A flexible film and its preparation

Abstract

The present invention discloses a flexible film and its preparation. The flexible film comprises a photothermal response layer, a mechanoelectric response layer and a photothermal response layer which are arranged in sequence from top to bottom. The mechanoelectric response layer is a polyvinyl alcohol / glycine mechanoelectric response layer, and the photothermal response layer is a collagen / conductive polymer photothermal response layer. The polyvinyl alcohol / glycine mechanoelectric response layer is a sandwich structure of polyvinyl alcohol-glycine-polyvinyl alcohol; the collagen / conductive polymer photothermal response layer uses a collagen network cross-linked by a cross-linking agent as a skeleton and a conductive polymer as a modified material, and the surface presents a double-exposed morphology of collagen and conductive polymer, and there are composite conductive fibers with collagen as a skeleton and conductive polymer composited inside. The flexible film has both photothermal stimulation response and passive electrical stimulation response functions, has good mechanoelectric conversion performance, electrochemical performance, photothermal performance and biocompatibility, and can be degraded under physiological conditions. The preparation process of the present invention is simple, easy to implement, and suitable for popularization and application.

Description

Technical Field

[0001] The invention relates to the fields of biomedicine and rehabilitation therapy, and in particular to a flexible film and preparation thereof. Background Art

[0002] As a commonly used external field stimulation method, electrical stimulation has been proven to have an effect on a variety of tissues and cells in the human body. Based on this, electrical stimulation has been widely studied as a treatment method in many fields such as neurological diseases, heart diseases and bone repair, and has achieved certain clinical application results. Current medical electrical stimulation treatments generally use implanted electrodes plus an external power supply. The electrochemical properties and biocompatibility of the surface of the electrical stimulation electrode are very important. The former determines the charge conversion efficiency of the electrode and affects the effect of electrical stimulation; the latter affects the side effects such as immune response caused by implantation. Due to the existence of internal ferroelectric domains, piezoelectric materials will generate a certain voltage signal when mechanically stimulated, which can convert mechanical energy into electrical energy. Mechanical effects caused by various movements are common in various tissues in the body, and piezoelectric materials have the potential to convert these mechanical signals into electrical signals.

[0003] Thermal stimulation is another commonly used external field stimulation method. Appropriate thermal stimulation therapy is used to repair bone tissue or skin tissue and treat diseases. In addition to direct thermal response materials, photothermal materials can convert light energy into heat energy under light of a specific wavelength.

[0004] In addition, it has been shown that the pathways by which electrical and thermal signals regulate cells are different. The former often achieves regulation with the help of integrins or calcium ion channels, while the latter achieves regulation through heat shock proteins. Currently, various biomedical / rehabilitation materials are mostly regulated by a single electrical signal or a single thermal signal. Summary of the invention

[0005] In view of this, the present invention provides a flexible film and its preparation, wherein the flexible film has the functions of photothermal stimulation response and passive electrical stimulation response, has good mechanoelectric conversion performance, electrochemical performance, photothermal performance and biocompatibility, and can be degraded under physiological environment.

[0006] In the first aspect of the present invention, the present invention provides a flexible film comprising a photothermal response layer, a mechanoelectric response layer and a photothermal response layer arranged in sequence from top to bottom, the mechanoelectric response layer is a polyvinyl alcohol / glycine mechanoelectric response layer, and the photothermal response layer is a collagen / conductive polymer photothermal response layer.

[0007] In some specific examples of the present invention, in the flexible film, the size of the mechanoelectric response layer is smaller than the size of the photothermal response layer, and the edges of the mechanoelectric response layer are encapsulated by an outer edge encapsulation layer formed by collagen.

[0008] In some specific examples of the present invention, in the flexible film, the polyvinyl alcohol / glycine electromechanical response layer is a sandwich structure of polyvinyl alcohol-glycine-polyvinyl alcohol; the collagen / conductive polymer photothermal response layer has a collagen network cross-linked by a cross-linking agent as a skeleton and a conductive polymer as a modified material, and the surface presents a double-exposed morphology of the collagen and the conductive polymer, and there are composite conductive fibers with the collagen as a skeleton and the conductive polymer compounded inside.

[0009] In some specific examples of the present invention, in the flexible film, the main crystal phase of glycine in the electromechanical response layer is γ-phase glycine.

[0010] In some specific examples of the present invention, in the flexible film, the cross-linking agent is one of glutaraldehyde, genipin, and carbodiimide-N-hydroxysuccinimide.

[0011] In some specific examples of the present invention, in the flexible film, the conductive polymer is polypyrrole or polyaniline.

[0012] In some specific examples of the present invention, in the flexible film, the thickness of the mechanoelectric response layer is 10 to 50 μm.

[0013] In some specific examples of the present invention, in the flexible film, the photothermal response layer has a thickness of 10 to 50 μm.

[0014] In a second aspect of the present invention, the present invention provides a method for preparing the above-mentioned flexible film, comprising the following steps:

[0015] (1) mixing a glycine aqueous solution having a concentration of 0.01 to 1 g / mL and a polyvinyl alcohol aqueous solution having a concentration of 0.01 to 1 g / mL in a volume ratio of 1:1 to 5:1, and stirring at 50 to 90° C. to obtain a glycine / polyvinyl alcohol mixed solution; injecting the glycine / polyvinyl alcohol mixed solution into a first container, drying at 50 to 90° C., taking out and cooling to room temperature to obtain a glycine / polyvinyl alcohol electromechanical response layer;

[0016] (2) taking a crosslinker solution with a crosslinker concentration of 5 to 20 mg / mL and a collagen solution with a collagen concentration of 1 to 5 mg / mL, adding the crosslinker solution to the collagen solution at a volume ratio of 0.2:1 to 1:1, and stirring to obtain a mixed solution; injecting the mixed solution into a second container, freezing it at -60 to -100°C, and then performing vacuum freeze drying after it is completely frozen to obtain a porous collagen network; mixing a conductive polymer monomer aqueous solution and an oxidant aqueous solution to form a polymerization reaction solution, wherein the concentration of the conductive polymer monomer is 0.01 to 0.05 mol / L, and the concentration of the oxidant is 0.01 to 1 mol / L; placing the porous collagen network into the polymerization reaction solution for reaction, taking it out after 10 to 50 minutes, and soaking and washing it in deionized water to obtain a collagen / conductive polymer photothermal response layer;

[0017] (3) The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 10 to 30 minutes and then taken out, and then two collagen / conductive polymer photothermal response layers and one glycine / polyvinyl alcohol electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and hot pressed at 30 to 60° C. for 1 to 12 hours to obtain the target film product.

[0018] In some specific examples of the present invention, in step (3), before hot pressing, 1 to 5 mg / mL of collagen solution is added to the peripheral edge of the electromechanical response layer between the two photothermal response layers.

[0019] In some specific examples of the present invention, in step (1), the stirring time is 1 to 3 hours.

[0020] In some specific embodiments of the present invention, in step (1), the drying time is 12 to 48 hours.

[0021] In some specific examples of the present invention, in step (1), the first container is a first culture dish.

[0022] In some specific examples of the present invention, in step (2), the cross-linking agent is one of glutaraldehyde, genipin, and carbodiimide-N-hydroxysuccinimide.

[0023] In some specific examples of the present invention, in step (2), the conductive polymer monomer is pyrrole or aniline.

[0024] In some specific examples of the present invention, in step (2), the oxidant is selected from one of ferric chloride and ammonium sulfite.

[0025] In some specific examples of the present invention, in step (2), the collagen solution with a collagen concentration of 1 to 5 mg / mL is obtained by fully dissolving the type I collagen gel with a hydrochloric acid solution or an acetic acid solution with a concentration of 0.01 to 1 mol / L.

[0026] In some specific examples of the present invention, in step (2), the stirring time is 0.5 to 2 hours.

[0027] In some specific embodiments of the present invention, in step (2), the freezing time is 12 to 48 hours.

[0028] In some specific embodiments of the present invention, in step (2), the vacuum freeze-drying time is 6 to 12 hours.

[0029] In some specific examples of the present invention, in step (2), the second container is a second culture dish.

[0030] In some specific examples of the present invention, in step (3), hot pressing is performed at a pressure of 100 to 1000 Pa.

[0031] In some specific examples of the present invention, in the flexible film, the main crystal phase of glycine in the electromechanical response layer is γ-phase glycine.

[0032] In some specific examples of the present invention, in the flexible film, the thickness of the mechanoelectric response layer is 10 to 50 μm.

[0033] In some specific examples of the present invention, in the flexible film, the photothermal response layer has a thickness of 10 to 50 μm.

[0034] In the present invention, room temperature generally refers to 20 to 25°C.

[0035] In the present invention, the conductive polymer monomer refers to a monomer that forms the conductive polymer.

[0036] In the present invention, the polyvinyl alcohol / glycine electromechanical response layer refers to a polyvinyl alcohol / glycine (composition) composite electromechanical response layer.

[0037] In the flexible film of the present invention, the mechanoelectric response layer and the photothermal response layer can be made by selecting a container of suitable size as needed or cut into a suitable size as needed. Generally speaking, in the assembled flexible film, the size of the mechanoelectric response layer is not larger than the size of the photothermal response layer. When the size of the mechanoelectric response layer is smaller than the size of the photothermal response layer, collagen can be used to encapsulate the edge of the mechanoelectric response layer to form a collagen encapsulation layer around the mechanoelectric response layer.

[0038] In the flexible film of the present invention, the electromechanical response layer is a polyvinyl alcohol / glycine electromechanical response layer. Both polyvinyl alcohol and glycine can be rapidly degraded in water. Moreover, in the polyvinyl alcohol-glycine-polyvinyl alcohol sandwich structure, in the presence of polyvinyl alcohol, glycine is oriented to form γ-phase glycine (γ-phase glycine has good piezoelectric properties and can be used for electromechanical conversion). At the same time, when the organism moves, each tissue has a certain mechanical action, which can be converted into a voltage signal. Combining the mechanical action in the organism and the piezoelectric coefficient of the electromechanical response layer in the present invention, a voltage signal of about tens of mV or hundreds of mV can be generated.

[0039] In the flexible film of the present invention, the photothermal response layer is a collagen / conductive polymer photothermal response layer, with a collagen network as a skeleton and a conductive polymer as a modified material. The surface presents a double-exposed morphology of collagen and conductive polymer, and there are conductive fibers with collagen as a skeleton and a conductive polymer compounded inside. The photothermal response layer has both good photothermal and electrical properties. It can generate controllable heat under near-infrared light, can perform precise and controllable photothermal therapy, and can ensure that the voltage signal generated by the electromechanical response layer can be efficiently transmitted to the surface. Moreover, the collagen in the photothermal response layer has good biocompatibility and can fit well with biological tissues. In addition, the biomaterials used in the photothermal response layer can be slowly degraded in a physiological environment, and the conductive polymer can be excreted from the body through metabolism after losing the skeleton.

[0040] The flexible film of the present invention is a sandwich structure formed by encapsulating the outer photothermal response layer and the middle mechanoelectric response layer. Among them, the mechanoelectric response layer provides mechanoelectric conversion capability, converting the mechanical movement in the organism into electrical signals; the photothermal response layer provides good electrochemical performance, and can conduct the electrical signals generated by the mechanoelectric response layer to the surface. At the same time, the photothermal response layer has good photothermal performance and can generate thermal signals in response to near-infrared light. The flexible film of the present invention has both photothermal stimulation response and passive electrical stimulation response functions.

[0041] The outermost layer of the flexible film of the present invention is a collagen / conductive polymer photothermal response layer. Therefore, the surface of the film shows good biocompatibility of collagen and can fit well with biological tissues. In addition, the collagen compounded with the conductive polymer in the photothermal response layer degrades slowly, and after being densified by hot pressing, the photothermal response layer can also play a role in protecting the electromechanical response layer, delaying the degradation of the electromechanical response layer. In a simulated body fluid environment, the flexible film of the present invention is degradable, the electromechanical response layer degrades and fails after 1 to 7 days, and the photothermal response layer substantially degrades and fails after 20 to 60 days.

[0042] The preparation of the flexible film of the present invention includes: firstly, obtaining a polyvinyl alcohol / glycine electromechanical response layer by a solvent evaporation method, then using a porous collagen network as a skeleton to composite a conductive polymer to form a photothermal response layer with good electrical conductivity and biocompatibility, and finally, hot-pressing and packaging the electromechanical response layer and the photothermal response layer to obtain a flexible film with both photothermal stimulation response and passive electrical stimulation response functions.

[0043] The flexible film obtained by the present invention has both photothermal stimulation response and passive electrical stimulation response functions. It can spontaneously convert the mechanical action generated by the movement of the organism into electrical signals in the body, and conduct them to the surface through the conductive polymer network in the photothermal response layer. At the same time, the photothermal response layer can generate heat signals in response to near-infrared light, forming electrical and thermal dual-functional stimulation. It can be used as a degradable therapeutic film and has great application prospects in the fields of biomedicine and rehabilitation therapy.

[0044] Compared with the prior art, the present invention has the following beneficial technical effects:

[0045] The flexible film of the present invention has a unique large sandwich structure of photothermal response layer-mechanical electric response layer-photothermal response layer, the mechanical electric response layer is a polyvinyl alcohol / glycine mechanical electric response layer, and the photothermal response layer is a collagen / conductive polymer photothermal response layer, so that the film has both photothermal stimulation response and passive electrical stimulation response functions. The flexible film of the present invention has good biocompatibility, can be well adhered to biological tissues, and is degradable. The preparation method of the flexible film of the present invention is simple in process, easy to implement, and is conducive to promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1a , Figure 1b and Figure 1c They are photos of the mechanoelectric response layer, photothermal response layer and target thin film product in Example 1 respectively.

[0047] Figure 2 It is a schematic structural diagram of the target film product of the present invention.

[0048] Figure 3 This is a scanning electron microscope image of the cross section of the electromechanical response layer in Example 1.

[0049] Figure 4 It is the XRD spectra of the mechanoelectric response layer in Example 1, the mechanoelectric response layer in Example 2, and the mechanoelectric response layer in Example 3.

[0050] Figure 5 These are fluorescent staining photos of the photothermal response layer in Example 1 and the photothermal response layer in Example 2.

[0051] Figure 6It is a comparison chart of the results of piezoelectric performance testing of the mechanoelectric response layer and the target thin film product in Example 1, and the mechanoelectric response layer and the target thin film product in Example 2, respectively.

[0052] Figure 7 It is a comparison chart of the results of electrochemical performance testing of the photothermal response layer in Example 1 and the photothermal response layer in Example 2.

[0053] Figure 8a It is a comparison chart of the photothermal performance test results of the photothermal response layer in Example 1 and the photothermal response layer in Example 2 in a dry state.

[0054] Figure 8b It is a comparison chart of the photothermal performance test results of the photothermal response layer in Example 1 and the photothermal response layer in Example 2 under liquid conditions. DETAILED DESCRIPTION

[0055] In order to better illustrate the present invention and facilitate understanding of the technical solution of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be understood that the following embodiments are only used to illustrate the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0056] In the following examples and comparative examples, the reagents or instruments used without indicating the manufacturer are all conventional products available on the market. For example, type I collagen gel was purchased from Beijing Yierkang Biotechnology Co., Ltd., SBF (Simulated Body Fluid) simulated body fluid was purchased from Shanghai Yuanye Biotechnology Co., Ltd., and genipin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0057] Example 1

[0058] (1) Preparation of electromechanical response layer

[0059] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 80° C. for 3 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.1 g / mL.

[0060] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 1 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.1 g / mL.

[0061] 30 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 80° C. for 3 h to obtain 40 mL of a glycine / PVA mixed solution.

[0062] Take 6 mL of the above glycine / PVA mixture and inject it into a culture dish with a diameter of 10 cm, dry it at 60°C for 24 hours, take it out and cool it naturally to room temperature (20-25°C) to obtain the glycine / PVA electromechanical response layer. Cut it into 1 cm × 1 cm size for later use. The photo of the cut electromechanical response layer is shown in the figure. Figure 1a shown.

[0063] (2) Preparation of photothermal response layer

[0064] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.1 mol / L dilute hydrochloric acid solution and stirred for 3 hours to prepare a collagen solution with a collagen concentration of 2 mg / mL.

[0065] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 10 mg / mL.

[0066] 5 mL of the genipin solution was added to 20 mL of the collagen solution and stirred for 1 h to obtain 25 mL of a mixed solution.

[0067] 2 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 24 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 8 h to obtain a porous collagen network.

[0068] 4 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.2 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0069] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 30 minutes, and then soaked and cleaned in deionized water for 18 hours to obtain the collagen / conductive polymer photothermal response layer. The photothermal response layer can be cut as needed. Figure 1b shown.

[0070] (3) Assembly of dual-functional films

[0071] The collagen / conductive polymer photothermal response layer obtained in step (2) was soaked in anhydrous ethanol for 20 minutes. Then, two photothermal response layers and one electromechanical response layer were stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 2 mg / mL was added (injected) to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 37°C (at a pressure of about 500 Pa) for 8 hours to obtain the target film product. The target film product is shown in the photo. Figure 1cshown.

[0072] In order to more conveniently illustrate the structure of the target film product, Figure 2 A structural diagram is given. Figure 2 As shown, the target film product includes: a photothermal response layer, a mechanoelectric response layer and a photothermal response layer arranged in sequence from top to bottom, forming a sandwich structure, and the middle mechanoelectric response layer is encapsulated by an outer edge encapsulation layer formed by collagen.

[0073] The target film product is a flexible film that can fit well with biological tissues.

[0074] The structural morphology of the photothermal response layer and the electromechanical response layer constituting the target thin film product is characterized as follows:

[0075] The cross section of the electromechanical response layer obtained in step (1) was observed using a scanning electron microscope, and the SEM image thereof is as follows: Figure 3 shown. Figure 3 In the figure, it is obvious that the electromechanical response layer is a sandwich structure, and the layers from top to bottom are PVA, glycine, and PVA. The thickness of the electromechanical response layer is about 40μm.

[0076] The crystal structure of the electromechanical response layer obtained in step (1) was analyzed by X-ray diffraction, and its XRD curve was marked as Example 1 and recorded in Figure 4 From the XRD spectrum, it can be observed that the gamma-phase glycine (gamma-phase glycine is a glycine crystal phase with piezoelectric effect) is obvious, that is, the main crystal phase of glycine is the gamma-phase glycine.

[0077] The photothermal response layer (undried) obtained in step (2) is placed on a glass substrate, and after drying, a photothermal layer attached to the glass substrate is obtained. A scratch is made on the photothermal response layer with a scraper, and the scratch depth is measured using a contact step measuring instrument. The measured data is the thickness of the photothermal response layer. The thickness of the photothermal response layer is about 13.29±3.04μm.

[0078] The collagen was specifically stained with fluorescent dye, and the photothermal response layer obtained in step (2) was placed under a laser confocal microscope for observation. The observation results were as follows: Figure 5 As shown in the photo corresponding to Example 1, specifically: in the fluorescence mode (left), the collagen part emits red light due to dyeing, and the conductive polymer does not emit light; in the bright field mode (middle), the collagen is transparent and colorless, and the conductive polymer is opaque and black. The two modes are superimposed (right), and the structure of the photothermal response layer can be presented: the black network structure of the conductive polymer is clearly visible and the red color of the collagen exposed on the surface. The surface shows a double exposure morphology of collagen and conductive polymer, and there are composite conductive fibers with collagen as the skeleton and conductive polymer composite inside.

[0079] In summary, it can be clearly understood that the structure of the above-mentioned target film product is as follows: a photothermal response layer, a mechanoelectric response layer, and a photothermal response layer are arranged in sequence from top to bottom, and the edges of the middle mechanoelectric response layer are encapsulated by an outer edge encapsulation layer formed by collagen; and the photothermal response layer is based on a collagen network cross-linked by a cross-linking agent genipin as a skeleton, and a conductive polymer polypyrrole as a modified material, and the surface presents a double-exposed morphology of collagen and conductive polymer, and there are composite conductive fibers with collagen as a skeleton and conductive polymer polypyrrole compounded inside; the mechanoelectric response layer is a sandwich structure of PVA-glycine-PVA.

[0080] The properties of the above-mentioned target thin film product and the various response layers constituting it are characterized as follows.

[0081] When a separate electromechanical response layer is mentioned below, it means that the electromechanical response layer prepared in the above step (1) is subjected to a performance test; similarly, when a separate photothermal response layer is mentioned below, it means that the photothermal response layer prepared in the above step (2) is subjected to a performance test after being dried.

[0082] (1) Degradation performance

[0083] The samples were immersed in SBF simulated body fluid and the degradation performance of the samples was observed.

[0084] Complete disappearance of the film is considered complete degradation, while obvious fragmentation and granulation of the film is considered gross degradation.

[0085] The samples are a separate electromechanical response layer, a separate photothermal response layer and a target thin film product.

[0086] The observation results show that:

[0087] In a simulated body fluid environment, it takes 1 to 30 minutes for the mechanoelectric response layer alone to completely degrade;

[0088] In a simulated body fluid environment, it takes 15 to 60 days for the photothermal response layer alone to degrade.

[0089] Under a simulated body fluid environment, the electromechanical response layer in the target thin film product completely degrades after 1 to 7 days, and the electromechanical response fails; the photothermal response layer in the target thin film product is largely degraded after 20 to 60 days, and the photothermal response fails.

[0090] (2) Piezoelectric performance

[0091] Place a separate electromechanical response layer sample on the D33 instrument and clamp it, and read the reading as the piezoelectric coefficient D33 value. Test five different data points for each sample, and take the average value as the piezoelectric coefficient of the electromechanical response layer sample.

[0092] Place the target thin film product sample on the D33 instrument and clamp it, and read the reading as the piezoelectric coefficient D33 value. Test five different data points for each sample, and take the average value as the piezoelectric coefficient of the target thin film product sample.

[0093] The test results are as follows Figure 6 As shown in Example 1 and Example 1, it can be seen that the piezoelectric coefficient D33 of the single mechanoelectric response layer sample is 2.18±0.67pC / N, and the piezoelectric coefficient of the target film product sample is 1.99±0.33pC / N.

[0094] (3) Electrochemical performance

[0095] A three-electrode system was used to perform AC impedance test on the single photothermal response layer using an electrochemical workstation, wherein the platinum electrode was used as the counter electrode, the Ag / AgCl electrode was used as the reference electrode, and the single photothermal response layer was used as the working electrode.

[0096] Test results such as Figure 7 As shown in Example 1, the impedance of the photothermal response layer is not linearly related to the frequency at 1-10 Hz, and the electrochemical impedance is 500-5000Ω at 1 Hz, which is much lower than 10000Ω (generally, the 1cm×1cm planar metal or ITO electrode is 10000-20000Ω). It shows good electrochemical performance at low frequency and can meet the requirements of electrical signal transmission.

[0097] (4) Photothermal performance

[0098] An 808nm laser was used to irradiate a separate photothermal response layer placed in the air at a distance of 10cm, and the corresponding temperature rise data was obtained using a thermal imaging camera. The test results are shown in Figure 2. Figure 8a As shown in Example 1, the maximum surface temperature rise of the photothermal response layer can reach 60-150° C. It can be seen that the photothermal response layer can provide a rapid and high temperature rise in the dry state, indicating that the photothermal response layer has significant photothermal performance.

[0099] An 808nm laser was used to irradiate a single photothermal response layer placed in 1mL of ultrapure water at a distance of 10cm, and the corresponding temperature rise data was obtained using a thermal imaging camera. Figure 8b As shown in Example 1, the maximum temperature rise of the photothermal response layer in 1 mL of ultrapure water is 1-15°C. It can be seen that in a liquid environment, the photothermal response layer can produce an efficient and appropriate temperature rise (within a dozen degrees), and it is adjustable according to the illumination time, indicating that the photothermal response layer has photothermal application value.

[0100] Since the photothermal properties of the above-mentioned target thin film product are determined by the photothermal properties of the photothermal response layer, and the photothermal properties of the photothermal response layer are provided by the conductive polymer component of the layer, the existence of the electromechanical response layer located in the middle layer of the target thin film product will not affect the response of the conductive polymer in the photothermal response layer located on the surface of the target thin film product to 808nm laser. Therefore, the photothermal performance test of the above-mentioned single photothermal response layer can reflect the photothermal properties of the target thin film product.

[0101] In summary, the flexible target film product prepared above has both photothermal stimulation response and passive electrical stimulation response, and can be used as a degradable therapeutic film.

[0102] Example 2

[0103] (1) Preparation of electromechanical response layer

[0104] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 80° C. for 3 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.1 g / mL.

[0105] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 1 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.1 g / mL.

[0106] 20 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 80° C. for 3 h to obtain 30 mL of a glycine / PVA mixed solution.

[0107] 6 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 60°C for 24 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0108] (2) Preparation of photothermal response layer

[0109] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.1 mol / L dilute hydrochloric acid solution and stirred for 3 hours to prepare a collagen solution with a collagen concentration of 2 mg / mL.

[0110] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 10 mg / mL.

[0111] 5 mL of the genipin solution was added to 20 mL of the collagen solution and stirred for 1 h to obtain 25 mL of a mixed solution.

[0112] 2 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 24 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 8 h to obtain a porous collagen network.

[0113] 4 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.2 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0114] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 50 minutes, and then immersed and cleaned in deionized water for 24 hours to obtain a collagen / conductive polymer photothermal response layer.

[0115] (3) Assembly of dual-functional films

[0116] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 30 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 2 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers. Then, the mixture is hot-pressed at 37°C (with a pressure of about 500 Pa) for 12 hours to obtain the target film product.

[0117] Example 3

[0118] (1) Preparation of electromechanical response layer

[0119] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 90° C. for 5 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 1 g / mL.

[0120] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 3 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 1 g / mL.

[0121] 50 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 90° C. for 3 h to obtain 60 mL of a glycine / PVA mixed solution.

[0122] 10 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 90°C for 48 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm×1 cm size for later use.

[0123] (2) Preparation of photothermal response layer

[0124] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.01 mol / L dilute hydrochloric acid solution and stirred for 1 hour to prepare a collagen solution with a collagen concentration of 1 mg / mL.

[0125] Glutaraldehyde (cross-linking agent) was dissolved and diluted with deionized water to obtain a glutaraldehyde solution with a cross-linking agent concentration of 5 mg / mL.

[0126] 3 mL of the above glutaraldehyde solution was added to 15 mL of collagen solution and stirred for 0.5 h to obtain 18 mL of a mixed solution.

[0127] 1 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -60°C for 12 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 6 h to obtain a porous collagen network.

[0128] 2 mmol of aniline monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain an aniline monomer solution; 0.02 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the aniline monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0129] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 10 minutes, and then immersed and cleaned in deionized water for 12 hours to obtain a collagen / conductive polymer photothermal response layer.

[0130] (3) Assembly of dual-functional films

[0131] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 30 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 1 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 60°C (with a pressure of about 500 Pa) for 12 hours to obtain the target thin film product.

[0132] Example 4

[0133] (1) Preparation of electromechanical response layer

[0134] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 50° C. for 1 h to completely dissolve the PVA to obtain a PVA solution with a concentration of 0.01 g / mL.

[0135] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 3 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.01 g / mL.

[0136] 10 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 50° C. for 1 h to obtain 20 mL of a glycine / PVA mixed solution.

[0137] 5 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 50°C for 12 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0138] (2) Preparation of photothermal response layer

[0139] Type I collagen gel (1.4 wt%) was fully dissolved in a 1 mol / L dilute hydrochloric acid solution and stirred for 10 h to prepare a collagen solution with a collagen concentration of 5 mg / mL.

[0140] Carbodiimide-N-hydroxysuccinimide (cross-linking agent) was dissolved and diluted with deionized water to obtain a carbodiimide-N-hydroxysuccinimide solution with a cross-linking agent concentration of 20 mg / mL.

[0141] 20 mL of the above carbodiimide-N-hydroxysuccinimide solution was added to 20 mL of the above collagen solution and stirred for 2 h to obtain 40 mL of a mixed solution.

[0142] 5 mL of the mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -100° C. for 48 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 12 h to obtain a porous collagen network.

[0143] 10 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.2 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0144] The porous collagen network was gently placed into the above-mentioned polymerization reaction solution for reaction, taken out after 50 minutes, and then immersed and cleaned in deionized water for 24 hours to obtain a collagen / conductive polymer photothermal response layer.

[0145] (3) Assembly of dual-functional films

[0146] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 10 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 5 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers. Then, hot pressing is performed at 30°C (with a pressure of 800 Pa) for 1 hour to obtain the target thin film product.

[0147] Example 5

[0148] (1) Preparation of electromechanical response layer

[0149] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 70° C. for 2 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.5 g / mL.

[0150] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 2 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.5 g / mL.

[0151] 40 mL of the glycine solution and 10 mL of the PVA solution were mixed, and stirred at 70° C. for 3 h to obtain 50 mL of a glycine / PVA mixed solution.

[0152] 8 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 90°C for 48 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0153] (2) Preparation of photothermal response layer

[0154] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.1 mol / L dilute hydrochloric acid solution and stirred for 5 h to prepare a collagen solution with a collagen concentration of 4 mg / mL.

[0155] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 10 mg / mL.

[0156] 6 mL of the genipin solution was added to 30 mL of the collagen solution and stirred for 1 h to obtain 36 mL of a mixed solution.

[0157] 3 mL of the mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 48 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 12 h to obtain a porous collagen network.

[0158] 6 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.02 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0159] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 20 minutes, and then immersed and cleaned in deionized water for 18 hours to obtain a collagen / conductive polymer photothermal response layer.

[0160] (3) Assembly of dual-functional films

[0161] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 20 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 4 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 50°C (with a pressure of about 300 Pa) for 8 hours to obtain the target thin film product.

[0162] Example 6

[0163] (1) Preparation of electromechanical response layer

[0164] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 80° C. for 3 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.05 g / mL.

[0165] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 3 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.05 g / mL.

[0166] 20 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 80° C. for 3 h to obtain 30 mL of a glycine / PVA mixed solution.

[0167] 10 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 90°C for 36 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0168] (2) Preparation of photothermal response layer

[0169] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.2 mol / L dilute hydrochloric acid solution and stirred for 5 hours to prepare a collagen solution with a collagen concentration of 3 mg / mL.

[0170] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 5 mg / mL.

[0171] 10 mL of the genipin solution was added to 20 mL of the collagen solution and stirred for 1 h to obtain 30 mL of a mixed solution.

[0172] 4 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 24 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 12 h to obtain a porous collagen network.

[0173] 6 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.04 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0174] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 30 minutes, and then immersed and cleaned in deionized water for 18 hours to obtain a collagen / conductive polymer photothermal response layer.

[0175] (3) Assembly of dual-functional films

[0176] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 15 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 3 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 50°C (with a pressure of 500 Pa) for 8 hours to obtain the target thin film product.

[0177] Example 7

[0178] (1) Preparation of electromechanical response layer

[0179] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 80° C. for 3 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.8 g / mL.

[0180] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 3 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.8 g / mL.

[0181] 30 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 80° C. for 3 h to obtain 40 mL of a glycine / PVA mixed solution.

[0182] 7 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 90°C for 24 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0183] (2) Preparation of photothermal response layer

[0184] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.2 mol / L dilute hydrochloric acid solution and stirred for 5 hours to prepare a collagen solution with a collagen concentration of 3 mg / mL.

[0185] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 6 mg / mL.

[0186] 8 mL of the genipin solution was added to 20 mL of the collagen solution and stirred for 1 h to obtain 28 mL of a mixed solution.

[0187] 5 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 24 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 12 h to obtain a porous collagen network.

[0188] 8 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.04 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0189] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 40 minutes, and then immersed and cleaned in deionized water for 18 hours to obtain a collagen / conductive polymer photothermal response layer.

[0190] (3) Assembly of dual-functional films

[0191] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 20 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 3 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 60°C (with a pressure of 500 Pa) for 8 hours to obtain the target film product.

[0192] Example 8

[0193] (1) Preparation of electromechanical response layer

[0194] Polyvinyl alcohol (PVA) was dissolved in deionized water and stirred at 80° C. for 3 h to completely dissolve the PVA, thereby obtaining a PVA solution with a concentration of 0.2 g / mL.

[0195] Glycine was dissolved in deionized water and stirred at room temperature (20-25° C.) for 3 h to completely dissolve the glycine to obtain a glycine solution with a concentration of 0.2 g / mL.

[0196] 30 mL of the glycine solution and 10 mL of the PVA solution were mixed and stirred at 80° C. for 3 h to obtain 40 mL of a glycine / PVA mixed solution.

[0197] 6 mL of the glycine / PVA mixture was injected into a culture dish with a diameter of 10 cm, dried at 90°C for 24 h, taken out and naturally cooled to room temperature (20-25°C) to obtain a glycine / PVA electromechanical response layer, which was cut into 1 cm × 1 cm size for later use.

[0198] (2) Preparation of photothermal response layer

[0199] Type I collagen gel (1.4 wt%) was fully dissolved in a 0.2 mol / L dilute hydrochloric acid solution and stirred for 5 h to prepare a collagen solution with a collagen concentration of 2 mg / mL.

[0200] Genipin (cross-linking agent) was dissolved and diluted with deionized water to obtain a genipin solution with a genipin concentration of 10 mg / mL.

[0201] 10 mL of the genipin solution was added to 20 mL of the collagen solution and stirred for 1 h to obtain 30 mL of a mixed solution.

[0202] 8 mL of the above mixed solution was injected into a culture dish with a diameter of 2 cm and frozen at -80°C for 24 h. Then, the completely frozen sample was taken out and vacuum freeze-dried for 8 h to obtain a porous collagen network.

[0203] 8 mmol of pyrrole monomer (conductive polymer monomer) was added into 100 mL of deionized water to obtain a pyrrole monomer solution; 0.04 mol of ferric chloride (oxidant) was added into 100 mL of deionized water to obtain a ferric chloride solution; then, the pyrrole monomer solution and the ferric chloride solution were mixed to form a polymerization reaction solution.

[0204] The porous collagen network was gently placed in the polymerization reaction solution, taken out after 30 minutes, and then immersed and cleaned in deionized water for 18 hours to obtain a collagen / conductive polymer photothermal response layer.

[0205] (3) Assembly of dual-functional films

[0206] The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 20 minutes. Then, two photothermal response layers and one electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and the above-prepared collagen solution with a collagen concentration of 2 mg / mL is added to the edge of the electromechanical response layer between the two photothermal response layers, and then hot-pressed at 60°C (with a pressure of 500 Pa) for 8 hours to obtain the target film product.

[0207] The target film products obtained in the above-mentioned embodiments 2 to 8 are all flexible films, having a structure basically the same as that in embodiment 1, including: a photothermal response layer, a mechanoelectric response layer and a photothermal response layer arranged in sequence from top to bottom, and the edges of the middle mechanoelectric response layer are encapsulated by an outer edge encapsulation layer formed by collagen; and the photothermal response layer is a collagen network cross-linked by different cross-linking agents as a skeleton, and different conductive polymers as modified materials, and the surface presents a double-exposed morphology of collagen and conductive polymer, and there are composite conductive fibers with collagen as a skeleton and conductive polymers compounded inside; the mechanoelectric response layer is a sandwich structure of PVA-glycine-PVA. Among them, the crystalline phase of glycine is mainly γ-phase glycine. For example, in Figure 4 In the XRD spectra corresponding to Example 2 (corresponding to the electromechanical response layer in Example 2) and Example 3 (corresponding to the electromechanical response layer in Example 3), the main crystalline phase of glycine is γ-phase glycine. Figure 5 In the figure, the structure of the photothermal response layer presented by the fluorescent staining photograph corresponding to Example 2 (corresponding to the photothermal response layer in Example 2) and the fluorescent staining photograph corresponding to Example 1 (corresponding to the photothermal response layer in Example 1) is roughly the same.

[0208] Similarly, the target film products obtained in the above-mentioned embodiments 2 to 8 have similar properties to those in embodiment 1, including: degradable properties; a piezoelectric coefficient D33 of the mechanoelectric response layer of 1 to 7 pC / N (for example, Figure 6 The data shown in Example 2 show that the piezoelectric coefficient D33 of the mechanoelectric response layer sample in Example 2 is 2.23±0.44 pC / N, and the piezoelectric coefficient of the target film product sample in Example 2 is 2.06±0.41 pC / N), and it shows good electrochemical performance at low frequency (for example, Figure 7The electrochemical performance curves of the photothermal response layer in Example 1 corresponding to Example 1 and the photothermal response layer in Example 2 corresponding to Example 2 are substantially the same), which can satisfy the transmission of electrical signals; the photothermal response layer has significant photothermal performance in a dry state (for example, Figure 8a The curve trends of the photothermal response layer in Example 1 corresponding to Example 1 and the photothermal response layer in Example 2 corresponding to Example 2 are roughly the same), and an efficient and appropriate temperature rise can be generated under liquid conditions and can be adjusted according to the illumination time, and has photothermal application value (for example, in Figure 8b The curve trends of the photothermal response layer in Example 1 corresponding to Example 1 and the photothermal response layer in Example 2 corresponding to Example 2 are roughly the same). The flexible target film products prepared in the above embodiments have both photothermal stimulation response and passive electrical stimulation response, and can be used as degradable therapeutic films.

[0209] The flexible film prepared as above has both photothermal stimulation response and passive electrical stimulation response functions. It can spontaneously convert the mechanical action generated by the movement of the organism into electrical signals in the body, and conduct them to the surface through the conductive polymer network in the photothermal response layer. At the same time, the photothermal response layer can respond to near-infrared light to generate thermal signals, forming electrical and thermal dual-functional stimulation, which has great application prospects in the fields of biomedicine and rehabilitation therapy.

[0210] It can be seen that the present invention has developed a flexible film that can use the different paths of electrical and thermal signals to regulate cells, so that the electrical and thermal signals act simultaneously to achieve a synergistic promotion effect. In addition, the flexible film with both electrical and thermal functions can be flexibly regulated by different stimulation signals at different stages of cells. The flexible film of the present invention has potential application value in the biomedical field.

[0211] It can be seen that the purpose of the present invention has been completely and effectively achieved. The functional and structural principles of the present invention have been demonstrated and explained in the embodiments. Without departing from the principles, the implementation methods can be modified arbitrarily. Therefore, the present invention includes all modified implementation methods based on the spirit and scope of the claims.

Claims

1. A flexible film, characterized in that: The film includes a photothermal response layer, a mechanoelectric response layer and a photothermal response layer arranged in sequence from top to bottom, the mechanoelectric response layer is a polyvinyl alcohol / glycine mechanoelectric response layer, the photothermal response layer is a collagen / conductive polymer photothermal response layer, and the polyvinyl alcohol / glycine mechanoelectric response layer is a sandwich structure of polyvinyl alcohol-glycine-polyvinyl alcohol; the collagen / conductive polymer photothermal response layer has a collagen network cross-linked by a cross-linking agent as a skeleton and a conductive polymer as a modified material, and the surface presents a double-exposed morphology of the collagen and the conductive polymer, and there are composite conductive fibers with the collagen as a skeleton and the conductive polymer compounded inside, and the conductive polymer is polypyrrole or polyaniline.

2. The flexible film according to claim 1, characterized in that The size of the mechanoelectric response layer is smaller than that of the photothermal response layer, and the edges of the mechanoelectric response layer are encapsulated by an outer edge encapsulation layer formed by collagen.

3. The flexible film according to claim 1 or 2, characterized in that: The main crystal phase of glycine in the electromechanical response layer is γ-phase glycine.

4. The flexible film according to claim 1 or 2, characterized in that: The cross-linking agent is one of glutaraldehyde, genipin and carbodiimide-N-hydroxysuccinimide.

5. The method for preparing a flexible film according to claim 1, characterized in that: The following steps are involved: (1) mixing a glycine aqueous solution having a concentration of 0.01 to 1 g / mL and a polyvinyl alcohol aqueous solution having a concentration of 0.01 to 1 g / mL in a volume ratio of 1:1 to 5:1, and stirring at 50 to 90°C to obtain a glycine / polyvinyl alcohol mixed solution; injecting the glycine / polyvinyl alcohol mixed solution into a first container, drying at 50 to 90°C, taking out and cooling to room temperature to obtain a glycine / polyvinyl alcohol electromechanical response layer; (2) taking a crosslinker solution with a crosslinker concentration of 5 to 20 mg / mL and a collagen solution with a collagen concentration of 1 to 5 mg / mL, adding the crosslinker solution to the collagen solution at a volume ratio of 0.2:1 to 1:1, and stirring to obtain a mixed solution; injecting the mixed solution into a second container, freezing it at -60 to -100 °C, and then performing vacuum freeze drying after it is completely frozen to obtain a porous collagen network; mixing a conductive polymer monomer aqueous solution and an oxidant aqueous solution to form a polymerization reaction solution, wherein the concentration of the conductive polymer monomer is 0.01 to 0.05 mol / L, and the concentration of the oxidant is 0.01 to 1 mol / L; placing the porous collagen network in the polymerization reaction solution for reaction, taking it out after 10 to 50 minutes, and soaking and washing it in deionized water to obtain a collagen / conductive polymer photothermal response layer; wherein the conductive polymer monomer is pyrrole or aniline; (3) The collagen / conductive polymer photothermal response layer obtained in step (2) is soaked in anhydrous ethanol for 10 to 30 minutes and then taken out. Then, two collagen / conductive polymer photothermal response layers and one glycine / polyvinyl alcohol electromechanical response layer are stacked in the order of photothermal response layer-electromechanical response layer-photothermal response layer from top to bottom, and hot pressed at 30 to 60° C. for 1 to 12 hours to obtain the target film product.

6. The method for preparing a flexible film according to claim 5, characterized in that: In step (3), before hot pressing, 1-5 mg / mL of collagen solution is added around the edges of the electromechanical response layer located between the two photothermal response layers.

7. The method for preparing a flexible film according to claim 5 or 6, characterized in that: In step (2), the cross-linking agent is one of glutaraldehyde, genipin, and carbodiimide-N-hydroxysuccinimide.

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