Photoelectric wound repair hydrogel dressing

Abstract

The invention relates to the technical field of medical instruments, in particular to a photo-piezoelectric hydrogel dressing for wound repair. The hydrogel dressing realizes self-energized micro-electrical stimulation and anti-oxidation-antibacterial-anti-inflammatory integrated treatment through'energy-drug 'double closed-loop synergy: the PVDF / ZnO nanofiber on the upper layer can convert human body micro-motion and external light into micro-electrical stimulation to promote cell migration, proliferation and angiogenesis; the curcumin at the lower layer cooperates with the nano-silver to block the'oxidative stress-inflammation-infection 'vicious circle of chronic wounds. The dressing is soft and fit, does not need an external power supply, is excellent in biocompatibility, provides a self-driven multifunctional nursing scheme for refractory wounds, and has wide clinical popularization and market application prospects.

Description

Technical Field

[0001] This application relates to the field of medical device technology, specifically to a photopiezoelectric wound repair hydrogel dressing. Background Technology

[0002] In recent years, electrostimulation therapy and phototherapy have been proven to effectively promote tissue repair and angiogenesis by regulating cell proliferation, migration, and inflammatory responses. Currently, research has developed a self-powered triboelectric nanogenerator (TENG) patch based on molybdenum disulfide and gelatin-methacrylyl hydrogel for diabetic wound healing. This TENG can harvest biomechanical energy and generate an electric field, while simultaneously utilizing the photothermal effect of MoS2 to synergistically promote cell migration, collagen deposition, and angiogenesis. Furthermore, phototherapy strategies such as ultraviolet (UVC) and near-infrared light can exert bactericidal, immune microenvironment-regulating, and re-epithelialization effects through photothermal or photochemical effects, providing diversified physical interventions for wound healing. However, existing phototherapy methods mostly rely on single photothermal and photochemical effects to promote tissue healing and generally suffer from problems such as the need for an external power source and poor biocompatibility. At the same time, existing dressings also struggle to integrate the "photoelectric self-powered - biomechanical energy conversion micro-electric stimulation" function within the same system to better promote wound healing.

[0003] Therefore, developing a dressing that can overcome the above limitations, integrate multiple mechanisms to synergistically promote wound healing, achieve self-powered operation without relying on an external power source, and possess excellent biocompatibility is of vital practical significance and application value for solving the clinical challenges of treating refractory wounds and improving wound healing efficiency and safety. Summary of the Invention

[0004] To address the aforementioned problems, one aspect of the present invention provides a flexible material comprising a gel layer and an energy conversion layer; The gel layer includes healing-promoting active substances and conductive functional substances; The energy conversion layer includes a piezoelectric material.

[0005] In some embodiments, the healing-promoting active substance is selected from at least one of natural products, synthetic small molecules, and biological macromolecules.

[0006] In some embodiments, the natural product is a natural active ingredient derived from plants, animals, microorganisms, or marine organisms.

[0007] In some embodiments, the natural product is selected from: curcumin, resveratrol, tanshinone, actinomycin D, streptomycin, chondroitin sulfate, seaweed polysaccharide, and bee venom peptide.

[0008] In some implementations, the natural product is curcumin.

[0009] In some embodiments, the synthetic small molecule is a low molecular weight active compound prepared by chemical synthesis or semi-synthesis; preferably, it is selected from at least one of nonsteroidal anti-inflammatory, antibacterial, cell proliferation-promoting, and antioxidant compounds.

[0010] In some embodiments, the synthetic small molecule is selected from: ibuprofen, naproxen, mupirocin, triclosan, nicotinamide, N-acetylcysteine, and pirfenidone.

[0011] In some embodiments, the biomacromolecule is a biologically active protein, polypeptide, nucleic acid, polysaccharide, or derivative thereof; preferably, it is selected from at least one of polypeptides, antimicrobial peptides, nucleic acids, and glycosaminoglycans.

[0012] In some embodiments, the biomacromolecule is selected from: recombinant human epidermal growth factor, keratinocyte growth factor, defensin, antimicrobial peptide LL-37, and hyaluronic acid.

[0013] In some embodiments, the conductive functional material includes at least one of metal nanoparticles, conductive polymers, and carbon-based nanomaterials.

[0014] In some embodiments, the metal nanoparticles are selected from: nano-silver, nano-gold, nano-copper, nano-platinum, and nano-palladium.

[0015] In some embodiments, the conductive polymer is selected from: polyaniline, polypyrrole, poly3,4-ethylenedioxythiophene, polythiophene, poly(p-phenylacetylene), polyaniline-sulfonic acid doped derivatives, and polypyrrole-polyethylene glycol composite derivatives.

[0016] In some embodiments, the carbon-based nanomaterials are selected from: carbon nanotubes, graphene oxide, reduced graphene oxide, graphene quantum dots, nitrogen-doped graphene, carbon quantum dots, carbon black, and mesoporous carbon.

[0017] In some implementations, the conductive functional material is a metal nanoparticle.

[0018] In some embodiments, the conductive functional material is at least one of nano-silver, nano-gold, and nano-copper.

[0019] In some implementations, the conductive functional material is nano-silver.

[0020] In some embodiments, the gel layer comprises a biocompatible polymer.

[0021] In some embodiments, the biocompatible polymer is selected from at least one of hyaluronic acid, sodium alginate, chitosan, collagen, gelatin, polylactic acid, polycaprolactone, hydroxypropyl methylcellulose, and polyvinyl alcohol.

[0022] In some embodiments, the biocompatible polymer is selected from at least one of hyaluronic acid, sodium alginate, chitosan, collagen, and gelatin.

[0023] In some embodiments, the biocompatible polymer is selected from at least one of hyaluronic acid, sodium alginate, and chitosan.

[0024] In some embodiments, the biocompatible polymer is sodium alginate.

[0025] In some embodiments, the piezoelectric material is selected from at least one of inorganic piezoelectric materials, organic piezoelectric materials, and composite piezoelectric materials.

[0026] In some embodiments, the inorganic piezoelectric material is selected from at least one of zinc oxide, barium titanate, lead zirconate titanate, lithium niobate, lead titanate, and potassium sodium niobate.

[0027] In some embodiments, the organic piezoelectric material is selected from at least one of polyvinylidene fluoride, polyvinylidene fluoride copolymer, polylactic acid, and polyhydroxyalkanoates; preferably polyvinylidene fluoride.

[0028] In some embodiments, the composite piezoelectric material is selected from at least one of: organic-inorganic piezoelectric composite materials, inorganic-inorganic piezoelectric composite materials, and piezoelectric material-polymer matrix composite materials.

[0029] In some embodiments, the organic-inorganic piezoelectric composite material is selected from: polyvinylidene fluoride / zinc oxide composite piezoelectric material, polyvinylidene fluoride / barium titanate composite piezoelectric material, polyvinylidene fluoride-trifluoroethylene / zinc oxide composite piezoelectric material, polyvinylidene fluoride-hexafluoropropylene / barium titanate composite piezoelectric material, polylactic acid / zinc oxide composite piezoelectric material, polylactic acid / barium titanate composite piezoelectric material, and polyhydroxyalkanoate / potassium sodium niobate composite piezoelectric material.

[0030] In some embodiments, the inorganic-inorganic piezoelectric composite material is selected from: zinc oxide / barium titanate composite piezoelectric material, lead zirconate titanate / zinc oxide composite piezoelectric material, and potassium sodium niobate / barium titanate composite piezoelectric material.

[0031] In some embodiments, the piezoelectric material-polymer matrix composite material is selected from: lead zirconate titanate / epoxy resin composite piezoelectric material, lead zirconate titanate / silicone rubber composite piezoelectric material, barium titanate / polyurethane composite piezoelectric material, and zinc oxide / polyvinyl alcohol composite piezoelectric material.

[0032] In some embodiments, the nanosilver has a particle size of 1-200 nm.

[0033] In some embodiments, the nanosilver has a particle size of 50-150 nm.

[0034] In some embodiments, the nanosilver has a particle size of 50-140 nm.

[0035] In some embodiments, the nanosilver has a particle size of 60-120 nm.

[0036] In some embodiments, the curcumin loading is 0.1%-50% of the total mass of the gel layer.

[0037] In some implementations, the curcumin loading is 1%-50%.

[0038] In some implementations, the curcumin loading is 5%-50%.

[0039] In some implementations, the curcumin loading is 5%-40%.

[0040] In some implementations, the curcumin loading is 5%-30%.

[0041] In some implementations, the curcumin loading is 5%-20%.

[0042] In some embodiments, the curcumin loading is 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%.

[0043] In some embodiments, the curcumin loading is 5%, 10%, 15%, or 20%.

[0044] In some embodiments, the piezoelectric material is a polyvinylidene fluoride / zinc oxide composite piezoelectric material; the gel layer includes nano-silver and curcumin.

[0045] In some implementations, the gel layer and the energy conversion layer are connected by electrospinning.

[0046] In some embodiments, the gel layer further comprises a piezoelectric material; the piezoelectric material is defined as described above.

[0047] In some embodiments, the piezoelectric material is an organic piezoelectric material.

[0048] In some embodiments, the piezoelectric material is polyvinylidene fluoride.

[0049] In another aspect, the present invention provides a method for preparing the aforementioned flexible material, comprising the following steps: Step 1: Dissolve zinc oxide and polyvinylidene fluoride-trifluoroethylene in N,N-dimethylformamide and stir magnetically overnight at room temperature to obtain a polyvinylidene fluoride / zinc oxide solution; Step 2: Prepare two bottom layer solutions, namely an N,N-dimethylformamide solution containing silver nanoparticles and polyvinylidene fluoride, and an aqueous solution containing polyvinyl alcohol and sodium alginate, respectively, and stir magnetically overnight at room temperature; Step 3: Prepare the first layer by electrospinning the polyvinylidene fluoride / zinc oxide solution and collect it on a rotating drum; Step 4: The two solutions at the bottom layer are spun into a second layer by electrospinning with dual nozzles, and the second layer is collected on a rotating drum to form a double-layer film; Step 5: Freeze-dry the double-layer membrane; Step 6: Crosslink the freeze-dried bilayer film in a calcium chloride solution to obtain the flexible material.

[0050] In some implementations, the mass fraction of zinc oxide in step 1 is 3%.

[0051] In some implementations, in step 1, the mass fraction of polyvinylidene fluoride-trifluoroethylene is 8%.

[0052] In some implementations, the mass fraction of silver nanoparticles in step 2 is 0.3%.

[0053] In some implementations, in step 2, the mass fraction of polyvinylidene fluoride is 8%.

[0054] In some implementations, in step 2, the mass fraction of polyvinyl alcohol is 9%.

[0055] In some implementations, the mass fraction of sodium alginate in step 2 is 2%.

[0056] In another aspect, the present invention provides a flexible material for promoting wound healing, or a flexible material obtained by the aforementioned preparation method.

[0057] Another aspect of the present invention provides the use of the aforementioned flexible material, or the flexible material obtained by the aforementioned preparation method, in the preparation of a medicament for promoting wound healing.

[0058] Beneficial effects The flexible material provided in this application combines optoelectronic semiconductors, nano-Ag conductors, piezoelectric materials, and bioactive ingredients, and is prepared using electrospinning technology. The flexible material consists of two layers: an upper layer of polyvinylidene fluoride / zinc oxide composite piezoelectric material as a photoelectric conversion layer, and a lower layer of hydrogel loaded with nano-silver and curcumin. This flexible material integrates photoelectric and piezoelectric conversion functions, converting mechanical and light energy into electrical energy to stimulate nerves and cells in the wound area and promote tissue repair. This dual energy self-conversion mechanism allows it to autonomously provide power support for wound healing without relying on an external power source, greatly improving the efficiency and quality of wound healing. It achieves dual-mode capture and conversion of surface mechanical energy and ambient light energy, and through a painless and non-invasive intelligent repair method, synergistically promotes the repair of difficult-to-heal wounds with the nano-silver and curcumin in the dressing. Attached Figure Description

[0059] Figure 1 This is an image showing the appearance of a nanofiber hydrogel dressing.

[0060] Figure 2 This diagram illustrates the mechanism by which nanofiber hydrogels intelligently repair wounds.

[0061] Figure 3 Characterization diagrams of nanofiber hydrogel dressings and their related properties and applications. Figure 3 (a) is a scanning electron microscope (SEM) image of the upper layer of the nanofiber hydrogel dressing; Figure 3 (b) in the image is a SEM image of the lower layer of the nanofiber hydrogel dressing; Figure 3 (c) in the figure represents the stress-strain curve of the nanofiber hydrogel dressing; Figure 3 (d) in the diagram is a schematic representation of the fiber dressing and the flexible sensor assembled from the dressing.

[0062] Figure 4 The image shows the antibacterial test results of the nanofiber hydrogel dressing; Ctrl represents the blank control group.

[0063] Figure 5 Figure 1 shows the experimental results of DPPH free radical scavenging of nanofiber hydrogel dressing.

[0064] Figure 6 Figure showing the results of blood compatibility and cell compatibility experiments on nanofiber hydrogel dressings; Figure 6 (a) in the image is an optical image of an in vitro hemolysis experiment; where ddH2O represents double-distilled water; PBS represents phosphate buffer; and Gauze represents ordinary medical gauze dressing that does not contain curcumin or other active ingredients. Figure 6 (b) in the figure is a bar chart showing the hemolysis rate of the nanofiber dressing; Figure 6 (c) shows the staining images of live and dead cells and the statistical graph of cell viability in co-culture of nanofiber hydrogel dressing and HaCat cells; where Ctrl represents the blank control group.

[0065] Figure 7 Characterization diagram of the photo-to-electric conversion performance of the nanofiber hydrogel sensor; Figure 7 (a) is a schematic diagram of the assembled structure of the nanofiber hydrogel sensor; Figure 7 (b) is a schematic diagram of photoelectric conversion of the nanofiber layer of the polyvinylidene fluoride / zinc oxide composite piezoelectric material; Figure 7 (c) in the figure is a graph of photovoltage test data of the nanofiber hydrogel sensor; Figure 7 (d) in the figure represents the photocurrent test data of the nanofiber hydrogel sensor.

[0066] Figure 8 The piezoelectric test results for the nanofiber hydrogel sensor are shown. Figure 8 (a) in the figure is a piezoelectric test line graph of nanofiber hydrogel sensors with different curcumin loadings. Figure 8 (b) shows the piezoelectric test of the nanofiber hydrogel sensor under a force of 1N. Figure 8 (c) shows the piezoelectric test of the nanofiber hydrogel sensor attached to the wrist joint.

[0067] Figure 9 Image showing the effect of nanofiber hydrogel dressing on promoting skin repair in mice; Figure 9 In the image (a), the nanofiber hydrogel dressing is used for wound healing in mice; where Ctrl represents the blank control group; and Gauze represents ordinary medical gauze dressing without curcumin or other active ingredients. Figure 9 (b) shows a section of mouse skin tissue stained with hematoxylin and eosin (HE) and Masson on day 10. Figure 9 (c) in the figure is a bar chart showing the statistical area of ​​wound healing in mice. Detailed Implementation

[0068] I. Definition As used herein, the terms “comprising” and “including” are open-ended definitions, meaning that the listed components, structures, or steps are essential components of the technical solution, but do not exclude the existence of other parts not explicitly listed, and these parts do not affect the core function and effect of the nanofiber hydrogel dressing described in this application.

[0069] The term "healing-promoting active substance" refers to a biologically active component that can directly or indirectly act on cells, tissues, or the microenvironment of the wound area, thereby promoting one or more physiological processes during wound healing, such as inflammation regulation, cell proliferation and migration, angiogenesis, tissue remodeling, or antibacterial activity.

[0070] The term "conductive functional material" refers to a class of functional materials that possess charge transport capabilities, enabling electronic or ion conduction within a material system. These materials can synergistically interact with other components in flexible materials, ensuring conductivity to meet the piezoelectric signal conduction requirements of the energy conversion layer while maintaining the core properties of flexible materials such as biocompatibility and mechanical flexibility. Their core functions include, but are not limited to: reducing the resistance of the material system to achieve efficient charge transfer; assisting in the conduction and output of electrical signals generated by piezoelectric materials; and, in some types (such as nano-silver), simultaneously imparting antibacterial properties to synergistically promote wound healing. Furthermore, during application, they must meet the requirements of being non-biotoxic, not interfering with the efficacy of healing-promoting active substances, and being stably dispersed in gel layers or other matrices.

[0071] The term "piezoelectric material" refers to a class of functional materials that exhibit the piezoelectric effect. Specifically, when subjected to mechanical stress (such as compression, tension, bending, etc.), the internal crystal structure deforms, causing a relative displacement of the positive and negative charge centers, thereby generating detectable polarization charges on the material surface (i.e., the positive piezoelectric effect). Simultaneously, when the material is placed in an external electric field, it undergoes mechanical deformation (i.e., the inverse piezoelectric effect), and the aforementioned piezoelectric effect is reversible, enabling the direct conversion between mechanical energy and electrical energy.

[0072] II. Examples All chemical reagents used in the embodiments of this application were analytical grade. The specific names, English labels, key specifications, and supplier information of each reagent are shown in Table 1.

[0073] Table 1: Information and sources of reagents used in this application Example 1: Preparation of Nanofiber Hydrogel Dressing Step 1: A polyvinylidene fluoride / zinc oxide solution was prepared by dissolving 3% (mass fraction) zinc oxide and 8% (mass fraction) polyvinylidene fluoride-trifluoroethylene in DMF, and then magnetically stirred overnight at room temperature.

[0074] Step 2: Prepare two bottom layer solutions separately: (i) DMF solutions containing 0.3% (mass fraction) silver nanoparticles, 5%, 10%, 20% curcumin (mass fraction) and 8% (mass fraction) polyvinylidene fluoride; (ii) An aqueous solution containing 9% (mass fraction) polyvinyl alcohol and 0.2% (mass fraction) sodium alginate. Both solutions were magnetically stirred overnight at room temperature and then electrospun.

[0075] Step 3: Prepare the first layer by electrospinning from the polyvinylidene fluoride / zinc oxide solution using a No. 22 needle at a feed rate of 20 μL / min under a voltage of 16 kV for 8 hours.

[0076] Step 4: Prepare the second layer by electrospinning with dual nozzles at feed rates of 20 μL / min and 8 μL / min respectively, for 8 hours.

[0077] Step 5: The spun double-layer film is collected on a rotating drum and freeze-dried for 24 hours.

[0078] Step 6: Crosslink the freeze-dried bilayer membrane in calcium chloride solution to obtain a bilayer nanofiber hydrogel membrane.

[0079] The upper and lower layers are directly woven together by electrospinning, without the need for additional materials as adhesives.

[0080] The appearance of the nanofiber hydrogel dressing prepared by the above method is as follows: Figure 1 As shown.

[0081] Test Example 1: Flexibility Test In the wound healing process, the flexibility and conformability of nanofiber hydrogel dressings are key performance parameters, directly affecting patient comfort and wound healing quality. Therefore, we conducted flexibility and stress-strain tests on the nanofiber hydrogel dressing prepared in Example 1. Figure 3 As shown in (c), 5% Cur, 10% Cur, and 20% Cur represent PVDF / ZnO@PVDF / Ag / SA bilayer nanofiber hydrogels loaded with curcumin. Experimental results (see details...) Figure 3 (d) The nanofiber hydrogel dressing of this application can conform well to the human wrist and joint areas, and can freely stretch and bend with body movement. Stress-strain curves are shown (see details). Figure 3 (c) As the curcumin content increases, the Young's modulus of the material improves, while still maintaining its flexibility. This excellent mechanical property effectively avoids secondary damage caused by dressing traction during wound healing, thus providing a stable and comfortable repair environment for the wound.

[0082] Table 2: Stress-strain data of nanofiber hydrogel dressings Test Example 2: Antibacterial Test In wound care, the antibacterial properties of dressings are one of the most crucial characteristics. Bacterial infection can significantly delay wound healing and may also lead to serious complications such as suppuration, inflammation, and even sepsis. Therefore, developing wound dressings with highly effective antibacterial properties is of great significance for preventing infection and promoting tissue repair. To verify the antibacterial effect of the nanofiber hydrogel dressing of this application, we selected *Escherichia coli* (E. coli)... Escherichia coli , E. coli ) and Staphylococcus aureus ( Staphylococcus aureus , S.aureus As a model strain, the antibacterial properties of the dressing film prepared in Example 1 were tested. Figure 4 As shown in the experimental results, the nanofiber hydrogel dressing of this application exhibits significant antibacterial activity against both Escherichia coli and Staphylococcus aureus. Specifically, the antibacterial rate of the nano-silver hydrogel dressing exceeds 90%, and the antibacterial rate of the curcumin-loaded hydrogel is almost 100%. This indicates that the nanofiber hydrogel dressing of this application possesses excellent antibacterial properties, which helps to significantly reduce the risk of wound infection, providing a sterile and stable healing environment for the wound, thereby accelerating the tissue repair process.

[0083] Test Example 3: Antioxidant Test Oxidative stress in the wound microenvironment is one of the core factors hindering healing. Therefore, antioxidant capacity has become a key indicator for evaluating functional dressings, especially for pathological wounds dominated by oxidative stress, such as diabetic foot ulcers, chronic ulcers in the elderly, and radiation injuries. The antioxidant properties of dressings are a crucial consideration affecting their repair efficacy. To this end, we conducted a DPPH free radical scavenging experiment, such as... Figure 5 As shown, the curcumin-loaded nanofiber hydrogel dressing significantly increased the DPPH free radical scavenging rate, proving that the curcumin-loaded nanofiber hydrogel dressing has antioxidant activity.

[0084] Test Example 4: Biocompatibility Test Skin wound dressings need to be in direct and prolonged contact with blood cells, immune cells, and keratinocytes, therefore, they must possess excellent blood compatibility and cell compatibility. To verify the suitability of the nanofiber hydrogel dressing of this application, in vitro hemolysis experiments and HaCaT cell compatibility evaluations were conducted. A 3% (v / v) red blood cell suspension was prepared using fresh anticoagulated human whole blood. Each group of nanofiber hydrogels (1 cm²) and the red blood cell suspension were incubated together at 37 ℃ for 1 h. ddH₂O was used as a positive control, and PBS as a negative control. Figure 6 (a) and Figure 6As shown in (b), the hemolysis rate of all curcumin-loaded nanofiber hydrogel excipients (5%, 10%, 20%, and 50% Cur) was less than 2%, indicating that the excipients had no significant destructive effect on erythrocyte membranes and good blood compatibility. After co-culturing HaCaT cells with each group of fiber gel extracts (0.1 g / mL, DMEM, 37 ℃) for 24 h, 48 h, and 72 h, cell viability was detected using the MTT assay. Figure 6 As shown in (c), the cell viability in all experimental groups was above 90%, with no statistically significant difference compared to the blank control group. 24-hour live / dead cell fluorescence staining further confirmed that the material extract did not induce significant cell membrane rupture or apoptosis. These results collectively demonstrate that the nanofiber hydrogel dressing of this application possesses good in vitro cell compatibility and meets the safety requirements for skin dressings.

[0085] Test Example 5: Photoelectric Properties Test Electrical stimulation, as an emerging wound treatment method, has been widely proven to significantly accelerate the wound healing process, shorten healing time, and improve the quality of tissue regeneration. The ZnO contained in the upper layer of the thin film is a high-performance photocatalytic material with excellent ultraviolet absorption capabilities. When ultraviolet light irradiates the upper layer of the film, electrons in the ZnO jump from the valence band to the conduction band, forming free electron-hole pairs, thereby generating a voltage, such as... Figure 7 As shown, we assembled a simple sensor device from ZnO thin films and conducted photoelectric tests. The experimental results showed that under irradiation with ultraviolet light at a wavelength of 254 nm, photovoltage and photocurrent can be generated, with the highest photovoltage and photocurrent reaching 5.5 V and 580 nA, respectively. This photoelectric conversion mechanism provides continuous energy support for wound healing, accelerates cell proliferation and tissue repair, and reduces inflammatory response and oxidative damage caused by ultraviolet exposure, significantly improving the quality and efficiency of wound healing.

[0086] Test Example 6: Piezoelectric Characteristic Test Besides photoelectric conversion performance, the piezoelectric properties of materials are also noteworthy. In this study, we designed a functional dressing film using polyvinylidene fluoride (PVDF) as the main material. PVDF is a typical piezoelectric polymer, capable of generating a considerable voltage output under external mechanical force, exhibiting excellent electromechanical conversion capabilities. The piezoelectric performance of the nanofiber hydrogel flexible sensor was tested, such as... Figure 8As shown, the PVDF film can output a stable voltage under various mechanical stimuli, with a maximum output voltage and current of 4.7 V and 98 nA, respectively. This indicates that the PVDF film can efficiently convert the mechanical energy generated during daily human activities into electrical energy, providing continuous low-intensity electrical stimulation to the wound area, thereby effectively regulating biological processes such as cell migration, proliferation, and angiogenesis, and promoting rapid wound healing.

[0087] Test Example 7: Mouse Wound Healing Test To fully verify the application potential of nanofiber hydrogel dressings in practical wound care, we applied them as wound dressings in mouse wound healing model experiments (e.g., Figure 9 (As shown in the figure). The experimental results show that the curcumin-loaded nanofiber hydrogel dressing significantly promotes the wound healing speed. Compared with other control groups, the healing effect is better, the wound closure time is shortened and the healing tissue is more intact.

[0088] In summary, this application utilizes electrospinning technology to prepare a bilayer "photoelectric self-powered - biomechanical energy conversion micro-electric stimulation" biosynthetic intelligent nanofiber hydrogel dressing. Under the synergistic effect of the "energy-drug" dual closed-loop system, the dressing achieves integrated treatment of self-powered micro-electric stimulation and anti-oxidation, antibacterial, and anti-inflammatory effects. The upper layer of PVDF / ZnO nanofibers possesses piezoelectric-photoelectric conversion properties, efficiently converting human micro-movements and external light into micro-electric stimulation, continuously promoting cell migration, proliferation, and angiogenesis. The lower layer of curcumin, as a natural polyphenol antioxidant, synergizes with nano-silver for broad-spectrum antibacterial activity and reduces inflammation, blocking the vicious cycle of "oxidative stress-inflammation-infection" in chronic wounds. Furthermore, this dressing is soft and conforms well to the skin, requires no external power source, and is self-powered solely by patient movement and ambient light, significantly reducing treatment complexity and cost, and exhibiting excellent biocompatibility. With its comprehensive advantages such as self-powered micro-electric stimulation, synergistic antioxidant-antibacterial-anti-inflammatory properties, environmental friendliness, and ease of wear, this double-layer film dressing provides a next-generation self-driven multifunctional wound care solution for refractory wounds, and has broad clinical promotion value and market application prospects.

Claims

1. A flexible material comprising a gel layer and an energy conversion layer; The gel layer includes healing-promoting active substances and conductive functional substances; The energy conversion layer includes a piezoelectric material.

2. The flexible material according to claim 1, wherein, The healing-promoting active substances are selected from at least one of the following: natural products, synthetic small molecules, and biological macromolecules; Preferably, the natural product is a natural active ingredient derived from plants, animals, microorganisms, or marine organisms; Preferably, the natural product is selected from: curcumin, resveratrol, tanshinone, actinomycin D, streptomycin, chondroitin sulfate, seaweed polysaccharide, and bee venom peptide; most preferably, it is selected from: curcumin; Preferably, the synthetic small molecule is a low molecular weight active compound prepared by chemical synthesis or semi-synthesis; preferably, it is selected from at least one of nonsteroidal anti-inflammatory, antibacterial, cell proliferation-promoting, and antioxidant compounds. Preferably, the synthetic small molecule is selected from: ibuprofen, naproxen, mupirocin, triclosan, nicotinamide, N-acetylcysteine, and pirfenidone; Preferably, the biomolecule is a biologically active protein, polypeptide, nucleic acid, polysaccharide, or derivative thereof; preferably, it is selected from at least one of polypeptides, antimicrobial peptides, nucleic acids, and glycosaminoglycans. Preferably, the biomolecules are selected from: recombinant human epidermal growth factor, keratinocyte growth factor, defensin, antimicrobial peptide LL-37, and hyaluronic acid.

3. The flexible material according to claim 1 or 2, wherein, The conductive functional material includes at least one of metal nanoparticles, conductive polymers, and carbon-based nanomaterials. Preferably, the metal nanoparticles are selected from: nano-silver, nano-gold, nano-copper, nano-platinum, and nano-palladium; Preferably, the conductive polymer is selected from: polyaniline, polypyrrole, poly3,4-ethylenedioxythiophene, polythiophene, poly(p-phenylacetylene), polyaniline-sulfonic acid doped derivative, and polypyrrole-polyethylene glycol composite derivative. Preferably, the carbon-based nanomaterials are selected from: carbon nanotubes, graphene oxide, reduced graphene oxide, graphene quantum dots, nitrogen-doped graphene, carbon quantum dots, carbon black, and mesoporous carbon. Preferably, the conductive functional material is metal nanoparticles; Preferably, the conductive functional material is at least one of nano-silver, nano-gold, and nano-copper; Preferably, the conductive functional material is nano-silver.

4. The flexible material according to any one of claims 1-3, wherein, The gel layer contains biocompatible polymers; Preferably, the biocompatible polymer is selected from at least one of the following: hyaluronic acid, sodium alginate, chitosan, collagen, gelatin, polylactic acid, polycaprolactone, hydroxypropyl methylcellulose, and polyvinyl alcohol. Preferably, the biocompatible polymer is selected from at least one of hyaluronic acid, sodium alginate, chitosan, collagen, and gelatin; Preferably, the biocompatible polymer is selected from at least one of hyaluronic acid, sodium alginate, and chitosan; Preferably, the biocompatible polymer is sodium alginate.

5. The flexible material according to any one of claims 1-4, wherein, The piezoelectric material is selected from at least one of the following: inorganic piezoelectric materials, organic piezoelectric materials, and composite piezoelectric materials; Preferably, the inorganic piezoelectric material is selected from at least one of the following: zinc oxide, barium titanate, lead zirconate titanate, lithium niobate, lead titanate, and potassium sodium niobate; Preferably, the organic piezoelectric material is selected from at least one of polyvinylidene fluoride, polyvinylidene fluoride copolymer, polylactic acid, and polyhydroxyalkanoates; more preferably, it is selected from polyvinylidene fluoride. Preferably, the composite piezoelectric material is selected from at least one of: organic-inorganic piezoelectric composite materials, inorganic-inorganic piezoelectric composite materials, and piezoelectric material-polymer matrix composite materials; Preferably, the organic-inorganic piezoelectric composite material is selected from: polyvinylidene fluoride / zinc oxide composite piezoelectric material, polyvinylidene fluoride / barium titanate composite piezoelectric material, polyvinylidene fluoride-trifluoroethylene / zinc oxide composite piezoelectric material, polyvinylidene fluoride-hexafluoropropylene / barium titanate composite piezoelectric material, polylactic acid / zinc oxide composite piezoelectric material, polylactic acid / barium titanate composite piezoelectric material, and polyhydroxyalkanoate / potassium sodium niobate composite piezoelectric material; Preferably, the inorganic-inorganic piezoelectric composite material is selected from: zinc oxide / barium titanate composite piezoelectric material, lead zirconate titanate / zinc oxide composite piezoelectric material, and potassium sodium niobate / barium titanate composite piezoelectric material; Preferably, the piezoelectric material-polymer matrix composite material is selected from: lead zirconate titanate / epoxy resin composite piezoelectric material, lead zirconate titanate / silicone rubber composite piezoelectric material, barium titanate / polyurethane composite piezoelectric material, and zinc oxide / polyvinyl alcohol composite piezoelectric material.

6. The flexible material according to any one of claims 1-5, wherein, The nano-silver has a particle size of 1-200 nm; Preferably, the particle size of the silver nanoparticles is 50-150 nm; Preferably, the particle size of the silver nanoparticles is 50-140 nm; Preferably, the particle size of the silver nanoparticles is 60-120 nm; Preferably, the curcumin loading is 0.1%-50% of the total mass of the gel layer; Preferably, the curcumin loading is 1%-50%; Preferably, the curcumin loading is 5%-50%; Preferably, the curcumin loading is 5%-40%; Preferably, the curcumin loading is 5%-30%; Preferably, the curcumin loading is 5%-20%; Preferably, the curcumin loading is 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. Preferably, the curcumin loading is 5%, 10%, 15%, or 20%.

7. The flexible material according to any one of claims 1-6, wherein, The piezoelectric material is a polyvinylidene fluoride / zinc oxide composite piezoelectric material; The gel layer comprises silver nanoparticles and curcumin; Preferably, the gel layer and the energy conversion layer are connected by electrospinning.

8. The flexible material according to any one of claims 1-7, wherein, The gel layer further comprises a piezoelectric material; the piezoelectric material is defined as described in any one of claims 1-7; Preferably, the piezoelectric material is an organic piezoelectric material; Preferably, the piezoelectric material is polyvinylidene fluoride.

9. A method for preparing the flexible material according to any one of claims 1-8, comprising the following steps: Step 1: Dissolve zinc oxide and polyvinylidene fluoride-trifluoroethylene in N,N-dimethylformamide and stir magnetically overnight at room temperature to obtain a polyvinylidene fluoride / zinc oxide solution; Step 2: Prepare two bottom layer solutions, namely an N,N-dimethylformamide solution containing silver nanoparticles and polyvinylidene fluoride, and an aqueous solution containing polyvinyl alcohol and sodium alginate, respectively, and stir magnetically overnight at room temperature; Step 3: Prepare the first layer by electrospinning the polyvinylidene fluoride / zinc oxide solution and collect it on a rotating drum; Step 4: The two solutions at the bottom layer are spun into a second layer by electrospinning with dual nozzles, and the second layer is collected on a rotating drum to form a double-layer film; Step 5: Freeze-dry the double-layer membrane; Step 6: Crosslink the freeze-dried bilayer film in a calcium chloride solution to obtain the flexible material; Preferably, in step 1, the mass fraction of zinc oxide is 3%; Preferably, in step 1, the mass fraction of polyvinylidene fluoride-trifluoroethylene is 8%; Preferably, in step 2, the mass fraction of silver nanoparticles is 0.3%; Preferably, in step 2, the mass fraction of polyvinylidene fluoride is 8%; Preferably, in step 2, the mass fraction of polyvinyl alcohol is 9%; Preferably, in step 2, the mass fraction of sodium alginate is 2%.

10. Use of the flexible material according to any one of claims 1-8, or the flexible material obtained by the preparation method according to claim 9, in the preparation of a medicament for promoting wound healing.

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