was calculated.

[0042] (3) CAT-like enzyme activity test: The generation of O2 was directly monitored using a portable dissolved oxygen meter. 40 mM H2O2 was mixed with different samples in PBS (pH = 7.4), and the amount of O2 generated within a certain time was detected using a dissolved oxygen meter. (4) Photothermal performance test: An appropriate amount of different samples was vertically irradiated at the center with a near-infrared light of 1.5 W cm -2 and a wavelength of 808 nm, and at the same time, an infrared camera was used to record the temperature rise of the samples within 90 s.

[0043] (5) Mechanical property test: Under a room temperature air environment, a high and low temperature double-column universal testing machine was used to test the mechanical properties of the prepared hydrogel. In the compression test, the hydrogel sample was made into a cylinder (d = 8 mm, h = 8 mm), and the compression rate was 5 mm / min.

[0044] (6) Swelling property test: The prepared hydrogel dressing was cut into a suitable size, fully freeze-dried and weighed. The freeze-dried samples were completely immersed in H2O or PBS respectively, and then carefully taken out and weighed at regular intervals. After weighing, they were completely immersed in H2O or PBS again for continued swelling.

[0045] (7) Anti-inflammatory ability test: Prepare samples containing different concentrations of Ce 0.1 Mn 0.9-MMON (100, 500, and 1000 μg / mL respectively) hydrogels were sterilized. The M1 macrophage suspension was dropped onto the hydrogels, and then 500 μL of culture medium was added for co-incubation for 24 h. After the culture, the cells were extracted and then stained with CD80. Finally, flow cytometry was used to collect and analyze the data to determine the polarization level of M1 macrophages.

[0046] (8) Antibacterial performance test: The in vitro antibacterial performance of the hydrogels was studied using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). First, the bacterial solution was diluted to 1×10 8 CFU / mL with PBS buffer solution at pH = 5.5, treated with four different methods respectively, and cultured at 37 °C for 4 h. Then, 100 μL of the bacterial suspension from each group was placed on LB agar and cultured at 37 °C for 24 h.

[0047] (9) Antibacterial adhesion test: The sterilized hydrogel samples were placed in solutions of Escherichia coli (OD600nm = 0.1) and Staphylococcus aureus (OD450nm = 0.05). The microplate was placed in a constant temperature shaker at 37 °C and cultured at 120 rpm for an appropriate time. After the co-culture, all samples were rinsed 3 times with sterile PBS, stained with the Live / Dead BacLight viability kit for 10 min in the dark, rinsed 3 times with sterile PBS again, and the bacterial adhesion on the surface of the samples was observed under an inverted fluorescence microscope.

[0048] (10) In vivo wound healing promotion experiment: A diabetic rat infected wound model was established to evaluate the performance of promoting wound healing. Dressings with different formulations were implanted at the wound site, and PBS and the commercial dressing Tegaderm were used as control groups. All wound dressings were sterilized by ultraviolet light. Digital photos of the wounds at different healing times (0, 3, 7, 14) were taken and recorded.

[0049] The different formulations of Ce x Mn y -MMON with POD-like, SOD-like, CAT enzyme activities and photothermal properties are shown in Table 2. When the ratio of Mn(CH3COO)2·4H2O to Ce(NO3)3·6H2O increases, the POD-like, SOD-like, CAT enzyme activities first increase and then decrease, and the activity is the largest when the ratio of Mn(CH3COO)2·4H2O to Ce(NO3)3·6H2O is 9:1, and it has the optimal photothermal properties, denoted as Ce 0.1 Mn 0.9-MMON. This is because the increase in the Mn doping amount is beneficial to generating more crystal defects and oxygen vacancies, thereby enhancing the catalytic activity. However, when the Mn doping amount is too large, the oxygen vacancies provided by Ce in the matrix and the mixed valence states of Ce 3+ and Ce 4+ decrease, resulting in a decline in the catalytic activity.

[0050] Table 2 Summary of POD-like, SOD-like, CAT-like enzyme activities and photothermal properties of nanozymes with different ratios of Mn(CH3COO)2·4H2O to Ce(NO3)3·6H2O

[0051]

[0052] The compressive strength and cyclic compression properties of the hydrogel dressings with different N,N-methylenebisacrylamide contents prepared in Examples 5 to 7 are shown in Table 3. When the N,N-methylenebisacrylamide content increases, the compressive strength of the hydrogel gradually increases, but its cyclic compression performance deteriorates (the complete compression process includes two stages: compression and release, and cyclic compression means that the complete compression can be repeated multiple times). As the crosslinker concentration increases, the mechanical properties of the hydrogel are enhanced, manifested as an increase in brittleness, but the shape memory property deteriorates, that is, the complete compression process cannot be completed.

[0053] Table 3 Compressive strength and cyclic compression properties of hydrogel dressings with different N,N-methylenebisacrylamide contents.

[0054] Concentration of N,N - methylenebisacrylamide 0.5 mol% 1 mol% 2 mol% Compressive strength (MPa) 0.14 0.35 0.56 Cyclic compression √ × ×

[0055] The compressive strength and cyclic compression properties of the hydrogel dressings with different carboxybetaine acrylamide concentrations prepared in Examples 5, 8, and 9 are shown in Table 4. When the carboxybetaine acrylamide concentration increases, the compressive strength of the hydrogel gradually increases, but its cyclic compression performance deteriorates. As the monomer concentration increases, the mechanical properties of the hydrogel are enhanced and become more brittle. The gel network is severely damaged during the compression process and cannot recover during the release process, so cyclic compression cannot be achieved.

[0056] Table 4 Compressive strength and cyclic compression properties of the hydrogel dressings prepared in Examples 5, 8, and 9.

[0057] Concentration of carboxybetaine acrylamide 0.5M 0.8M 1M Compressive strength (MPa) 0.14 0.28 0.38 Cyclic compression √ × ×

[0058] The scanning electron microscope images of the hydrogel dressing prepared in Example 5 are as Figure 1 shown. It can be seen from Figure 1 that a uniform pore network structure connected to each other can be observed in the hydrogel, which is beneficial to cell adsorption and growth and promotes wound repair.

[0059] The swelling ratios of the hydrogel dressing prepared in Example 5 in H2O and PBS are asFigure 2 As shown in Figure 2 It can be seen that the hydrogel dressing has a high swelling rate and can absorb liquids far exceeding its own volume, which is beneficial to absorbing wound exudate.

[0060] The polarization level of M1 macrophages after co-incubating the hydrogel dressing prepared in Example 5 with M1 macrophages for 24 hours is as Figure 3 shown in Figure 3 It can be seen from 0.1 Ce 0.9 -MMON has equivalent anti-inflammatory effects at concentrations of 100 μg / mL and 500 μg / mL, and can effectively reduce the polarization of M1 macrophages. However, when the concentration increases to 1000 μg / mL, the anti-inflammatory ability decreases. Ce 0.1 Mn 0.9 -MMON, although having good biocompatibility, as a foreign substance, when the concentration of Ce 0.1 Mn 0.9 -MMON is too high, it will still cause an inflammatory reaction, attributed to the fact that the anti-inflammatory ability it provides is weaker than the induced inflammatory reaction, ultimately resulting in a decrease in the anti-inflammatory effect.

[0061] The schematic diagram of the plate colonies after co-culturing the hydrogel dressing prepared in Example 5 with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial solutions for 1 day is as Figure 4 shown in Figure 4 It can be seen that the hydrogel dressing can effectively resist bacterial infection.

[0062] The fluorescence microscope images of bacterial adhesion after co-culturing the hydrogel dressing prepared in Example 5 with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial solutions for 1 day are as Figure 5 shown in Figure 5 It can be seen that the hydrogel dressing can effectively resist bacterial adhesion.

[0063] The digital photos of the effect of promoting wound healing of the hydrogel dressing prepared in Example 5 in a diabetic rat infected wound model are as Figure 6 shown, where tegaderm is a commercially available dressing. It can be seen from Figure 6 that in the hydrogel dressing group, most rats showed less severe infections, and the wounds also achieved faster repair, indicating that the hydrogel dressing can effectively promote healing.

[0064] The above-mentioned numerous test results show that the preparation method of the present invention is simple, efficient and environmentally friendly, and is friendly to the environment; the hydrogel dressing is made of zwitterions and N,N-methylenebisacrylamide; the nanozyme in the hydrogel dressing sterilizes by simulating peroxidase activity and synergistic photothermal performance, and simulates superoxide dismutase activity and catalase activity to scavenge excess reactive oxygen species in the wound microenvironment; the present invention has appropriate mechanical properties, antibacterial properties, antioxidant properties, biocompatibility and excellent in vivo wound healing effect.

Claims

1. A preparation method of a hydrogel dressing encapsulating a multifunctional nanozyme for diabetic wound healing, characterized in that, The preparation method includes the following preparation steps: 1) Cerium-manganese mixed metal-organic framework was obtained using cerium nitrate hexahydrate, manganese acetate tetrahydrate, and trimesic acid as raw materials, denoted as Ce x Mn y -BTC; 2) Anneal Ce x Mn y -BTC to obtain a cerium-manganese mixed metal oxide nanocomposite, denoted as Ce x Mn y -MMON; 3) Prepare a mixed solution of zwitterionic monomer, crosslinking agent, Ce x Mn y -MMON and initiator; 4) Deoxygenate the mixed solution and remove the bubbles in the mixed solution to obtain a pre-solution; 5) Uniformly inject the pre-solution into a transparent mold and polymerize it under ultraviolet light. After the reaction is completed, a uniform hydrogel dressing encapsulating multifunctional nanozymes for diabetic wound healing is obtained.

2. The preparation method according to claim 1, characterized in that, In step 1), the molar ratio of cerium nitrate hexahydrate to manganese acetate tetrahydrate is 1:1 to 20; the total molar ratio of cerium nitrate hexahydrate and manganese acetate tetrahydrate to trimesic acid is 1:

1.

3. The preparation method according to claim 1, wherein In step 2), the annealing environment is air; the annealing temperature is 350 °C; the annealing time is 2 h.

4. The preparation method according to claim 1, characterized in that, The concentration of the zwitterionic monomer in the mixed solution of step 3) is 0.5 to 1 mol / L; the concentration of the crosslinking agent is 0.0005 to 0.002 mol% relative to the zwitterionic monomer; the initiator concentration is 0.004 mol% relative to the zwitterionic monomer; the preparation process is to dissolve the zwitterionic monomer, the crosslinking agent, Ce x Mn y -MMON and the initiator in water and then stir evenly.

5. The preparation method according to claim 1 or 4, characterized in that In step 3), the zwitterionic monomer is carboxybetaine acrylamide; the crosslinking agent is N,N-methylenebisacrylamide; Ce x Mn y -MMON is Ce 0.1 Mn 0.9 -MMON, with a concentration of 100 - 500 μg / mL; the initiator is I2959.

6. The preparation method according to claim 1, wherein In step 4), deoxygenation is carried out by introducing nitrogen or an inert gas to reduce the solubility of oxygen; the method for removing the bubbles in the mixed solution is centrifugation.

7. The preparation method according to claim 1, characterized in that, In step 5), the transparent mold is a glass mold; the ultraviolet light wavelength is 350 - 380 nm; the ultraviolet light irradiation time is 6 h.

8. A hydrogel dressing for diabetic wound healing using an encapsulated multifunctional nanozyme prepared by the preparation method described in any one of claims 1-7, characterized in that, The hydrogel dressing contains nanozymes, and the hydrogel dressing is an amphoteric ion polymer.