A photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation and its application

Abstract

The present invention discloses a photocatalytic heterojunction material for co-producing hydrogen and degrading glucose and its application, belonging to the technical field of biomedicine. The photocatalytic heterojunction material is a two-dimensional nanosheet, including elemental bismuth, oxygen-deficient Bi2WO6 and hydrogen-doped TiO2. Bi2WO6 is prepared by a solvothermal reaction using Na2WO4·2H2O and Bi(NO3)3·5H2O; then Bi2WO6 / TiO2 is prepared by a hydrothermal reaction using tetrabutyl titanate and Bi2WO6; finally, the photocatalytic heterojunction is obtained by vacuum calcination of sodium borohydride and Bi2WO6 / TiO2. The photocatalytic heterojunction constructed by the present invention broadens the spectral response range and improves the transfer utilization rate of photo-generated carriers and the photon absorption utilization rate, enabling the material to photocatalytically decompose water to produce hydrogen using glucose as a sacrificial agent in the visible light range. The functional hydrogel material prepared from this material treats DFU by co-regulating the DFU wound microenvironment.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a photocatalytic heterojunction material for synergistically producing hydrogen and degrading glucose and an application thereof. Background Art

[0002] At present, the number of diabetic patients worldwide is very large, about 529 million people, and it is expected that the number of patients will reach 1.31 billion by 2050. Diabetic foot ulcer (DFU) is one of the most common and serious complications of diabetes. The inflammation and oxidative stress response induced by hyperglycemia hinder wound healing, making DFU difficult to heal. It is estimated that the lifetime incidence of diabetic foot is about 30%. DFU has a high disability and mortality rate and a low cure rate, which seriously affects the quality of life of patients. It is generally believed that the reason why DFU is difficult to heal mainly comes from its complex microenvironment. The high blood sugar environment of the patient's wound induces the overexpression of advanced glycation end products to produce excessive RONS, and excessive RONS has been shown to promote the expression of inflammatory cells, specifically preventing the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages, causing the DFU wound to face a series of problems such as high blood sugar, high ROS, high inflammation, hypoxia, and infection. In addition, due to poor blood circulation caused by vascular lesions in DFU patients, the most common intravenous antibiotic treatment is difficult to reach the lesions. Based on this, local topical drugs combined with dressing changes are favored by DFU patients for their convenience and economy. However, simple antibiotic treatment cannot directly reduce the inflammatory response caused by infection, and it will also delay wound healing. Moreover, due to the long course of the disease, patients often develop a certain degree of resistance to conventional hypoglycemic drugs and antibiotics, and frequent dressing changes are also prone to cause secondary damage to the wound surface. Only by reducing inflammation and clearing ROS while reducing blood sugar concentration at the wound surface and changing the DFU microenvironment can DFU be completely cured. Therefore, the development of new alternative drugs is imminent.

[0003] As a new type of medical gas, H2 has higher biosafety and tissue penetration ability than well-known gas signal molecules such as NO, CO, and H2S. H2 has been proven to have antioxidant, anti-inflammatory, and anti-apoptotic effects, can improve ischemia-reperfusion injury, promote angiogenesis, promote cell proliferation and migration, and induce collagen synthesis, thereby helping to accelerate wound healing. Currently, the existing methods of hydrogen delivery mainly include hydrogen inhalation, hydrogen-rich water drinking, and hydrogen-rich saline injection, but on the one hand, they are limited by the inconvenience of hydrogen storage and transportation, and on the other hand, due to the low solubility of hydrogen in water, it is difficult to ensure that sufficient hydrogen continues to penetrate into the wound tissue. Insufficient administration time makes it difficult to achieve the ideal therapeutic effect. Therefore, the development of a new drug delivery system that can continuously deliver hydrogen is crucial for the treatment of chronic wounds.

[0004] Photocatalytic in-situ water decomposition can achieve the purpose of continuously supplying H2 to the wound surface. In addition, to fundamentally solve the problem of DFU difficult to heal, regulating the microenvironment of high blood sugar in the wound surface cannot be ignored. Professor He Qianjun of the Hydrogen Science Center of Shanghai Jiaotong University proposed a new concept of photocatalytic "treating both the symptoms and the root causes" of diabetic foot. By opening hydrogen-doped titanium oxide nanorods (HTON) photocatalysts, visible light response in-situ hydrogen production and in-situ glucose deprivation prevented the glycation reaction and the expression of advanced glycation end product receptors, achieving the purpose of efficient synergistic treatment of diabetic foot. However, it is well known that single semiconductors have the problem of high recombination rate of photogenerated carriers, which limits their catalytic activity. To improve the therapeutic effect, it is necessary to improve the hydrogen production activity and stability. The construction of semiconductor heterojunctions is the most common method to improve the separation mobility of photogenerated carriers. The construction of heterojunctions needs to take into account the band structure and lattice matching of the two semiconductors to ensure that effective charge transfer can occur at the interface of the two photocatalysts. In addition, the biocompatibility of materials is also an important consideration for screening semiconductor materials and designing therapeutic platforms. Therefore, it is necessary to develop a heterojunction with a band structure and lattice matching that can not only improve the photocatalytic and hydrogen production effects but also have good biocompatibility for the treatment of diabetic foot ulcers. Summary of the invention

[0005] In view of the above-mentioned prior art, the purpose of the present invention is to provide a photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation and its application. The present invention prepares a photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation by solvothermal reaction and vacuum calcination, realizing the transformation of the material from nanoparticles to two-dimensional nanosheets. Hydrogen doping and the construction of heterostructures broaden the spectral response range and improve the transfer utilization rate and absorption utilization rate of photogenerated carriers, so that the material can produce hydrogen by photolysis of water with glucose as a sacrificial agent in the visible light range. The functionalized hydrogel material prepared with the material treats DFU by synergistically regulating the DFU wound microenvironment.

[0006] To achieve the above object, the present invention adopts the following technical solution:

[0007] In a first aspect of the present invention, a photocatalytic heterojunction material for synergistically producing hydrogen and degrading glucose is provided, wherein the photocatalytic heterojunction material comprises elemental bismuth, oxygen-deficient Bi2WO6, and hydrogen-doped TiO2;

[0008] The photocatalytic heterojunction material is prepared by the following method:

[0009] (1) Na2WO4·2H2O and Bi(NO3)3·5H2O are added to ethylene glycol and mixed to carry out a solvothermal reaction. After the reaction is completed, centrifugation, washing and drying are performed to obtain Bi2WO6;

[0010] (2) Tetrabutyl titanate, ethylene glycol and water are mixed, and the Bi2WO6 prepared in step (1) is added, and pure water is added after stirring to carry out a hydrothermal reaction. After the reaction is completed, centrifugation, washing and drying are performed to obtain Bi2WO6 / TiO2;

[0011] (3) Sodium borohydride and the Bi2WO6 / TiO2 prepared in step (2) are fully ground and mixed, and vacuum calcined to obtain Bi / VO-Bi2WO6 / H-TiO2, i.e., a photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation.

[0012] Preferably, in step (1), the molar ratio of Na2WO4·2H2O to Bi(NO3)3·5H2O is 1:2; the temperature of the solvent thermal reaction is 160°C and the time is 24 hours.

[0013] Preferably, in step (2), the ratio of the added amounts of tetrabutyl titanate, ethylene glycol and Bi2WO6 is 4 mL:4 mL:0.2 g; the stirring time is 30 min; the temperature of the hydrothermal reaction is 200°C and the time is 24 h.

[0014] Preferably, in step (3), the mass ratio of sodium borohydride to Bi2WO6 / TiO2 is 1:1; the heating rate of the vacuum calcination is 5°C / min, the temperature of the vacuum calcination is 450°C, and the time of the vacuum calcination is 2h.

[0015] The second aspect of the present invention provides the use of a photocatalytic heterojunction material in at least one of the following 1) to 3):

[0016] 1) Photocatalytic hydrogen production;

[0017] 2) Degradation of glucose or triethanolamine;

[0018] 3) Prepare medicines for diabetic foot ulcers.

[0019] A third aspect of the present invention provides a diabetic foot ulcer medicament, which has a photocatalytic heterojunction material as a main component.

[0020] Preferably, the diabetic foot ulcer drug is prepared by the following method:

[0021] (1) Dissolving hyaluronic acid and NaIO4 in deionized water to form a precursor solution, then stirring in the dark to react, adding ethylene glycol to terminate the reaction, dialysis purification, and freeze-drying to obtain HA-ALD;

[0022] (2) Dissolve hyaluronic acid in MES buffer, add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBT), add adipic acid dihydrazide (HA-ADH) after mixing, react at room temperature, dialyze the reaction product and freeze-dry to obtain HA-ADH;

[0023] (3) Dissolving the photocatalytic heterojunction material and HA-ALD in a PBS solution to form a precursor A; dissolving HA-ADH in a PBS solution to form a precursor B; and mixing the precursor A with the precursor B to obtain a diabetic foot ulcer drug.

[0024] Preferably, in step (1), the mass ratio of hyaluronic acid to NaIO4 is 1:1.

[0025] Preferably, in step (2), the ratio of the added amounts of hyaluronic acid, MES buffer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1-hydroxybenzotriazole and adipic acid dihydrazide is 1 g:100 mL:2 g:0.9 g:4.5 g.

[0026] Preferably, in step (3), in the precursor A, the concentration of Bi2WO6 / TiO2 is 1 mg / mL, and the content of HA-ALD is 3 wt%; in the precursor B, the content of HA-ADH is 3 wt%; and the pH of the PBS solution is 7.4.

[0027] Beneficial effects of the present invention:

[0028] (1) The present invention first prepares a Bi2WO6 / TiO2 heterojunction, and then performs hydrogen doping by calcination. Hydrogen doping enters TiO2 and simultaneously forms oxygen defects in Bi2WO6, and also reduces part of the bismuth in Bi2WO6, thereby forming a Bi / VO-Bi2WO6 / H-TiO2 heterojunction. The construction of hydrogen doping and heterostructure broadens the spectral response range and improves the utilization rate of photogenerated carriers, enabling the material to produce hydrogen by photolysis of water using glucose as a sacrificial agent in the visible light range.

[0029] (2) The present invention uses Bi-based semiconductors and TiO2 with high biosafety as semiconductor primitives, and designs and synthesizes Bi cluster-modified Vo-rich Bi2WO6 / H-TiO2 (Bi / VO-Bi2WO6 / H-TiO2) semiconductor heterojunction photocatalysts, which have a suitable Z-type energy band arrangement, and the two-dimensional layered structure provides more reactive sites, which continuously degrade glucose and produce hydrogen under visible light irradiation. The photocatalyst is uniformly encapsulated into the hydrogel by dispersing it into the precursor and then mixing it, further improving its biocompatibility. It is covered on the wound surface, and continuously deprives glucose under visible light irradiation. At the same time, hydrogen is generated and penetrates into the tissue, exerting hypoglycemic, anti-oxidant, and anti-inflammatory effects to coordinately improve the wound microenvironment, effectively alleviate chronic inflammation of DFU, and promote angiogenesis and tissue repair. Considering the complexity of the DFU wound microenvironment, this photocatalytic integrated synergistic treatment platform has great development and application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 : Structural characterization of Bi2WO6 nanoparticles, including (a) SEM electron micrograph of Bi2WO6 with a scale bar of 200 nm, (b) SEM electron micrograph of Bi2WO6 with a scale bar of 100 nm, (c) TEM electron micrograph of Bi2WO6, and (d) schematic diagram of the electron micrograph lattice of HRTEM of Bi2WO6;

[0031] Figure 2 : Schematic diagram of element mapping electron microscope of Bi2WO6 / TiO2, including (a) HAADF-STEM of Bi2WO6 / TiO2, (b) element fusion map of Bi2WO6 / TiO2, (c) distribution of titanium in Bi2WO6 / TiO2, (d) distribution of oxygen in Bi2WO6 / TiO2, (e) distribution of bismuth in Bi2WO6 / TiO2, (f) distribution of tungsten in Bi2WO6 / TiO2;

[0032] Figure 3 : Comparison of the morphologies of heterojunction materials before and after calcination, where (a) the SEM electron microscope image of Bi2WO6 / TiO2 with a scale bar of 200 nm, (b) the SEM electron microscope image of Bi2WO6 / TiO2 with a scale bar of 100 nm, (c) the SEM electron microscope image of Bi / VO-Bi2WO6 / H-TiO2 with a scale bar of 200 nm, and (d) the SEM electron microscope image of Bi / VO-Bi2WO6 / H-TiO2 with a scale bar of 100 nm;

[0033] Figure 4:Structural characterization of Bi / VO-Bi2WO6 / H-TiO2, including (a) TEM electron microscope image of Bi / VO-Bi2WO6 / H-TiO2, (b) TEM electron microscope image of the local area within the red circle in Figure a, (c) HRTEM electron microscope lattice diagram of Bi / VO-Bi2WO6 / H-TiO2, (d) HAADF-STEM in the element mapping electron microscope diagram of Bi / VO-Bi2WO6 / H-TiO2, (e) element fusion electron microscope image of Bi / VO-Bi2WO6 / H-TiO2, (f) Ti element distribution in Bi / VO-Bi2WO6 / H-TiO2, (g) O element distribution in Bi / VO-Bi2WO6 / H-TiO2, (h) Bi element distribution in Bi / VO-Bi2WO6 / H-TiO2, (i) W element distribution in Bi / VO-Bi2WO6 / H-TiO2, (j) TiO2, XRD diffraction patterns of Bi2WO6, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2;

[0034] Figure 5 : XPS spectra of photocatalytic materials, (a) High resolution Ti 2p XPS spectra of TiO2, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2 samples, (b) High resolution O 1s XPS spectra of TiO2, Bi2WO6, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2 samples, (c) High resolution Bi 4f XPS spectra of Bi2WO6, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2 samples, (d) High resolution W 4f XPS spectra of Bi2WO6, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2 samples;

[0035] Figure 6 : Comparison of the morphology of TiO2 before and after calcination, (a) TEM electron microscope image of TiO2, (b) HRTEM electron microscope image of TiO2, (c) TEM electron microscope image of H-TiO2, (d) HRTEM electron microscope image of H-TiO2;

[0036] Figure 7 : Schematic diagram of element mapping electron microscope of H-TiO2, including (a) HAADF-STEM of H-TiO2, (b) element fusion map of H-TiO2, (c) distribution of titanium in H-TiO2, (d) distribution of oxygen in H-TiO2;

[0037] Figure 8 : XRD diffraction patterns of TiO2 and H-TiO2;

[0038] Fig. 9 : Photocatalytic hydrogen production and glucose degradation activities, including (a) photocatalytic hydrogen production activities of Bi2WO6, TiO2, Bi2WO6 / TiO2, VO-Bi2WO6, H-TiO2 and Bi / VO-Bi2WO6 / H-TiO2 in triethanolamine solution under full light, (b) photocatalytic hydrogen production activity and stability of Bi / VO-Bi2WO6 / H-TiO2 under visible light in triethanolamine solution and glucose solution, respectively, (c) glucose-lowering activity of Bi / VO-Bi2WO6 / H-TiO2 in 10, 15, 20 mmol / L glucose solutions;

[0039] Fig.10 : Energy band structure and carrier migration of photocatalysts, including (a) UV-visible absorption spectra of TiO2, H-TiO2, Bi2WO6, VO-Bi2WO6, Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2, (b) Tauc plots of TiO2, H-TiO2, Bi2WO6 and VO-Bi2WO6, (c) XPS valence band schematics of TiO2 and H-TiO2, (d) XPS valence band schematics of Bi2WO6 and VO-Bi2WO6, (e) schematic diagram of the energy band structure of Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2;

[0040] Fig.11 : Characterization of the physicochemical properties of the hydrogel, including (a) the gelation process of Bi / VO-Bi2WO6 / H-TiO2-Gel, (b) the injectability of Bi / VO-Bi2WO6 / H-TiO2-Gel, (c) the swelling rate curve of Bi / VO-Bi2WO6 / H-TiO2-Gel, (d) the SEM electron micrograph of a single hydrogel, (e) the SEM electron micrograph of Bi / VO-Bi2WO6 / H-TiO2-Gel, (f) the rheological properties study of Bi / VO-Bi2WO6 / H-TiO2-Gel, (g) the step strain measurement of Bi / VO-Bi2WO6 / H-TiO2-Gel, (h) the elasticity and tightness of Bi / VO-Bi2WO6 / H-TiO2-Gel in the joints, (i) the adhesion of Bi / VO-Bi2WO6 / H-TiO2-Gel in the joints;

[0041] Fig.12 : Observation of the gelation rate of hydrogel, including (a) the photo of Bi / VO-Bi2WO6 / H-TiO2-Gel before gelation, (b) the photo of Bi / VO-Bi2WO6 / H-TiO2-Gel after gelation;

[0042] Fig.13: Schematic diagram of element mapping electron microscope of Bi / VO-Bi2WO6 / H-TiO2-Gel, including (a) element fusion map of Bi / VO-Bi2WO6 / H-TiO2-Gel, (b) distribution of titanium element in Bi / VO-Bi2WO6 / H-TiO2-Gel, (c) distribution of bismuth element in Bi / VO-Bi2WO6 / H-TiO2-Gel, (d) distribution of tungsten element in Bi / VO-Bi2WO6 / H-TiO2-Gel, (e) distribution of oxygen element in Bi / VO-Bi2WO6 / H-TiO2-Gel, (f) distribution of carbon element in Bi / VO-Bi2WO6 / H-TiO2-Gel;

[0043] Fig.14 :In vitro biocompatibility and ROS scavenging activity of Bi / VO-Bi2WO6 / H-TiO2-Gel, including (a) toxicity of different concentrations of Bi / VO-Bi2WO6 / H-TiO2 to HUVEC cells, (b) toxicity of hydrogel to HUVEC cells, (c) hemolysis experiment of Bi / VO-Bi2WO6 / H-TiO2-Gel, (d) fluorescence image comparison of HUVEC cell DCFH-DA probe, in which the normal group used standard culture medium; the H2O2 group used standard culture medium and H2O2 co-incubation; the Bi / VO-Bi2WO6 / H-TiO2+H2O2 group used standard culture medium and H2O2 co-incubation for 24 hours, and then added Bi / VO-Bi2WO6 / H-TiO2 and co-incubated for another 24 hours; (e) fluorescence quantitative analysis of HUVEC cell DCFH-DA probe, in which “+” "-" indicates that H2O2 or Bi / VO-Bi2WO6 / H-TiO2 was added, "-" indicates that H2O2 or Bi / VO-Bi2WO6 / H-TiO2 was not added; if both H2O2 and Bi / VO-Bi2WO6 / H-TiO2 in the normal group were "-", it means that neither H2O2 nor Bi / VO-Bi2WO6 / H-TiO2 was added to the normal group;

[0044] Fig.15 : In vivo photocatalytic treatment of diabetic wounds promoted by Bi / VO-Bi2WO6 / H-TiO2-Gel, including (a) representative photos of wound healing in different treatment groups of mice (0, 3, 7 and 11 days after the start of treatment), (b) statistical data of the residual area of ​​wounds during photocatalytic treatment, (c) pathological analysis of wound healing on the 14th day after photocatalytic treatment by H&E staining, and (d) pathological analysis of wound healing on the 14th day after photocatalytic treatment by Masson staining;

[0045] Fig.16:Photos of tail-cutting hemostasis experiment in diabetic mice: PBS group and Bi / VO-Bi2WO6 / H-TiO2-Gel group;

[0046] Fig.17 : H&E staining of major organs (heart, liver, spleen, lung, and kidney) after 14 days of treatment, scale bar: 100 μm. DETAILED DESCRIPTION

[0047] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0048] As introduced in the background technology section, most titanium dioxide catalysts require ultraviolet light for catalysis, although there have been reports of using visible light response to in-situ hydrogen production and in-situ glucose deprivation to prevent glycation reactions and advanced glycation end product receptor expression, achieving the purpose of efficient synergistic treatment of diabetic foot. However, it is well known that single semiconductors have the problem of high recombination rate of photogenerated carriers, which limits their catalytic activity.

[0049] Based on this, the purpose of the present invention is to provide a photocatalytic heterojunction material and its application for synergistic hydrogen production and glucose degradation. Both Bi-based nanomaterials and TiO2 have good biocompatibility. The Bi element is considered to be one of the least toxic heavy metals. Bi-based nanomaterials are widely studied and applied in the biomedical field. TiO2 also has high biocompatibility and is approved for use in the fields of cosmetics and medicine. Therefore, the present invention uses Bi and TiO2 as raw materials, and first prepares a Bi2WO6 / TiO2 heterojunction through a solvent thermal method and a calcination method, and then hydrogen is doped through calcination. Hydrogen is doped into TiO2 and oxygen defects are formed in Bi2WO6 at the same time, and part of the bismuth in Bi2WO6 is reduced, thereby forming a Bi / VO-Bi2WO6 / H-TiO2 heterojunction. Both Bi2WO6 and TiO2 have good photocatalytic activity, and a Bi / VO-Bi2WO6 / H-TiO2 heterojunction is obtained, thereby reducing the recombination rate of photogenerated carriers, thereby improving the photocatalytic activity. After calcination, the band gap of the material becomes narrower, widening from the ultraviolet to the visible light region. The energy band structures of the two semiconductors are staggered, and the photogenerated electrons and holes are transferred to TiO2 and Bi2WO6 respectively, and reduction-oxidation half-reactions occur on their surfaces. In addition, the Bi single-substance nanocrystals reduced and precipitated on the catalyst surface cause the localized surface plasmon resonance effect (LSPR), which is beneficial to improve the visible light absorption efficiency and the photogenerated carrier separation efficiency, and as a low-cost non-metallic co-catalyst, improve the catalytic ability. A Z-type heterojunction is constructed between Bi2WO6 and TiO2, which is one of the reasons why the photocatalytic activity of the composite material is significantly improved.

[0050] This preparation method realizes the transformation of materials from nanoparticles to two-dimensional nanosheets. The two-dimensional nanomaterials have a larger specific surface area, which greatly improves the photon absorption utilization rate, enabling the material to produce hydrogen by photolysis of water using sacrificial agents in the visible light range.

[0051] In order to enable those skilled in the art to more clearly understand the technical solution of the present application, the technical solution of the present application will be described in detail below in conjunction with specific embodiments.

[0052] Note: All cells used in the experiments were purchased from Meisen CTCC Cell Standard Supply Center.

[0053] The test materials used in the examples of the present invention are all conventional test materials in the art and can be purchased through commercial channels.

[0054] Example 1: Preparation of Bi / VO-Bi2WO6 / H-TiO2

[0055] (1) Preparation of Bi2WO6 nanomaterials: 1 mmol Na2WO4·2H2O and 2 mmol Bi(NO3)3·5H2O were mixed and dissolved in 20 mL ethylene glycol, stirred for 30 min, and reacted at 160°C in a polytetrafluoroethylene-lined autoclave for 24 h. After the reaction, the mixture was centrifuged, washed with water and ethanol three times in sequence, and dried in an oven at 60°C to obtain Bi2WO6.

[0056] (2) Preparation of Bi2WO6 / TiO2 nanomaterials: 4 mL of tetrabutyl titanate, 4 mL of ethylene glycol solution, 8 mL of pure water and 0.2 g of Bi2WO6 were added to a beaker and stirred for 30 min. Then 10 mL of pure water was added. The mixture was poured into a 50 mL polytetrafluoroethylene reactor and heated to 200°C for 24 h. After the reaction, the mixture was centrifuged and the precipitate was washed three times with distilled water and ethanol in turn and dried in an oven at 60°C to obtain Bi2WO6 / TiO2.

[0057] (3) Preparation of Bi / VO-Bi2WO6 / H-TiO2 nanomaterials: 160 mg sodium borohydride and 160 mg Bi2WO6 / TiO2 were thoroughly ground and mixed, placed in a porcelain boat, and heated at 5°C / min. -1 The reaction mixture was heated to 450°C at a heating rate of 1000 ℃ and calcined at 450°C for 2 h. The resulting powder was washed three times with distilled water and ethanol, centrifuged, and dried in an oven at 60°C.

[0058] Comparative Example 1: Preparation of VO-Bi2WO6

[0059] 160 mg of sodium borohydride and 160 mg of Bi2WO6 were thoroughly ground and mixed, and then placed in a porcelain boat and heated at 5 °C min -1 The reaction mixture was heated to 450°C at a heating rate of 1000 ℃ and calcined at 450°C for 2 h. The powder was centrifugally washed and dried in an oven at 60°C.

[0060] Comparative Example 2: Preparation of H-TiO2

[0061] 160 mg of sodium borohydride and 160 mg of TiO2 were thoroughly ground and mixed, and then placed in a porcelain boat and heated at 5 °C min -1 The reaction mixture was heated to 450°C at a heating rate of 1000 ℃ and calcined at 450°C for 2 h. The resulting powder was washed three times with distilled water and ethanol, centrifuged, and dried in an oven at 60°C.

[0062] Comparative Example 3: Preparation of Bi2WO6 / TiO2

[0063] The same steps (1) and (2) as in Example 1 are followed to finally obtain Bi2WO6 / TiO2.

[0064] Example 2: Diabetic foot ulcer drug (Bi / VO-Bi2WO6 / H-TiO2-Gel)

[0065] (1) Deionized modified HA (HA-ALD): 1.0 g hyaluronic acid (Mw = 1000-2000 kDa) and 1.0 g NaIO4 were dissolved in 100 mL deionized water to form a precursor solution. The precursor solution was then stirred vigorously for 3 h in the dark, and 10 mL ethylene glycol was added to terminate the reaction. After 1 h, the solution was dialyzed with distilled water for 3 days, and the portion with Mw>3500 Da was retained. The resulting polymer was freeze-dried to obtain HA-ALD, which was stored at 4 °C for later use.

[0066] (2) Hydrazide-modified HA (HA-ADH): 1.0 g hyaluronic acid (Mw = 10 kDa) was dissolved in 100 mL of MES buffer. Then 2 g EDC and 0.9 g HOBT were added and stirred for 1 h. After that, 4.5 g HA-ADH was added and reacted at room temperature for 24 h. The reaction product was dialyzed for 3 days, and the portion with Mw > 14 kDa was retained and freeze-dried to obtain HA-ADH.

[0067] (3) Synthesis of Bi / VO-Bi2WO6 / H-TiO2-Gel: Bi / VO-Bi2WO6 / H-TiO2 prepared in Example 1 and HA-ALD were dissolved in a PBS solution at pH = 7.4 to form a precursor A, with the concentration of Bi / VO-Bi2WO6 / H-TiO2 being 1 mg / mL and the concentration of HA-ALD being 3 wt %. HA-ADH was dissolved in a PBS solution at pH = 7.4 to form a precursor B, with the concentration of HA-ADH being 3 wt %. Precursor A and precursor B were mixed in equal volumes to obtain Bi / VO-Bi2WO6 / H-TiO2-Gel.

[0068] Comparative Example 4: Single Hydrogel

[0069] The HA-ALD prepared in step (1) of Example 2 was dissolved in a PBS solution at pH = 7.4 to form a precursor A, so that the concentration of HA-ALD was 3 wt %. HA-ADH was dissolved in a PBS solution at pH = 7.4 to form a precursor B, so that the concentration of HA-ADH was 3 wt %. Precursors A and B were mixed in equal volumes to obtain a single hydrogel.

[0070] Example 3: Characterization

[0071] The Bi2WO6 nanoparticles prepared in step (1) of Example 1 were characterized: Figure 1 The SEM and TEM shown in the figure show that the size is within 10 nm and the dispersion is good. The HRTEM and XRD show that the crystallinity is good. Then, the Bi2WO6 / TiO2 heterojunction prepared in step (2) of Example 1 was analyzed. Figure 2 As shown, the mapping electron microscope shows that the elements are evenly distributed. Finally, the Bi / VO-Bi2WO6 / H-TiO2 prepared in step (3) of the embodiment is characterized: Figure 3 As shown in the figure, the SEM electron microscope image shows that the morphology of Bi2WO6 / TiO2 has undergone a huge change after NaBH4 heat treatment, evolving from ellipsoidal nanoparticles within 10nm to clusters composed of nanosheets; TEM electron microscope observations show that the product has a very thin nanosheet structure after heat treatment, such as Figure 4 As shown; Figure 4 (c) The HRTEM electron microscope image shows that the thin nanosheets are dotted with nanocrystals with a size of about 3 nm, with clear lattice fringes and a lattice spacing of 0.328 nm, which corresponds to the lattice spacing of the (012) crystal plane of metallic Bi. Figure 4 (d) ~ Figure 4 (i) Mapping electron microscopy images confirm that Ti, O, Bi and W are uniformly dispersed on the nanosheets. Figure 4(j) XRD shows that the peak positions of Bi2WO6 / TiO2 before NaBH4 heat treatment correspond well to Bi (44-1246), Bi2WO6 (39-0256), and TiO2 (21-1272), respectively, which is a superposition of three diffraction peaks, and there are no other impurity peaks, proving that the product is the coexistence of the three. However, after calcination, only the characteristic peak of Bi (44-1246) can be observed in Bi / VO-Bi2WO6 / H-TiO2, indicating that the crystal phase structure has changed greatly. This is because the H2 produced by the decomposition of NaBH4 during the calcination process, as a reducing gas, introduces oxygen defects and hydrogen doping into Bi2WO6 and TiO2, destroying the original crystal phase structure. Part of Bi2WO6 is reduced to Bi metal single substance nanocrystals, and TiO2 is transformed into amorphous. Comparative Example 2 subjected single TiO2 to NaBH4 heat treatment, confirming that the morphology and crystal phase structure of TiO2 before and after calcination have changed greatly, such as Figure 6-8 As shown, the rutile TiO2 nanocrystals with a size of about 5nm evolve into amorphous ultrathin TiO2 nanosheets.

[0072] In order to further study the surface chemical composition and valence state of Bi / VO-Bi2WO6 / H-TiO2, XPS analysis and test were carried out on Bi2WO6, TiO2, Bi2WO6 / TiO2, and Bi / VO-Bi2WO6 / H-TiO2. Figure 5 As shown in (a), the two peaks at 457.24 eV and 462.97 eV correspond to the Ti 2p 3 / 2 and Ti 2p 1 / 2 The peaks appear respectively, indicating Ti 4+ existence. Figure 5 (b) The O1s spectrum has two different peaks at 528.83 eV and 530.86 eV, which are assigned to Ti-O and Ti-OH, respectively. In addition, the O1s peak of Bi / VO-Bi2WO6 / H-TiO2 at 530.86 eV is much higher than that of other samples, which means that abundant bridging hydroxyl groups (Ti-OH) are formed on the catalyst surface. Figure 5 (c) shows that the Bi 4f spectrum is deconvoluted into four peaks, which means the formation of a bimetallic state, Bi4f 7 / 2 and Bi 4f 5 / 2 The binding energies at 164.35 eV and 159.03 eV differ by 5.3 eV, indicating the presence of Bi in Bi / VO-Bi2WO6 / H-TiO2. 3+ In addition, two peaks centered at 161.53 eV and 156.43 eV appear in both Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2, corresponding to Bi 4f 7 / 2and Bi 4f 5 / 2 , which means that Bi (3-x)+ The formation of oxygen vacancies on the sample surface. In addition, it can be seen that Bi in Bi / VO-Bi2WO6 / H-TiO2 (3-x)+ The relative content of Bi2WO6 / TiO2 is significantly higher than that of Bi2WO6 / TiO2, indicating that NaBH4 heat treatment introduces a lot of oxygen vacancies on the catalyst surface. Figure 5 As shown in (d), in Bi2WO6 / TiO2 and Bi / VO-Bi2WO6 / H-TiO2, the peak of W is convoluted into three peaks, one of which is the double peak of W 4f 7 / 2 and W4f 5 / 2 , a single peak for Ti 3p 3 / 2 The highest peak at 35.84 eV corresponds to the Ti 3p 3 / 2 The other two peaks overlap on the W4f peak, and are located at 34.23 eV and 36.98 eV, corresponding to W 4f 7 / 2 and W 4f 5 / 2 , confirming that the W element is W 6+ In addition, the peak position of the complex shifts toward the direction of high binding energy, indicating that there is electron transfer between the components, proving the formation of a heterojunction.

[0073] Example 4: Study on Photocatalytic Hydrogen Production / Glycemic Reduction Activity

[0074] (1) Using triethanolamine (TEOA) solution (prepared by adding 10 mL TEOA into 90 mL ultrapure water) as sacrificial reagent and a 300 W Xe lamp without a filter as light source, the experiment was divided into four groups: VO-Bi2WO6, H-TiO2, Bi2WO6 / TiO2, and Bi / VO-Bi2WO6 / H-TiO2 prepared in Comparative Examples 1 to 3 and Example 1 were used as catalysts.

[0075] The specific test method is as follows: 20 mg of the catalyst is dispersed in the above TEOA solution and dispersed uniformly by ultrasonication. The solution is passed through N2 for 30 min to remove air. During the reaction, a 300 W xenon lamp is used. After full light irradiation for 1 hour, the gas is extracted with a syringe, and the H2 yield under visible light irradiation is detected using a gas chromatograph (GC D7980P, TCD detector, N2 carrier). During the entire reaction process, the system is continuously stirred using a magnetic stirrer.

[0076] The results of photocatalytic hydrogen production in each group are shown in Fig. 9 As shown in (a), the results show that the hydrogen production activity of Bi2WO6 / TiO2 prepared in Comparative Example 3 is 49.87 μmol·h -1 ·g -1After NaBH4 heat treatment, the hydrogen production activity of Bi / VO-Bi2WO6 / H-TiO2 was significantly increased to 154.97 μmol·h -1 ·g -1 , which is 3 times that of Bi2WO6 / TiO2 and 5.8 times that of H-TiO2, while VO-Bi2WO6 has no hydrogen production activity. The improvement in photocatalytic performance indicates that the heterojunction formed between Bi2WO6 and TiO2 plays an important role in suppressing the recombination of photogenerated carriers.

[0077] Visible light was obtained by installing a 420 nm filter on a xenon lamp light source, and the visible light response of catalysts such as VO-Bi2WO6, H-TiO2, Bi2WO6 / TiO2, Bi / VO-Bi2WO6 / H-TiO2 prepared in Comparative Examples 1 to 3 and Example 1 was tested. The specific method is: 20 mg of the photocatalyst is dispersed in the above-mentioned TEOA solution and ultrasonically dispersed uniformly. The solution is passed through N2 for 30 mins to remove air. During the reaction, a 300 W xenon lamp is used, and a filter with a wavelength greater than 420 nm is configured. After visible light irradiation for 1 hour, the gas is extracted with a syringe, and the H2 yield under visible light irradiation is detected using a gas chromatograph (GC D7980P, TCD detector, N2 carrier). During the entire reaction process, the system is continuously stirred using a magnetic stirrer.

[0078] according to Fig. 9 As shown in (b), only Bi / VO-Bi2WO6 / H-TiO2 has visible light hydrogen production activity, which is 16.37 μmol·h -1 ·g -1 After the sacrificial agent was replaced by TEOA with glucose solution (80 mmol / L), it was found that the hydrogen production activity was still there under visible light, and the hydrogen production capacity was increased to 24.78 μmol·h -1 ·g -1 Further stability tests found that the hydrogen production increased steadily within 4 hours, proving that Bi / VO-Bi2WO6 / H-TiO2 has good sustainable hydrogen production activity. Given the experimental results that Bi / VO-Bi2WO6 / H-TiO2 is beneficial to improving the hydrogen production activity in glucose solution, it is speculated that in H + While being reduced to H2 by photogenerated electrons, glucose is oxidized and degraded.

[0079] In order to further confirm the speculation, a set of experiments was set up: Bi / VO-Bi2WO6 / H-TiO2 was used as catalyst, and gradient concentration glucose solution (10, 15, 20mM) was used as sacrificial agent for photocatalytic reaction, and the glucose concentration after illumination was detected in real time by iodine titration. The results are shown in Figure 2. Fig. 9As shown in (c), as the photocatalytic time increases, the glucose concentration in the reactor gradually decreases. Although the decrease is limited and does not reach the normal blood sugar level, it also contributes to the regulation of the DFU wound microenvironment. It can be combined with the anti-inflammatory and antioxidant effects of hydrogen to play a synergistic role in promoting the healing of chronic wounds.

[0080] Example 5: Mechanism Exploration

[0081] In order to explore the reason why the spectral response range of Bi / VO-Bi2WO6 / H-TiO2 obtained after NaBH4 treatment of Bi2WO6 / TiO2 is broadened to the visible light region, UV-visible diffuse reflectance tests were carried out on TiO2, Bi2WO6 and Bi2WO6 / TiO2 before and after heat treatment. Fig.10 (a); and further utilize (αhν) 1 / 2 The tauc plot is plotted against hν to obtain the band gap, see Fig.10 (b). The maximum absorption edges of the original TiO2 and Bi2WO6 are located at 398 nm and 468 nm, respectively, with band gaps of 3.12 eV and 2.69 eV, respectively. The maximum absorption edges of the heat-treated H-TiO2 and VO-Bi2WO6 are located at 530 nm and 486 nm, respectively, with band gaps of 2.35 eV and 2.55 eV, respectively. The absorption curve of the TiO2-Bi2WO6 heterojunction has a larger slope than that of TiO2, and the absorption spectrum has red-shifted. The maximum absorption band edge of the heat-treated Bi / VO-Bi2WO6 / H-TiO2 further red-shifts to 478 nm. In addition, the heat-treated samples all have a continuous additional absorption band from 400 nm to 800 nm, which can be attributed to the introduction of oxygen defects, which makes the sample appear locally with obvious surface plasmon resonance effect. Therefore, the light absorption capacity of H-TiO2 and Bi / VO-Bi2WO6 / H-TiO2 in the visible-near infrared region is enhanced, resulting in the sample color deepening to black. The XPS valence band spectra show that the EVB (XPS) of the original TiO2 and Bi2WO6 are 2.64 eV and 3.35 eV, respectively, and the EVB (XPS) after heat treatment are 2.11 eV and 3.11 eV, respectively. Fig.10 (c) and Fig.10 (d) According to the formula: EVB = φ + EVB (XPS) - 4.44, the VB of the normal hydrogen electrode can be calculated. Fig.10 (b)- Fig.10 The band gap value and VB value in (d) can be used to draw the band structure diagram of the material, see Fig.10(e) It is found that the band gap narrows after heat treatment and widens from the ultraviolet to the visible light region. The energy band structures of the two semiconductors are staggered, and the photogenerated electrons and holes are transferred to TiO2 and Bi2WO6 respectively and undergo reduction-oxidation half-reactions on their surfaces. In addition, the Bi single-substance nanocrystals precipitated by reduction on the Bi / VO-Bi2WO6 / H-TiO2 surface cause the localized surface plasmon resonance effect (LSPR), which is beneficial to improve the visible light absorption efficiency and the photogenerated carrier separation efficiency, and as a low-cost non-metallic co-catalyst, improve the catalytic ability. The above tests confirm that a Z-type heterojunction is constructed between Bi2WO6 and TiO2, which is why the photocatalytic activity of the composite material is significantly improved.

[0082] Example 6: Preparation and characterization of photocatalytic functionalized hydrogel

[0083] In order to further improve the biocompatibility of the material and increase its close fit with the wound surface, the photocatalytic material of Example 1 was compounded with the hydrogel to prepare the functionalized hydrogel of Example 2. Fig.11 The overall gelation process of functionalized hydrogels is as follows: Fig.11 As shown in (a), Bi / VO-Bi2WO6 / H-TiO2 is uniformly dispersed in aldehyde-modified hyaluronic acid (HA-ALD) by vigorous stirring, and then an equal volume of hydrazide-modified hyaluronic acid (HA-ADH) is added to the mixed solution, and the mixture is stirred and mixed evenly. The hydrogel is quickly formed by the efficient Schiff base interaction between the hydrazide part of HA-ADH and the aldehyde part of HA-ALD ( Fig.12 ). In addition, due to the mild reaction and the absence of byproducts, the gelation process is non-toxic to cells. Given that the early hydrogel is weak, a double-barrel three-valve syringe can be used to quickly mix the precursors and then inject them into the wound. The operation is simple, and the gel can be injected in appropriate amounts according to the shape of the wound to better fit the wound. The mixed hydrogel was pushed out of the needle by the above method, and the stable letters "SDS" were successfully written without any clogging of the needle, proving its injectability. Fig.11 (b).

[0084] In order to verify the absorption of exudate by the functionalized hydrogel prepared in Example 2 and whether it can provide a water-rich environment for nanomaterials to facilitate photocatalytic reaction, the swelling rate of the hydrogel was evaluated. Fig.11(c). The swelling rate of Bi / VO-Bi2WO6 / H-TiO2-Gel was determined by recording the change in wet weight: Bi / VO-Bi2WO6 / H-TiO2-Gel (500 μL) was immersed in 5 mL PBS solution at 37°C. At time points of 0, 5, 10, 15, 20, 30, 40 and 60 min, the hydrogel was removed from the solution and excess water was removed with filter paper. The weight of Bi / VO-Bi2WO6 / H-TiO2-Gel was measured and the swelling rate was evaluated using the formula: Swelling rate = (W t -W0) / W0× 100%, where W t is the weight of Bi / VO-Bi2WO6 / H-TiO2-Gel after incubation in PBS solution, and W0 is the initial weight of Bi / VO-Bi2WO6 / H-TiO2-Gel. The results show that it has excellent water absorption capacity, can effectively absorb wound exudate and maintain the optimal moisture level, which is crucial for the repair of DFU.

[0085] The surface characteristics and porous network structure of the single hydrogel prepared in Comparative Example 4 and the functionalized hydrogel prepared in Example 2 were studied by SEM. Fig.11 (d) shows that the interior of a single hydrogel is smooth, while Fig.11 (e) shows that the inner wall of the functionalized hydrogel prepared in Example 2 is rough. Fig.13 The EDS images showed the presence of Ti, Bi, W, O, and C elements in the functionalized hydrogel, indicating that Bi / VO-Bi2WO6 / H-TiO2 nanoparticles were successfully loaded into the hydrogel to prepare functionalized hydrogel (Bi / VO-Bi2WO6 / H-TiO2-Gel).

[0086] Usually, hydrogel excipients must have certain bioadhesion and self-healing properties to effectively adapt to the ever-changing complex wound environment. Therefore, the rheological behavior of functionalized hydrogels has been studied, such as Fig.11 As shown in (f), it is found that G' (storage modulus) and G" (loss modulus) show an upward trend over time, indicating that its cross-linking behavior gradually strengthens, and G' remains higher than G", indicating that it has elasticity. The hydrogel was injected in situ into the skin of the finger joint, as shown in Fig.11 Figure (h) and Fig.11 As shown in (i), it was found that it adhered tightly to the skin and changed its state with the bending of the joint. It did not fall off when the finger was turned up and down, which confirmed that it had good viscoelasticity. Continuous shear strain tests were performed by alternating low strain and high strain, such as Fig.11As shown in (g), it was found that G' and G" remained stable under low strain (0.1%), while under high strain (100%), the storage modulus G' decreased significantly and G" exceeded G', indicating that the hydrogel broke. However, when the strain was restored to 0.1%, both G' and G" returned to their initial states. The periodic destruction and repair of the hydrogel network demonstrated its significant self-healing properties. Based on the above tests, it was demonstrated that the prepared functionalized hydrogel has the characteristics of injectability, adhesion, and self-healing, laying the foundation for its application in complex wounds.

[0087] Test Example 1: Biocompatibility Test

[0088] The biocompatibility of dressings is crucial for wound healing. In order to evaluate the biocompatibility of the prepared hydrogel, the cytotoxicity of Bi / VO-Bi2WO6 / H-TiO2 material was detected by CCK8 assay. Fig.14 The results of (a) show that after incubating HUVEC cells with Bi / VO-Bi2WO6 / H-TiO2 solutions of different concentrations (0.025-1 mg / mL) for 24 hours, the average cell survival rate of each treatment group remained above 90%. This indicates that Bi / VO-Bi2WO6 / H-TiO2 composites of different concentrations have good biocompatibility and can maintain cell growth without producing toxic effects.

[0089] Similarly, the cytotoxicity of the hydrogel dressing was also evaluated. The Bi / VO-Bi2WO6 / H-TiO2 hydrogel prepared in Example 2 was immersed in DMEM basal medium containing HUVEC cells for 24 hours to obtain a hydrogel extract. HUVEC cells (5×10 3 Cells / well) were seeded in a 96-well plate and incubated at 37°C for 24 hours. After the cells adhered to the wall, the cell culture medium was removed and replaced with the hydrogel extract. After incubating with the cells for 24 hours, the CCK8 reagent was used to detect the cell survival rate after hydrogel treatment. Fig.14 As shown in (b), after 24 hours of co-culture, the survival rate of cells in each treatment group was above 95% compared with the normal group (DMEM basal medium without hydrogel).

[0090] Finally, a hemolysis test was conducted on the functionalized hydrogel material by sampling blood from the mouse orbit. Fig.14 (c), the hemolysis rate is less than 2%. The above experimental results all prove that the Bi / VO-Bi2WO6 / H-TiO2-Gel material prepared in Example 2 has good cell compatibility. The hemolysis rate HR (Hemolysis Ratio) is calculated according to the following formula:

[0091] Hemolysis rate (%) = (experimental group - negative control) / (positive control - negative control) × 100%

[0092] The absorbance of red blood cells in deionized water (positive control) was used to define complete hemolysis (100%); the negative control was the absorbance of red blood cells in PBS buffer.

[0093] Test Example 2: In vitro cell test

[0094] The standard green fluorescent probe DCFH-DA was used to detect the ROS level in HUVEC cells. The cells in the logarithmic growth phase of subculture were collected. HUVEC cells (5×10 4 / well) were inoculated in 6-well plates and incubated at 37℃ for 24 hours until the cells adhered to the wall. The normal group was cultured with DMEM basal medium, and the other two groups (H2O2 group and Bi / VO-Bi2WO6 / H-TiO2+H2O2 group) were incubated with 100 μm H2O2 for 1 hour. The normal group and H2O2 group were cultured with DMEM basal medium, and the Bi / VO-Bi2WO6 / H-TiO2+H2O2 group was co-cultured with DMEM basal medium containing Bi / VO-Bi2WO6 / H-TiO2 for 24 hours. The cell culture medium was removed, and the DCFH-DA probe diluted with serum-free culture medium (concentration of 10 μmol / L) was added and incubated in a 37℃ incubator for 30 minutes. Wash with PBS 2-3 times to wash away the DCFH-DA that did not fully enter the cells. Photographs were taken using a confocal laser scanning microscope.

[0095] No obvious green fluorescence was observed in the normal group, indicating that normal HUVEC cells almost do not produce ROS. Then HUVEC cells were placed in a medium containing H2O2 and incubated for 24 hours. The DCFH-DA fluorescent probe showed strong green fluorescence, indicating that a large amount of ROS was induced. After Bi / VO-Bi2WO6 / H-TiO2 was incubated with the above HUVEC cells for 24 hours, Fig.14 (d) and Fig.14 The green fluorescence in (e) is significantly weakened, indicating that the H2 released by catalysis in the functionalized hydrogel has a significant function in regulating oxidative stress and can effectively remove ROS in cells. This provides a possibility for improving the survival rate of cells in the DFU microenvironment.

[0096] Experimental Example 3: In vivo photocatalytic wound healing test

[0097] (1) The in vivo photocatalytic therapeutic effect of the functionalized hydrogel on DFU wounds was further evaluated. Fig.15The diabetic model of C57 mice (Jinan Pengyue Experimental Animal Breeding Co., Ltd., 6-week-old male mice) was established by intraperitoneal injection of streptozotocin (STZ). Wounds were established on the backs of diabetic mice with blood glucose levels ≥16.7 mmol / L 10 days after STZ injection and treated.

[0098] A Bi / VO-Bi2WO6 / H-TiO2 loading of 1 mg / mL was selected to obtain a considerable transmittance. The diabetic mice were randomly divided into 6 groups (6 mice in each group): a normal group (normal mice without diabetes), a hyperglycemia group, a single hydrogel group (Gel) prepared in Comparative Example 4, a single hydrogel + illumination group (Gel+VIS) prepared in Comparative Example 4, a Bi / VO-Bi2WO6 / H-TiO2-Gel group (Bi / VO-Bi2WO6 / H-TiO2-Gel) prepared in Example 2, and a Bi / VO-Bi2WO6 / H-TiO2-Gel + illumination group (Bi / VO-Bi2WO6 / H-TiO2-Gel+VIS) prepared in Example 2, wherein illumination refers to visible light, and the illumination time is 15 minutes each time, and the dressing is changed every other day and illuminated once. The specific dressing change method is as follows: the hydrogel is pushed out of the needle and injected into the wound surface, and the amount of injection is determined according to the shape of the wound surface, so that the gel is closely attached to the wound surface.

[0099] Pictures of wounds during treatment Fig.15 As can be seen from (a) and 15 (b), the wound closure rate of mice in the functionalized hydrogel + light group was significantly higher than that in other groups. The wound healing rate exceeded 50% on the 3rd day and was completely healed on the 11th day, which was better than that of mice in the normal group. This shows that the functionalized hydrogel isolates bacteria in the external environment and provides a moist healing environment for the wound, which is beneficial to wound healing.

[0100] In order to further verify the healing ability of functionalized hydrogel materials on DFU wounds, the wound tissues of each group were taken for HE and Masson staining on the 7th and 14th days of treatment. HE staining showed that the histological results of the functionalized hydrogel + light group were the best. Fig.15 As shown in (c), a large number of fibroblasts, blood vessels and hair follicles can be observed in the abundant granulation tissue, while there are still more neutrophils and lymphocytes in the other treatment groups, indicating that the inflammatory response persists in the wound surface. Masson staining analyzed the collagen deposition of skin tissue, such as Fig.15 As shown in (d), collagen deposition was most obvious in the functionalized hydrogel + light irradiation group, indicating that photocatalytic therapy accelerated collagen deposition and promoted the proliferation and migration of skin cells in the DFU wound site, which was consistent with the in vitro cell experiment.

[0101] In addition, HE staining was performed on the main organs (heart, liver, spleen, lung, and kidney) of mice treated for 14 days ( Fig.17 ), showing no significant abnormalities, inflammation or damage, indicating that the prepared functionalized hydrogel material has good biocompatibility.

[0102] (2) Through the mouse tail amputation experiment, 6 diabetic mice were randomly divided into two groups, 3 mice in each group. The mice were anesthetized in a chamber containing 1.5% isoflurane and 60% oxygen, and then disinfected with alcohol cotton at 1 / 3 of the distance from the base of the tail. 2 / 3 of the tail was cut off with surgical scissors. The wound was treated with PBS solution (PBS group) and the functionalized hydrogel prepared in Example 2 (Bi / VO-Bi2WO6 / H-TiO2-Gel group), and the amount of bleeding was recorded by taking pictures. It was confirmed that the functionalized hydrogel had the effect of promoting hemostasis on the wound ( Fig.16 ), while photocatalytic degradation of glucose and hydrogen production helped improve the microenvironment at the DFU wound, thereby accelerating wound healing.

[0103] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation, characterized in that: The photocatalytic heterojunction material comprises elemental bismuth, oxygen-deficient Bi2WO6 and hydrogen-doped TiO2; the photocatalytic heterojunction material is a two-dimensional nanosheet, and the TiO2 is an amorphous ultra-thin TiO2 nanosheet; The photocatalytic heterojunction material is prepared by the following method: (1) Na2WO4·2H2O and Bi(NO3)3·5H2O are added to ethylene glycol and mixed to perform a solvothermal reaction. After the reaction is completed, the mixture is centrifuged, washed, and dried to obtain Bi2WO6; the molar ratio of Na2WO4·2H2O to Bi(NO3)3·5H2O is 1:2; the temperature of the solvothermal reaction is 160°C and the time is 24 hours; (2) Tetrabutyl titanate, ethylene glycol and water are mixed, and the Bi2WO6 prepared in step (1) is added, and pure water is added after stirring to carry out a hydrothermal reaction. After the reaction is completed, centrifugation, washing and drying are carried out to obtain Bi2WO6 / TiO2; the ratio of the added amount of tetrabutyl titanate, ethylene glycol and Bi2WO6 is 4mL:4mL:0.2g; the stirring time is 30min; the temperature of the hydrothermal reaction is 200°C and the time is 24h; (3) Sodium borohydride and the Bi2WO6 / TiO2 prepared in step (2) are fully ground and mixed, and vacuum calcined to obtain Bi / VO-Bi2WO6 / H-TiO2, i.e., a photocatalytic heterojunction material for synergistic hydrogen production and glucose degradation; the mass ratio of the sodium borohydride to Bi2WO6 / TiO2 is 1:1; the heating rate of the vacuum calcination is 5°C / min, the temperature of the vacuum calcination is 450°C, and the time of the vacuum calcination is 2h.

2. Use of the photocatalytic heterojunction material according to claim 1 in at least one of the following 1) to 3): 1) Photocatalytic hydrogen production; 2) Degradation of glucose or triethanolamine; 3) Prepare medicines for diabetic foot ulcers.

3. A diabetic foot ulcer drug, characterized in that: The photocatalytic heterojunction material according to claim 1 is used as the main component.

4. The diabetic foot ulcer medicament according to claim 3, characterized in that: The diabetic foot ulcer medicine is prepared by the following method: (1) Dissolving hyaluronic acid and NaIO4 in deionized water to form a precursor solution, then stirring in the dark to react, adding ethylene glycol to terminate the reaction, dialysis purification, and freeze-drying to obtain HA-ALD; (2) Dissolve hyaluronic acid in MES buffer, add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 1-hydroxybenzotriazole, mix, add adipic acid dihydrazide, react at room temperature, dialyze the reaction product, and freeze-dry to obtain HA-ADH; (3) Dissolving the photocatalytic heterojunction material described in claim 1 and HA-ALD in a PBS solution to form a precursor A; dissolving HA-ADH in a PBS solution to form a precursor B; and mixing the precursor A with the precursor B to obtain a diabetic foot ulcer drug.

5. The diabetic foot ulcer medicament according to claim 4, characterized in that: In step (1), the mass ratio of hyaluronic acid to NaIO4 is 1:

1.

6. The diabetic foot ulcer medicament according to claim 4, characterized in that: In step (2), the ratio of the added amounts of hyaluronic acid, MES buffer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1-hydroxybenzotriazole and adipic acid dihydrazide is 1 g:100 mL:2 g:0.9 g:4.5 g.

7. The diabetic foot ulcer medicament according to claim 4, characterized in that: In step (3), in the precursor A, the concentration of Bi2WO6 / TiO2 is 1 mg / mL, and the content of HA-ALD is 3 wt%; in the precursor B, the content of HA-ADH is 3 wt%; and the pH of the PBS solution is 7.4.

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