Photo-thermal-thermoelectric synergistic material, photo-thermal-thermoelectric synergistic composite material, preparation method and application thereof

Abstract

The present application relates to photothermal-thermoelectric synergistic material, photothermal-thermoelectric synergistic composite material, preparation method and application thereof, the photothermal-thermoelectric synergistic material includes bismuth selenide-gold composite material, bismuth selenide-gold composite material is hexagonal, gold material is located in the central hexagon.The advantage lies in, gold nanoparticles located in the center of hexagon are used as "heat source core", under the excitation of near infrared light, stable radial temperature gradient is formed with the base bismuth selenide, and then endogenous micro-current is generated based on the Seebeck effect of bismuth selenide, this wireless, non-invasive "photothermal-stable temperature difference-thermoelectric" cascade signal can effectively simulate the bioelectric environment of bone tissue, and the osteogenic differentiation of bone marrow mesenchymal stem cells is significantly promoted;The photothermal-thermoelectric synergistic material of the present application can effectively remove active oxygen, and has good antioxidant property.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a photothermal-thermoelectric synergistic material and its preparation method and application, and a photothermal-thermoelectric synergistic composite material and its preparation method and application. Background Technology

[0002] Bone defects are a common biomedical challenge in clinical practice, often caused by various factors such as trauma, tumor resection, infection, and congenital malformations. They severely impact patients' skeletal function and quality of life. Therefore, the development of high-performance bone repair materials has become a research hotspot and focus in the field of biomedical materials. An ideal bone repair material not only needs to possess good biocompatibility, biodegradability, and mechanical properties, but also needs to be able to adapt to the complex and varied irregular shapes of bone defects encountered in clinical practice. Simultaneously, it should possess the ability to actively stimulate osteogenic regeneration to efficiently induce bone tissue regeneration and accelerate the repair and healing of the defect site.

[0003] Currently, commonly used bone repair materials in clinical and research fields mainly include metallic materials, ceramic materials, polymer materials, and various composite materials. Among them, while metallic and ceramic materials possess certain mechanical support properties, they suffer from drawbacks such as excessive rigidity, limited biocompatibility, and difficulty in processing and shaping to match irregular bone defects. Furthermore, they cannot provide active osteogenic stimulation signals, and problems such as material loosening, displacement, or poor integration with host bone are prone to occur in the later stages of repair, making it difficult to meet the needs of precise clinical repair.

[0004] Polymer hydrogel materials have become an important development direction in bone repair materials in recent years due to their good biocompatibility, biodegradability, and flexibility, and their ability to be injected into irregular bone defects. Methacrylamide gelatin (GelMA), as a natural polymeric modified material, combines the bioactivity and photocrosslinking properties of gelatin and is widely used in the preparation of bone repair hydrogel scaffolds. However, most existing GelMA-based bone repair hydrogel scaffolds only provide passive support and lack active stimulation signals that can effectively promote osteogenic differentiation. They cannot simulate the natural bioelectrical environment of bone tissue, resulting in low efficiency in inducing osteogenic differentiation of bone marrow mesenchymal stem cells and a long bone repair cycle.

[0005] To address the aforementioned problem of insufficient active osteogenic stimulation, researchers have attempted to introduce functional nanomaterials such as photothermal and thermoelectric materials into hydrogel scaffolds, hoping to achieve active osteogenic regulation through physical signals generated by external stimulation. Bismuth selenide (Bi₂Se₃), a typical thermoelectric material, possesses excellent Seebeck effect and can generate microcurrents under temperature differences, potentially mimicking the bioelectrical environment of bone tissue. Gold (Au) nanoparticles, due to their excellent photothermal conversion properties, are often used as photothermal agents. However, in existing technologies, the combination of bismuth selenide and gold nanomaterials in bone repair hydrogels often employs simple mixing methods, making it difficult to form a structurally stable and controllable heterojunction structure. This results in low photothermal conversion efficiency, uneven temperature distribution, and an inability to generate stable endogenous microcurrents, hindering the achievement of efficient "photothermal-thermoelectric" synergistic osteogenic stimulation.

[0006] In addition, most existing bone repair hydrogel scaffolds that incorporate functional nanomaterials do not have good injectability and in-situ cross-linking ability, making it difficult to fill irregular bone defect sites through minimally invasive methods and achieve rapid curing and shaping, which limits their application in the repair of complex bone defects in clinical practice.

[0007] In summary, the field of bone repair materials still faces numerous unresolved technical challenges: existing materials either struggle to match the shapes of irregular bone defects, resulting in poor applicability to minimally invasive surgery; or they lack active osteogenic stimulation signals, failing to effectively simulate the bioelectrical environment of bone tissue and exhibiting low osteogenic induction efficiency; even attempts to introduce functional nanomaterials suffer from issues such as unreasonable heterostructure design and poor signal synergy, failing to meet the high efficiency and precision requirements of clinical bone repair. Therefore, developing a bone repair hydrogel scaffold that combines injectability, in-situ cross-linking capability, and active thermoelectric synergistic osteogenic stimulation has become a crucial technical problem urgently requiring solutions from those skilled in the art. Summary of the Invention

[0008] The purpose of this application is to address the shortcomings of existing technologies by providing a photothermal-thermoelectric synergistic material and its preparation method and application, as well as a photothermal-thermoelectric synergistic composite material and its preparation method and application, in order to at least solve the problems of inability to match irregular shapes, low osteogenic induction efficiency, and poor synergistic effect in related technologies.

[0009] To achieve the above objectives, the technical solution adopted in this application is as follows: In the first aspect, a photothermal-thermoelectric synergistic material is provided, including bismuth selenide-gold composite material; The bismuth selenide-gold composite material is hexagonal, with the gold material located in the exact center of the hexagon.

[0010] In some of these embodiments, the molar ratio of bismuth selenide to gold is 100 to 500:1.

[0011] In some of these embodiments, the gold material is gold nanoparticles with a particle size of 25 nm to 55 nm.

[0012] In a second aspect, a method for preparing a photothermal-thermoelectric synergistic material is provided, for preparing the photothermal-thermoelectric synergistic material as described in the first aspect, comprising: Bismuth nitrate pentahydrate, sodium selenite, and gold material are added to an ethylene glycol solution in a predetermined ratio to obtain a precursor solution. The crystal growth guide, reducing agent and inorganic acid are added to the ethylene glycol solution in a preset ratio and heated to a preset temperature to obtain the reaction solution. The precursor solution is added to the reaction solution and reacted for a preset time to obtain a mixed solution; The mixed solution was subjected to solid-liquid separation and washing in sequence to obtain photothermal-thermoelectric synergistic materials.

[0013] In some of these embodiments, the molar ratio of bismuth nitrate pentahydrate to sodium selenite is 1:1.4 to 1.6.

[0014] In some of these embodiments, the gold material is a dispersion containing gold material, the volume of which is 0.5% to 2% of the volume of the ethylene glycol solution.

[0015] In some of these embodiments, the mass ratio of crystal growth guide agent to reducing agent is 1:50~70.

[0016] In some of these embodiments, the amount of inorganic acid used is 1.5 μL / mL to 2.5 μL / mL.

[0017] In some of these embodiments, the preset temperature is 160°C to 200°C.

[0018] In some of these embodiments, the preset time is 10 min to 20 min.

[0019] In some of these embodiments, solid-liquid separation includes centrifugation and filtration.

[0020] In some of these embodiments, washing is performed at least once with anhydrous ethanol and / or deionized water.

[0021] Thirdly, a photothermal-thermoelectric synergistic composite material is provided, comprising the photothermal-thermoelectric synergistic material as described in the first aspect or the photothermal-thermoelectric synergistic material and hydrogel material prepared by the preparation method described in the second aspect; Among them, the photothermal-thermal-electric synergistic composite material is composed of photothermal-thermal-electric synergistic material and hydrogel material.

[0022] In some of these embodiments, the amount of photothermal-thermoelectric synergistic material used is 100ppm to 600ppm.

[0023] Fourthly, a method for preparing a photothermal-thermoelectric synergistic composite material is provided, for preparing the photothermal-thermoelectric synergistic composite material as described in the third aspect, comprising: Methacrylamide gelatin and photoinitiator were added to phosphate buffer at a predetermined ratio to obtain a hydrogel solution. The photothermal-thermoelectric synergistic material as described in the first aspect or the photothermal-thermoelectric synergistic material prepared by the preparation method as described in the second aspect is added to a phosphate buffer solution to obtain a dispersion solution. The dispersion solution was added to the hydrogel solution and mixed under light-protected conditions to obtain a photosensitizing precursor solution; In-situ photocrosslinking of the photosensitive precursor solution was performed to obtain a photothermal-thermoelectric synergistic composite material.

[0024] In some of these embodiments, the concentration of methacrylamide gelatin in the photosensitive precursor solution is 5% to 20% w / v.

[0025] In some of these embodiments, the amount of photothermal-thermoelectric synergistic material used in the photosensitive precursor solution is 100 ppm to 600 ppm.

[0026] In some of these embodiments, the conditions for in-situ photocrosslinking are: a UV light source with a wavelength of 365 nm and an intensity of 400 mW / cm². 2 .

[0027] Fifthly, an application is provided for a photothermal-thermoelectric synergistic material or a photothermal-thermoelectric synergistic composite material in the preparation of bone defect repair materials. The photothermal-thermoelectric synergistic material is the photothermal-thermoelectric synergistic material as described in the first aspect or the photothermal-thermoelectric synergistic material prepared by the preparation method as described in the second aspect. The photothermal-thermoelectric synergistic composite material is the photothermal-thermoelectric synergistic composite material as described in the third aspect or the photothermal-thermoelectric synergistic composite material prepared by the preparation method as described in the fourth aspect.

[0028] Compared with related technologies, the photothermal-thermoelectric synergistic materials, their preparation methods and applications, and the photothermal-thermoelectric synergistic composite materials, their preparation methods and applications provided in this application have the following technical effects: 1) Utilizing gold nanoparticles located at the center of a hexagon as a "heat source core," a stable radial temperature gradient is formed with the substrate bismuth selenide under near-infrared light excitation, thereby generating an endogenous microcurrent based on the Seebeck effect of bismuth selenide. This wireless, non-invasive "photothermal-stable temperature difference-thermoelectric" cascade signal can effectively simulate the bioelectrical environment of bone tissue and significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells.

[0029] 2) The photothermal-thermoelectric synergistic material of the present invention can effectively remove reactive oxygen species and has good antioxidant properties. Attached Figure Description

[0030] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings: Figure 1 These are transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and elemental surface scan images of the prepared Bi2Se3-Au nanosheets; Figure 2 This is a scanning electron microscope (SEM) cross-sectional image of pure GelMA hydrogel and Bi2Se3-Au@GelMA composite scaffold; Figure 3 The results are the infrared spectroscopy, rheological properties and compressive mechanical properties of the Bi2Se3-Au@GelMA composite scaffold. Figure 4 This is the UV-Vis-NIR full-band absorption spectrum of the Bi2Se3-Au@GelMA composite scaffold; Figure 5 These are infrared thermal images and temperature rise curves of stents with different concentrations under near-infrared light irradiation. Figure 6 These are the thermoelectric performance test curves of Bi2Se3-Au nanosheets (including resistivity, Seebeck coefficient, carrier concentration, and power factor). Figure 7 This image shows fluorescent staining of reactive oxygen species (ROS) in cells under H2O2-induced oxidative stress. Figure 8 Results of mitochondrial membrane potential (TMRE), alkaline phosphatase (ALP), and alizarin red (ARS) staining in bone marrow mesenchymal stem cells. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of this application clearer, the application is described and illustrated below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application. All other embodiments obtained by those skilled in the art based on the embodiments provided in this application without inventive effort are within the scope of protection of this application.

[0032] Obviously, the accompanying drawings described below are merely some examples or embodiments of this application. Those skilled in the art can apply this application to other similar scenarios based on these drawings without any inventive effort. Furthermore, it is understood that although the efforts made in this development process may be complex and lengthy, for those skilled in the art related to the content disclosed in this application, any changes to design, manufacturing, or production based on the technical content disclosed in this application are merely conventional technical means and should not be construed as insufficient disclosure of the content of this application.

[0033] In this application, the reference to "embodiment" means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that is mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described in this application may be combined with other embodiments without conflict.

[0034] Unless otherwise defined, the technical or scientific terms used in this application shall have the ordinary meaning understood by one of ordinary skill in the art to which this application pertains. The terms “a,” “an,” “an,” “the,” and similar words used in this application do not indicate quantity limitation and may indicate singular or plural. The terms “comprising,” “including,” “having,” and any variations thereof used in this application are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or device that includes a series of steps or modules (units) is not limited to the listed steps or units, but may also include steps or units not listed, or may include other steps or units inherent to these processes, methods, products, or devices. The terms “connected,” “linked,” “coupled,” and similar words used in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. “Multiple” used in this application refers to two or more. “And / or” describes the relationship between related objects, indicating that three relationships may exist; for example, “A and / or B” can represent: A alone, A and B simultaneously, and B alone. The character " / " generally indicates that the preceding and following objects are in an "or" relationship. The terms "first," "second," and "third" used in this application are merely to distinguish similar objects and do not represent a specific ordering of the objects.

[0035] Example 1 This embodiment relates to the photothermal-thermoelectric synergistic material, preparation method, and application of the present invention.

[0036] An illustrative embodiment of the present invention is a photothermal-thermoelectric synergistic material, which is a hexagonal bismuth selenide-gold composite material (Bi2Se3-Au), with the gold material located in the center of the hexagon.

[0037] In some of these embodiments, the molar ratio of bismuth selenide to gold is 100 to 500:1.

[0038] In some embodiments, the gold material is gold nanoparticles with a particle size of 25 nm to 55 nm. Preferably, the particle size of the gold material is 30 nm to 50 nm. Specifically, the particle size of the gold material includes, but is not limited to, 35 nm, 40 nm, and 45 nm.

[0039] It should be noted that bismuth selenide-gold composite materials are generally sheet-like structures, such as nanosheets.

[0040] The preparation method of the photothermal-thermoelectric synergistic material of the present invention includes: Step S101: Add bismuth nitrate pentahydrate, sodium selenite and gold material to ethylene glycol solution in a preset ratio to obtain precursor solution; Step S102: Add the crystal growth guide agent, reducing agent and inorganic acid to the ethylene glycol solution in a preset ratio, and heat to a preset temperature to obtain a reaction solution; Step S103: Add the precursor solution to the reaction solution and react for a preset time to obtain a mixed solution; Step S104: Separate the solid and liquid components and wash the mixed solution sequentially to obtain a photothermal-thermoelectric synergistic material.

[0041] In step S101, the molar ratio of bismuth nitrate pentahydrate to sodium selenite is 1:1.4~1.6, and the amount of gold material used is 50μL~200μL.

[0042] In some embodiments, step S101 includes: Step S1011: Add bismuth nitrate pentahydrate and sodium selenite to the ethylene glycol solution in a predetermined ratio; Step S1012: Add the solution containing gold material to step S1011 to obtain a precursor solution.

[0043] In step S1012, the concentration of gold material in the solution containing gold material is 0.025 mg / mL to 0.1 mg / mL. Specifically, the concentration of gold material includes, but is not limited to, 0.05 mg / mL and 0.075 mg / mL.

[0044] In step S1012, the volume ratio of the solution containing gold material to the volume of the ethylene glycol solution is 0.005~0.02:1. That is, the volume of the solution containing gold material is 0.5%~2% of the volume of the ethylene glycol solution.

[0045] It should be noted that the solution containing gold material is a dispersion of gold nanoparticles. Specifically, a predetermined mass of gold nanoparticles is dispersed in deionized water to obtain a dispersion of gold nanoparticles.

[0046] In step S102, the mass ratio of crystal growth guide agent to reducing agent is 1:50~70.

[0047] In step S102, the amount of inorganic acid used is 1.5 μL / mL to 2.5 μL / mL. Specifically, the amount of inorganic acid used is relative to the amount of ethylene glycol solution used in step S102.

[0048] In some of these embodiments, the crystal growth guiding agent includes, but is not limited to, polyvinylpyrrolidone (PVP).

[0049] In some of these embodiments, the reducing agent includes, but is not limited to, ascorbic acid.

[0050] In some embodiments, the inorganic acid includes, but is not limited to, hydrochloric acid. The concentration of the hydrochloric acid is 36% to 38%.

[0051] In some embodiments, the preset temperature is 160℃~200℃. Preferably, the preset temperature is 170℃~190℃. Specifically, the preset temperature includes, but is not limited to, 172℃, 175℃, 178℃, 180℃, 182℃, 185℃, and 188℃.

[0052] In some embodiments, the preset time is 10 to 20 minutes. Preferably, the preset time is 12 to 18 minutes. Specifically, the preset time includes, but is not limited to, 13 minutes, 15 minutes, and 17 minutes.

[0053] In some of these embodiments, solid-liquid separation includes centrifugation and filtration.

[0054] In some of these embodiments, washing is performed at least once with anhydrous ethanol and / or deionized water.

[0055] In some embodiments, anhydrous ethanol and deionized water are used for alternating washing. The alternating washing is performed at least once, that is, once with anhydrous ethanol and once with deionized water.

[0056] The photothermal-thermoelectric synergistic material of this invention can be used to prepare bone defect repair materials. Its technical effects are as follows: By utilizing gold nanoparticles located at the center of a hexagon as a "heat source core," a stable radial temperature gradient is formed with the substrate bismuth selenide under near-infrared light excitation, thereby generating an endogenous microcurrent based on the Seebeck effect of bismuth selenide. This wireless, non-invasive "photothermal-stable temperature difference-thermoelectric" cascade signal can effectively simulate the bioelectrical environment of bone tissue and significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells.

[0057] Furthermore, the photothermal-thermoelectric synergistic material of the present invention can effectively remove reactive oxygen species and has good antioxidant properties.

[0058] Example 2 This embodiment relates to the photothermal-thermoelectric synergistic composite material, its preparation method, and its application.

[0059] An illustrative embodiment of the present invention provides a photothermal-thermoelectric synergistic composite material, which is composed of the photothermal-thermoelectric synergistic material as described in Example 1 and a hydrogel material.

[0060] In some of these embodiments, the amount of photothermal-thermoelectric synergistic material used is 100ppm to 600ppm.

[0061] In some of these embodiments, the photothermal-thermoelectric composite material also includes a photoinitiator.

[0062] In some of these embodiments, the photoinitiator includes, but is not limited to, lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP for short).

[0063] In some of these embodiments, the morphology of the photothermal-thermoelectric composite material includes, but is not limited to, solid and gel states.

[0064] It should be noted that, due to the introduction of photoinitiators, under the action of a light source of a certain wavelength (such as photocuring or photocrosslinking), the photothermal-thermoelectric composite material can be transformed from a gel state to a solid state.

[0065] The preparation method of the photothermal-thermoelectric synergistic composite material of the present invention includes: Step S201: Add methacrylamide gelatin and photoinitiator to phosphate buffer according to a preset ratio to obtain a hydrogel solution; Step S202: Add the photothermal-thermoelectric synergistic material as described in Example 1 to the phosphate buffer solution to obtain a dispersion solution; Step S203: Add the dispersion solution to the hydrogel solution and mix under light-protected conditions to obtain a photosensitizing precursor solution; Step S204: Perform in-situ photocrosslinking of the photosensitive precursor solution to obtain a photothermal-thermoelectric synergistic composite material.

[0066] In step S201, the concentration of the photoinitiator is 0.25%. It should be noted that the concentration of the photoinitiator = mass of the photoinitiator / volume of the photosensitizing precursor solution.

[0067] In step S203, the concentration of methacrylamide gelatin in the photosensitizing precursor solution is 5% to 20% w / v. Specifically, the concentration of methacrylamide gelatin includes, but is not limited to, 7.5% w / v, 10% w / v, and 15% w / v.

[0068] It should be noted that the concentration of methacrylamide gelatin is calculated as the mass of methacrylamide gelatin divided by (the volume of the hydrogel solution in phosphate buffer + the volume of the dispersion solution in phosphate buffer).

[0069] In step S203, the amount of photothermal-thermoelectric synergistic material used in the photosensitive precursor solution is 100ppm to 600ppm.

[0070] In step S204, the conditions for in-situ photocrosslinking are: the wavelength of the ultraviolet light source is 365 nm and the intensity is 400 mW / cm². 2 .

[0071] Furthermore, after step S204, the method further includes: Step S205: Sterilize the photothermal-thermoelectric composite material.

[0072] In some of these embodiments, sterilization is performed by gamma ray irradiation.

[0073] The photothermal-thermoelectric synergistic composite material of the present invention can be used to prepare bone defect repair materials. Its usage method is as follows: The gel-state photothermal-thermoelectric synergistic material (i.e., the photosensitive precursor solution in step S203) is injected into a mold, and then in-situ photocrosslinking is performed (i.e., step S204) to obtain the solid-state photothermal-thermoelectric synergistic material.

[0074] The technical effects of the photothermal-thermoelectric synergistic composite material of the present invention are the same as those of the photothermal-thermoelectric synergistic material in Example 1, and will not be repeated here.

[0075] Example 3 This embodiment relates to a specific implementation of photothermal-thermoelectric synergistic materials.

[0076] In this embodiment, the photothermal-thermoelectric synergistic material, namely bismuth selenide-gold nanosheets, is prepared by the following method: Step 1: Prepare the precursor solution Weigh out 4-6 mg of bismuth nitrate pentahydrate (Bi(NO3)3·5H2O) and 2-3.5 mg of sodium selenite (Na2SeO3), and dissolve them separately in 2-3 mL of ethylene glycol. After mixing, add pre-prepared gold nanoparticle seeds with a diameter of approximately 40 nm.

[0077] Step 2: Prepare the reaction solution Take another 8 mL to 12 mL of ethylene glycol and place it in a reaction flask. Add 9 mg to 13 mg of polyvinylpyrrolidone (PVP, as a crystal growth guide), 500 mg to 800 mg of ascorbic acid (AA, as a reducing agent), and 15 μL to 25 μL of hydrochloric acid (HCl). Heat the solution to 175 °C to 185 °C with magnetic stirring.

[0078] Step 3: Rapid Injection and Growth The mixed precursor containing gold seeds from step 1 was rapidly injected into the high-temperature reaction solution preheated to 180°C in step 2. At this point, the color of the reaction system changed rapidly.

[0079] Step 4: Reaction and Post-processing The reaction was maintained at 180°C for 15 minutes. During this process, bismuth selenide, with gold seeds as its core, underwent epitaxial growth along the hexagonal crystal plane under PVP regulation. After the reaction was completed, the mixture was allowed to cool naturally, and the product was collected by centrifugation. The product was then washed three times alternately with ethanol and deionized water to finally obtain hexagonal Bi₂Se₃-Au nanosheets with gold particles at the very center.

[0080] In this embodiment, the experimental groups are set up as shown in the table below.

[0081] The bismuth selenide-gold nanosheets prepared in experimental groups 1, 2, and 3 were analyzed, and the results are as follows: 1) Experimental Group 1: 2) Experimental Group 2: Nanosheets with core-shell structure can still be synthesized under conditions of lower raw material concentration and fewer seed crystals; due to the reduction in the number of seed crystals (50μL), the growth raw material obtained by a single seed crystal is relatively increased, and the average lateral size of the resulting hexagonal nanosheets is slightly larger than that of Experimental Group 1, but Au is still in the middle. 3) Experimental Group 3: Under conditions of higher raw material concentration and more seed crystals, smaller but densely distributed nanosheets were prepared; due to the increase in the number of seed crystals (200 μL), the number of nucleation sites increased, and the average size of the resulting hexagonal nanosheets was slightly smaller than that of Experimental Group 1, but the yield was higher.

[0082] Example 4 This embodiment relates to a specific implementation of a photothermal-thermoelectric synergistic composite material.

[0083] In this embodiment, the photothermal-thermoelectric synergistic composite material, namely Bi2Se3-Au@GelMA photocrosslinked hydrogel, is prepared by the following method: Step 1: Prepare hydrogel solution Weigh 0.1g~0.3g of methacrylamide gelatin (GelMA) and 4~6mg of photoinitiator (LAP), and dissolve them in 1mL~3mL of PBS (phosphate buffer) at 50℃ until the solution is clear.

[0084] Step 2: Prepare Bi2Se3-Au dispersion Weigh 0.2 mg to 1 mg of Bi2Se3-Au nanosheets and dissolve them in 0.25 mL to 2 mL of PBS (phosphate buffer) at 50 °C. Mix thoroughly.

[0085] Step 3: Prepare the photosensitizer precursor solution The Bi2Se3-Au dispersion from step 2 was added to the hydrogel solution from step 1 and mixed evenly under light-protected conditions to obtain a Bi2Se3-Au@GelMA photosensitizer solution with a GelMA concentration of 5% w / v to 20% w / v.

[0086] Step 4: Photocrosslinking molding The Bi2Se3-Au@GelMA photosensitive precursor solution from step 3 was injected into the mold and placed at a wavelength of 365 nm and an intensity of 400 mW / cm². 2 Irradiation with ultraviolet light. The solution rapidly undergoes in-situ photocrosslinking within seconds, forming a solid hydrogel scaffold. All samples were sterilized by gamma-ray irradiation before use.

[0087] It should be noted that for step 2, the Bi2Se3-Au dispersion can be omitted. That is, in step 3, the Bi2Se3-Au nanosheets can be directly added to the hydrogel solution in step 1.

[0088] In this embodiment, the experimental groups are set up as shown in the table below.

[0089] The Bi2Se3-Au@GelMA photocrosslinked hydrogels prepared in experimental groups 4, 5, and 6 were analyzed, and the results are as follows: 1) Experimental group 4: 2) Experimental Group 5: Due to its low hydrogel matrix concentration (7.5%), it can meet the needs of cartilage or soft tissue repair; in addition, this Bi2Se3-Au@GelMA photocrosslinked hydrogel (scaffold morphology) has a low modulus and a large pore size, which is conducive to early cell migration. 3) Experimental group 6: Due to the high concentration of hydrogel matrix (15%), it can provide stronger mechanical support; in addition, the mechanical strength of this Bi2Se3-Au@GelMA photocrosslinked hydrogel (scaffold morphology) is significantly improved and the degradation rate is slowed down, making it suitable for bone defect repair in the weight-bearing area.

[0090] Example 5 This embodiment verifies and analyzes photothermal-thermoelectric synergistic materials (i.e., Bi2Se3 nanosheets) and photothermal-thermoelectric synergistic composite materials (i.e., Bi2Se3-Au@GelMA photocrosslinked hydrogel).

[0091] For Bi2Se3 nanosheets, such as Figure 1 As shown, the preparation method of the present invention can be used to successfully prepare a core-shell heterojunction structure in which Au nanoparticles are precisely located at the center of a hexagonal Bi2Se3 nanosheet.

[0092] For Bi2Se3-Au@GelMA photocrosslinked hydrogels, such as Figure 2 As shown, compared with pure GelMA, the Bi2Se3-Au@GelMA photocrosslinked hydrogel maintains a uniform three-dimensional porous network structure that is conducive to cell adhesion and nutrient delivery.

[0093] like Figure 3 As shown, the preparation method of the present invention can be used to successfully prepare Bi2Se3-Au@GelMA photocrosslinked hydrogel, which has rapid in-situ photocrosslinking gelation ability and good mechanical support strength.

[0094] like Figure 4 As shown, the Bi2Se3-Au@GelMA photocrosslinked hydrogel exhibits a significant light absorption peak in the near-infrared region, providing a physical basis for the subsequent photothermal-thermoelectric response. UV-Vis-NIR absorption spectroscopy reveals that the Bi2Se3-Au@GelMA photocrosslinked hydrogel displays strong light absorption characteristics across the entire near-infrared band. Particularly noteworthy is the material's excellent light-trapping performance at 1064 nm (NIR-II region). This superior light absorption at 1064 nm implies that this scaffold can utilize NIR-II lasers with deeper penetration and a higher maximum permissible skin irradiation threshold as excitation sources in clinical applications, thereby more effectively addressing the challenges of repairing deep bone defects and providing a more flexible and robust physical basis for driving the cascade response of "photothermal-stable temperature difference-thermoelectric".

[0095] The photothermal and thermoelectric properties of the Bi2Se3-Au@GelMA photocrosslinked hydrogel were tested by irradiating it with a 1064nm near-infrared laser. Infrared thermography revealed that the temperature of the Bi2Se3-Au@GelMA photocrosslinked hydrogel increased rapidly with irradiation time. Specifically, as shown... Figure 5 As shown, the Bi2Se3-Au@GelMA photocrosslinked hydrogel exhibits excellent concentration-dependent photothermal conversion efficiency and good photothermal stability, demonstrating significant concentration-dependent photothermal conversion behavior. Specifically, under near-infrared laser irradiation at the same power density (e.g., 1.0 W / cm²), the heating rate and final equilibrium temperature of the hydrogel are positively correlated with the doping concentration of the Bi2Se3-Au nanosheets. As the concentration increases from low (100 ppm) to high (600 ppm), the material can reach the effective treatment temperature more quickly, while the temperature change of the pure GelMA group is negligible, proving that the excellent photothermal conversion efficiency originates from the Bi2Se3-Au heterostructure. This can meet the needs of long-term, repeated photothermal-thermoelectric therapy in bone repair.

[0096] Simultaneously, tests conducted using an electrochemical workstation showed that the support generated a stable nanoampere-level photocurrent the instant the light was turned on, confirming the "photothermal-temperature difference-thermoelectric" conversion mechanism. Specifically, such as... Figure 6 As shown, the thermoelectric parameters (including conductivity, Seebeck coefficient, and power factor) of the Bi2Se3-Au heterojunction nanosheets were systematically characterized, confirming their excellent thermoelectric conversion potential. Specifically, due to the excellent thermoelectric properties of the Bi2Se3 semiconductor itself and the introduction of highly conductive Au nanoparticles, this composite material exhibits high conductivity and a significant Seebeck coefficient. This means that under extremely small temperature gradients, Bi2Se3-Au can efficiently drive the directional movement of charge carriers, outputting stable millivolt-level thermal voltages or nanoampere-level microcurrents. This efficient thermoelectric conversion capability provides a solid energy foundation for simulating the endogenous bioelectrical environment of bone tissue and activating cellular ion channels.

[0097] The antioxidant properties of Bi2Se3-Au@GelMA photocrosslinked hydrogel were tested. An oxidative stress model was established by treating bone marrow mesenchymal stem cells (BMSCs) with H2O2. After co-culturing with Bi2Se3-Au@GelMA photocrosslinked hydrogel, intracellular reactive oxygen species (ROS) were detected using the DCFH-DA probe. Fluorescence microscopy showed a significant reduction in green fluorescence in the scaffold group, demonstrating that the material effectively scavenged ROS. Figure 7As shown, the DCFH-DA fluorescent probe was used to evaluate the material's ability to scavenge intracellular reactive oxygen species (ROS) under H2O2-induced oxidative stress. The results showed that cells in the H2O2-treated damage model group exhibited strong green fluorescence, indicating a high level of oxidative stress. In contrast, co-culturing with Bi2Se3-Au@GelMA photocrosslinked hydrogel significantly reduced the intensity of intracellular green fluorescence, approaching the level of the normal control group. This superior antioxidant performance is attributed to the significant nanozyme activity of the Bi2Se3-Au heterojunction.

[0098] In vitro osteogenic activity was tested using Bi2Se3-Au@GelMA photocrosslinked hydrogels. BMSCs were seeded onto the scaffold surface and divided into a no-light group and a NIR-light group. After 7 days of culture, alkaline phosphatase (ALP) staining was performed; the light-light group showed the deepest blue-purple precipitation. After 14 days of culture, Alizarin Red (ARS) staining was performed; numerous red calcium nodules were observed in the light-light group. The results demonstrate that thermoelectric synergistic stimulation significantly promoted osteogenic differentiation of stem cells. Figure 8 As shown, in alkaline phosphatase (ALP) staining after 7 days of co-culture, the light-treated group showed the largest area and the deepest blue-purple precipitate, indicating that thermoelectric stimulation significantly upregulated the activity of osteogenic-related enzymes in the early stage; in Alizarin Red (ARS) staining after 14 days of co-culture, a large number of dense red calcium nodules were observed in the light-treated group.

[0099] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0100] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A photothermal-thermoelectric synergistic material, characterized in that, Including bismuth selenide-gold composite materials; The bismuth selenide-gold composite material is hexagonal, with the gold material located in the exact center of the hexagon; The gold material consists of gold nanoparticles with a particle size of 25nm to 55nm.

2. The photothermal-thermoelectric synergistic material according to claim 1, characterized in that, The molar ratio of bismuth selenide to gold is 100~500:

1.

3. A method for preparing a photothermal-thermoelectric synergistic material, used to prepare the photothermal-thermoelectric synergistic material as described in any one of claims 1 to 2, characterized in that, include: Bismuth nitrate pentahydrate, sodium selenite, and gold material are added to an ethylene glycol solution in a predetermined ratio to obtain a precursor solution. The crystal growth guide, reducing agent and inorganic acid are added to the ethylene glycol solution in a preset ratio and heated to a preset temperature to obtain the reaction solution. The precursor solution is added to the reaction solution and reacted for a preset time to obtain a mixed solution; The mixed solution was subjected to solid-liquid separation and washing in sequence to obtain photothermal-thermoelectric synergistic materials.

4. The preparation method according to claim 3, characterized in that, The molar ratio of bismuth nitrate pentahydrate to sodium selenite is 1:1.4~1.6; and / or The gold material is a dispersion containing gold, and its volume is 0.5% to 2% of the volume of the ethylene glycol solution; and / or The mass ratio of crystal growth guide agent to reducing agent is 1:50~70; and / or The volume of inorganic acid used is 1.5 μL / mL to 2.5 μL / mL; and / or The preset temperature is 160℃~200℃; and / or The preset time is 10-20 minutes; and / or Solid-liquid separation includes centrifugation, vacuum filtration; and / or Washing shall be performed at least once with anhydrous ethanol and / or deionized water.

5. A photothermal-thermoelectric synergistic composite material, characterized in that, Includes photothermal-thermoelectric synergistic materials as described in any one of claims 1 to 2, or photothermal-thermoelectric synergistic materials and hydrogel materials prepared by the preparation methods described in any one of claims 3 to 4; Among them, the photothermal-thermal-electric synergistic composite material is composed of photothermal-thermal-electric synergistic material and hydrogel material.

6. The photothermal-thermoelectric synergistic composite material according to claim 5, characterized in that, The dosage of photothermal-thermoelectric synergistic materials is 100ppm~600ppm.

7. A method for preparing a photothermal-thermoelectric synergistic composite material, used to prepare the photothermal-thermoelectric synergistic composite material as described in any one of claims 5-6, characterized in that, include: Methacrylamide gelatin and photoinitiator were added to phosphate buffer at a predetermined ratio to obtain a hydrogel solution. The photothermal-thermoelectric synergistic material as described in any one of claims 1 to 2 or the photothermal-thermoelectric synergistic material prepared by the preparation method as described in any one of claims 3 to 4 is added to a phosphate buffer solution to obtain a dispersion solution. The dispersion solution was added to the hydrogel solution and mixed under light-protected conditions to obtain a photosensitizing precursor solution; In-situ photocrosslinking of the photosensitive precursor solution was performed to obtain a photothermal-thermoelectric synergistic composite material.

8. The preparation method according to claim 7, characterized in that, In the photosensitive precursor solution, the concentration of methacrylamide gelatin is 5%–20% w / v; and / or In the photosensitive precursor solution, the amount of photothermal-thermoelectric synergistic material is 100ppm~600ppm; and / or Conditions for in-situ photocrosslinking: wavelength of ultraviolet light source is 365nm, intensity is 400mW / cm². 2 .

9. The application of a photothermal-thermoelectric synergistic material or a photothermal-thermoelectric synergistic composite material in the preparation of bone defect repair materials, characterized in that, The photothermal-thermoelectric synergistic material is the photothermal-thermoelectric synergistic material as described in any one of claims 1 to 2 or the photothermal-thermoelectric synergistic material prepared by the preparation method as described in any one of claims 3 to 4. The photothermal-thermoelectric synergistic composite material is the photothermal-thermoelectric synergistic composite material as described in any one of claims 5 to 6 or the photothermal-thermoelectric synergistic composite material prepared by the preparation method as described in any one of claims 7 to 8.

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