A dual-network composite hydrogel and a preparation method and application thereof

Abstract

This application relates to the field of hydrogel dressing technology, specifically disclosing a dual-network composite hydrogel, its preparation method, and its applications. The dual-network composite hydrogel is formed by loading composite nanoparticles onto a conductive hydrogel matrix. The conductive hydrogel matrix is ​​composed of polyvinyl alcohol, polyacrylic acid, and lithium chloride. The composite nanoparticles are core-shell structured composite nanosheets formed by electrostatic self-assembly of quaternary ammonium chitosan and molybdenum disulfide. The preparation method involves dispersing quaternary ammonium chitosan-coated molybdenum disulfide composite nanoparticle powder in a conductive gel formed from polyvinyl alcohol, polyacrylic acid, and lithium chloride, removing air bubbles under vacuum, and then photocuring. The dual-network composite hydrogel of this application can be used to prepare flexible wearable strain sensors, possessing the potential to provide data support for wound healing and motion monitoring by enabling real-time monitoring of tensile and compressive stress at the wound site.

Description

Technical Field

[0001] This application relates to the field of hydrogel dressing technology, and more specifically, to a dual-network composite hydrogel, its preparation method, and its application. Background Technology

[0002] As the largest organ in the human body, the skin plays a crucial role in protection and thermoregulation. Wound healing after skin injury is a complex biological process susceptible to bacterial infection, involving four overlapping stages: hemostasis, inflammation, proliferation, and remodeling. With the increasing overuse of antibiotics, bacterial resistance has become a major challenge in global public health, and traditional antibiotic-dependent treatment strategies are becoming increasingly ineffective. Therefore, developing novel functional wound dressings that can effectively prevent or treat infections and promote wound healing is of significant clinical importance.

[0003] Existing wound dressings are divided into traditional dressings and modern synthetic dressings. The former has poor water absorption and is prone to adhesion to tissues, causing secondary damage, while the latter, although improved, has limitations such as limited absorption capacity, poor biocompatibility, and lack of healing-promoting active ingredients. Hydrogels, due to their high water content, good biocompatibility, and extracellular matrix-like structure, have become ideal candidates for wound dressings and are widely used in wastewater treatment, soil water retention, tissue engineering, drug release, flexible sensing, and wound dressing.

[0004] Regarding the aforementioned technologies, the inventors have discovered that although significant progress has been made in the research of hydrogel dressings, there are still obvious shortcomings that limit their clinical application. First, existing hydrogel dressings suffer from prominent mechanical property defects, lacking elasticity and prone to irreversible deformation under external force. Second, they lack stable, sustained, and highly effective antibacterial capabilities; dressings relying solely on physical adsorption or antibiotic release often have short-lasting antibacterial effects and are prone to inducing drug resistance. Furthermore, some antibacterial agents based on silver ions or natural extracts may indiscriminately attack normal cells. Third, they have poor environmental adaptability; complex external environments such as high temperature, high humidity, or low temperature can easily lead to the failure of traditional hydrogel structures and functions. Finally, their functionality is inconsistent; most existing hydrogel dressings focus only on wound management and lack the ability to dynamically monitor the wound healing process. Summary of the Invention

[0005] This application aims to provide a dual-network composite hydrogel, its preparation method, and its application. When used as a wound dressing, the dual-network composite hydrogel has excellent mechanical properties and efficient and stable antibacterial properties. It has real-time strain monitoring capabilities, can adapt to complex external environments, and can monitor the tensile and compressive stress at the wound site in real time, providing data support for wound healing and motion monitoring.

[0006] In a first aspect, this application provides a method for preparing a dual-network composite hydrogel, employing the following technical solution: A method for preparing a dual-network composite hydrogel includes the following steps: S1: Molybdenum disulfide nanosheets were dispersed in a quaternary ammonium salt chitosan solution and stirred to perform electrostatic self-assembly, resulting in a quaternary ammonium salt chitosan-coated molybdenum disulfide composite nanoparticle dispersion. After freeze-drying, the composite nanoparticle powder was formed. S2: Add polyvinyl alcohol to water, heat and stir to dissolve, then add polyacrylic acid, stir evenly, add functional additives, then add lithium chloride, and continue stirring to form a hydrogel prepolymer. S3: Add the composite nanoparticle powder to the hydrogel prepolymer liquid, stir evenly, remove air bubbles under vacuum, and obtain the double-network composite hydrogel after photocuring.

[0007] Optionally, the functional additives include crosslinking agents and initiators.

[0008] By adopting the above technical solution, the inventors encapsulated composite nanoparticles in hydrogel, effectively combining the two to form a stable three-dimensional network structure, which can effectively maintain the structure and function of nanomaterials. The addition of LiCl provides conductivity to the hydrogel, enabling the material to be used as a strain sensor, which provides a technical basis for motion sensing.

[0009] The layered nanosheet structure of molybdenum disulfide provides a more effective contact area and high conductivity with bacteria during bacterial infection treatment, accelerating electron transfer from bacterial cells to the cellular level. Furthermore, it has the ability to combine with near-infrared light irradiation. Under near-infrared light, it absorbs the light energy and converts it into heat and generates reactive oxygen species, acting as a photothermal agent to achieve physical photothermal sterilization by generating localized high heat. Further, the inventors coated the surface of molybdenum disulfide nanosheets with quaternary ammonium chitosan via electrostatic assembly. The contact antibacterial ability of quaternary ammonium chitosan itself, combined with molybdenum disulfide, creates a dual-effect synergistic antibacterial mechanism of chemical contact sterilization and physical photothermal sterilization, which is less likely to induce drug resistance. In addition, the modification with quaternary ammonium chitosan improves the poor hydrophilicity of molybdenum disulfide, allowing it to be more uniformly and stably dispersed in the hydrogel matrix.

[0010] Furthermore, the inventors introduced lithium chloride into the hydrogel matrix, whose unique hydration ability allows it to form Li+ with water molecules. + (H2O) n The ability of hydration structures, when immersed in a gel, will form Li + (H2O) nThe hydration structure allows free water inside the gel to combine with lithium ions, forming a "water-in-salt" (WIS) electrolyte within the hydrogel. This reduces the free water content in the hydrogel and transforms it into bound water that is less prone to freezing. This effectively lowers the freezing point of the hydrogel, enabling it to remain soft and conductive at low temperatures, and significantly improves the antifreeze properties of the composite hydrogel.

[0011] Optionally, in step S2, a silk fibroin-polyethylene glycol graft copolymer is added to the mixed solution of polyvinyl alcohol and polyacrylic acid before heating and stirring.

[0012] Optionally, the mass ratio of the polyvinyl alcohol and the silk fibroin-polyethylene glycol graft copolymer is 2:(5-10).

[0013] Optionally, the preparation method of the silk fibroin-polyethylene glycol graft copolymer includes the following steps: Silk fibroin was dissolved in lithium bromide solution to prepare a silk fibroin solution; Polyethylene glycol glycidyl ether was added to the silk fibroin solution, and the mixture was subjected to ultrasonic treatment followed by heating. After the reaction was completed, the mixture was purified by dialysis and then freeze-dried to obtain the final product.

[0014] Optionally, the raw material for the polyethylene glycol glycidyl ether includes polyethylene glycol with a molecular weight of 1000-2000.

[0015] By employing the aforementioned technology, polyvinyl alcohol (PVA) and polyacrylic acid (PAA) synergistically construct a physical-chemical double crosslinked network, exhibiting characteristics such as high strength, high elasticity, hydrophilicity, stable mechanical properties, and high sensitivity. The silk fibroin-polyethylene glycol graft copolymer modified with polyethylene glycol glycidyl ether possesses the β-sheet structure of silk fibroin and the hydrophilic flexible long chains of polyethylene glycol. Introducing this into the PVA-PAA network allows for stronger physical crosslinking through hydrogen bonds and hydrophobic interactions, serving as a reinforcing and toughening unit for the network. This significantly improves the mechanical properties of the conductive hydrogel matrix. Furthermore, the introduction of the polyethylene glycol structure greatly improves the dispersibility and compatibility of silk fibroin in the conductive hydrogel matrix, while also endowing the hydrogel surface with superior hydrophilicity and cell affinity. When applied as a medical dressing to wounds, it maintains a moist environment in the wound, promotes cell adhesion and migration, promotes cell proliferation and collagen deposition, and accelerates wound healing.

[0016] Optionally, hydroxybutyl chitosan is also added in step S1. Specifically, molybdenum disulfide nanosheets are dispersed in a quaternary ammonium salt chitosan solution, and electrostatic self-assembly is performed by stirring to obtain a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan. Then, hydroxybutyl chitosan is added to the dispersion, and stirring is continued to obtain a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan and hydroxybutyl chitosan. After freeze-drying, composite nanoparticle powder is formed.

[0017] Optionally, the mass ratio of the quaternary ammonium salt chitosan to hydroxybutyl chitosan is 1:(0.5-1.5).

[0018] By adopting the above technical solution, this application obtains molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan through electrostatic self-assembly, and then adds hydroxybutyl chitosan to the dispersion for physical winding and coating. Compared with the technique of directly adding hydroxybutyl chitosan to the hydrogel matrix, the composite hydrogel obtained by the technique of this application has superior mechanical properties and antibacterial properties. The antibacterial core wrapped with hydroxybutyl chitosan further forms a coated independent unit, which can effectively regulate the release of the antibacterial ability of the internal antibacterial core to achieve long-term antibacterial effect. On the other hand, it further enhances the dispersion uniformity of molybdenum disulfide nanosheets in the hydrogel matrix and optimizes the interfacial bonding ability between nanoparticles and matrix network.

[0019] Furthermore, the inventors discovered that the composite hydrogel formed by introducing hydroxybutyl chitosan using the technical means of this application significantly improves the sensitivity and sensing stability of strain and human physiological signal monitoring responses. On one hand, this may be because the steric hindrance generated by the hydrophilic chains of the molybdenum disulfide composite nanoparticles co-coated with hydroxybutyl chitosan and quaternary ammonium chitosan further improves the monodispersity of the molybdenum disulfide nanosheets in the dispersion and in the hydrogel matrix, forming a finer and more uniform conductive permeation network. This helps to easily separate the originally fragile tunnel junctions or contact points between closely adjacent molybdenum disulfide nanosheets under small strains, leading to increased resistance and thus achieving high sensitivity. On the other hand, the hydroxyl groups of the hydroxybutyl chitosan molecular chain can form a dense hydrogen bond network with the hydrogel aggregate. The hydroxybutyl group of the molybdenum disulfide nanoparticles exhibits hydrophobic interactions, allowing them to be firmly and elastically anchored within the three-dimensional network. During cyclic deformation, the particles are confined to a fixed position and undergo minute oscillations. After each deformation and recovery, the conductive network returns to its initial state, thus maintaining a stable sensing signal. Furthermore, hydroxybutyl chitosan itself is water- and alcohol-soluble, possessing excellent water retention capabilities. In synergy with lithium chloride, it can more effectively bind free water in the hydrogel, not only slowing down water evaporation in dry environments and further lowering the freezing point, but also helping the composite hydrogel maintain a stable internal water content. This ensures the consistency of electrical properties (such as ionic conductivity) and mechanical properties in complex environments or long-term use, guaranteeing long-term stability of the sensing signal.

[0020] Secondly, this application provides a dual-network composite hydrogel, which is prepared by the method of this application for preparing dual-network composite hydrogel.

[0021] Thirdly, this application provides an application of a dual-network composite hydrogel as a flexible wearable strain sensor.

[0022] In summary, this application has the following beneficial effects: 1. Because this application encapsulates the composite nanoparticles formed by coating molybdenum disulfide with quaternary ammonium salt in a hydrogel matrix, it forms a dual-effect synergistic antibacterial core with chemical contact sterilization and physical photothermal sterilization. Molybdenum disulfide and lithium chloride together construct a stable conductive path in the hydrogel matrix, which can be used to prepare flexible wearable strain sensors. As an intelligent dressing system with wound treatment and healing monitoring functions, it can detect changes in electrical signals based on changes in human movement, monitor the tensile and compressive stress at the wound site in real time, and provide data support for wound healing and motion monitoring.

[0023] 2. In this application, it is preferred to obtain molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan through electrostatic self-assembly, then add hydroxybutyl chitosan to the dispersion for physical winding and coating to form structural units, and then add them to the hydrogel matrix. This significantly improves the long-term antibacterial stability of the composite hydrogel, while also improving the stress response sensitivity and high-speed sensing stability of the composite hydrogel in complex environments, enabling it to adapt to the monitoring of human physiological signals in different environments.

[0024] 3. The dual-network composite hydrogel of this application uses polyvinyl alcohol, polyacrylic acid and silk fibroin-polyethylene glycol graft copolymer as hydrogel matrix, which effectively improves the mechanical property stability of the hydrogel, has softness and stretchability matching human skin, and at the same time endows the composite hydrogel with stronger hydrophilicity and cell affinity. When applied as a medical dressing to wounds, it can maintain the moist environment of the wound and accelerate wound healing. Attached Figure Description

[0025] Figure 1 This is a graph showing the relative resistance change of the dual-network composite hydrogel of this application in response to dynamic changes in human pulse. Figure 2 This is a graph showing the relative resistance change of the dual-network composite hydrogel of this application in response to the dynamic changes of human smiles; Figure 3 This is a graph showing the relative resistance change of the dual-network composite hydrogel of this application in response to dynamic changes in human swallowing. Figure 4 This is a graph showing the relative resistance change of the dual-network composite hydrogel of this application in response to dynamic changes in the human wrist; Figure 5 This is a curve showing the relative resistance change of the dual-network composite hydrogel of this application in response to dynamic changes in the human elbow. Figure 6 This is a graph showing the relative resistance change of the dual-network composite hydrogel of this application in response to dynamic changes in the human knee. Detailed Implementation

[0026] The present application will be further described in detail below with reference to embodiments and comparative examples. raw material

[0027] Unless otherwise specified, all raw materials used in the embodiments and comparative examples in this application are commercially available products, specifically: Polyvinyl alcohol, CAS: 9002-89-5; Polyacrylic acid, CAS: 9003-01-4; Quaternary ammonium salt chitosan, selected from Shanghai Yuanye Biotechnology Co., Ltd., S26618; Hydroxybutyl chitosan is thermosensitive, has a degree of substitution ≥0.85, and a molecular weight range of 200-500 kDa; Silk fibroin, selected from Shanghai Yuanye Biotechnology Co., Ltd., S36042. Example Example 1

[0028] A method for preparing a dual-network composite hydrogel includes the following steps: S1: Take 1.5g thiourea and 1.25g sodium molybdate tetrahydrate, add 50ml deionized water to the reaction vessel, place it in an oven at 180℃ and react at a constant temperature for 24h, cool naturally to room temperature, centrifuge and take the supernatant for filtration, dialysis, and then freeze-dry to obtain molybdenum disulfide nanosheets. S2: Molybdenum disulfide nanosheets and quaternary ammonium salt chitosan were dispersed in deionized water at a mass ratio of 1:10, wherein the concentration of quaternary ammonium salt chitosan was 10wt%. The mixture was stirred for 12h to carry out electrostatic self-assembly, and a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan was obtained. The composite nanoparticle powder was obtained by freeze drying. S3: Add 0.2g of polyvinyl alcohol to 5mL of deionized water, heat and stir to dissolve, then add 3.3g of polyacrylic acid, stir until homogeneous to form a homogeneous solution, then add 0.02g of N,N-methylenebisacrylamide (MBA) and 0.05g of lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP), then add 0.1g of lithium chloride, and continue stirring until homogeneous to form a hydrogel prepolymer solution; S4: Add the composite nanoparticle powder to the hydrogel prepolymer solution and stir until a mixture is formed, so that the final concentration of the mixture in the hydrogel prepolymer solution is 0.3% (w / v). Then, place the mixture in a desiccator under vacuum conditions to remove air bubbles. Then, cast the mixture into a mold and irradiate it with blue light for 5 minutes in the dark to form a double network composite hydrogel. Example 2

[0029] A method for preparing a dual-network composite hydrogel differs from Example 1 only in that the hydrogel prepolymer solution in step S3 further includes a silk fibroin-polyethylene glycol graft copolymer. Step S3 specifically comprises: (1) Dissolve silk fibroin in 9.3 mol / L lithium bromide solution at 65℃ to prepare a silk fibroin solution with a concentration of 2.5 wt%. (2) 0.05 mol of polyethylene glycol with a molecular weight of 2000 was mixed with 0.3 mol of epichlorohydrin, 0.1 mol of potassium hydroxide and 0.002 mol of tetrabutylammonium bromide and dissolved in dichloromethane at a ratio of 1:20. The mixture was heated to 50°C and refluxed for 10 h. After filtration, the filtrate was extracted three times with dichloromethane, dried with anhydrous sodium sulfate, and distilled under reduced pressure to obtain polyethylene glycol glycidyl ether. (3) Polyethylene glycol glycidyl ether was added to the silk fibroin solution, wherein the mass ratio of polyethylene glycol glycidyl ether to silk fibroin was 7:10. After ultrasonic treatment, the solution was heated to react. After the reaction was completed, the solution was purified by dialysis and then freeze-dried to obtain the final product. (4) Add 0.2g of polyvinyl alcohol to 5mL of deionized water, heat and stir to dissolve, then add 3.3g of polyacrylic acid and 0.5g of silk fibroin-polyethylene glycol graft copolymer in sequence, stir evenly to form a homogeneous solution, then add 0.02g of N,N-methylenebisacrylamide (MBA) and 0.05g of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (LAP), then add 0.1g of lithium chloride, and continue to stir evenly to form a hydrogel prepolymer. Example 3

[0030] A method for preparing a dual-network composite hydrogel differs from Example 2 only in that polyethylene glycol with a molecular weight of 1500 is used in step S3(2), and the amount of silk fibroin-polyethylene glycol graft copolymer added in S3(4) is 0.7g. Example 4

[0031] A method for preparing a dual-network composite hydrogel differs from Example 2 only in that polyethylene glycol with a molecular weight of 1000 is used in step S3(2), and the amount of silk fibroin-polyethylene glycol graft copolymer added in S3(4) is 1g. Example 5

[0032] A method for preparing a dual-network composite hydrogel differs from Example 2 only in that polyethylene glycol with a molecular weight of 3000 is used in step S3(2). Example 6

[0033] A method for preparing a dual-network composite hydrogel differs from Example 4 only in that polyethylene glycol with a molecular weight of 600 is used in step S3(2). Example 7

[0034] A method for preparing a dual-network composite hydrogel differs from Example 3 only in that hydroxybutyl chitosan is added in step S2. Step S2 specifically involves: Molybdenum disulfide nanosheets and quaternary ammonium chitosan were dispersed in deionized water at a mass ratio of 1:10, with the quaternary ammonium chitosan concentration being 10 wt%. The mixture was stirred for 12 h to allow electrostatic self-assembly, resulting in a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium chitosan. Hydroxybutyl chitosan was then added, with a mass ratio of quaternary ammonium chitosan to hydroxybutyl chitosan of 1:0.5. The mixture was stirred for another 16 h to obtain a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium chitosan and hydroxybutyl chitosan. After freeze-drying, the resulting composite nanoparticle powder was formed. Example 8

[0035] A method for preparing a dual-network composite hydrogel differs from Example 7 only in that the mass ratio of quaternary ammonium chitosan to hydroxybutyl chitosan is 1:1. Example 9

[0036] A method for preparing a dual-network composite hydrogel differs from Example 7 only in that the mass ratio of quaternary ammonium chitosan to hydroxybutyl chitosan is 1:1.5. Example 10

[0037] A method for preparing a dual-network composite hydrogel differs from Example 3 only in that step S4 specifically involves: The composite nanoparticle powder was added to the hydrogel prepolymer solution to achieve a final concentration of 0.3% (w / v). Then, hydroxybutyl chitosan was added, with a mass ratio of hydroxybutyl chitosan to quaternary ammonium chitosan of 1:1. The mixture was stirred until homogeneous and then placed in a vacuum desiccator to remove air bubbles. The mixture was then cast into a mold and irradiated with blue light in the dark for 5 minutes to form a double-network composite hydrogel. Comparative Example

[0038] Comparative Example 1 A method for preparing a composite hydrogel includes the following steps: Add 0.2g of polyvinyl alcohol to 5mL of deionized water, heat and stir to dissolve, then add 3.3g of polyacrylic acid and stir until homogeneous to form a homogeneous solution. Then add 0.02g of N,N-methylenebisacrylamide (MBA) and 0.05g of lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP), followed by 0.1g of lithium chloride. Continue stirring until homogeneous to form a hydrogel prepolymer. Then place the mixture in a desiccator under vacuum to remove air bubbles. Finally, cast the mixture into a mold and irradiate with blue light in the dark for 5 minutes to form a composite hydrogel.

[0039] Comparative Example 2 A method for preparing a dual-network composite hydrogel differs from Example 1 only in that lithium chloride is not added in step S3.

[0040] Comparative Example 3 A method for preparing a dual-network composite hydrogel differs from Example 8 only in that lithium chloride is not added in step S3. Performance testing Test Example 1

[0041] The antifreeze properties of the composite hydrogels prepared in Examples 1-10 and Comparative Examples 1-3 were tested. Each test was performed three times, and the average value of the test results was taken as the final result and recorded in Table 1.

[0042] Freeze-thaw resistance: The hydrogel sample was cut into specimens with dimensions of 40mm×10mm×2mm and tested using an electronic universal testing machine at a working speed of 20mm / min. First, the maximum tensile strength of the hydrogel specimen was tested at room temperature (25℃). Then, the hydrogel was placed in a refrigerator (-20℃) for 2 hours of freezing storage. After taking it out, the maximum tensile strength of the frozen hydrogel specimen was tested. Conductivity and Sensing Performance Testing: The hydrogel sample was cut into specimens with dimensions of 10mm × 10mm × 2mm. Its resistance was measured using the linear scanning voltammetry method on an electrochemical workstation. The conductivity was calculated as σ = L / RS, where σ (S / m) represents the conductivity of the hydrogel sample, R (Ω) represents the resistance of the hydrogel sample, and L and S are the length (mm) and cross-sectional area (mm²) of the hydrogel sample, respectively. 2 ); The hydrogel sample from Example 1 was encapsulated with 3M ultra-high adhesion tape (VHB) and used as a strain sensor. It was fixed to different parts of the human body (e.g., pulse, smiling, swallowing, wrist, elbow, knee) to test its sensing capability. The relative resistance change ΔR / R0 of the hydrogel sensor under a constant voltage of 0.5V was measured using the It curve test method on an electrochemical workstation. Figure 1-6 As shown, the formula for calculating the relative resistance change ΔR / R0 of the hydrogel is: ΔR / R0=(R-R0) / R0×100%, where R0 and R are the resistance at no strain and the real-time resistance under a certain strain, respectively.

[0043] Table 1

[0044] Figure 1-6 This paper demonstrates the relative resistance changes of the strain sensor prepared by the composite hydrogel in this application at different parts of the human body (such as pulse, smile, swallowing, wrist, elbow, and knee). It can be seen that the dual-network composite hydrogel of this application can be effectively used as a strain sensor. It shows that the dual-network composite hydrogel has the ability to monitor strain in real time when used as a wound dressing. It can adapt to complex external environments, monitor the tensile and compressive stress at the wound site in real time, and provide data support for wound healing and motion monitoring.

[0045] As can be seen from the performance test results of Examples 1-10 and Comparative Examples 1-3 in Table 1, the dual-network composite hydrogel with added lithium chloride in this application has excellent antifreeze and conductivity, which also means that the dual-network composite hydrogel in this application can still maintain soft and stable sensing performance at low temperatures.

[0046] The performance test results of Examples 1 and 2-6 show that the silk fibroin-polyethylene glycol graft copolymer modified with polyethylene glycol glycidyl ether has the β-sheet structure of silk fibroin and the hydrophilic flexible long chain of polyethylene glycol. When introduced into the PVA-PAA network, it can form stronger physical crosslinks such as hydrogen bonds and hydrophobic interactions with the two, and as a reinforcing and toughening unit of the network, it effectively improves the mechanical and electrical properties of the conductive hydrogel matrix.

[0047] Furthermore, based on the performance test results of Examples 1, 7-9, and Comparative Example 3, it can be seen that by introducing hydroxybutyl chitosan into the composite hydrogel formed using the technical means of this application, the mechanical properties of the hydrogel after freezing are significantly better than those of the group without added hydroxybutyl chitosan. This also demonstrates that the addition of hydroxybutyl chitosan can synergistically enhance the hydrogel's ability to bind free water with lithium chloride, significantly slow down water evaporation in dry environments and further lower the freezing point, and also help the hydrogel maintain the stability of its internal water content, ensuring the consistency of electrical and mechanical properties in complex environments or long-term use. This allows the hydrogel to ensure the long-term stability of the sensing signal when used as a flexible wearable strain sensor, even with the generation of small strains. In Comparative Example 3, which only used hydroxybutyl chitosan, it was difficult to achieve the same effect.

[0048] The technique of directly adding hydroxybutyl chitosan to the hydrogel matrix in Example 10 is also obviously insufficient. This may be because the encapsulation of hydroxybutyl chitosan to form a coated independent unit further enhances the dispersion uniformity of molybdenum disulfide nanosheets in the hydrogel matrix, optimizes the interfacial bonding ability between nanoparticles and matrix network, and enables the hydrogel to maintain high conductivity while ensuring sensing sensitivity. Test Example 2

[0049] The composite hydrogels prepared in Examples 1-4, Examples 7-10 and Comparative Example 1 were used to conduct in vivo antibacterial animal experiments for the treatment of wound healing. This experiment followed the basic principles of animal ethics, fully considered the welfare of the experimental animals, and ensured that the scientific nature of the experiment was respected and protected, and that the basic rights of the animals were respected and protected.

[0050] S1: Establish a rat model of bacterial wound defects: After thorough disinfection of the laboratory workbench, female BALB / c mice (6 weeks old, 15–18 g) were taken and injected intraperitoneally with 100 μL of sodium amobarbital. Once the mice were anesthetized, the hair on their backs was removed, and a circular wound approximately 6 mm in diameter was created in the hairless area of ​​the back. 10 μL of a cultured bacterial suspension (E. coli or S. aureus, 2.0 × 10⁻⁶) was then injected. 8 CFU·mL −1Injected into the wound to establish an infected wound model for subsequent experiments; S2: Evaluation of in vivo antibacterial therapy and wound healing using composite hydrogel: Mice that had undergone wound infection were randomly divided into the following groups 24 hours later, with 5 mice in each group: (1) Blank control group; (2) Control group: Comparative example 1; (3) Experimental group: Composite hydrogel group of Examples 1-4 and Examples 7-10; The above groups were then tested under photothermal (808 nm laser irradiation of the wound for 5 minutes) and non-photothermal conditions (room temperature laboratory conditions). According to the photothermal experiment, the temperature can reach 50℃ under 808 nm laser irradiation, reaching the sterilization temperature. Photographs of the wound were taken on days 0, 2, 5, 7, and 10, and the wound size was measured. The calculation formula is as follows: S = π × (d / 2) 2 S represents the wound area, and d represents the average diameter of the wound. The wound healing rates at 2d, 5d, 7d, and 10d are calculated respectively.

[0051] Table 2

[0052] As can be seen from the performance test results in Table 2, the composite nanoparticles formed by coating molybdenum disulfide with quaternary ammonium salt are encapsulated in the hydrogel matrix. Under photothermal conditions, a dual-effect synergistic antibacterial core is formed, which combines chemical contact sterilization and physical photothermal sterilization. This effectively improves the therapeutic effect of hydrogel as a medical dressing on wounds.

[0053] According to the performance test results of Examples 1 and 2-4, the silk fibroin-polyethylene glycol grafted group modified with polyethylene glycol glycidyl ether showed a significant improvement in wound healing effect. This is because the introduction of the polyethylene glycol structure greatly improves the dispersibility and compatibility of silk fibroin in the conductive hydrogel matrix, and on the other hand, it endows the hydrogel surface with better hydrophilicity and cell affinity. When applied as a dressing to wounds, it can better maintain the moist environment of the wound, promote cell adhesion and migration, promote cell proliferation and collagen deposition, and accelerate wound healing.

[0054] Furthermore, in Examples 7-10, molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan were obtained through electrostatic self-assembly. Hydroxybutyl chitosan was then added to the dispersion for physical winding and coating to form structural units before being incorporated into the hydrogel matrix. It can be seen that the introduction of hydroxybutyl chitosan further enhanced the wound-healing effect of the dressing, and showed a more significant effect compared to directly adding hydroxybutyl chitosan to the hydrogel matrix. This may be because hydroxybutyl chitosan effectively enhances the dressing's water-locking ability. It forms a strong hydrogen bond network with water molecules, converting free water into bound water, effectively preventing excessive evaporation of moisture during wound healing and preventing excessive loss of wound exudate. This maintains a moderately moist environment suitable for wound healing on the wound surface. On the other hand, hydroxybutyl chitosan is thermosensitive, which allows the composite hydrogel dressing to form a denser, more adhesive physical barrier on the wound surface when in contact with the wound (body temperature approximately 37°C). This barrier adheres more closely to the wound, reducing the stimulation of adverse external environmental factors.

[0055] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A method for preparing a dual-network composite hydrogel, characterized in that, Includes the following steps: S1: Molybdenum disulfide nanosheets were dispersed in a quaternary ammonium salt chitosan solution and stirred to perform electrostatic self-assembly, resulting in a quaternary ammonium salt chitosan-coated molybdenum disulfide composite nanoparticle dispersion. After freeze-drying, the composite nanoparticle powder was formed. S2: Add polyvinyl alcohol to water, heat and stir to dissolve, then add polyacrylic acid, stir evenly, add functional additives, then add lithium chloride, and continue stirring to form a hydrogel prepolymer. S3: Add the composite nanoparticle powder to the hydrogel prepolymer liquid, stir evenly, remove air bubbles under vacuum, and obtain the double-network composite hydrogel after photocuring.

2. The method for preparing the dual-network composite hydrogel according to claim 1, characterized in that, In step S2, silk fibroin-polyethylene glycol graft copolymer is added to the mixed solution of polyvinyl alcohol and polyacrylic acid before heating and stirring.

3. The method for preparing the dual-network composite hydrogel according to claim 2, characterized in that, The mass ratio of the polyvinyl alcohol and silk fibroin-polyethylene glycol graft copolymer is 2:(5-10).

4. The method for preparing the dual-network composite hydrogel according to claim 2, characterized in that, The preparation method of the silk fibroin-polyethylene glycol graft copolymer includes the following steps: Silk fibroin was dissolved in lithium bromide solution to prepare a silk fibroin solution; Polyethylene glycol glycidyl ether was added to the silk fibroin solution, and the mixture was subjected to ultrasonic treatment followed by heating. After the reaction was completed, the mixture was purified by dialysis and then freeze-dried to obtain the final product.

5. The method for preparing the dual-network composite hydrogel according to claim 4, characterized in that, The raw material for the polyethylene glycol glycidyl ether includes polyethylene glycol with a molecular weight of 1000-2000.

6. The method for preparing the dual-network composite hydrogel according to claim 1, characterized in that, In step S1, hydroxybutyl chitosan was also added. Specifically, molybdenum disulfide nanosheets were dispersed in a quaternary ammonium salt chitosan solution, and electrostatic self-assembly was carried out by stirring to obtain a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan. Then, hydroxybutyl chitosan was added to the dispersion, and stirring was continued to obtain a dispersion of molybdenum disulfide composite nanoparticles coated with quaternary ammonium salt chitosan and hydroxybutyl chitosan. After freeze-drying, composite nanoparticle powder was formed.

7. The method for preparing the dual-network composite hydrogel according to claim 6, characterized in that, The mass ratio of the quaternary ammonium salt chitosan to hydroxybutyl chitosan is 1:(0.5-1.5).

8. A dual-network composite hydrogel, characterized in that, It is prepared by the preparation process of the dual-network composite hydrogel according to any one of claims 1-7.

9. The application of the dual-network composite hydrogel according to claim 8 in the preparation of flexible wearable strain sensors.

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