Photocatalytic antibacterial hydrogel as well as preparation method and application thereof

Abstract

The invention provides photocatalytic antibacterial hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological antibacterial materials. The CuO2 / MoS2 photocatalytic composite material is prepared through a one-step in-situ reduction method, light energy can be converted into heat energy under short-time illumination, the antibacterial performance is improved, the technological process is simple, the cost is low, and resources are saved. The multifunctional CuO2 / MoS2-PDA-HA composite hydrogel is constructed on the basis of a synergistic antibacterial mechanism of CuO2 and MoS2 and in combination with anti-inflammatory and repair promoting functions of polydopamine (PDA) and hyaluronic acid (HA), can effectively promote wound healing while remarkably improving antibacterial activity, has good biocompatibility, avoids drug resistance risks caused by traditional antibiotics, and has good application prospects. The wide application prospect of wound repair is shown.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological antibacterial materials, and particularly relates to a photocatalytic antibacterial hydrogel as well as a preparation method and application thereof. BACKGROUND

[0002] In recent years, bacterial infections, especially infections with drug-resistant bacteria, are closely related to morbidity and mortality, and pose a serious threat to the medical system and public health. In particular, infection with Staphylococcus aureus can interfere with the natural wound healing process, prolong recovery time, and can spread to adjacent tissues, thereby increasing the range of tissue infection. Although the introduction of antibiotics has significantly reduced the incidence of bacterial infections, the overuse and misuse of these drugs have led to an increase in antibiotic-resistant bacteria. Due to the long development cycle of new antibiotics and the rapid evolution of superbugs, it is urgent to develop effective antibacterial strategies to combat drug-resistant bacteria.

[0003] At present, the rapid development of nanotechnology based on nanomaterials provides a brand-new alternative solution to fight bacterial infections. Compared with traditional antibiotics, the unique nature of nanomaterials is that they have higher surface activity, the ability to penetrate the bacterial cell wall, and the ability to be designed for specific bacteria. Among them, two-dimensional nanomaterials (TMDs) have excellent physical, chemical and electronic properties, and exhibit a wide range of applications in supercapacitors, photocatalysis, solar cells, sensors and electronics, etc. In recent years, the high anticancer and antibacterial properties of TMDs have attracted a lot of attention in the biomedical field. The larger specific surface area and the characteristics of easy surface modification enable two-dimensional nanomaterials to better adhere to the bacterial membrane. At the same time, antibacterial agents based on two-dimensional nanomaterials can be applied at low doses, which helps to reduce certain side effects and overcome the problem of drug resistance. Among the currently reported TMDs, molybdenum disulfide (MoS2) has significant photothermal properties in the near-infrared spectrum, as well as high absorption rate, wide surface area and photodynamic properties, which enable it to have great application potential in the biomedical field, such as biological imaging, detection sensors, cancer treatment, drug delivery and antibacterial therapy, etc. Despite these excellent properties, the application of pure-phase MoS2 in the biomedical field still has some limitations if not properly functionalized. In addition, in the application of bactericidal in vivo, high-temperature therapy alone is often insufficient. Although higher temperatures are necessary for effective bacterial killing, they can cause damage to adjacent healthy cells and tissues. Therefore, mild temperatures have become an important antibacterial strategy, but they are insufficient in achieving the best bactericidal effect.

[0004] Therefore, how to provide a MoS2-based photothermal / photodynamic synergistic antibacterial system has become a technical problem to be solved in the field. SUMMARY

[0005] The application aims to provide a photocatalytic antibacterial hydrogel, a preparation method and application thereof.

[0006] In order to achieve the above-mentioned application purposes, the application provides the following technical solutions. The application provides a preparation method of a photocatalytic antibacterial hydrogel, comprising the following steps. (1) mixing a soluble copper salt, water and a sodium hydroxide solution to perform a double decomposition reaction, then adding a hydrogen peroxide solution, and finally adding polyvinylpyrrolidone to obtain a mixed solution; (2) mixing the mixed solution obtained in the step (1) and MoS2 to obtain CuO2 / MoS2; (3) mixing CuO2 / MoS2 obtained in the step (2) and a solvent to obtain a CuO2 / MoS2 solution, then mixing the CuO2 / MoS2 solution, a phosphate buffer solution, dopamine hydrochloride and an ammonium persulfate solution, and finally adding hyaluronic acid to obtain the photocatalytic antibacterial hydrogel.

[0007] Preferably, the mass ratio of the soluble copper salt to the polyvinylpyrrolidone in the step (1) is (5-10):(0.2-0.5).

[0008] Preferably, the preparation method of MoS2 in the step (1) comprises: mixing thioacetamide, sodium molybdate dihydrate and water to perform a hydrothermal reaction to obtain MoS2.

[0009] Preferably, the holding temperature of the hydrothermal reaction is 100-200 DEG C, and the holding time of the hydrothermal reaction is 8-24 h.

[0010] Preferably, the mass ratio of the soluble copper salt in the step (1) to MoS2 in the step (2) is 1:(5-20).

[0011] Preferably, the mass percentage content of CuO2 in CuO2 / MoS2 in the step (2) is 1-10%.

[0012] Preferably, the concentration of the CuO2 / MoS2 solution in the step (3) is (0.1-1) mg / mL.

[0013] Preferably, the volume ratio of the CuO2 / MoS2 solution and the phosphate buffer solution in the step (3) is (100-2000) muL:(2-4) mL, the volume ratio of the CuO2 / MoS2 solution and the mass of the dopamine hydrochloride is (100-2000) muL:(0.12-0.36) g, the volume ratio of the CuO2 / MoS2 solution and the ammonium persulfate solution is (100-2000) muL:(125-375) muL, and the volume ratio of the CuO2 / MoS2 solution and the mass of the hyaluronic acid is (100-2000) muL:(0.2-1) g.

[0014] The application provides the photocatalytic antibacterial hydrogel prepared by the preparation method.

[0015] The application provides an application of the photocatalytic antibacterial hydrogel in preparing a wound dressing.

[0016] The application provides a preparation method of a photocatalytic antibacterial hydrogel, which comprises the following steps: (1) mixing a soluble copper salt, water and a sodium hydroxide solution, then performing a metathesis reaction, finally adding a hydrogen peroxide solution and polyvinylpyrrolidone to obtain a mixed solution; (2) mixing the mixed solution obtained in the step (1) and MoS2 to obtain CuO2 / MoS2; (3) mixing the CuO2 / MoS2 obtained in the step (2) and a solvent to obtain a CuO2 / MoS2 solution, then mixing the CuO2 / MoS2 solution, a phosphate buffer solution, dopamine hydrochloride and an ammonium persulfate solution, and finally adding hyaluronic acid to obtain the photocatalytic antibacterial hydrogel. The CuO2 / MoS2 photocatalytic composite material is prepared by one-step in-situ reduction, can convert light energy into heat energy under short-time light irradiation, improves the antibacterial performance, has a simple process flow, is low in cost and saves resources. Based on the synergistic antibacterial mechanism of CuO2 and MoS2, the multifunctional CuO2 / MoS2-PDA-HA composite hydrogel is constructed by combining the anti-inflammatory and repair-promoting functions of polydopamine (PDA) and hyaluronic acid (HA), can significantly improve the antibacterial activity, effectively promotes wound healing, has good biocompatibility, avoids the drug resistance risk caused by traditional antibiotics, and has a wide application prospect in wound repair.

[0017] The preparation method is simple, the material precursors are environmentally friendly and easy to obtain, and the cost is low; the photocatalytic antibacterial hydrogel has excellent antibacterial property, anti-inflammatory performance and wound repair-promoting performance, and can realize efficient antibacterial and wound repair under infrared light irradiation. The application expands the photothermal technology to the field of biological wound repair, greatly promotes wound healing, and has great economic value.

[0018] The results of the embodiments show that, relative to the blank control group, MoS2 / PDA-HA+NIR and CuO2 / PDA-HA+NIR, the photocatalytic antibacterial hydrogel provided by the application has higher sterilization performance on Staphylococcus aureus and Escherichia coli under near-infrared light, and has better biocompatibility, anti-inflammatory performance and performance of promoting wound repair. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 XRD patterns of the photocatalytic antibacterial hydrogel provided for Examples 1-3, CuO2 provided for Comparative Example 3 and MoS2 provided for Comparative Example 4; Figure 2 Fourier infrared spectra of the photocatalytic antibacterial hydrogel provided for Examples 1-3, CuO2 provided for Comparative Example 3 and MoS2 provided for Comparative Example 4; Figure 3 Adhesion of the photocatalytic antibacterial hydrogel provided for Example 1 to different materials; Figure 4 Antibacterial real object diagram of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on Staphylococcus aureus and Escherichia coli; Figure 5 Comparison diagram of antibacterial rate of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on Staphylococcus aureus and Escherichia coli; Figure 6 Wound healing effect real object diagram of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on mice; Figure 7 Comparison diagram of wound healing rate of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on mice; Figure 8 Comparison diagram of biocompatibility of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on mice wounds; Figure 9 Comparison diagram of anti-inflammatory effect of the hydrogel provided for Examples 1 and Comparative Examples 1-2 on mice wounds. DETAILED DESCRIPTION

[0020] The application provides a preparation method of a photocatalytic antibacterial hydrogel, comprising the following steps: (1) mixing a soluble copper salt, water and a sodium hydroxide solution, then performing a double decomposition reaction, then adding a hydrogen peroxide solution, and finally adding polyvinylpyrrolidone to obtain a mixed solution; (2) mixing the mixed solution obtained in the step (1) and MoS2 to obtain CuO2 / MoS2; (3) mixing the CuO2 / MoS2 obtained in the step (2) and a solvent to obtain a CuO2 / MoS2 solution, then mixing the CuO2 / MoS2 solution, a phosphate buffer solution, a dopamine hydrochloride solution and an ammonium persulfate solution, and finally adding hyaluronic acid to obtain the photocatalytic antibacterial hydrogel.

[0021] In the present application, the raw materials used in the present application are all commercially available products well known to those skilled in the art, unless otherwise specified.

[0022] In the present application, the soluble copper salt, water and sodium hydroxide solution are mixed to carry out a double decomposition reaction, then hydrogen peroxide solution is added, and finally polyvinylpyrrolidone is added to obtain a mixed solution.

[0023] In the present application, the soluble copper salt is preferably copper chloride dihydrate, and the water is preferably deionized water or ultrapure water. The present application does not have special limitations on the specific amount of the soluble copper salt and water, which can be determined according to the technical knowledge of those skilled in the art, as long as the soluble copper salt can be completely dissolved in water.

[0024] The present application does not have special limitations on the concentration and amount of the sodium hydroxide solution, which can be determined according to the technical knowledge of those skilled in the art, as long as the copper ions in the soluble copper salt can be completely precipitated. In the present application, the sodium hydroxide solution is preferably added dropwise. As an embodiment of the present application, the amount of the sodium hydroxide solution is preferably higher than the theoretical amount required for the complete precipitation of copper ions, i.e., an excess amount of sodium hydroxide solution is added. In the present application, the soluble copper salt reacts with the sodium hydroxide solution to form a double decomposition reaction, thereby converting the copper ions into blue copper hydroxide precipitate, which facilitates subsequent conversion. By adding the sodium hydroxide solution dropwise, the amount of the sodium hydroxide solution can be effectively controlled.

[0025] In the present application, the mass concentration of the hydrogen peroxide solution is preferably 20-50%, more preferably 30-40%. The present application does not have special limitations on the amount of the hydrogen peroxide solution, which can be determined according to the technical knowledge of those skilled in the art, as long as the copper hydroxide precipitate can be completely dissolved. In the present application, the addition of the hydrogen peroxide solution can react with the copper hydroxide to form a complex reaction, in which the hydrogen peroxide is not decomposed and the valence state of copper does not change, forming a blue solution.

[0026] In the present application, the mass ratio of the soluble copper salt to polyvinylpyrrolidone is preferably (5-10):(0.2-0.5). As an embodiment of the present application, the mass ratio of the soluble copper salt to polyvinylpyrrolidone can be (6-9):(0.3-0.4), or (7-8):(0.3-0.4). In the present application, the addition of polyvinylpyrrolidone can act as a stabilizer to form well-dispersed CuO2 particles.

[0027] In the present application, the polyvinylpyrrolidone is preferably dissolved by stirring. The present application does not have a special limitation on the stirring rate and stirring time of the stirring dissolution, and the stirring dissolution can be performed until the polyvinylpyrrolidone is completely dissolved. As an embodiment of the present application, the stirring dissolution can be performed for 30 minutes.

[0028] The present application promotes the formation of CuO2 particles by first allowing CuCl2 and NaOH to react to generate Cu(OH)2 precipitate, and then adding H2O2, and is a continuous process composed of a double decomposition reaction (to generate an intermediate) and a coordination oxidation-reduction reaction (to generate a final product). If the order is confused, the reaction can not occur or the yield is extremely low, and the specific reactions are as follows: CuCl2+2NaOH→Cu(OH)2↓+2NaCl; Cu(OH)2+H2O2→CuO2↓+2H2O; Total reaction: CuCl2+2NaOH+H2O2→CuO2↓+2NaCl+2H2O.

[0029] After obtaining the mixed solution, the present application mixes the mixed solution and MoS2 to obtain CuO2 / MoS2.

[0030] In the present application, the preparation method of the MoS2 preferably comprises: mixing thioacetamide, sodium molybdate dihydrate and water, and then performing a hydrothermal reaction to obtain MoS2.

[0031] In the present application, the water is preferably deionized water. In the present application, the mass ratio of the thioacetamide and sodium molybdate dihydrate is preferably (0.1-1):1; the mass of the thioacetamide and the volume of the water are preferably (0.1-1) g:(30-35) mL. The present application does not have special limitations on the amount of water, which can be determined according to the technical knowledge of those skilled in the art, as long as the raw materials can be completely dissolved. As an embodiment of the present application, the mass ratio of the thioacetamide and sodium molybdate dihydrate can be 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1 or 1:1; the mass of the thioacetamide and the volume of the water can be 0.1 g:(30-35) mL, 0.2 g:(30-35) mL, 0.3 g:(30-35) mL, 0.4 g:(30-35) mL, 0.5 g:(30-35) mL, 0.6 g:(30-35) mL, 0.7 g:(30-35) mL, 0.8 g:(30-35) mL, 0.9 g:(30-35) mL or 1 g:(30-35) mL. By controlling the amount of thioacetamide and sodium molybdate dihydrate, the present application can make them react to form MoS2 and improve the reaction efficiency of the raw materials.

[0032] In the present application, the mixing method of the thioacetamide, sodium molybdate and water is preferably magnetic stirring. The present application does not have special limitations on the stirring rate and stirring time of the magnetic stirring, which can be determined according to the technical knowledge of those skilled in the art, as long as they can be uniformly mixed.

[0033] In the present application, the hydrothermal reaction is preferably carried out in a hydrothermal reaction kettle. The present application does not have special limitations on the specific model and source of the hydrothermal reaction kettle, which can be a commercially available hydrothermal reaction kettle known to those skilled in the art.

[0034] In the present application, the holding temperature of the hydrothermal reaction is preferably 100-200℃; the holding time of the hydrothermal reaction is preferably 8-24 h. As an embodiment of the present application, the holding temperature of the hydrothermal reaction can be 100℃, 110℃, 120℃, 130℃, 140℃, 150℃, 160℃, 170℃, 180℃, 190℃ or 200℃; the holding time of the hydrothermal reaction can be 8 h, 10 h, 12 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h or 24 h. By controlling the parameters of the hydrothermal reaction, the present application can ensure that the thioacetamide and sodium molybdate react to form MoS2.

[0035] After the hydrothermal reaction, the application preferably further comprises sequentially washing and drying the product of the hydrothermal reaction. In the application, the washing is preferably sequentially washing with ultrapure water and anhydrous ethanol. The application does not have special limitations on the specific operation of the ultrapure water and anhydrous ethanol washing, which can be determined according to the technical common sense of those skilled in the art, and the impurities can be removed. In the application, the drying is preferably performed in a vacuum oven. The application does not have special limitations on the temperature and time of the drying, which can be determined according to the technical common sense of those skilled in the art, and the drying can be performed until the constant weight. As an embodiment of the application, the drying time can be 5-15h, and can also be 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h or 14h. Through washing and drying, the application can remove impurities in the product and obtain high-purity MoS2.

[0036] In the application, the mass ratio of the soluble copper salt and MoS2 is preferably 1: (5-20). As an embodiment of the application, the mass ratio of the soluble copper salt and MoS2 can be 1:5, 1:6, 1:7, 1:7.45, 1:8, 1:9, 1:10, 1:10.65, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:18.13, 1:19 or 1:20. By controlling the mass ratio of the soluble copper salt and MoS2, the application is conducive to controlling the amount ratio of CuO2 and MoS2 in CuO2 / MoS2.

[0037] In the application, the mixing method of the mixed solution and MoS2 is preferably stirring mixing. The application does not have special limitations on the stirring rate and stirring time of the stirring mixing, which can be determined according to the technical common sense of those skilled in the art, and the mixing can be uniform. As an embodiment of the application, the mixing time can be 30min.

[0038] The application preferably further comprises sequentially centrifuging, washing and drying the mixed product. The application does not have special limitations on the specific operation of the centrifuging, washing and drying, which can be determined according to the technical common sense of those skilled in the art, and the impurities can be completely removed. As an embodiment of the application, the drying can be performed in a vacuum oven; and the drying time can be 10-26h.

[0039] In the present application, the mass percentage of CuO2 in the CuO2 / MoS2 is preferably 1-10%. As an embodiment of the present application, the mass percentage of CuO2 in the CuO2 / MoS2 can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%. In the CuO2 / MoS2 provided by the present application, nanoscale copper peroxide (CuO2) as a metal peroxide is a promising chemical dynamic therapy (CDT) agent. When exposed to weakly acidic conditions (such as a chronic diabetic wound microenvironment pH of 5.5), CuO2 can decompose into Cu 2+ and H2O2, generating hydroxyl radicals (·OH). A large number of hydroxyl radicals can cause great damage to cells, such as DNA breakage, protein carbonylation and lipid peroxidation, and ultimately cause cell death. In addition, Cu 2+ can simulate hypoxia at the wound site, helping to stabilize the expression of hypoxia-inducible factor (HIF-1) and downstream target genes, including vascular endothelial growth factor (VEGF), thereby enhancing angiogenesis and promoting wound healing. This heterogeneous composite material can significantly enhance the antibacterial effect of the material through the synergistic effect of PTT (photothermal therapy) and CDT (chemical dynamic therapy). After being combined with MoS2, the photocatalytic antibacterial hydrogel has greatly improved antibacterial performance through the combined application of various antibacterial treatment methods.

[0040] After obtaining CuO2 / MoS2, the present application mixes the CuO2 / MoS2 and a solvent to obtain a CuO2 / MoS2 solution, then mixes the CuO2 / MoS2 solution, a phosphate buffer solution, dopamine hydrochloride and an ammonium persulfate solution, and finally adds hyaluronic acid to obtain a photocatalytic antibacterial hydrogel (CuO2 / MoS2 / PDA-HA composite hydrogel).

[0041] In the present application, the solvent is preferably methanol; the concentration of the CuO2 / MoS2 solution is preferably (0.1-1) mg / mL. As an embodiment of the present application, the concentration of the CuO2 / MoS2 solution is preferably 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL or 1 mg / mL.

[0042] In the present application, the volume ratio of the CuO2 / MoS2 solution and the phosphate buffer solution is preferably (100-2000) μL:(2-4) mL; the volume ratio of the CuO2 / MoS2 solution and the mass of the dopamine hydrochloride is preferably (100-2000) μL:(0.12-0.36) g; and the volume ratio of the CuO2 / MoS2 solution and the ammonium persulfate solution is preferably (100-2000) μL:(125-375) μL. As an embodiment of the present application, the volume ratio of the CuO2 / MoS2 solution and the phosphate buffer solution can be 100 μL:2 mL, 500 μL:2 mL, 1000 μL:2 mL, 1500 μL:2 mL, 2000 μL:2 mL, 100 μL:3 mL, 500 μL:3 mL, 1000 μL:3 mL, 1500 μL:3 mL, 2000 μL:3 mL, 100 μL:4 mL, 500 μL:4 mL, 1000 μL:4 mL, 1500 μL:4 mL, or 2000 μL:4 mL; the volume ratio of the CuO2 / MoS2 solution and the mass of the dopamine hydrochloride can be 100 μL:0.12 g, 500 μL:0.12 g, 1000 μL:0.12 g, 1500 μL:0.12 g, 2000 μL:0.12 g, 100 μL:0.24 g, 500 μL:0.24 g, 1000 μL:0.24 g, 1500 μL:0.24 g, 2000 μL:0.24 g, 100 μL:0.36 g, 500 μL:0.36 g, 1000 μL:0.36 g, 1500 μL:0.36 g, or 2000 μL:0.36 g; and the volume ratio of the CuO2 / MoS2 solution and the ammonium persulfate solution can be 100 μL:125 μL, 500 μL:125 μL, 1000 μL:125 μL, 1500 μL:125 μL, 2000 μL:125 μL, 100 μL:250 μL, 500 μL:250 μL, 1000 μL:250 μL, 1500 μL:250 μL, 2000 μL:250 μL, 100 μL:375 μL, 500 μL:375 μL, 1000 μL:375 μL, 1500 μL:375 μL, or 2000 μL:375 μL.

[0043] The present application does not have special limitations on the specific operation of mixing the CuO2 / MoS2 solution, the phosphate buffer solution, the dopamine hydrochloride, and the ammonium persulfate solution, and the mixing can be performed uniformly. As an embodiment of the present application, the mixing of the CuO2 / MoS2 solution, the phosphate buffer solution, the dopamine hydrochloride, and the ammonium persulfate solution can be performed by adding the phosphate buffer solution, the dopamine hydrochloride, and the ammonium persulfate solution to the CuO2 / MoS2 solution and then standing for 5-20 min.

[0044] In the present application, the ratio of the volume of the CuO2 / MoS2 solution to the mass of the hyaluronic acid is preferably (100-2000) μL:(0.2-1) g. As an embodiment of the present application, the ratio of the volume of the CuO2 / MoS2 solution to the mass of the hyaluronic acid can be 100 μL:0.2 g, 500 μL:0.2 g, 1000 μL:0.2 g, 1500 μL:0.2 g, 2000 μL:0.2 g, 100 μL:0.3 g, 500 μL:0.3 g, 1000 μL:0.3 g, 1500 μL:0.3 g, 2000 μL:0.3 g, 100 μL:0.4 g, 500 μL:0.4 g, 1000 μL:0.4 g, 1500 μL:0.4 g, 2000 μL:0.4 g, 100 μL:0.5 g, 500 μL:0.5 g, 1000 μL:0.5 g, 1500 μL:0.5 g, 2000 μL:0.5 g, 100 μL:0.6 g, 500 μL:0.6 g, 1000 μL:0.6 g, 1500 μL:0.6 g, 2000 μL:0.6 g, 100 μL:0.7 g, 500 μL:0.7 g, 1000 μL:0.7 g, 1500 μL:0.7 g, 2000 μL:0.7 g, 100 μL:0.8 g, 500 μL:0.8 g, 1000 μL:0.8 g, 1500 μL:0.8 g, 2000 μL:0.8 g, 100 μL:0.9 g, 500 μL:0.9 g, 1000 μL:0.9 g, 1500 μL:0.9 g, 2000 μL:0.9 g, 100 μL:1 g, 500 μL:1 g, 1000 μL:1 g, 1500 μL:1 g, or 2000 μL:1 g.

[0045] In the present application, the adding method of the hyaluronic acid is preferably stirring and mixing. The present application does not have special limitations on the specific operation of the stirring and mixing, and the hyaluronic acid can be completely dissolved.

[0046] The CuO2 / MoS2 photocatalytic composite material is prepared by one-step in-situ reduction method, which can convert light energy into heat energy under short time light irradiation, improve the antibacterial performance, has simple process flow, low cost, and saves resources. Based on the synergistic antibacterial mechanism of CuO2 and MoS2, combined with the anti-inflammatory and repair function of polydopamine (PDA) and hyaluronic acid (HA), a multifunctional CuO2 / MoS2-PDA-HA composite hydrogel is constructed, which can significantly improve the antibacterial activity, effectively promote wound healing, has good biocompatibility, avoids the drug resistance risk caused by traditional antibiotics, and has broad application prospect in wound repair.

[0047] The preparation method is simple, the material precursor is environmentally friendly and easy to obtain, and the cost is low; the photocatalytic antibacterial hydrogel prepared by the application has excellent antibacterial property, anti-inflammatory property and wound repair promoting property, and can realize efficient antibacterial and wound repair under infrared light radiation. The application expands the photothermal technology to the field of biological wound repair, greatly improves the wound healing, and has great economic value.

[0048] The application provides the photocatalytic antibacterial hydrogel prepared by the preparation method.

[0049] In the application, the photocatalytic antibacterial hydrogel is a CuO2 / MoS2 / PDA-HA composite hydrogel.

[0050] The photocatalytic antibacterial hydrogel provided by the application uses CuO2 / MoS2 as a photocatalyst and has high photocatalytic antibacterial performance, then uses hyaluronic acid as a hydrogel base to promote wound healing, and finally forms a CuO2 / MoS2-PDA-HA photocatalytic antibacterial hydrogel with good antibacterial and wound healing promoting performance.

[0051] The application also provides application of the photocatalytic antibacterial hydrogel in preparation of a wound dressing.

[0052] The application is not specially limited to the specific preparation method of the photocatalytic antibacterial hydrogel into a wound dressing, and a method for preparing a wound dressing by using a hydrogel known to those skilled in the art can be used.

[0053] The wound dressing prepared from the photocatalytic antibacterial hydrogel can be used for photothermal antibacterial and wound repair promotion.

[0054] The technical solutions in the application will be clearly and completely described below by combining with the embodiments in the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0055] Embodiment 1 A preparation method of a photocatalytic antibacterial hydrogel includes the following steps: (1) mixing copper chloride dihydrate and 50 mL ultrapure water, adding sodium hydroxide solution dropwise until no blue precipitate is generated, then adding a hydrogen peroxide solution with a mass concentration of 30%, and finally adding 0.3 g polyvinylpyrrolidone and stirring and dissolving for 30 min to obtain a mixed solution; (2) the mixed solution obtained in step (1) and MoS2 are stirred and mixed for 30 min, and then centrifugation, washing and drying in a vacuum oven for 24 h are sequentially performed to obtain CuO2 / MoS2; the mass ratio of copper chloride dihydrate in step (1) to MoS2 in step (2) is 1:10.65; the mass percentage of CuO2 in the CuO2 / MoS2 is 5%; (3) the CuO2 / MoS2 obtained in step (2) and methanol are mixed to obtain a CuO2 / MoS2 solution with a concentration of 1 mg / mL, then phosphate buffer solution, dopamine hydrochloride and ammonium persulfate solution are added to the CuO2 / MoS2 solution and left to stand for 10 min, finally hyaluronic acid is added and stirred until completely dissolved to obtain a photocatalytic antibacterial hydrogel; the ratio of the volume of the CuO2 / MoS2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution is 500 μL:2 mL:0.12 g:125 μL; the ratio of the volume of the CuO2 / MoS2 solution to the mass of hyaluronic acid is 500 μL:0.2 g; In step (2), the MoS2 is prepared by mixing thioacetamide, sodium molybdate dihydrate and deionized water, then performing magnetic stirring, then performing hydrothermal reaction at a temperature of 150 ℃ in a hydrothermal reaction kettle for 24 h, then sequentially washing with ultrapure water and anhydrous ethanol, and finally drying in a vacuum oven for 12 h to obtain MoS2; the mass ratio of thioacetamide to sodium molybdate is 0.625:1, and the mass of thioacetamide to the volume of deionized water is 0.15 g:35 mL.

[0056] Example 2 A method for preparing a photocatalytic antibacterial hydrogel comprises the following steps: (1) copper chloride dihydrate and 50 mL of ultrapure water are mixed, sodium hydroxide solution is added dropwise until no blue precipitate is generated, then hydrogen peroxide solution with a mass concentration of 30% is added, finally 0.3 g of polyvinylpyrrolidone is added and stirred and dissolved for 30 min to obtain a mixed solution; (2) the mixed solution obtained in step (1) and MoS2 are stirred and mixed for 30 min, and then centrifugation, washing and drying in a vacuum oven for 24 h are sequentially performed to obtain CuO2 / MoS2; the mass ratio of copper chloride dihydrate in step (1) to MoS2 in step (2) is 1:18.13; the mass percentage of CuO2 in the CuO2 / MoS2 is 3%; (3) mixing CuO2 / MoS2 obtained in step (2) and methanol to obtain a CuO2 / MoS2 solution with a concentration of 1 mg / mL, then adding a phosphate buffer solution, dopamine hydrochloride and an ammonium persulfate solution into the CuO2 / MoS2 solution and standing for 10 min, finally adding hyaluronic acid and stirring until completely dissolved to obtain a photocatalytic antibacterial hydrogel; the ratio of the volume of the CuO2 / MoS2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution is 1000 μL:4 mL:0.24 g:250 μL; the ratio of the volume of the CuO2 / MoS2 solution and the mass of hyaluronic acid is 1000 μL:0.4 g; The preparation method of MoS2 in step (2) is the same as that in Example 1.

[0057] Example 3 A preparation method of a photocatalytic antibacterial hydrogel is the following steps: (1) mixing cupric chloride dihydrate and 50 mL of ultrapure water, adding sodium hydroxide solution dropwise until no blue precipitate is generated, then adding a hydrogen peroxide solution with a mass concentration of 30%, and finally adding 0.3 g of polyvinylpyrrolidone and stirring to dissolve for 30 min to obtain a mixed solution; (2) stirring and mixing the mixed solution obtained in step (1) and MoS2 for 30 min, and then sequentially performing centrifugation, washing and drying in a vacuum oven for 24 h to obtain CuO2 / MoS2; the mass ratio of cupric chloride dihydrate in step (1) to MoS2 in step (2) is 1:7.45; the mass percentage content of CuO2 in the CuO2 / MoS2 is 7%; (3) mixing CuO2 / MoS2 obtained in step (2) and methanol to obtain a CuO2 / MoS2 solution with a concentration of 1 mg / mL, then adding a phosphate buffer solution, dopamine hydrochloride and an ammonium persulfate solution into the CuO2 / MoS2 solution and standing for 10 min, finally adding hyaluronic acid and stirring until completely dissolved to obtain a photocatalytic antibacterial hydrogel; the ratio of the volume of the CuO2 / MoS2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution is 1500 μL:6 mL:0.36 g:375 μL; the ratio of the volume of the CuO2 / MoS2 solution and the mass of hyaluronic acid is 1500 μL:0.6 g; The preparation method of MoS2 in step (2) is the same as that in Example 1.

[0058] Example 4 A preparation method of a photocatalytic antibacterial hydrogel is the following steps: (1) mixed copper chloride dihydrate and 50 mL ultrapure water, added sodium hydroxide solution dropwise until no blue precipitate was generated, then added hydrogen peroxide solution with a mass concentration of 30%, finally added 0.3 g polyvinylpyrrolidone and stirred for 30 min to dissolve, to obtain a mixed solution; (2) mixed the mixed solution obtained in step (1) and MoS2 and stirred for 30 min, then sequentially performed centrifugation, washing and drying in a vacuum oven for 24 h to obtain CuO2 / MoS2; the mass ratio of copper chloride dihydrate in step (1) to MoS2 in step (2) was 1:8.78; the mass percentage of CuO2 in the CuO2 / MoS2 was 6%; (3) mixed the CuO2 / MoS2 obtained in step (2) and methanol to obtain a CuO2 / MoS2 solution with a concentration of 1 mg / mL, then added phosphate buffer solution, dopamine hydrochloride and ammonium persulfate solution into the CuO2 / MoS2 solution and stood for 10 min, finally added hyaluronic acid and stirred until completely dissolved to obtain a photocatalytic antibacterial hydrogel; the ratio of the volume of the CuO2 / MoS2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution was 500 μL:2 mL:0.12 g:125 μL; the ratio of the volume of the CuO2 / MoS2 solution and the mass of hyaluronic acid was 500 μL:0.2 g. The preparation method of MoS2 in step (2) was the same as that in Example 1.

[0059] Comparative Example 1 A preparation method of a hydrogel was as follows: (1) mixed copper chloride dihydrate and 50 mL ultrapure water, added sodium hydroxide solution dropwise until no blue precipitate was generated, then added hydrogen peroxide solution with a mass concentration of 30%, finally added 0.3 g polyvinylpyrrolidone and stirred for 30 min to dissolve, to obtain a mixed solution; (2) sequentially performed centrifugation, washing and drying in a vacuum oven for 24 h to obtain CuO2 from the mixed solution obtained in step (1); (3) mixed the CuO2 obtained in step (2) and methanol to obtain a CuO2 solution with a concentration of 1 mg / mL, then added phosphate buffer solution, dopamine hydrochloride and ammonium persulfate solution into the CuO2 solution and stood for 10 min, finally added hyaluronic acid and stirred until completely dissolved to obtain a hydrogel; the ratio of the volume of the CuO2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution was 500 μL:2 mL:0.12 g:125 μL; the ratio of the volume of the CuO2 / MoS2 solution and the mass of hyaluronic acid was 500 μL:0.2 g.

[0060] Comparative Example 2 A preparation method of a hydrogel is the following steps: (1) thioacetamide, sodium molybdate dihydrate and deionized water are mixed and subjected to magnetic stirring, then subjected to hydrothermal reaction at 150℃ in a hydrothermal reactor for 24h, then sequentially washed with ultrapure water and anhydrous ethanol, and finally dried in a vacuum oven for 12h to obtain MoS2; the mass ratio of thioacetamide to sodium molybdate is 0.625:1, and the mass of thioacetamide to the volume of deionized water is 0.15g:35mL; (2) MoS2 obtained in step (1) is mixed with methanol to obtain a MoS2 solution with a concentration of 1mg / mL, then phosphate buffer solution, dopamine hydrochloride and ammonium persulfate solution are added to the MoS2 solution and left to stand for 10min, finally hyaluronic acid is added and stirred until completely dissolved to obtain a photocatalytic antibacterial hydrogel; the ratio of the volume of the MoS2 solution, the volume of the phosphate buffer solution, the mass of dopamine hydrochloride and the volume of the ammonium persulfate solution is 500μL:2mL:0.12g:125μL; the ratio of the volume of the MoS2 solution to the mass of hyaluronic acid is 500μL:0.2g.

[0061] Comparative Example 3 A preparation method of CuO2 is the following steps: (1) copper chloride dihydrate and 50mL of ultrapure water are mixed, sodium hydroxide solution is added dropwise until no blue precipitate is generated, then hydrogen peroxide solution with a mass concentration of 30% is added, finally 0.3g of polyvinylpyrrolidone is added and stirred to dissolve for 30min to obtain a mixed solution; (2) the mixed solution obtained in step (1) is sequentially subjected to centrifugation, washing and drying in a vacuum oven for 24h to obtain CuO2.

[0062] Comparative Example 4 A preparation method of MoS2 is the following steps: thioacetamide, sodium molybdate dihydrate and deionized water are mixed and subjected to magnetic stirring, then subjected to hydrothermal reaction at 150℃ in a hydrothermal reactor for 24h, then sequentially washed with ultrapure water and anhydrous ethanol, and finally dried in a vacuum oven for 12h to obtain MoS2; the mass ratio of thioacetamide to sodium molybdate is 0.625:1, and the mass of thioacetamide to the volume of deionized water is 0.15g:35mL.

[0063] The photocatalytic antibacterial hydrogel provided by Examples 1~3, CuO2 provided by Comparative Example 3 and MoS2 provided by Comparative Example 4 are analyzed by X-ray diffractometer, and the obtained XRD patterns are as shown in Figure 1 .

[0064] The photocatalytic antibacterial hydrogels provided in Examples 1-3, CuO2 provided in Comparative Example 3, and MoS2 provided in Comparative Example 4 were analyzed using Fourier transform infrared spectroscopy. The obtained Fourier transform infrared spectra are shown below. Figure 2 As shown.

[0065] The adhesiveness of the photocatalytic antibacterial hydrogel provided in Example 1 was tested. A layer of the photocatalytic antibacterial hydrogel was coated on iron, glass, and plastic, respectively. The adhesiveness was then observed by touching the surface with a finger. The results are as follows: Figure 3 As shown. By Figure 3 It can be seen that the photocatalytic antibacterial hydrogel provided by the present invention has good adhesion to different materials.

[0066] Application Example 1 The antibacterial activity of the hydrogels provided in Example 1 and Comparative Examples 1-2 was tested using the following methods: (1) The prepared hydrogels were made into hydrogel blocks with a size of 1cm×1cm×0.8cm using a quantitative mold of 1cm×1cm×0.8cm; (2) The hydrogel blocks were placed in each well of a 48-well plate, and 300μl of Escherichia coli (E. coli) was immediately added to each hydrogel block. E. coli ) or Staphylococcus aureus ( S. aureus (3) After the irradiation treatment (the initial bacterial concentration was the same), each well was exposed to near-infrared (NIR) light at a wavelength of 980 nm for 7 min. At the same time, a control group (as a control to evaluate the basic growth of bacteria) and a dark group (to measure the inherent antibacterial properties of the hydrogel block without light enhancement) were set up. The control group used the same bacteria as above, without adding hydrogel block and without irradiation treatment. The dark group used the same hydrogel block and bacteria as above and stored in the dark environment (without irradiation treatment). (4) After the irradiation treatment (the control group and the dark group were kept in the dark for the same time), 20 μl of bacterial suspension was taken from each well and spread on an agar plate. The agar plate was cultured for 24 h under conditions suitable for bacterial growth. After 24 h, images of all agar plates were taken using a mobile phone camera.

[0067] Bacterial colonies formed on the plates were counted and compared, and the bactericidal rate was calculated using Formula I to evaluate the antibacterial effect. Antibacterial rate (%) = ((A1-A2) / A1)×100% Equation I In Formula I, when evaluating the antibacterial effect of the hydrogel, A1 is the number of colonies cultured in the control group and A2 is the number of colonies cultured in the dark group; when evaluating the effect of near-infrared light irradiation on antibacterial activity, A1 is the number of colonies cultured in the dark group and A2 is the number of colonies cultured in the experimental group.

[0068] The antibacterial results of the hydrogels provided by Example 1 and Comparative Examples 1-2 are shown in Table 1. Figure 4 As shown in Table 2, the antibacterial rates against S. aureus and E. coli are shown in Table 2. Figure 5 As shown in Table 3, Figure 4 and Figure 5 It can be seen that after near-infrared light treatment, the number of E. coli and S. aureus in the experimental group added with the photocatalytic antibacterial hydrogel provided by the application is significantly lower than that in the other three groups, indicating that the photocatalytic antibacterial hydrogel provided by the application has better antibacterial performance. When not treated with near-infrared light, the number of E. coli and S. aureus does not decrease significantly relative to the control group, indicating that the photocatalytic antibacterial hydrogel provided by the application can convert light energy into heat energy under short-time light irradiation, thereby improving the antibacterial performance.

[0069] Application Example 2 The in vivo potential of the hydrogels provided by Example 1 and Comparative Examples 1-2 in treating skin wound infection was tested, and the test method was as follows: (1) full-thickness wound injury (diameter = 1 cm) was made on 6-8-week-old ICR male mice, and then the wounds were infected with S. aureus at a concentration of 10 8 CFU / mL; (2) 36 h after infection, the mice were randomly divided into four groups (blank control group, MoS2 / PDA-HA+NIR, CuO2 / PDA-HA+NIR, and CuO2 / MoS2 / PDA-HA+NIR), with five mice in each group. The wounds of the blank control group were only covered with sterile gauze, and the wounds of the other groups were locally smeared with 50 μl of each hydrogel at a concentration of 20 μg / mL on the first day to the third day; (3) after smearing the hydrogel, the wounds were exposed to near-infrared light for 7 min on the first day to the third day, and all the treated wounds were covered with sterile gauze. Photographs were taken every 48 h to record the healing process within 8 days.

[0070] The actual photos of the wound healing effect of the hydrogels provided by Example 1 and Comparative Examples 1-2 on mice are shown in Table 3, the comparison chart of the wound healing rate is shown in Table 4, the comparison chart of the biocompatibility is shown in Table 5, and the comparison chart of the anti-inflammatory effect is shown in Table 6. Figure 6 Figure 7 Figure 8 Figure 9 Figures 6~9 It can be seen that the healing effect of the mice treated with the photocatalytic antibacterial hydrogel provided by the application is significantly higher than that of the other control groups, indicating that the photocatalytic antibacterial hydrogel provided by the application can promote the wound repair performance, and has better biocompatibility and anti-inflammatory effect.

[0071] ​​​​The above merely describes the preferred embodiments of the present application, and it should be pointed out that, for those skilled in the art, several improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A method for preparing a photocatalytic antibacterial hydrogel, comprising the following steps: (1) Mix soluble copper salt, water and sodium hydroxide solution and carry out double decomposition reaction, then add hydrogen peroxide solution, and finally add polyvinylpyrrolidone to obtain a mixed solution; (2) Mix the mixed solution obtained in step (1) with MoS2 to obtain CuO2 / MoS2; (3) Mix the CuO2 / MoS2 obtained in step (2) with a solvent to obtain a CuO2 / MoS2 solution. Then mix the CuO2 / MoS2 solution, phosphate buffer solution, dopamine hydrochloride and ammonium persulfate solution. Finally, add hyaluronic acid to obtain a photocatalytic antibacterial hydrogel.

2. The preparation method according to claim 1, characterized in that, In step (1), the mass ratio of the soluble copper salt to the polyvinylpyrrolidone is (5~10):(0.2~0.5).

3. The preparation method according to claim 1, characterized in that, The preparation method of MoS2 in step (1) includes: mixing thioacetamide, sodium molybdate dihydrate and water and then carrying out a hydrothermal reaction to obtain MoS2.

4. The preparation method according to claim 3, characterized in that, The holding temperature for the hydrothermal reaction is 100~200℃, and the holding time for the hydrothermal reaction is 8~24h.

5. The preparation method according to claim 1, characterized in that, The mass ratio of the soluble copper salt in step (1) to the MoS2 in step (2) is 1:(5~20).

6. The preparation method according to claim 1, characterized in that, In step (2), the mass percentage of CuO2 in CuO2 / MoS2 is 1~10%.

7. The preparation method according to claim 1, characterized in that, The concentration of the CuO2 / MoS2 solution in step (3) is (0.1~1) mg / mL.

8. The preparation method according to claim 1, characterized in that, In step (3), the volume ratio of CuO2 / MoS2 solution to phosphate buffer solution is (100~2000) μL: (2~4) mL, the volume ratio of CuO2 / MoS2 solution to dopamine hydrochloride mass is (100~2000) μL: (0.12~0.36) g, the volume ratio of CuO2 / MoS2 solution to ammonium persulfate solution is (100~2000) μL: (125~375) μL, and the volume ratio of CuO2 / MoS2 solution to hyaluronic acid mass is (100~2000) μL: (0.2~1) g.

9. The photocatalytic antibacterial hydrogel prepared by the preparation method according to any one of claims 1 to 8.

10. The application of the photocatalytic antibacterial hydrogel of claim 9 in the preparation of wound dressings.

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