Bionic electrothermal coupling composite material based on pyroelectric effect, medical kit and use

Abstract

Disclosed in the present invention are a bionic electrothermal coupling composite material based on a pyroelectric effect, a medical kit and a use. The composite material subjected to corona poling treatment of the present invention has a surface potential of about 80 mv, the composite material can generate a pyroelectric effect by loading near-infrared light in vitro, and as can be seen from a diagram showing the variation of pyroelectric current with temperature, charge release occurs during temperature increase, thereby establishing correlation between electrical and thermal properties of a material, and realizing electrothermal effect-driven bionic coupling of the material. The synergistic effect of the piezoelectric properties and the pyroelectric effect is achieved by coupling, achieving the effects of promoting macrophage polarization and promoting tissue repair or healing. In exemplary embodiments, the charge generation capability of a material can be improved by controlling near-infrared light in vitro in a non-invasive manner, on-demand power supply based on a near-infrared light external field is realized, and the problem of insufficient long-term performance of a charged material after implanted into the body is solved.

Description

Biomimetic electrothermal coupling composite materials based on pyroelectric effect, medical kits and their applications

[0001] Cross-reference to related applications

[0002] This application claims priority to application number CN202410494067.9, filed on April 24, 2024, entitled "Bionic Electrothermal Coupling Composite Material Based on Pyroelectric Effect, Medical Kit and Application", and application number CN202410494061.1, filed on April 24, 2024, entitled "A Method and Application of Treating Nanocomposite Films by Near-Infrared Light", the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This invention relates to the field of photothermal therapy and pyroelectric effects combined, and more specifically to electrothermal biomimetic coupling composite materials based on pyroelectric effects and their use in promoting tissue repair or healing. Background Technology

[0004] The bone immune microenvironment plays a crucial regulatory role in biomaterial-mediated bone regeneration. Among these factors, the immune response of macrophages is a key element in inducing osteogenic stem cell formation. Macrophages are regulated and induced by various factors within the microenvironment, resulting in different functional states; this functional plasticity is known as macrophage polarization. Inflammatory macrophages are referred to as classically activated or M1 macrophages, while macrophages active in tissue regeneration are alternately activated or M2 macrophages. Studies have shown that regulating the M1 / M2 ratio may be used as a strategy to promote bone regeneration.

[0005] Cellular electrical signals are considered a major factor regulating the function of human macrophages. Some studies have constructed biomimetic electric fields to enhance intracellular calcium... 2+ Ion influx enhanced macrophage activation and phagocytosis. Piezo1 is an important gated ion channel for macrophages to sense and activate mechanical stimuli from implanted materials both in vivo and in vitro; it can regulate cellular calcium levels. 2+ Influx of calcium into macrophages activates downstream signaling pathways. 2+It targets and activates the Wnt / β-catenin signaling pathway, activating Arg1 and IL-10 transcription through the calcium-sensitive receptor CaSR, promoting cell polarization towards the M2 phenotype. Researchers found that the biomimetic electrical microenvironment of the BaTiO3 / P(VDF-TrFE) composite membrane attenuates pro-inflammatory M1 macrophage polarization under high glucose conditions, transforming it into a pro-healing M2 phenotype. This demonstrates that mimicking the endogenous electrical microenvironment can promote macrophage-mediated osteogenic differentiation of bone marrow mesenchymal stem cells, thereby promoting bone regeneration. These studies suggest that the electrical properties of biomaterials can regulate macrophage polarization towards promoting healing and osteogenic processes, and cellular mechanics and mechanosensory mechanisms may be potential targets.

[0006] Studies have reported that maintaining an appropriate temperature plays a decisive role in effective tissue repair, with the optimal temperature for bone tissue healing being 40-42℃. Increased temperature in the bone defect area promotes vasodilation and blood flow, ensuring the supply of oxygen and nutrients; it also enhances stem cell recruitment and osteogenic differentiation. Research has found that continuous or cyclic thermal stimulation can promote high expression of markers such as ALP and Runx2 in osteoblasts or pre-osteoblasts, and enhance the formation of mineralized nodules. These studies indicate that the thermal microenvironment plays a crucial role in tissue repair.

[0007] Currently, the application of photothermal therapy in immunology is mainly limited to regulating the immune microenvironment of tumor cells. Among various targeted external stimuli, near-infrared light (NIR) stands out due to its high tissue penetration, minimal damage to normal tissues, and ease of remote control, becoming one of the important means of current photothermal therapy. Researchers have utilized NIR to induce the photothermal effect of AuNPs, achieving better anti-tumor effects while reducing the release of inflammatory factors from macrophages.

[0008] The mechanism by which photothermal therapy affects macrophage polarization remains unclear. Heat shock proteins (HSPs) are believed to play an important role in cellular responses to external stimuli such as high temperature and ultraviolet radiation. Studies have shown that heat stimulation at 41°C increases the expression of HSP70 in monocytes and promotes cell polarization from the classically activated M1 type to the non-classically activated M2 type. Researchers used whole-genome sequencing to investigate the mechanism by which the photothermal properties of AuPd nanomaterials affect osteogenic differentiation of MC3T3 cells, finding that Wnt and Ca2+ are mainly upregulated by HSPs and BMP2. 2+ Signaling pathways are activated. Other studies have reported that HSPA1A (HSP70 homolog) overexpression promotes osteogenic differentiation of MSCs and is closely related to the Wnt / β-catenin signaling pathway. These studies suggest that HSP proteins and Ca2+ are involved in this process. 2+ The Wnt / β-catenin signaling pathway may play an important role in the photothermal properties of cell-responsive materials.

[0009] In summary, the effects of the electrical and thermal properties of biomaterials on promoting M2 polarization and osteogenic formation in macrophages, as well as their effectiveness in promoting bone regeneration, have been confirmed. However, existing research has mostly focused on the biological effects of single physical properties of materials. This is not compatible with the multi-factor comprehensive regulation process of the natural bone repair microenvironment and cannot be highly adapted to natural tissue formation. This may be one of the main factors contributing to the unsatisfactory bone repair effects of biomaterials at present.

[0010] The information in the background section is merely intended to illustrate the general background of the invention and should not be construed as an admission or implication in any way that such information constitutes prior art known to those skilled in the art. Summary of the Invention

[0011] To address at least some of the technical problems in the prior art, this invention provides a biomimetic electrothermal coupling composite material based on the pyroelectric effect and its use in promoting tissue repair and / or healing. It also provides a method for treating a nanocomposite film with near-infrared light, and the application of this method in promoting tissue repair and healing. Specifically, this invention includes the following:

[0012] In a first aspect, the present invention provides a biomimetic electrothermal coupling composite material based on the pyroelectric effect, comprising a polymer and inorganic photosensitive particles dispersed therein, wherein the polymer is selected from piezoelectric polymers and the inorganic photosensitive particles are inorganic fine particles coated with dopamine.

[0013] A second aspect of the present invention provides a method for preparing a biomimetic electrothermal coupling composite material based on the pyroelectric effect, comprising:

[0014] Steps for providing inorganic photosensitive particle dispersions and piezoelectric polymer solutions;

[0015] The step of mixing the dispersion with the piezoelectric polymer solution to obtain a suspension; and

[0016] Steps for preparing membrane materials using suspensions.

[0017] A third aspect of the present invention provides a medical kit for tissue repair or healing, comprising an energy generating unit and an energy receiving unit, wherein the energy generating unit is configured to generate light energy, and the energy receiving unit comprises the composite material described in the first aspect and is configured to be implanted in or disposed on the surface of a body, and to generate an electrothermal coupling effect when receiving light energy that has passed through tissue to reach the energy receiving unit within the body.

[0018] In some embodiments, the medical kit according to the third aspect, wherein the polymer is selected from at least one of polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and polylactic acid.

[0019] In some embodiments, according to the medical kit described in the third aspect, the inorganic photosensitizing particles are nanoscale ceramic particles.

[0020] In some embodiments, the medical kit according to the third aspect, wherein the nanoscale ceramic particles are selected from at least one of barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate.

[0021] In some embodiments, according to the medical kit of the third aspect, the energy generating unit is configured to generate a laser capable of generating continuous illumination and / or pulsed illumination.

[0022] A fourth aspect of the invention provides the use of a composite material in the preparation of a medical kit for tissue repair or healing, wherein the composite material is a biomimetic electrothermal coupling composite material based on the pyroelectric effect according to the first aspect.

[0023] A fifth aspect of the present invention provides a method for regulating immune cell polarization using a biomimetic electrothermal coupling composite material based on the pyroelectric effect, comprising the following steps:

[0024] (1) The steps for constructing a culture system using immune cells and composite materials; and

[0025] (2) The step of irradiating the culture system with light;

[0026] The composite material comprises a polymer and inorganic photosensitive particles dispersed therein; the light treatment comprises irradiating the composite material with near-infrared light, and the light treatment comprises continuous light treatment and / or pulsed light treatment; the regulation is to promote the differentiation of macrophages from M1 to M2 type.

[0027] In some implementations, the regulation refers to upregulating IL-10 expression in immune cells or increasing the proportion of CD206-positive cells in the immune cell population.

[0028] In a sixth aspect, the present invention provides an immune cell obtained by the method described in the fifth aspect.

[0029] In a seventh aspect, the present invention provides a method for treating a nanocomposite film with near-infrared light. The nanocomposite film is composed of nano-ceramic particles with an organic coating uniformly dispersed in a polymer matrix. The nanocomposite film undergoes corona polarization treatment, and the surface potential of the treated nanocomposite film is at the same level as the intrinsic potential of the human body, i.e., about 80mV. The near-infrared light treatment involves heating the corona-polarized nanocomposite film with near-infrared laser and / or pulsed light, and the surface temperature of the treated nanocomposite film reaches 40-42°C.

[0030] Furthermore, the corona polarization treatment conditions for the nanocomposite film in the method are as follows: the distance between the electrode tip and the sample being treated is 10-20 mm, the applied voltage is 13 kV, and the treatment time is 20-35 min.

[0031] Furthermore, when the method employs near-infrared laser irradiation, the radiation wavelength is 808 nm and the laser power intensity is 0.4 W / cm². 2 ~0.7W / cm 2 The laser emitter is about 6 to 10 cm away from the material.

[0032] Furthermore, when the method employs near-infrared laser irradiation, the radiation wavelength is 808 nm and the laser power intensity is 0.6 W / cm². 2 The laser emitter is about 8cm away from the material.

[0033] Furthermore, when using near-infrared laser irradiation, the method employs continuous irradiation for 25–30 minutes.

[0034] Furthermore, when using pulsed light treatment, the method employs intermittent irradiation; when using intermittent irradiation, each irradiation lasts 10 minutes with a 5-minute interval before the next irradiation, for a total of 3 irradiations; or each irradiation lasts 5 minutes with a 5-minute interval before the next irradiation, for a total of 6 irradiations.

[0035] Furthermore, the nanocomposite film treated with near-infrared light in the method reaches a temperature of 40-42°C when applied.

[0036] Furthermore, the nano-ceramic particles are composed of one or more of barium titanate, strontium titanate, barium strontium titanate, lithium niobate, and sodium potassium niobate; the polymer matrix is ​​composed of one or more of polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and L-polylactic acid; and the organic layer is composed of polydopamine.

[0037] Furthermore, the thickness of the nanocomposite film is 20–30 μm.

[0038] The nanocomposite film involved in the method can be prepared by the following steps:

[0039] (1) Prepare an organic aqueous solution of 0.01 mol / L to 0.05 mol / L, ultrasonically disperse the nano-ceramic particles in the organic aqueous solution, stir at 50℃-80℃ for 8-15 h, and after centrifugation, washing and drying, obtain the organic-coated nano-ceramic particles.

[0040] (2) The organic-coated nano-ceramic particles were uniformly dispersed in an organic solvent by ultrasonic oscillation to obtain a suspension with a mass percentage concentration of 40-80 wt%; the polymer matrix was dissolved in the organic solvent and stirred evenly to obtain a suspension with a mass percentage concentration of 20-70 wt%; the two suspensions were mixed and stirred overnight, vacuum dried to remove bubbles, cast into a film, and heated to completely evaporate the organic solvent to obtain a nanocomposite film with a thickness of 20-30 μm;

[0041] Furthermore, the organic aqueous solution in step (1) is an aqueous solution of dopamine hydrochloride.

[0042] Furthermore, the organic solvent used in step (2) is DMF.

[0043] Furthermore, the nano-ceramic particles are composed of one or more of barium titanate, strontium titanate, barium strontium titanate, lithium niobate, and sodium potassium niobate; the polymer matrix is ​​composed of one or more of polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and L-polylactic acid; and the organic layer is composed of polydopamine.

[0044] This invention also provides the application of a method for treating nanocomposite films with near-infrared light in the preparation of materials that are antimicrobial, anti-inflammatory, and promote tissue repair and healing in animals, wherein the nanocomposite films implanted at the affected site are subjected to near-infrared light irradiation.

[0045] Furthermore, in the above applications, the surface potential of the nanocomposite film after corona polarization treatment is at the same level as the internal potential of the human body, that is, about 80mV; the near-infrared light treatment is to heat the nanocomposite film after corona polarization treatment by using near-infrared laser and / or pulsed light irradiation.

[0046] Furthermore, the corona polarization treatment conditions for the nanocomposite film in the application are as follows: the distance between the electrode tip and the treated sample is 10-20 mm, the applied voltage is 13 kV, and the treatment time is 20-35 min.

[0047] Furthermore, when the application uses near-infrared laser illumination, the radiation wavelength is 808 nm and the laser power intensity is 0.4 W / cm². 2 ~0.7W / cm 2 The laser emitter is about 6 to 10 cm away from the material.

[0048] Furthermore, when the application uses near-infrared laser illumination, the radiation wavelength is 808 nm and the laser power intensity is 0.6 W / cm². 2 The laser emitter is about 8cm away from the material.

[0049] Furthermore, when using near-infrared laser irradiation, the method employs continuous irradiation for 25–30 minutes.

[0050] Furthermore, when the application uses pulsed light treatment, intermittent irradiation is employed; when using intermittent irradiation, each irradiation lasts 10 minutes with a 5-minute interval before the next irradiation, for a total of 3 irradiations; or each irradiation lasts 5 minutes with a 5-minute interval before the next irradiation, for a total of 6 irradiations.

[0051] Furthermore, the near-infrared light-treated nanocomposite film used in the application reaches a temperature of 40–42°C during application.

[0052] Furthermore, in the application, the nano-ceramic particles are composed of one or more of barium titanate, strontium titanate, barium strontium titanate, lithium niobate, and sodium potassium niobate; the polymer matrix is ​​composed of one or more of polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and L-polylactic acid; and the organic layer is composed of polydopamine.

[0053] Furthermore, the thickness of the nanocomposite film in the application is 20–30 μm.

[0054] Furthermore, in the above applications, the conditions for near-infrared light treatment can be adjusted according to the different amounts of electricity required for different stages of antimicrobial infection, anti-inflammation, and tissue repair and healing in animals.

[0055] The treatment of inflammatory diseases and the repair and healing of damaged tissues is a complex process. In typical bone remodeling, bone tissue needs to adapt to changes in its surrounding microenvironment. When abnormalities occur in the body, such as bone defects and accompanying infections, the temperature of surrounding tissues and the electrical environment around immune cells change, thus affecting bone tissue and the immune system. Various signaling pathways related to macrophage polarization play important roles in this process; they cross-link, interfere with, and influence each other, forming a comprehensive network regulatory system. For example, in the treatment of periodontitis, different types of damaged tissue, chronic inflammation, inappropriate immune responses, microecological imbalances, and individual differences all affect the complexity of the treatment process. Post-infected skin tissue, due to a series of complex physiological and immune responses caused by infection, faces the influence of factors such as inflammation and infection control, immune response, tissue remodeling, wound management, scar formation, and individual differences. The method described in this invention can regulate the electrical supply using near-infrared light to target the different electrical demands at different stages of anti-infection, anti-inflammation, and tissue repair, maximizing the influence of signaling pathways on macrophage polarization. This also makes it more possible to create personalized treatment plans.

[0056] After corona polarization and phototreatment, the nanocomposite membrane possesses both photothermal heating properties and piezoelectric properties. Under 808nm near-infrared light irradiation, the nanocomposite membrane heats up rapidly and maintains a stable temperature, while also exhibiting a pyroelectric effect, where temperature changes cause the material surface to release electrical charges. The synergistic coupling effect of these electrothermal properties enables the nanocomposite membrane to significantly promote the differentiation of macrophages from M1 to M2 types, and to substantially increase IL-10 expression in immune cells or the proportion of CD206-positive cells in the immune cell population, thereby significantly promoting the healing of animal tissues, especially bone defects.

[0057] This invention establishes the interrelationship between the electrical and thermal properties of materials, achieving biomimetic coupling of the material's electrothermal effects. This coupling enables the piezoelectric properties and pyroelectric effects to synergistically promote macrophage polarization and tissue repair or healing. In an exemplary embodiment, non-invasive manipulation of near-infrared light in vitro can enhance the material's charge-carrying properties, achieving on-demand charging based on the near-infrared field and solving the problem of insufficient long-term performance of charged materials after implantation. Attached Figure Description

[0058] Figure 1 shows the membranes composed of different materials at 0.6 W / cm². 2 Heating curve under power conditions with 808nm laser irradiation.

[0059] Figure 2 shows the ultraviolet-visible absorption spectra of films composed of different materials.

[0060] Figure 3 shows the UV-Vis absorbance values ​​of films composed of different materials at a wavelength of 808 nm.

[0061] Figure 4 shows the photothermal performance analysis of the nanocomposite film.

[0062] Figure 5 shows the pyroelectric coefficient of the polarized composite film material as a function of temperature in the temperature range of 35-45℃.

[0063] Figure 6 shows the results of CD206 immunofluorescence staining and its quantitative statistics after macrophages were cultured with nanocomposite materials and subjected to continuous / pulsed light irradiation. In Figure 6b, the columns from left to right represent the polarized group, non-polarized group, continuous NIR+ polarized group, and intermittent NIR+ polarized group, respectively. Figure 6c includes three columns for IL-10, TNF-α, and IL-b, with each column representing the polarized group, non-polarized group, continuous NIR+ polarized group, and intermittent NIR+ polarized group, respectively, from left to right. Figure 6d also includes three columns for IL-10, TNF-α, and IL-b, with each column representing the polarized group, non-polarized group, continuous NIR+ polarized group, and intermittent NIR+ polarized group, respectively, from left to right.

[0064] Figure 7 shows the expression and quantitative analysis of CD86 and CD206 in macrophages on the material under different stimuli on the third day (top) and the fifth day (bottom).

[0065] Figure 8. Skin wound healing under different stimuli.

[0066] Figure 9 shows the micro-CT analysis and quantitative results of the defect area 4 weeks (top) and 12 weeks (bottom) after material implantation.

[0067] Figure 10 shows the results of macrophage analysis in vivo after material implantation.

[0068] Figure 11 shows the polarization results of macrophages during in vitro simulation of in vivo experiments.

[0069] Figure 12 is a KPFM analysis diagram of the nanocomposite membrane of the present invention. Detailed Implementation

[0070] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0071] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0072] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0073] [Composite Materials]

[0074] In one aspect, the present invention provides a biomimetic electrothermal coupling composite material based on the pyroelectric effect, comprising a polymer and inorganic photosensitive particles dispersed therein. The polymer is selected from piezoelectric polymers, and the inorganic photosensitive particles are dopamine-coated inorganic fine particles.

[0075] In this invention, biomimetic electrothermal coupling refers to the synergistic effect of piezoelectric effect and pyroelectric effect, which can greatly promote the repair and / or healing of tissues in vivo.

[0076] In this invention, piezoelectric polymers refer to crystalline polymer materials that exhibit a voltage between their two end faces when subjected to pressure. Examples include, but are not limited to, polyvinylidene fluoride (PVDF), PVDF-trifluoroethylene copolymer, PVDF-hexafluoropropylene copolymer, PVDF-tetrafluoroethylene copolymer, polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), and polylactic acid (PLA). This invention may use one of the above polymers or a combination of two or more.

[0077] In this invention, inorganic photosensitive particles refer to particles that are sensitive to light, particularly particles that can accumulate heat energy when exposed to infrared light. Inorganic photosensitive particles are generally modified particles, and exemplarily, they include an inorganic core and a polydopamine layer.

[0078] In some embodiments, the inorganic photosensitive particles of the present invention are obtained by dispersing nano-sized ceramic particles in an aqueous solution of dopamine hydrochloride, heating and stirring the reaction, followed by washing and drying. The ratio of dopamine hydrochloride to nano-sized ceramic particles is important in the preparation of the inorganic photosensitive particles. Generally, the weight ratio of dopamine hydrochloride to nano-sized ceramic particles is 1:10-1:30, that is, based on 1 part by weight of dopamine hydrochloride, there are 10-30 parts by weight of nano-sized ceramic particles, preferably 12-28 parts by weight, more preferably 14-26 parts by weight, such as 15 parts by weight or 23 parts by weight. If the amount of dopamine hydrochloride is too small, the photosensitivity of the obtained particles tends to decrease, and may even fail to achieve the aggregation and endothermic function required for pyroelectricity. On the other hand, if the amount of dopamine hydrochloride is too large, the polydopamine thickness on the surface of the obtained particles becomes larger, affecting the piezoelectric properties.

[0079] When preparing inorganic photosensitive particles, it is preferable to control the heating and stirring reaction conditions to be sufficient to form a polydopamine layer with a thickness of 25-50 μm on the surface of the nano-sized ceramic particles. For this purpose, the reaction temperature is generally controlled at 40-80°C, and the reaction time is 5-20 hours. Optionally, the reaction temperature can be, for example, 50°C, 60°C, 65°C, 70°C, 75°C, etc. Optionally, the reaction time can be 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, etc. Those skilled in the art can freely choose the specific temperature and time within the above ranges. Preferably, the process further includes a step of ultrasonically treating the dispersion before the heating and stirring reaction. The ultrasonic treatment time can be from 10 minutes to 1 hour, thereby making the nano-sized ceramic particles more uniformly dispersed.

[0080] Optionally, the preparation of inorganic photosensitive particles may further include a step of washing the resulting nanoscale ceramic particles coated with a polydopamine layer. Washing can be performed using water and alcohol, and typically multiple washes are required. Exemplarily, washing is first performed with water, followed by washing with alcohol. Washing may be repeated multiple times.

[0081] Optionally, the preparation of inorganic photosensitive particles may further include a step of drying the washed particles. Drying is preferably performed by heating, at a temperature of, for example, 40-60°C, preferably 45-55°C.

[0082] Optionally, the preparation of inorganic photosensitizing particles may further include a step of dissolving dopamine hydrochloride in a solvent. The solvent here includes an aqueous solvent. The concentration of dopamine hydrochloride is controlled at 0.5-5 mg / ml, such as 0.8 mg / ml, 1 mg / ml, 1.5 mg / ml, 2 mg / ml, 2.5 mg / ml, 3 mg / ml, 3.5 mg / ml, 4 mg / ml, or 4.5 mg / ml. Concentrations that are too high or too low are detrimental to obtaining high photosensitivity.

[0083] In this invention, the nanoscale ceramic particles are not particularly limited, but examples include, but are not limited to, barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate. This invention may use one or more of the above-mentioned substances in combination.

[0084] [Preparation Method]

[0085] In another aspect, the present invention provides a method for preparing a biomimetic electrothermal coupling composite material based on the pyroelectric effect, comprising the steps of providing an inorganic photosensitive particle dispersion and a piezoelectric polymer solution; mixing the dispersion and the piezoelectric polymer solution to obtain a suspension; and using the suspension to prepare a membrane material.

[0086] In this invention, the amounts of inorganic photosensitive particles and solvent in the inorganic photosensitive particle dispersion are not limited, generally 40-100 mg / ml, preferably 45-80 mg / ml, such as 50 mg / ml, 60 mg / ml, 70 mg / ml, etc. Examples of solvents include, but are not limited to, N,N-dimethylformamide. Dispersion is preferably promoted by stirring or sonication during the preparation of the dispersion.

[0087] In this invention, the concentration of the polymer in the piezoelectric polymer solution is generally 10-100 mg / ml, preferably 20-80 mg / ml, more preferably 25-60 mg / ml, such as 30 mg / ml, 40 mg / ml, 50 mg / ml, 60 mg / ml, etc.

[0088] This invention further includes a step of treating the suspension by placing it in a vacuum drying oven for vacuum defoaming. In addition, to prevent impurity contamination, the substrate, such as a quartz glass plate, is cleaned with anhydrous ethanol and pure water during the preparation of the membrane material. After the quartz glass plate is completely dry, the suspension is poured onto it, and a scraper from a casting machine is used to ensure a uniform thickness.

[0089] This invention further includes a step of evaporating the solvent. Exemplarily, this involves placing a quartz glass plate horizontally on a heating platform within a fume hood and heating it at 30-65°C for 5 hours until the solvent is completely evaporated. The final membrane material thickness obtained by this invention is generally 20-50 μm, 25 μm, 30 μm, or 35 μm.

[0090] In some embodiments, the preparation method of the present invention further includes a step of polarizing the composite material. Exemplary polarization parameters include, but are not limited to: the polarizing medium being either air or methyl silicone oil, the polarization voltage being 1kV-30kV, the distance between the electrode head and the sample being 1mm-50mm, the polarization temperature being 25℃-100℃, and the polarization time being 1 minute-60 minutes.

[0091] In some embodiments, the preparation method of the present invention further includes an annealing treatment. An exemplary annealing treatment includes placing the composite film at 80-150°C for 5-30 minutes. The annealing temperature can be, for example, 85°C, 90°C, 95°C, 100°C, 120°C, 140°C, etc.

[0092] [Medical kit for tissue repair or healing]

[0093] In another aspect, the present invention provides a medical kit for tissue repair or healing, comprising an energy generating unit and an energy receiving unit, wherein the energy generating unit is configured to generate energy light, particularly energy light capable of penetrating tissue, and the energy receiving unit comprises the composite material described above and is configured to be implanted in the body or disposed on the surface of tissue, and, when in the body, to generate an electrothermal coupling effect when receiving energy light that has penetrated the tissue to reach the energy receiving unit. Exemplarily, the energy receiving unit is configured to reach a temperature of 35-45°C, preferably 41°C, after receiving energy. The present invention has found that optimal tissue repair and healing effects are achieved when the temperature of the energy receiving unit reaches this range.

[0094] In this invention, the energy generating unit includes a laser. Generally, the laser of this invention is configured to generate energy, such as light, that can penetrate tissues like skin and enter the body. In particular, it is a near-infrared laser, such as a 600-1000 nm near-infrared laser. The laser can generate near-infrared laser continuously or in a pulsed manner. Preferably, the laser of this invention can automatically generate pulsed near-infrared laser light, with the pulse frequency not limited and freely set as needed. For this purpose, the laser may be equipped with, for example, a timer and a control unit, thereby controlling the generation of pulsed laser light.

[0095] In this invention, the energy receiving unit comprises the composite material described herein, particularly a composite membrane. The composite material has been described in detail above and will not be repeated here. Preferably, the energy receiving unit is configured to be implantable inside or on the surface of an organism and to receive energy generated by the energy generating unit, particularly light energy.

[0096] In this invention, the medical kit includes a combination of energy generating units and energy receiving units. The number of energy generating units and energy receiving units is not limited; a single medical kit may contain one energy generating unit corresponding to multiple energy generating units, or it may contain multiple energy generating units and multiple energy receiving units. Exemplarily, the energy generating units in the medical kit can be reused multiple times, or different units from different medical kits can be combined or used in conjunction. For example, the energy generating unit of a first medical kit can be combined with the energy receiving unit of a second medical kit.

[0097] In this invention, tissue repair or healing includes soft tissue repair such as skin tissue repair, as well as bone tissue repair or healing, especially repair or regeneration after bone defects.

[0098] Methods for regulating immune cell polarization

[0099] In another aspect, the present invention provides a method for regulating immune cell polarization based on a biomimetic electrothermal coupling composite material with pyroelectric effect, comprising the following steps:

[0100] (1) The steps for constructing a culture system using immune cells and composite materials; and

[0101] (2) The step of irradiating the culture system with light.

[0102] In this invention, the composite material has been described in detail above and will not be repeated here.

[0103] In this invention, light treatment refers to irradiating the composite material with near-infrared light, and the light treatment includes continuous light treatment and / or pulsed light treatment. The conditions for continuous light treatment and / or pulsed light treatment are preferably such that the temperature of the treated area rises to the desired temperature. The desired temperature is generally 35-45°C, such as 37°C, 40°C, 42°C, 44°C, and 45°C. For this purpose, the pulsed light treatment conditions of this invention include, for example, irradiation for 1-20 minutes, with intervals of 0.5-20 minutes, repeated once or multiple times as needed.

[0104] In this invention, regulation includes promoting or initiating the differentiation of immune cells from M1 to M2 types. The polarization in this invention can be achieved through in vitro methods, thereby preparing M2-polarized immune cells. In this invention, the immune cells are not limited, and examples include, but are not limited to, macrophages.

[0105] In this invention, the culture system comprises a composite material and a suitable culture medium. The culture medium is known in the art and commercially available products can be used.

[0106] Example

[0107] I. Design and Construction of Bionic Electrothermal Coupling Effect

[0108] A nanocomposite system with electrothermal binary physical properties was designed and constructed. The composite material was prepared using the piezoelectric polymer polyvinylidene fluoride-trifluoroethylene P (VDF-TrFE) as the matrix and polydopamine (PDA)-encapsulated BTO as the filler. The specific steps included:

[0109] 1. Preparation of PDA@BTO / P(VDF-TrFE) nanocomposite film

[0110] Weigh a certain amount (0.3 g) of dopamine hydrochloride granules and dissolve them in pure water (150 mL). Stir for 10 minutes while heating in a 60°C water bath until completely dissolved. Then weigh a certain amount (6 g) of barium titanate (BTO) nanoparticles and place them in the dopamine hydrochloride aqueous solution. Sonicate the solution and continue heating in a 60°C water bath with stirring overnight. After standing and separating the layers, collect the supernatant and wash it three times alternately with pure water and anhydrous ethanol until the supernatant is clear. Discard the supernatant and place the solution in a constant temperature drying oven (55°C) to obtain dried dopamine-coated BTO nanoparticles.

[0111] A certain mass of PDA-coated BTO nanopowder was weighed and dissolved in DMF, and ultrasonically stirred to ensure uniform dispersion of the nanopowder. Simultaneously, a certain mass (1 g) of P(VDF-TrFE) polymer particles was weighed and dissolved in 3 mL of DMF. The two liquids were mixed and stirred thoroughly. To prevent evaporation, a beaker was covered with plastic wrap and stirred overnight to obtain a uniform and stable suspension. This suspension was then placed in a vacuum drying oven for defoaming. To prevent impurities, a quartz glass plate was cleaned with anhydrous ethanol and pure water. After the quartz glass plate was completely dry, the suspension was poured onto it, and a scraper from a casting machine was used to ensure a uniform thickness. The quartz glass plate was then placed horizontally on a heating platform in a fume hood and heated to 55°C to completely evaporate the solvent, ultimately obtaining a 30-micron-thickness nanopiezoelectric composite film.

[0112] 2. Polarization of PDA@BTO / P(VDF-TrFE) nanocomposite films

[0113] The prepared material was cut into 40×40mm pieces and placed flat on the metal plate of the corona polarization instrument. The electrode tip was adjusted to be 20mm above the center of the material. The applied voltage was adjusted to 13kV. The polarization time for each material was 30 minutes, and the temperature was room temperature.

[0114] 3. In vitro photothermal performance testing of materials

[0115] The PDA@BTO / P(VDF-TrFE) nanocomposite film material was cut into 40×40mm pieces and fixed in a self-made device, ensuring the material was flat and free of obstructions on its top and bottom surfaces to avoid affecting measurement accuracy. The probe of an 808nm near-infrared laser emitter was fixed directly below the PDA@BTO / P(VDF-TrFE) nanocomposite film, ensuring accurate and uniform laser irradiation onto the nanocomposite film material. The camera of a thermal imaging instrument was aimed at the nanocomposite film material, and the power of the 808nm near-infrared laser emitter was adjusted to monitor the temperature change of the material in real time after irradiation with 808nm near-infrared light. The data was recorded and analyzed in the software.

[0116] To simulate the temperature rise performance of PDA@BTO / P(VDF-TrFE) nanocomposite membranes implanted on the surface of animal bone defects, the equipment was placed in a 37°C incubator during in vitro temperature rise testing. Near-infrared irradiation experiments were then conducted after the material surface temperature reached 37°C, as observed by a thermal imager. When PDA@BTO / P(VDF-TrFE) nanocomposite membranes repair bone defects in animals, tissue fluid is present in the defect area. To simulate this phenomenon, the equipment was placed in a 37°C incubator with a small amount of PBS solution added to the material surface during in vitro temperature rise testing. Near-infrared irradiation experiments were then conducted after the surface water temperature reached 37°C, as observed by a thermal imager. Other control materials were measured using the same method.

[0117] II. Thermal Properties of Composite Materials

[0118] Figure 1 shows the heating curves of films composed of different materials under 808nm laser irradiation under certain power conditions. As can be seen from Figure 1, under certain light irradiation power, both polarized and unpolarized PDA-BTO / P (VDF-TrFE) nanocomposite films can be heated to the target temperature of about 40℃ within 1 minute in vitro; and this temperature can be maintained.

[0119] Figure 2 shows the ultraviolet-visible absorption spectra of films composed of different materials.

[0120] Figure 3 shows the UV-Vis absorbance values ​​of films composed of different materials at a wavelength of 808 nm. As can be seen from Figure 3, the UV-Vis and near-infrared spectra indicate that PDA-BTO / P (VDF-TrFE) has the desired absorption in the NIR-I region at 808 nm.

[0121] In Figure 4, a shows the temperature rise curve of the nanocomposite membrane in the dry state under NIR irradiation; b shows the infrared thermographic image of the nanocomposite membrane in the dry state under NIR irradiation over time; c shows the temperature rise curve of the nanocomposite membrane in PBS under NIR irradiation; and d shows the temperature rise curve of the nanocomposite membrane in an animal under NIR irradiation. Whether in the dry state, in PBS solution, or after implantation into a bone defect in an animal and subsequent irradiation with near-infrared light, the temperature of the nanocomposite membrane rapidly increases and remains constant. This indicates that it can efficiently achieve photothermal conversion under near-infrared light irradiation, converting light energy into heat energy, thereby rapidly and significantly increasing the surface solution temperature and tissue temperature, exhibiting excellent photothermal conversion efficiency.

[0122] III. Electrical Properties of Composite Materials

[0123] When the PDA@BTO / P(VDF-TrFE) nanocomposite film material is corona-polarized, it exhibits macroscopic polarization, and its temperature changes produce a pyroelectric effect. As mentioned below, the optimal temperature for promoting bone tissue therapy is 42℃, and the maximum heating temperature should not exceed 43℃. Therefore, the pyroelectric coefficient of the polarized composite film material was observed as a function of temperature within the range of 35-45℃ (Figure 5). It can be seen that within the temperature range of 35-45℃, the pyroelectric coefficients of the PDA@BTO / P(VDF-TrFE) nanocomposite film, BTO / P(VDF-TrFE) nanocomposite film, and P(VDF-TrFE) nanocomposite film at the same temperature show a decreasing order. Among them, the pyroelectric coefficient of the PDA@BTO / P(VDF-TrFE) nanocomposite film is significantly higher than that of the other composite films. At 42℃, the pyroelectric coefficients of PDA@BTO / P(VDF-TrFE) nanocomposite film, BTO / P(VDF-TrFE) nanocomposite film, and P(VDF-TrFE) nanocomposite film were 89.1, 5.37, and -0.939 μC / m, respectively. 2 (℃). As the temperature increases, the pyroelectric coefficient increases within the temperature range of 35-45℃. This indicates that when the material temperature changes, the internal polarization intensity also changes, thereby causing a change in the bound charge density.

[0124] Furthermore, as shown in Figure 12, the surface potential of the nanocomposite film after corona polarization is around 80mV, which is at the same level as the intrinsic potential of the human body.

[0125] IV. The Influence of Composite Materials on Immune Cell Polarization

[0126] BMDM macrophages were seeded onto PDA@BTO / P(VDF-TrFE) nanocomposite membranes and incubated overnight to allow complete cell adhesion to the material surface. Near-infrared irradiation was then applied to the polarized PDA@BTO / P(VDF-TrFE) nanocomposite membranes. The membranes were kept in a cell culture incubator throughout the irradiation process. The irradiation wavelength was 808 nm. The laser power and the distance between the laser beam and the material were adjusted. Pulsed irradiation was performed for 10 minutes per well, with a 5-minute interval between each irradiation, for a total of 3 cycles. Continuous irradiation was performed for 30 minutes per well. After near-infrared irradiation, the macrophages were cultured in a 37°C cell incubator. The camera of a thermal imaging instrument was pointed at the six-well plate to monitor the temperature change in real time after 808 nm near-infrared irradiation, maintaining the temperature rise between 3-4°C.

[0127] Figure 6 shows the following: (ab) CD206 immunofluorescence staining results and quantitative statistics of macrophages cultured with PDA@BTO / P(VDF-TrFE) nanocomposite material for one day after continuous / pulsed light irradiation for 0.5 h; (c) Expression of M1 and M2 polarization-related genes of macrophages cultured with PDA@BTO / P(VDF-TrFE) nanocomposite material for one day after continuous / pulsed light irradiation for 0.5 h; (d) Expression of M1 and M2 polarization-related genes of macrophages cultured with PDA@BTO / P(VDF-TrFE) nanocomposite material for seven days after continuous / pulsed light irradiation for 0.5 h.

[0128] Furthermore, this invention also tested the expression and quantitative analysis of CD86 and CD206 in macrophages on the material under different stimuli on the third day using flow cytometry, and the results are shown in Figure 7. In each column of Figure 7, from left to right, are UN, N-30, N-3*10, and N-6*5. UN represents no irradiation and no temperature increase; N-30 represents polarized and continuous irradiation for 30 minutes; N-3*10 represents 10 minutes of irradiation (41℃), followed by a 5-minute pause, repeated 3 times; N-6*5 represents 5 minutes of irradiation (41℃), followed by a 5-minute pause, repeated 6 times. In vitro results showed that when the temperature was raised to approximately 41℃ under irradiation, macrophages transformed from M1 (CD86) to M2 (CD206). Flow cytometry analysis of macrophage CD86 and CD206 showed that the N-3*10 group significantly promoted the conversion of macrophages from M1 (CD86) to M2 (CD206) in the early (day 3) and late (day 5) stages of wound healing compared to other experimental groups, thereby promoting wound healing.

[0129] V. Research on the role of composite materials in wound healing

[0130] Figure 8 shows the wound healing under different stimuli. In Figure 8A: UN indicates no irradiation and no temperature increase; N-30 indicates continuous irradiation for 30 minutes, maintaining a temperature of 41℃; N-3*10 indicates 10 minutes of irradiation (41℃), followed by a 5-minute break, repeated 3 times; N-6*5 indicates 5 minutes of irradiation (41℃), followed by a 5-minute break, repeated 6 times. Figure 8B shows the quantitative results analysis of the comparative experiment. The results show that the N-3*10 group has a better promoting effect on both early and late wound healing than the other groups, and the N-6*5 group is significantly better than the other groups in promoting late wound healing.

[0131] VI. Research on the regulation of bone immune microenvironment by composite materials to promote the healing of critical bone defects

[0132] A 5mm critical bone defect model of SD rat skull was constructed. Flow cytometry and immunofluorescence were used to evaluate the immune responses in the early healing stage, including macrophage adhesion, polarization phenotype, and cytokine release in the local tissue fluid and on the surface of the covering material. Micro-CT and tissue sections were used to evaluate the osteogenic effect. In vivo studies were conducted on the regulatory role of the biomimetic electro-thermal coupling effect of PDA@BTO / P(VDF-TrFE) nanocomposite material on the immune microenvironment and its promoting effect on bone defect healing.

[0133] Figure 9 illustrates the regulatory effect of the electrothermal coupling effect of the above-mentioned materials on bone defect repair. (a) and (c) show micro-CT analysis of the defect area 4 / 12 weeks after material implantation, and (b) and (d) show quantitative micro-CT analysis of the defect area 4 / 12 weeks after material implantation. UP represents the blank group; N+UP represents the simple light irradiation group, i.e., implantation of PDA@BTO / P(VDF-TrFE) nanocomposite film treated with light as described in the reference example; P represents the polarization group, i.e., implantation of polarized PDA@BTO / P(VDF-TrFE) nanocomposite film; N+P represents the photopolarization group, i.e., implantation of polarized PDA@BTO / P(VDF-TrFE) nanocomposite film treated with light as described in the reference example, specifically with a near-infrared irradiation temperature increased by 4 degrees Celsius, a frequency of 10 minutes of irradiation followed by a 5-minute pause, repeated 3 times. As shown in Figure 9, 4 weeks after implantation of the test material, the photopolarization group (N+P) showed significantly better osteogenic promotion in animals than the other groups.

[0134] Figure 10 shows the results of macrophage analysis in vivo after material implantation. (A) shows the expression and quantitative analysis of CD86 and CD206 in macrophages in the tissue fluid of the defect area one day and seven days after material implantation; (B) shows the immunofluorescence results and quantitative analysis of CD206 and CD86 in macrophages on the material seven days after implantation in the defect area. UP represents the blank group; N+UP represents the simple light-irradiation group, i.e., implantation of PDA@BTO / P(VDF-TrFE) nanocomposite membranes treated with light heating as described above; P represents the polarization group, i.e., implantation of polarized PDA@BTO / P(VDF-TrFE) nanocomposite membranes; N+P represents the photopolarization group, i.e., implantation of polarized PDA@BTO / P(VDF-TrFE) nanocomposite membranes treated with the above pulsed light method.

[0135] In the study of electrothermal coupling regulation of early immune responses to bone defects in vivo, flow cytometry and immunofluorescence results showed that, in animal experiments, pulsed electrothermal coupling of PDA-BTO / P (VDF-TrFE) materials promoted the differentiation of macrophages M1 (CD86) type in the early immune response, compared with electrical stimulation and thermal stimulation alone. In the late immune response, M1 promoted the transformation to M2 (CD206) type.

[0136] Figure 11 shows the polarization results of macrophages in the in vitro simulation of in vivo experiments. In the in vitro simulation of in vivo experiments, the electrothermal coupling of PDA-BTO / P (VDF-TrFE) material promoted M1 polarization of macrophages on day 1 and promoted M2 polarization on day 7, consistent with in vivo results, compared with electrical stimulation and thermal stimulation alone. The electrothermal coupling of PDA-BTO / P (VDF-TrFE) material upregulated the expression of osteogenic-related genes on day 4, compared with electrical stimulation and thermal stimulation alone. In Figure 11: (A) Immunofluorescence results of CD206 and CD86 in macrophages on the material under different stimuli; (B) Quantitative immunofluorescence analysis of CD206 and CD86 in macrophages on the material under different stimuli, from left to right: UP group, N+UP group, P group, and N+P group; (C) Flow cytometry analysis of CD86 and CD206 expression in macrophages on the material under different stimuli; (D) Quantitative analysis of CD86 and CD206 expression in macrophages on the material under different stimuli. For the CD86 and CD206 groups, from left to right, they are the UP group, N+UP group, P group, and N+P group; (E) Expression of M1 and M2 polarization-related genes in macrophages on the material under different stimuli. Among them, for the CD206, IL-10, Fizz-1, INOS, and 7NF-a groups, from left to right, they are the UP group, N+UP group, P group, and N+P group; (F) Immunofluorescence results of BMP2 expression, an osteogenic-related gene, in bone marrow mesenchymal stem cells on the material under different stimuli on the fourth day; (G) Quantitative immunofluorescence analysis of BMP2 expression, an osteogenic-related gene, in bone marrow mesenchymal stem cells on the material under different stimuli on the fourth day, from left to right, they are the UP group, N+UP group, P group, and N+P group; (H) Quantitative analysis of osteogenic-related gene expression in bone marrow mesenchymal stem cells on the material under different stimuli on the fourth day. Among them, for each of the ALP, OPN, RUNX2, and BMP2 groups, from left to right they are the UP group, N+UP group, P group, and N+P group.

[0137] Although the invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. A biomimetic electrothermal coupling composite material based on the pyroelectric effect, characterized in that, It includes a polymer and inorganic photosensitive particles dispersed therein, wherein the polymer is selected from piezoelectric polymers and the inorganic photosensitive particles are inorganic fine particles coated with dopamine.

2. A method for preparing a biomimetic electrothermal coupling composite material based on the pyroelectric effect, characterized in that, include: Steps for providing inorganic photosensitive particle dispersions and piezoelectric polymer solutions; The step of mixing the dispersion with the piezoelectric polymer solution to obtain a suspension; and The steps for preparing membrane materials using the suspension.

3. A medical kit for tissue repair or healing, characterized in that, It includes an energy generating unit and an energy receiving unit, wherein the energy generating unit is configured to generate light energy, and the energy receiving unit comprises the composite material according to claim 1 and is configured to be implanted in the body or disposed on the surface of the body, and generates an electrothermal coupling effect when receiving light energy.

4. The medical kit according to claim 3, characterized in that, The polymer is selected from at least one of polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and polylactic acid.

5. The medical kit according to claim 3, characterized in that, The inorganic photosensitive particles are nano-sized ceramic particles.

6. The medical kit according to claim 5, characterized in that, The nanoscale ceramic particles are selected from at least one of barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate.

7. The medical kit according to claim 3, characterized in that, The energy generation unit is configured to generate a laser capable of producing continuous illumination and / or pulsed illumination.

8. The use of composite materials in the preparation of medical kits for tissue repair or healing, characterized in that, The composite material is the biomimetic electrothermal coupling composite material based on the pyroelectric effect as described in claim 1.

9. A method for regulating immune cell polarization based on a biomimetic electrothermal coupling composite material with pyroelectric effect, comprising the following steps: (1) Steps for constructing a culture system using immune cells and composite materials; and (2) The step of irradiating the culture system with light; The composite material comprises a polymer and inorganic photosensitive particles dispersed therein; the light treatment comprises irradiating the composite material with near-infrared light, and the light treatment comprises continuous light treatment and / or pulsed light treatment; the regulation is to promote the differentiation of macrophages from M1 to M2 type.

10. An immune cell, characterized in that, Obtained by the method described in claim 9.

11. A method for treating a nanocomposite film with near-infrared light, wherein the nanocomposite film is composed of nano-ceramic particles with an organic coating uniformly dispersed in a polymer matrix, characterized in that, The nanocomposite film undergoes corona polarization treatment, and the surface potential of the treated nanocomposite film is at the same level as the internal potential of the human body, that is, about 80mV; the near-infrared light treatment is to heat the nanocomposite film after corona polarization treatment by using near-infrared laser and / or pulsed light irradiation.

12. The method for treating a nanocomposite film with near-infrared light according to claim 11, characterized in that, The corona polarization treatment conditions for the nanocomposite film were as follows: the distance between the electrode tip and the sample being treated was 10–20 mm, the applied voltage was 13 kV, and the treatment time was 20–35 min.

13. A method for treating a nanocomposite film with near-infrared light according to claim 11 or 12, characterized in that, When using near-infrared laser illumination, the radiation wavelength is 808 nm and the laser power intensity is 0.4 W / cm². 2 ~0.7W / cm 2 The laser emitter is about 6-10 cm away from the material, and the laser is continuously irradiated for 25-30 minutes.

14. The method for treating a nanocomposite film with near-infrared light according to claim 13, characterized in that, When using near-infrared laser irradiation, the radiation wavelength is 808 nm and the laser power intensity is 0.6 W / cm². 2 The laser emitter was about 8cm away from the material and continuously irradiated for 30 minutes.

15. A method for treating a nanocomposite film with near-infrared light according to claim 11 or 12, characterized in that, When using pulsed light treatment, intermittent irradiation is employed; each irradiation lasts 10 minutes with a 5-minute interval before the next irradiation, for a total of 3 irradiations; or each irradiation lasts 5 minutes with a 5-minute interval before the next irradiation, for a total of 6 irradiations.

16. The method for treating a nanocomposite film with near-infrared light according to claim 11, characterized in that, When applied, the temperature of the nanocomposite film treated with near-infrared light is maintained at 40–42°C.

17. The application of the nanocomposite membrane treated by the method of claim 11 as a material for promoting tissue repair and healing in animals, characterized in that, The nanocomposite membrane implanted at the affected site was subjected to near-infrared light irradiation after corona polarization treatment.

18. The application according to claim 17, characterized in that, The surface potential of the nanocomposite film after corona polarization treatment is at the same level as the internal potential of the human body, that is, about 80mV; the near-infrared light treatment is to heat the nanocomposite film after corona polarization treatment by using near-infrared laser and / or pulsed light irradiation.

19. The application according to claim 18, characterized in that, The corona polarization treatment conditions for the nanocomposite film were as follows: the distance between the electrode tip and the sample was 10–20 mm, the applied voltage was 13 kV, and the treatment time was 20–35 min. When using near-infrared laser irradiation, the radiation wavelength was 808 nm, and the laser power intensity was 0.4 W / cm². 2 ~0.7W / cm 2 The laser emitter is about 6-10 cm away from the material, and it is continuously irradiated for 25-30 minutes. When using pulsed light irradiation, intermittent irradiation is used. Each irradiation lasts for 10 minutes, with a 5-minute interval before the next irradiation, for a total of 3 irradiations; or each irradiation lasts for 5 minutes, with a 5-minute interval before the next irradiation, for a total of 6 irradiations.

20. The application according to claim 19, characterized in that, The conditions for near-infrared light treatment are adjusted according to the different amounts of electricity required for different stages of antimicrobial infection, anti-inflammation, and tissue repair and healing in animals.

Images