Preparation method of novel antibacterial nano composite hydrogel for repairing diabetic oral ulcer

Abstract

The invention relates to the technical field of biological materials, and discloses a preparation method of novel antibacterial nano composite hydrogel for repairing diabetic oral ulcer. Comprising the following steps: grafting 2-formylphenylboronic acid on titanium carbide (MXene) nanosheets to form MXene (at) FPBA nanoparticles, carrying out an amidation reaction on lipoic acid and recombinant collagen to obtain modified recombinant collagen, doping the MXene (at) FPBA into the modified recombinant collagen system, and carrying out photo-crosslinking to obtain the novel antibacterial nano composite hydrogel. The hydrogel combines the strong anti-oxidation and anti-inflammatory capabilities of lipoic acid, does not need to add anti-inflammatory drugs, and also has good adhesiveness; the MXene (at) FPBA nano particles can be used for capturing bacteria and carrying out efficient sterilization; and the raw materials used by the material have biological safety. Therefore, the hydrogel has the antibacterial property and the anti-inflammatory function, and can comprehensively and efficiently manage and treat diabetic oral ulcer wounds.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, specifically to a method for preparing a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers. Background Technology

[0002] The oral mucosa, covering the surface of the mouth, serves as a protective barrier and a sensory organ for taste. In daily life, mechanical trauma, imbalances in the oral microbiota, fatigue, and stress often lead to damage to the oral mucosal epithelium, resulting in oral ulcers. Globally, over 25% of the population has experienced or is currently experiencing oral ulcers, and the Chinese market for oral ulcer treatment drugs is projected to reach approximately RMB 18 billion by 2025. Compared to non-diabetic patients, diabetic patients with oral ulcers are more prone to bacterial infection, imbalanced inflammatory responses, and impaired oxidative stress due to high glucose levels at the wound site, all of which severely hinder normal mucosal healing.

[0003] For oral ulcers, the main treatments currently available on the market are oral patches, powders, and ointments. However, due to the moist and highly dynamic environment in the mouth, these substances are easily washed away by food, liquids, or even saliva, shortening their duration of action in the mouth and reducing the concentration of the drug at the lesion site. This ultimately weakens the treatment effect, and commercially available drugs are unlikely to achieve the dual effects of antibacterial and anti-inflammatory properties.

[0004] To effectively treat diabetic oral ulcers, there is an urgent need to develop an oral patch with good wet mucosal adhesion, capable of automatically regulating the wound microenvironment, including managing inflammation, bacterial infection and natural cell activity, and providing long-term protection to the damaged area in a saliva-rich environment to support mucosal regeneration.

[0005] Hydrogels are high-water-content materials (typically 70-99%), and due to their unique physical properties, such as extracellular matrix-like structure, tunable mechanical properties, and breathability and softness, they are excellent candidates as oral mucosal patches. However, ordinary hydrogels lack antibacterial and anti-inflammatory capabilities, making it difficult to meet the complex needs of repairing diabetic oral ulcers. Summary of the Invention

[0006] The technical problem to be solved by this invention is to address the shortcomings of the prior art by providing a method for preparing a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers. This method uses a modified recombinant collagen system containing MXene@FPBA nanoparticles as the main raw material, and obtains a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers through ultraviolet light irradiation. This hydrogel can closely adhere to the ulcer wound, possessing both antibacterial and anti-inflammatory properties, and can comprehensively and efficiently manage and treat oral ulcer wounds.

[0007] To achieve the above objectives, this invention provides a method for preparing a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers, comprising the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; Step 2: Modify recombinant collagen with lipoic acid to obtain modified recombinant collagen; Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation; Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 8%~16%. Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 1 min to 2 min to obtain system A; Step 6: Irradiate system A described in step 5 with ultraviolet light for 2 to 3 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers.

[0008] Furthermore, the preparation method of MXene@FPBA nanoparticles in step one specifically includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 12h~96h, centrifuge, and dry to obtain MXene multilayer nanosheets; Step 102: Peel the MXene multilayer nanosheets obtained in step 101 with tetrapropylammonium hydroxide solution for 12h~48h, centrifuge, and dry to obtain few-layer MXene nanosheets; Step 103: Disperse the MXene nanosheets described in step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 12-48 h, then add 3-aminopropyltriethoxysilane and stir for 12-48 h, collect by centrifugation, and dry under vacuum at 60 °C for 12 h to obtain MXene-NH2; Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5-10 min, mechanically stir at room temperature for 12-48 h, collect the product by centrifugation, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45°C for 12 h to obtain MXene@FPBA nanoparticles.

[0009] Further, in step 101, the mass of hydrofluoric acid is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of hydrofluoric acid is 30% to 45%; in step 102, the mass of tetrapropylammonium hydroxide solution is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 25% to 50%.

[0010] Further, in step 103, the volume ratio of ethanol, water, and ammonia in the mixed solution is 16:1:(1~2), the mass ratio of MXene nanosheets to the volume of the mixed solution is (5~6):1, and the volume ratio of 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:(46~47), where mass is in mg and volume is in mL; in step 104, the mass ratio of MXene-NH2 to anhydrous methanol is (6~7):1, the mass of 2-formylphenylboronic acid is 150%~220% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 250~300% of the mass of MXene-NH2, where mass is in mg and volume is in mL.

[0011] Furthermore, the modification methods in step two specifically include: Step 201: Dissolve lipoic acid, EDC and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir the mixed solution at a temperature of 20℃~37℃ for 1h~3h to obtain an activated lipoic acid solution. Step 202: Mix the activated thioctic acid solution and recombinant collagen solution from step 201, and stir the mixture at 20℃~37℃ for 8h~12h. Dialyze the system after stirring and freeze-dry it to obtain modified recombinant collagen.

[0012] Further, the pH of the mixed solution in step 201 is 5-6, the mass of the lipoic acid is 15%-20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC and NHS is (1-1.5):4:2.

[0013] Further, the recombinant collagen mentioned in step 202 is recombinant collagen CF-1552, the amount of lipoic acid in step 201 is 5 to 6 times the amount of recombinant collagen, and the recombinant collagen solution is a solution prepared by dissolving recombinant collagen in dimethyl sulfoxide, wherein the mass percentage of recombinant collagen in the solution is 3% to 4%.

[0014] Furthermore, the mass percentage of MXene@FPBA nanoparticles in system A described in step five is 0.2%~0.5%.

[0015] Furthermore, in step six, the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0016] The advantages and positive effects of the preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers described in this invention are as follows: 1. This invention uses a modified recombinant collagen system containing MXene@FPBA nanoparticles as the main raw material. After ultraviolet light irradiation, a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers is obtained. It can closely adhere to the ulcer wound and has both antibacterial and anti-inflammatory properties, enabling comprehensive and efficient management and treatment of oral ulcer wounds.

[0017] 2. The present invention preferably uses MXene@FPBA nanostructures obtained by modifying MXene nanosheets with 2-formylphenylboronic acid. Incorporating MXene@FPBA nanostructures into the hydrogel system can effectively improve the antibacterial properties of the hydrogel.

[0018] 3. The present invention uses recombinant collagen, which can provide beneficial components for wounds and significantly promote wound healing. The preferred recombinant collagen is CF-1552. Compared with other animal-derived collagen, CF-1552 has excellent biocompatibility, good water solubility, no virus and low immunogenicity.

[0019] 4. In this invention, lipoic acid is preferred to modify recombinant collagen to obtain modified recombinant collagen. Through chemical modification, the recombinant collagen combines the strong antioxidant and anti-inflammatory capabilities of lipoic acid, so that no anti-inflammatory drugs need to be added to the hydrogel system, while achieving good adhesion to the oral mucosa.

[0020] 5. The preparation method of this invention is simple, has good reproducibility, and has good application prospects.

[0021] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the preparation process of few-layer MXene nanosheets and MXene@FPBA nanoparticles of the present invention; Figure 2 The image shows the XPS spectra of the MXene@FPBA nanoparticles of the present invention, where A is the full XPS spectrum of MXene and MXene@FPBA, and B is the high-resolution XPS spectrum of C1s, N1s, and B1s of MXene@FPBA. Figure 3 The images show the TEM image and mapping elemental distribution of the MXene@FPBA nanoparticles of this invention. Figure 4 The image shows the FTIR spectrum of the modified recombinant collagen in Example 1 of this invention. CF-1552 represents recombinant collagen, and CF-LA represents modified recombinant collagen. Figure 5 The modified recombinant collagen of Example 1 of this invention 1 1H NMR spectra, CF-1552 is recombinant collagen, and CF-LA is modified recombinant collagen; Figure 6 This is a morphology image of the novel antibacterial nanocomposite hydrogel used for the repair of diabetic oral ulcers in Example 1 of the present invention; Figure 7 This is a SEM image of the novel antibacterial nanocomposite hydrogel used for repairing diabetic oral ulcers in Example 1 of the present invention. Figure 8 The results of cytotoxicity tests are for the novel antibacterial nanocomposite hydrogel used for repairing diabetic oral ulcers in Example 1 of this invention. Figure 9 The results of the cell migration promotion test of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in Example 1 of this invention; Figure 10 For different concentrations of MXene@FPBA S.aureus and E. coli The antibacterial effect, where A represents different concentrations of MXene@FPBA and S.aureus and E. coli Co-cultured bacterial colony diagram, B represents different concentrations of MXene@FPBA and... S.aureus The bacterial clearance rate of co-culture, where C represents different concentrations of MXene@FPBA and E. coli Bacterial clearance rate during co-culture; Figure 11 For different hydrogels S.aureus The antibacterial effect, where A represents the effect of different treatment regimens. S.aureus Colony photographs and corresponding scanning electron microscope images, B shows different treatment regimens. S.aureus The bacterial clearance rate; Figure 12 For different hydrogels E. coli The antibacterial effect, where A represents the effect of different treatment regimens. E. coli Colony photographs and corresponding scanning electron microscope images, B shows different treatment regimens. E. coli The bacterial clearance rate. Detailed Implementation

[0023] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0024] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention. Experimental methods in the following embodiments that do not specify specific conditions are generally determined according to national standards. Experimental instruments, equipment, and reagents in the following embodiments that do not specify their sources are all commercially available materials.

[0025] Unless otherwise defined or stated, all technical and scientific terms used in this invention have the same meaning as those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein can be applied to the methods of this invention. It should be noted that, unless otherwise specified, the embodiments and features described in this invention can be combined with each other.

[0026] The recombinant collagen described in the following examples is CF-1552, which is derived from the Institute of Biomedical Research, School of Chemical Engineering, Northwest University. The recombinant collagen CF-1552 is obtained by reverse transcription of human collagen mRNA to generate cDNA, which is then expressed in Escherichia coli BL21. Its structure and acquisition method can be found in the patent application document with patent number ZL01106757.8, entitled "A human-like collagen and its production method", or in the literature Recombinant collagen for the repair of skin wounds and photo-aging damage, Regenerative Biomaterials, 2024, 11, rbae108.

[0027] The present invention provides a method for preparing a novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers, comprising the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; a schematic diagram of the preparation process of few-layer MXene nanosheets and MXene@FPBA nanoparticles is shown below. Figure 1 The specific preparation methods include...

[0028] Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 12h~96h, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 30%~45%.

[0029] Step 102: Peel the MXene multilayer nanosheets obtained in step 101 with tetrapropylammonium hydroxide solution for 12h~48h, centrifuge, and dry to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 25%~50%.

[0030] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 12-48 h, then add 3-aminopropyltriethoxysilane and stir for 12-48 h. After centrifugation and collection, vacuum dry at 60°C for 12 h to obtain MXene-NH2. The volume ratio of ethanol, water and ammonia in the mixed solution is 16:1:(1-2), the mass ratio of the MXene nanosheets to the volume of the mixed solution is (5-6):1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:(46-47). The unit of mass is mg and the unit of volume is mL.

[0031] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5-10 min, mechanically stir at room temperature for 12-48 h, collect the product by centrifugation, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to the volume of anhydrous methanol is (6-7):1, the mass of 2-formylphenylboronic acid is 150%-220% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 250-300% of the mass of MXene-NH2, where the mass unit is mg and the volume unit is mL.

[0032] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), and NHS (N-hydroxysuccinimide) in dimethyl sulfoxide to obtain a mixed solution. Activate the mixed solution by stirring at 20°C to 37°C for 1 to 3 hours to obtain an activated lipoic acid solution. The pH of the mixed solution is 5 to 6, the mass of the lipoic acid is 15% to 20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC, and NHS is (1 to 1.5):4:2. Step 202: Mix the activated lipoic acid solution from step 201 with the recombinant collagen solution, and stir the mixture at 20℃~37℃ for 8h~12h. Dialyze the system after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 5 to 6 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 3%~4%.

[0033] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation.

[0034] Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 8% to 16%.

[0035] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 1 min to 2 min to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.2% to 0.5%.

[0036] Step 6: Irradiate system A described in step 5 with ultraviolet light for 2 to 3 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365 nm and the power is 10 W.

[0037] Example 1: The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in this embodiment includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; the specific preparation method includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 24 hours, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 5 times the mass of titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 40%.

[0038] Step 102: The MXene multilayer nanosheets obtained in step 101 are peeled with tetrapropylammonium hydroxide solution for 12 hours, centrifuged, and dried to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 5 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 25%.

[0039] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 12 h, then add 3-aminopropyltriethoxysilane and stir for 12 h. After centrifugation at 8000 rpm, collect the solution and vacuum dry at 60°C for 12 h to obtain MXene-NH2. The volume ratio of ethanol, water and ammonia in the mixed solution is 16:1:2, the mass ratio of the MXene nanosheets to the volume of the mixed solution is 5.5:1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:46. The units of mass are mg and the units of volume are mL.

[0040] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5 min, mechanically stir at room temperature for 12 h, centrifuge at 8000 rpm to collect the product, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to anhydrous methanol is 7:1, the mass of 2-formylphenylboronic acid is 150% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 270% of the mass of MXene-NH2, where the unit of mass is mg and the unit of volume is mL.

[0041] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir and activate the mixed solution at 25°C for 1 hour to obtain an activated lipoic acid solution. The pH of the mixed solution is 5, the mass of the lipoic acid is 15% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC and NHS is 1:4:2.

[0042] Step 202: Mix the activated lipoic acid solution and recombinant collagen solution from Step 201, and stir the mixture at 25°C for 8 hours. Dialyze the mixture after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 5 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 3%.

[0043] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation.

[0044] Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 8%.

[0045] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 1 min to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.2%.

[0046] Step 6: Irradiate system A described in step 5 with ultraviolet light for 2 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0047] Example 2: The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in this embodiment includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; the specific preparation method includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 12 hours, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 5 times the mass of the titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 35%.

[0048] Step 102: The MXene multilayer nanosheets obtained in step 101 are peeled with tetrapropylammonium hydroxide solution for 24 hours, centrifuged, and dried to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 7 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 40%.

[0049] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 12 hours, then add 3-aminopropyltriethoxysilane and stir for 12 hours. Centrifuge at 8000 rpm, collect the samples, and vacuum dry at 60°C for 12 hours to obtain MXene-NH2. The volume ratio of ethanol, water, and ammonia in the mixed solution is 16:1:1, the mass ratio of the MXene nanosheets to the volume of the mixed solution is 5:1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:46. The units of mass are mg and the units of volume are mL.

[0050] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5 min, mechanically stir at room temperature for 24 h, centrifuge at 8000 rpm to collect the product, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to anhydrous methanol is 6:1, the mass of 2-formylphenylboronic acid is 180% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 250% of the mass of MXene-NH2, where the unit of mass is mg and the unit of volume is mL.

[0051] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir and activate the mixed solution at 20°C for 1.5 h to obtain an activated lipoic acid solution. The pH of the mixed solution is 5, the mass of the lipoic acid is 17% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC and NHS is 1:4:2.

[0052] Step 202: Mix the activated lipoic acid solution and recombinant collagen solution from Step 201, and stir the mixture at 20°C for 10 hours. Dialyze the mixture after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 5 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 3.5%.

[0053] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation.

[0054] Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 10%.

[0055] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 1 min to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.3%.

[0056] Step 6: Irradiate system A described in step 5 with ultraviolet light for 2.5 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0057] Example 3: The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in this embodiment includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; the specific preparation method includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 36 hours, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 5 times the mass of titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 40%.

[0058] Step 102: The MXene multilayer nanosheets obtained in step 101 are peeled off with tetrapropylammonium hydroxide solution for 18 hours, centrifuged, and dried to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 10 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 30%.

[0059] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 24 h, then add 3-aminopropyltriethoxysilane and stir for 24 h. After centrifugation at 8000 rpm, collect the solution and vacuum dry at 60 °C for 12 h to obtain MXene-NH2. The volume ratio of ethanol, water and ammonia in the mixed solution is 16:1:1, the mass ratio of the MXene nanosheets to the volume of the mixed solution is 6:1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:47. The units of mass are mg and the units of volume are mL.

[0060] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 8 min, mechanically stir at room temperature for 12 h, centrifuge at 8000 rpm to collect the product, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to anhydrous methanol is 6.5:1, the mass of 2-formylphenylboronic acid is 150% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 300% of the mass of MXene-NH2, where the unit of mass is mg and the unit of volume is mL.

[0061] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC, and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir and activate the mixed solution at 25°C for 2 hours to obtain an activated lipoic acid solution. The pH of the mixed solution is 5.5, the mass of the lipoic acid is 20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC, and NHS is 1.5:4:2.

[0062] Step 202: Mix the activated lipoic acid solution and recombinant collagen solution from Step 201, and stir the mixture at 25°C for 10 hours. Dialyze the mixture after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 5.5 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 3.5%.

[0063] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation.

[0064] Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 12%.

[0065] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 2 minutes to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.4%.

[0066] Step 6: Irradiate system A described in step 5 with ultraviolet light for 3 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0067] Example 4: The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in this embodiment includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; the specific preparation method includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 24 hours, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 7.5 times the mass of titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 45%.

[0068] Step 102: The MXene multilayer nanosheets obtained in step 101 are peeled with tetrapropylammonium hydroxide solution for 24 hours, centrifuged, and dried to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 5 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 30%.

[0069] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 24 hours, then add 3-aminopropyltriethoxysilane and stir for another 24 hours. Centrifuge at 8000 rpm, collect the samples, and vacuum dry at 60°C for 12 hours to obtain MXene-NH2. The volume ratio of ethanol, water, and ammonia in the mixed solution is 16:1:1.5, the mass ratio of the MXene nanosheets to the volume of the mixed solution is 5.5:1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:46. The units of mass are mg and the units of volume are mL.

[0070] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 10 min, mechanically stir at room temperature for 24 h, centrifuge at 8000 rpm to collect the product, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to anhydrous methanol is 6:1, the mass of 2-formylphenylboronic acid is 200% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 300% of the mass of MXene-NH2, where the unit of mass is mg and the unit of volume is mL.

[0071] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC, and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir and activate the mixed solution at 25°C for 2.5 hours to obtain an activated lipoic acid solution. The pH of the mixed solution is 6, the mass of the lipoic acid is 20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC, and NHS is 1:4:2.

[0072] Step 202: Mix the activated lipoic acid solution and recombinant collagen solution from Step 201, and stir the mixture at 25°C for 12 hours. Dialyze the mixture after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 6 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 4%.

[0073] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation; Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 16%.

[0074] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 2 minutes to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.5%.

[0075] Step 6: Irradiate system A described in step 5 with ultraviolet light for 3 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0076] Example 5: The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers in this embodiment includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; the specific preparation method includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 96 hours, centrifuge, and dry to obtain MXene multilayer nanosheets; the mass of the hydrofluoric acid is 10 times the mass of the titanium aluminum carbide, and the mass percentage of the hydrofluoric acid is 30%.

[0077] Step 102: The MXene multilayer nanosheets obtained in step 101 are peeled with tetrapropylammonium hydroxide solution for 48 hours, centrifuged, and dried to obtain few-layer MXene nanosheets; the mass of the tetrapropylammonium hydroxide solution is 5 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 50%.

[0078] Step 103: Disperse the MXene nanosheets obtained in Step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 48 h, then add 3-aminopropyltriethoxysilane and stir for 48 h. After centrifugation at 8000 rpm, collect the solution and vacuum dry at 60 °C for 12 h to obtain MXene-NH2. The volume ratio of ethanol, water and ammonia in the mixed solution is 16:1:1.5, the mass ratio of the MXene nanosheets to the volume of the mixed solution is 5:1, and the volume ratio of the 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:47. The units of mass are mg and the units of volume are mL.

[0079] Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5 min, mechanically stir at room temperature for 48 h, centrifuge at 8000 rpm to collect the product, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45℃ for 12 h to obtain MXene@FPBA nanoparticles; the mass ratio of MXene-NH2 to anhydrous methanol is 6.5:1, the mass of 2-formylphenylboronic acid is 220% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 270% of the mass of MXene-NH2, where the unit of mass is mg and the unit of volume is mL.

[0080] Step 2: Modify recombinant collagen using lipoic acid to obtain modified recombinant collagen; specific modification methods include: Step 201: Dissolve lipoic acid, EDC, and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir and activate the mixed solution at 37°C for 3 hours to obtain an activated lipoic acid solution. The pH of the mixed solution is 6, the mass of the lipoic acid is 20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC, and NHS is 1.5:4:2.

[0081] Step 202: Mix the activated lipoic acid solution and recombinant collagen solution from Step 201, and stir the mixture at 37°C for 12 hours. Dialyze the mixture after stirring and freeze-dry it to obtain modified recombinant collagen. The amount of lipoic acid is 6 times the amount of recombinant collagen. The recombinant collagen solution is prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 4%.

[0082] Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation.

[0083] Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 16%.

[0084] Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 2 minutes to obtain System A; the mass percentage of MXene@FPBA nanoparticles in System A is 0.2%.

[0085] Step 6: Irradiate system A described in step 5 with ultraviolet light for 2 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers; the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

[0086] Performance evaluation: The dried MXene@FPBA nanoparticle powder sample prepared according to this invention was placed in an X-ray electron spectrometer, and the full spectrum and corresponding high-resolution spectrum were set to analyze the elemental valence state of the sample surface. Figure 2 As shown, XPS detection of MXene@FPBA nanoparticles confirmed the coexistence of C and B. The peaks of the C 1s XPS signal at 281.4, 284.8, 286.6 and 288.6 eV correspond to C-Ti, CC, CO / CN and C=O, respectively, while the peak of the B 1s spectrum at 190.8 eV corresponds to BO.

[0087] The MXene@FPBA nanoparticles prepared in this invention were ultrasonically and uniformly dispersed in ethanol, diluted to a certain concentration, dropped onto the surface of a copper mesh, and allowed to dry. The morphology of the sample was observed using a transmission electron microscope, and the elemental composition of the nanoparticles was detected by energy-dispersive X-ray spectroscopy (EDS mapping). The results are shown in […]. Figure 3 The mapping of MXene@FPBA elements shows the distribution of N and B elements, proving the synthesis of MXene@FPBA nanoparticles.

[0088] The modified recombinant collagen powder sample prepared in Example 1 of this invention was placed on a tablet press for sample preparation, and the FT-IR spectrum of the sample was recorded using an infrared spectrometer with a wavenumber range of 500 cm⁻¹. -1 Up to 4000cm -1 The results are shown below. Figure 4 CF-1552 is recombinant collagen, and CF-LA is modified recombinant collagen; in the spectral lines of CF-1552, 3290 cm⁻¹ -1 The absorption peak originates from the stretching vibration of the OH group in the carboxylic acid group, at 1629 cm⁻¹. -1 The point is the stretching vibration of the amide bond C=O, at 1544 cm⁻¹. -1It is the deformation vibration of NH, and compared to the ungrafted CF-1552, CF-LA is at 547 cm⁻¹. -1 There is a characteristic peak at this point, which belongs to the SS bond, so it can be preliminarily determined that CF-LA has been successfully prepared.

[0089] Figure 5 For CF-1552 and CF-LA samples 1 In the 1H NMR spectrum of CF-LA, the characteristic peak at 2.59 ppm is attributed to the hydrogen atom far from the S atom in the five-membered ring, and the characteristic peaks at 2.62 ppm and 2.75 ppm are attributed to the hydrogen atoms on the carbon atoms adjacent to the S atom in the five-membered ring of LA. This further proves that CF-LA was successfully prepared.

[0090] Figure 6 The image shows the morphology of the novel antibacterial nanocomposite hydrogel used for repairing diabetic oral ulcers in Example 1 of this invention. As can be seen from the image, the novel antibacterial nanocomposite hydrogel has a moist and soft morphology.

[0091] The novel antibacterial nanocomposite hydrogel prepared in Example 1 of this invention was rapidly frozen in liquid nitrogen for 20 minutes, then freeze-dried in a freeze dryer for 3-4 days. The sample was then subjected to brittle fracture and gold sputtering treatment, and its morphology was observed using a scanning electron microscope. The results are shown below. Figure 7 As can be seen from the figure, the internal structure of the novel antibacterial nanocomposite hydrogel exhibits a uniform and porous network.

[0092] Use DMEM medium at 1.0 × 10⁶ ppm per well 4 L929 cells were initially seeded at a density of 100 cells / well in 96-well plates and incubated in a cell culture incubator for 24 h. The hydrogel of this invention was then immersed in DMEM medium at a concentration of 0.1 g / mL for 2-3 days to obtain a hydrogel extract. This hydrogel extract was used to replace the original culture medium, and the cells were incubated in a cell culture incubator for 24-48 h. Cytotoxicity was tested using the CCK-8 colorimetric assay. Results are shown below. Figure 8 The results showed that the cell survival rate of the hydrogel remained above 99%.

[0093] Cell scratch assay was used to investigate cell migration behavior. DMEM medium was used at a concentration of 4 × 10⁶ cells / well. 5 L929 cells were initially seeded at a density of [number] cells per well in 6-well plates and incubated for 24 hours. A straight line was drawn in the center of each well using a 200 μL sterile pipette tip. Cells were washed with PBS, and the original culture medium was replaced with the aforementioned hydrogel extraction buffer. Cells were incubated for another 24 hours, and cell growth was observed under a microscope. Results are shown below. Figure 9 The results showed that the hydrogel could promote the migration of L929 cells and had the effect of promoting wound healing. Figure 8 and9 All studies show that the hydrogel has excellent biocompatibility.

[0094] Samples of different concentrations of MXene@FPBA were placed in 1 mL S.aureus suspension (10 5 The bacterial suspension was co-cultured in a solution of CFU / mL at 37°C on a shaker (100 rpm) for 12 hours, while the control group contained only 1 mL of bacterial suspension. After co-culture, the bacterial suspension was diluted to 10⁻⁶ CFU / mL. -4 Double the volume of the culture medium, thoroughly resuspend 100 μL, and drop it onto a solid culture medium. Spread the medium evenly using a spreader, and incubate at 37°C for 12 hours. Observe the colony count and calculate the bacterial clearance rate. E. coli The in vitro antibacterial experiment was the same as above. Results are shown below. Figure 10 As can be seen from the figure, MXene@FPBA nanoparticles exhibit significant antibacterial properties against both types of bacteria. At a concentration of 2 mg / mL MXene@FPBA, S.aureus The clearance rate reached 98.8%. E. coli The clearance rate reached 97.3%, mainly due to Gram-negative bacteria. E. coli The external protective lipid barrier in the cell wall can protect them from direct damage by MXene nanoknife.

[0095] Figure 11 , Figure 12 Different hydrogel pairs S.aureus and E. coli In vitro antibacterial experiments and bacterial clearance rates were conducted. The boron dihydroxyl groups on the surface of the MXene@FPBA nanoparticles designed in this invention can bind to lipopolysaccharides / peptidoglycans on bacterial cell walls, thereby capturing bacteria and achieving efficient sterilization. Different hydrogel samples were placed in… S.aureus suspension (10 5 The bacterial suspension was co-cultured for 12 hours at 37°C on a shaker (100 rpm) in a solution of CFU / mL, while the control group contained only bacterial suspension. After co-culture, the bacterial suspension was diluted to 10⁻⁶ CFU / mL. -4 Double the volume of the culture medium, thoroughly resuspend 100 μL, and drop it onto a solid culture medium. Spread the medium evenly using a spreader, and incubate at 37°C for 12 hours. Observe the colony count and calculate the bacterial clearance rate. E. coli The in vitro antibacterial experiments were the same as above. The comparison shows that adding MXene@FPBA significantly improves the antibacterial properties of the hydrogel compared to adding MXene.

[0096] Therefore, this invention discloses a method for preparing a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers. The method involves grafting 2-formylphenylboronic acid onto titanium carbide (MXene) nanosheets to form MXene@FPBA nanoparticles, performing an amidation reaction between lipoic acid and recombinant collagen to obtain modified recombinant collagen, incorporating MXene@FPBA into the modified recombinant collagen system, and then photocrosslinking to obtain the novel antibacterial nanocomposite hydrogel. This hydrogel combines the potent antioxidant and anti-inflammatory capabilities of lipoic acid, eliminating the need for additional anti-inflammatory drugs, and also exhibits good adhesion; the MXene@FPBA nanoparticles can capture bacteria for highly efficient sterilization; and all raw materials used in this material are biosafety-free. In summary, this hydrogel possesses both antibacterial and anti-inflammatory properties, enabling comprehensive and efficient management and treatment of diabetic oral ulcer wounds.

[0097] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for preparing a novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers, characterized in that, Includes the following steps: Step 1: MXene@FPBA nanoparticles were prepared by modifying MXene with 2-formylphenylboronic acid; Step 2: Modify recombinant collagen with lipoic acid to obtain modified recombinant collagen; Step 3: Sterilize the MXene@FPBA nanoparticles prepared in Step 1 by Co60 irradiation; Step 4: Dissolve the modified recombinant collagen from Step 2 in deionized water to obtain a modified recombinant collagen solution with a mass concentration of 8%~16%. Step 5: Mix the sterilized MXene@FPBA nanoparticles from Step 3 with the modified recombinant collagen solution from Step 4, and stir for 1 min to 2 min to obtain system A; Step 6: Irradiate system A described in step 5 with ultraviolet light for 2 to 3 minutes to obtain a novel antibacterial nanocomposite hydrogel for the repair of diabetic oral ulcers.

2. The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 1, characterized in that, The preparation method of MXene@FPBA nanoparticles in step one specifically includes: Step 101: Etch titanium aluminum carbide with hydrofluoric acid for 12h~96h, centrifuge, and dry to obtain MXene multilayer nanosheets; Step 102: Peel the MXene multilayer nanosheets obtained in step 101 with tetrapropylammonium hydroxide solution for 12h~48h, centrifuge, and dry to obtain few-layer MXene nanosheets; Step 103: Disperse the MXene nanosheets described in step 102 in ethanol, add water and ammonia, stir vigorously at room temperature for 12-48 h, then add 3-aminopropyltriethoxysilane and stir for 12-48 h, collect by centrifugation, and dry under vacuum at 60 °C for 12 h to obtain MXene-NH2; Step 104: Disperse the MXene-NH2 obtained in step 103 in anhydrous methanol, add 2-formylphenylboronic acid and sodium cyanoborohydride, sonicate for 5-10 min, mechanically stir at room temperature for 12-48 h, collect the product by centrifugation, wash with anhydrous methanol, 5% sodium bicarbonate and distilled water respectively, and finally vacuum dry at 45°C for 12 h to obtain MXene@FPBA nanoparticles.

3. The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 2, characterized in that, In step 101, the mass of hydrofluoric acid is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of hydrofluoric acid is 30% to 45%. In step 102, the mass of tetrapropylammonium hydroxide solution is 5 to 10 times the mass of titanium aluminum carbide, and the mass percentage of tetrapropylammonium hydroxide in the tetrapropylammonium hydroxide solution is 25% to 50%.

4. The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 2, characterized in that, In step 103, the volume ratio of ethanol, water, and ammonia in the mixed solution is 16:1:(1~2), the mass ratio of MXene nanosheets to the volume of the mixed solution is (5~6):1, and the volume ratio of 3-aminopropyltriethoxysilane to the volume of the mixed solution is 1:(46~47). All these measurements are in mg and mL. In step 104, the mass ratio of MXene-NH2 to anhydrous methanol is (6~7):1, the mass of 2-formylphenylboronic acid is 150%~220% of the mass of MXene-NH2, and the mass of sodium cyanoborohydride is 250%~300% of the mass of MXene-NH2. All these measurements are in mg and mL.

5. The method for preparing the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 1, characterized in that, The modification methods in step two specifically include: Step 201: Dissolve lipoic acid, EDC and NHS in dimethyl sulfoxide to obtain a mixed solution. Stir the mixed solution at a temperature of 20℃~37℃ for 1h~3h to obtain an activated lipoic acid solution. Step 202: Mix the activated thioctic acid solution and recombinant collagen solution from step 201, and stir the mixture at 20℃~37℃ for 8h~12h. Dialyze the system after stirring and freeze-dry it to obtain modified recombinant collagen.

6. The method for preparing the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 5, characterized in that, The pH of the mixed solution in step 201 is 5-6, the mass of the lipoic acid is 15%-20% of the mass of dimethyl sulfoxide, and the molar ratio of lipoic acid, EDC and NHS is (1-1.5):4:

2.

7. The preparation method of the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 5, characterized in that, The recombinant collagen mentioned in step 202 is recombinant collagen CF-1552. The amount of lipoic acid in step 201 is 5 to 6 times the amount of recombinant collagen. The recombinant collagen solution is a solution prepared by dissolving recombinant collagen in dimethyl sulfoxide, and the mass percentage of recombinant collagen in the solution is 3% to 4%.

8. The method for preparing the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 1, characterized in that, In step five, the mass percentage of MXene@FPBA nanoparticles in system A is 0.2% to 0.5%.

9. The method for preparing the novel antibacterial nanocomposite hydrogel for repairing diabetic oral ulcers according to claim 1, characterized in that, In step six, the wavelength of the ultraviolet lamp is 365nm and the power is 10W.

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