Nanometer composite film as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biological medicine, and discloses a nano-composite film as well as a preparation method and application thereof. The nano composite membrane comprises a fiber membrane and polydopamine modified on the surface of the fiber membrane, and the fiber membrane contains polyvinylidene fluoride copolymer and barium titanate. The preparation method of the nano composite membrane comprises the following steps: S1, in the presence of a solvent, mixing barium titanate and a polyvinylidene fluoride copolymer, and carrying out electrostatic spinning to obtain a fiber membrane; s2, dopamine and the fiber membrane are subjected to a contact reaction, so that the surface of the fiber membrane is modified with polydopamine. The nano-composite film has continuous and cyclic oxidation resistance, and has long-acting and active inhibition on prosthetic capsule contracture.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a nanocomposite membrane and a preparation method and application thereof. Background Art

[0002] Breast reconstruction surgery is an important treatment for breast cancer patients recovering after surgery, and breast prostheses are often used as reconstruction materials. However, capsular contracture is a common complication after breast prosthesis implantation, which seriously affects the treatment effect and may cause prosthesis failure. Capsular contracture refers to the abnormal proliferation and contraction of the fibrous capsule surrounding the prosthesis, causing the prosthesis to shift or deform, and even cause pain. The occurrence of capsular contracture is closely related to inflammatory response. After prosthesis implantation, the immune system produces an immune response to the prosthetic material. The activation of immune cells such as macrophages and the release of cytokines play a key role in the capsule formation and fibrosis process. This persistent inflammatory response promotes fibroblast proliferation and collagen synthesis, accelerating the occurrence of capsular contracture. Therefore, regulating the inflammatory response has become one of the important strategies to inhibit capsular contracture.

[0003] During implant use, stress concentration caused by breast movement is a major factor contributing to capsular contracture. Existing implant fixation devices have limitations in preventing capsular contracture, typically employing passive designs and lacking active adjustment capabilities. In recent years, the critical role of biomechanical and bioelectrical interactions in regulating tissue repair and remodeling has garnered widespread attention. In particular, research into the coupling mechanisms between mechanical stress and bioelectricity has provided important insights for the development of novel implantable devices. Mechanoelectric coupling occurs naturally in human tissue and is a key source of bioelectrical signals. Electrical signals can effectively prevent capsular contracture through various mechanisms. First, electrical signals can regulate fibroblast activity, inhibiting their proliferation and collagen fiber synthesis, thereby reducing excessive fibrosis and reducing capsular thickness. Second, electrical signals can reduce the risk of capsular contracture by inhibiting inflammatory responses. Electrical stimulation can modulate the release of inflammatory cells and inflammatory factors, reducing local inflammatory responses and thereby diminishing the fibrotic process caused by inflammation. Studies have shown that electrical stimulation can reduce the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thereby reducing the progression of fibrosis.

[0004] Reactive oxygen species (ROS) generated by friction during breast movement are considered another key factor in capsular contracture. Excessive accumulation of ROS triggers a local inflammatory response, promoting immune cell activation and cytokine release, thereby accelerating the fibrotic process and ultimately leading to capsular contracture. ROS damage cellular components through oxidation, induce apoptosis, and exacerbate the local inflammatory environment. Therefore, eliminating excess ROS has become a potential strategy for inhibiting capsular contracture. One traditional approach is to eliminate ROS by introducing artificial superoxide dismutase (SOD)- and catalase (CAT)-like enzymes. These enzymes can effectively reduce superoxide and hydrogen peroxide, reducing ROS accumulation. However, these enzymes may induce side effects during their action, generating highly cytotoxic hydroxyl radicals (OH·), which can cause irreversible damage to cells. To overcome this problem, researchers have recently focused on strategies that utilize reducing agents to scavenge ROS through direct redox reactions. However, these reducing agents typically lose their activity after reacting with ROS, limiting their long-term antioxidant efficacy. Therefore, how to achieve the "cleaning" of inactivated antioxidants and improve their antioxidant properties and sustained effects becomes the key to improving therapeutic effects.

[0005] The traditional method of inhibiting capsular contracture is mainly achieved by loading anti-inflammatory drugs into the prosthetic fixation device. However, this method has the problems of limited drug release rate and short duration, and cannot effectively guarantee the long-term stability and service life of the prosthesis.

[0006] Therefore, a new long-term method to inhibit capsular contracture is urgently needed to ensure that the prosthesis remains stable for a longer period of time and reduce the occurrence of complications. Summary of the Invention

[0007] The purpose of the present invention is to overcome the problems of limited drug release rate and short duration in the prior art, and to provide a nanocomposite membrane and its preparation method and application. The nanocomposite membrane has continuous and cyclic antioxidant properties and has long-term and active inhibition of prosthetic capsular contracture.

[0008] To achieve the above objectives, the present invention provides a nanocomposite membrane in a first aspect. The nanocomposite membrane includes a fiber membrane and polydopamine modified on the surface of the fiber membrane. The fiber membrane contains a polyvinylidene fluoride copolymer and barium titanate.

[0009] Preferably, the polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer.

[0010] Further preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6.

[0011] A second aspect of the present invention provides a method for preparing a nanocomposite film, the method comprising the following steps:

[0012] S1. In the presence of a solvent, barium titanate and polyvinylidene fluoride copolymer are mixed and electrospun to obtain a fiber membrane;

[0013] S2. Contacting dopamine with the fiber membrane to react, so that the surface of the fiber membrane is modified with polydopamine.

[0014] Preferably, the solvent is N,N-dimethylformamide and / or acetone.

[0015] More preferably, the solvent is N,N-dimethylformamide and acetone.

[0016] Further preferably, the volume ratio of the N,N-dimethylformamide to the acetone is 1:0.3-0.5.

[0017] Preferably, in step S1, the polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer.

[0018] Further preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6.

[0019] Preferably, in step S1, the mixing conditions include at least: a temperature of 50-70°C, a stirring speed of 300-500 rpm, and a time of 3-5 hours.

[0020] Preferably, in step S1, the electrospinning conditions include at least: a temperature of 20-35°C, an applied voltage of 16-20 kV, a collection distance of 13-18 cm, and a propulsion rate of 0.7-0.9 mL / h.

[0021] Preferably, step S2 further comprises: annealing the fiber membrane before the contact reaction.

[0022] More preferably, the annealing treatment conditions at least include: a temperature of 120-140° C. and a time of 1-3 hours.

[0023] Preferably, the contact reaction conditions include at least: temperature of 20-35° C., pH of 8-9, and time of 11-13 h.

[0024] The third aspect of the present invention provides use of the nanocomposite film described in the first aspect or the nanocomposite film prepared by the method described in the second aspect in preparing a breast prosthesis.

[0025] Through the above technical solution, the nanocomposite membrane provided by the present invention uses a fiber membrane composed of polyvinylidene fluoride copolymer and barium titanate, and polydopamine is modified on the surface of the fiber membrane, so that the nanocomposite membrane has continuous and cyclic antioxidant properties, and has long-term and active inhibition of prosthesis capsular contracture; in terms of piezoelectric performance, through the synergistic effect of the specific fiber membrane and polydopamine, the open circuit voltage fluctuation range of the nanocomposite membrane is significantly increased, and it has better electromechanical conversion ability. It is further found that the nanocomposite membrane has obvious advantages in biocompatibility and can inhibit the inflammation-mediated fibrosis process and prevent the occurrence of capsular contracture; the nanocomposite membrane effectively and actively inhibits prosthesis capsular contracture in the long term through electromechanical coupling and "self-cleaning" antioxidant strategy, providing a new and effective solution for the stable use of prostheses in breast reconstruction surgery, which is expected to improve the quality of life of breast cancer patients after surgery and has broad prospects in clinical application. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a comparison chart of mechanical properties tests of the nanocomposite film sample prepared in Example 1 of the present invention and the film samples prepared in Comparative Examples 1-3;

[0027] Figure 2 1 is a comparison chart of the piezoelectric performance test of the nanocomposite film sample prepared in Example 1 of the present invention and the film samples prepared in Comparative Examples 1-3;

[0028] Figure 3 These are immunofluorescence staining images and data comparison graphs of the nanocomposite membrane sample prepared in Example 1 of the present invention and the membrane samples prepared in Comparative Examples 1-3 when co-cultured with RAW264.7 mouse-derived macrophages;

[0029] Figure 4 It is a staining diagram and data comparison diagram of intracellular reactive oxygen species when the nanocomposite membrane sample prepared in Example 1 of the present invention and the membrane samples prepared in Comparative Examples 1-3 are co-cultured with human bone marrow mesenchymal stem cells (BMSC). DETAILED DESCRIPTION

[0030] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0031] A first aspect of the present invention provides a nanocomposite membrane, which includes a fiber membrane and polydopamine modified on the surface of the fiber membrane, wherein the fiber membrane contains a polyvinylidene fluoride copolymer and barium titanate.

[0032] While developing a nanocomposite membrane, the inventors unexpectedly discovered that by spinning a polyvinylidene fluoride copolymer and barium titanate together to form a specific fiber membrane, and then modifying the fiber membrane surface with polydopamine, the built-in electric field within the nanocomposite membrane can enhance the efficiency of carrier separation and migration. The released electrons can participate in the catalysis of oxidized quinone groups and convert them back to polyphenol groups, thereby reproducing their antioxidant properties. As a result, the nanocomposite membrane has continuous and cyclic antioxidant properties, and has long-lasting, active inhibition of prosthetic capsular contracture. In terms of piezoelectric performance, the synergistic effect of the specific fiber membrane and polydopamine significantly increases the open-circuit voltage fluctuation range of the nanocomposite membrane, resulting in superior electromechanical conversion capabilities.

[0033] In the present invention, the polydopamine modification on the surface of the fiber membrane may be that the polydopamine is coated on a portion of the surface of the fiber membrane, or the polydopamine is coated on the entire surface of the fiber membrane to form a polydopamine coating.

[0034] According to the present invention, preferably, the polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer. The inventors have found that the above preferred embodiment can further improve the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term and active inhibition of prosthetic capsular contracture.

[0035] According to the present invention, further preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6, specifically 1:4, 1:4.5, 1:5, 1:5.5, 1:6, or any value in between. The inventors have discovered that employing this preferred embodiment further enhances the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0036] According to the present invention, the barium titanate preferably utilizes nanoscale barium titanate powder, more preferably, the particle size of the barium titanate is ≤100 nm. The inventors have discovered that employing this preferred embodiment further enhances the continuous and cyclic antioxidant properties of the nanocomposite film, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0037] A second aspect of the present invention provides a method for preparing a nanocomposite film, the method comprising the following steps:

[0038] S1. In the presence of a solvent, barium titanate and polyvinylidene fluoride copolymer are mixed and electrospun to obtain a fiber membrane;

[0039] S2. Contacting dopamine with the fiber membrane to react, so that the surface of the fiber membrane is modified with polydopamine.

[0040] The inventors discovered that by preparing a fiber membrane from a polyvinylidene fluoride copolymer and barium titanate and modifying the fiber membrane surface with polydopamine through a dopamine self-assembly polymerization reaction, the nanocomposite membrane possesses continuous and cyclic antioxidant properties. The polydopamine (PDA) coating is modified through non-covalent self-assembly, allowing the piezoelectric properties of the nanocomposite membrane to respond to the mechanical stress generated by breast movement. This creates a built-in electric field through mechanoelectric conversion, thereby reconstructing the electrical microenvironment of the breast area. Furthermore, the PDA coating on the surface of the nanocomposite membrane acts as an antioxidant due to the reduction potential of its polyphenol groups during redox reactions with environmental ROS. The built-in electric field within the nanocomposite membrane enhances the efficiency of carrier separation and migration, and the released electrons can participate in the catalysis of oxidized quinone groups and switch them back to polyphenol groups, thereby reproducing their antioxidant properties. This piezocatalytic strategy overcomes the one-time and inefficient ROS scavenging limitations of chemical reagents, while the continuous and cyclic antioxidant properties, combined with mechanoelectric coupling, promote the suppression of oxidative stress and the reconstruction of the breast inflammatory microenvironment. By applying this strategy, long-term, active inhibition of prosthesis capsular contracture can be achieved.

[0041] The present invention does not impose strict restrictions on the solvent; conventional solvents in the art may be used. Preferably, the solvent is N,N-dimethylformamide and / or acetone, specifically N,N-dimethylformamide alone, acetone alone, or a mixture of N,N-dimethylformamide and acetone. Further preferably, the solvent is a mixture of N,N-dimethylformamide and acetone. The inventors have discovered that employing this preferred embodiment further enhances the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0042] According to the present invention, further preferably, the volume ratio of N,N-dimethylformamide to acetone is 1:0.3-0.5, specifically 1:0.3, 1:0.35, 1:0.4, 1:0.45, 1:0.5, or any value in between. The inventors have discovered that employing this preferred embodiment can further enhance the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0043] In the present invention, preferably, the mass volume ratio (w / v) of the barium titanate to the solvent is 1:20-30.

[0044] According to the present invention, preferably, in step S1, the polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer. The inventors have found that adopting the above preferred embodiment can further improve the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0045] According to the present invention, further preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6, specifically 1:4, 1:4.5, 1:5, 1:5.5, 1:6, or any value in between. The inventors have discovered that employing this preferred embodiment further enhances the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0046] According to the present invention, preferably, the particle size of barium titanate is ≤100 nm. The inventors have found that the above preferred embodiment can further improve the continuous and cyclic antioxidant properties of the nanocomposite film, thereby improving the long-term and active inhibition of prosthetic capsular contracture.

[0047] According to the present invention, preferably, in step S1, the mixing conditions include at least: a temperature of 50-70°C, specifically 50°C, 55°C, 60°C, 65°C, 70°C, or any value between the above two values; a stirring speed of 300-500 rpm, specifically 300 rpm, 350 rpm, 400 rpm, 450 rpm, 500 rpm, or any value between the above two values; and a time of 3-5 hours, specifically 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, or any value between the above two values. The inventors have found that when the above preferred embodiment is adopted, the continuous and cyclic antioxidant properties of the nanocomposite film can be further improved, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0048] In the present invention, the electrospinning equipment can be commonly used in the prior art. For example, a mixed solution containing barium titanate and polyvinylidene fluoride-trifluoroethylene copolymer is prepared into a uniformly mixed electrospinning precursor solution, and then the precursor solution is transferred to a syringe, and the precursor solution is extruded through a 21G metal needle for electrospinning. The spun fibers can be collected on a rotating aluminum foil substrate.

[0049] According to the present invention, preferably, the electrospinning conditions include at least: a temperature of 20-35°C, specifically 20°C, 25°C, 30°C, 35°C, or any value between the above two values; an applied voltage of 16-20kV, specifically 16kV, 17kV, 18kV, 19kV, 20kV, or any value between the above two values; a collection distance of 13-18cm, specifically 13cm, 14cm, 15cm, 16cm, 17cm, 18cm, or any value between the above two values; a propulsion rate of 0.7-0.9mL / h, specifically 0.7mL / h, 0.75mL / h, 0.8mL / h, 0.85mL / h, 0.9mL / h, or any value between the above two values. The inventors have found that when the above preferred embodiment is adopted, the continuous and cyclic antioxidant properties of the nanocomposite membrane can be further improved, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0050] According to the present invention, preferably, step S2 further comprises: annealing the fiber membrane prior to the contact reaction. Further preferably, the fiber membrane is dried prior to annealing to remove residual solvent. Drying can be performed using conventional methods in the art. Exemplarily, vacuum drying can be performed at 60-80°C for 12-14 hours. The inventors have discovered that employing this preferred embodiment further enhances the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0051] According to the present invention, further preferably, the annealing conditions include at least: a temperature of 120-140°C, specifically 120°C, 125°C, 130°C, 135°C, 140°C, or any value in between; and a duration of 1-3 hours, specifically 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, or any value in between. The inventors have discovered that employing this preferred embodiment can further enhance the continuous and cyclic antioxidant properties of the nanocomposite film, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0052] According to the present invention, preferably, the conditions for the contact reaction include at least: a temperature of 20-35°C, specifically 25°C, 30°C, 35°C, or any value between the above two values; a pH of 8-9, specifically 8, 8.5, 9, or any value between the above two values; and a time of 11-13 hours, specifically 11 hours, 12 hours, 13 hours, or any value between the above two values. For example, dopamine hydrochloride can be prepared into an aqueous solution with a pH of 8-9, and the fiber membrane is immersed in the dopamine hydrochloride aqueous solution. The concentration of dopamine in the dopamine hydrochloride aqueous solution is not strictly limited and can be a conventional concentration in the art to ensure that dopamine self-assembly polymerization occurs on the fiber membrane surface. The polymerization reaction principle is based on the unique chemical structure and properties of dopamine. Dopamine molecules contain catechol groups and amino groups. In a weakly alkaline aerobic environment, a series of complex reactions will occur, achieving self-polymerization and forming a polydopamine coating on the fiber membrane surface. Preferably, the dopamine concentration in the aqueous dopamine hydrochloride solution is 2-4 mg / mL, specifically 2 mg / mL, 2.5 mg / mL, 3 mg / mL, 3.5 mg / mL, 4 mg / mL, or any value in between. The inventors have discovered that the use of this preferred embodiment can further enhance the continuous and cyclic antioxidant properties of the nanocomposite membrane, thereby improving the long-term, active inhibition of prosthetic capsular contracture.

[0053] According to the present invention, preferably, the contact reaction further includes post-processing of the nanocomposite film, and the post-processing operations include conventional operations such as cleaning, drying, and disinfection. The nanocomposite film may also be cut and tailored according to circumstances.

[0054] As a relatively preferred embodiment of the present invention, the nanocomposite film can be prepared by the following method:

[0055] S1. Barium titanate (BaTiO3, particle size ≤ 100 nm) is dispersed in a solvent formed by mixing N,N-dimethylformamide and acetone in a volume ratio of 1:0.3-0.5, so that the mass volume ratio (w / v) of barium titanate to the solvent is 1:20-30, and ultrasonic treatment is performed for 30-40 minutes to ensure that the barium titanate is uniformly dispersed in the solvent, and then mixed with polyvinylidene fluoride-trifluoroethylene copolymer (PVDF) so that the mass ratio of barium titanate to polyvinylidene fluoride-trifluoroethylene copolymer is 1: 4-6. Mix for 3-5 hours at a temperature of 50-70°C and a stirring speed of 300-500 rpm to form a uniform electrospinning precursor solution; transfer the precursor solution into a syringe and electrospin through a 21G metal needle at a temperature of 20-35°C. The electrospinning parameters are set as follows: applied voltage of 16-20 kV, collection distance of 13-18 cm, and propulsion rate of 0.7-0.9 mL / h; the spun fibers are collected on a rotating aluminum foil substrate to prepare a fiber membrane.

[0056] S2. The fiber membrane obtained in step S1 is vacuum dried at a temperature of 60-80°C for 12-14 hours, and then heated at a temperature of 120-140°C for 1-3 hours for annealing; the annealed fiber membrane is immersed in a 2-4 mg / mL dopamine hydrochloride aqueous solution (using Tris-HCl buffer, pH of about 8-9), and gently stirred at a temperature of 20-35°C for 11-13 hours to allow self-assembled dopamine polymerization reaction to occur on the surface of the fiber membrane, and then vacuum dried at 60-80°C for 12-14 hours to obtain a nanocomposite membrane (PVDF+BaTiO3+PDA).

[0057] The third aspect of the present invention provides use of the nanocomposite film described in the first aspect or the nanocomposite film prepared by the method described in the second aspect in preparing a breast prosthesis.

[0058] The nanocomposite membrane provided by the present invention is not limited to the application in the preparation of breast prostheses, but can also be used in the preparation of other prostheses to prevent capsular contracture after the prosthesis is transplanted into the patient's body.

[0059] The present invention will be described in detail below through examples.

[0060] In the following examples, the mechanical properties of the nanocomposite membranes were tensile tested using an electronic universal testing machine (Instron 3343, USA); barium titanate was purchased from Sigma-Aldrich Co., Ltd. with a product number of 467634 and a particle size of <100 nm; polyvinylidene fluoride-trifluoroethylene copolymer was purchased from Sigma-Aldrich Co., Ltd. with a product number of 427160; dopamine hydrochloride was purchased from Sigma-Aldrich Co., Ltd. with a product number of D2960000; all other raw materials or reagents used were commercially available unless otherwise specified.

[0061] In the following examples, unless otherwise specified, the room temperature is 25±5°C.

[0062] Example 1

[0063] S1. Disperse 0.2 g of barium titanate (BaTiO3, particle size <100 nm) in 5 mL of N,N-dimethylformamide and acetone solvent, with the volume ratio of N,N-dimethylformamide to acetone in the solvent being 1:0.4. Ultrasonic treatment is performed for 30 minutes to ensure that the barium titanate is uniformly dispersed in the solvent. Then, the mixture is mixed with 1 g of polyvinylidene fluoride-trifluoroethylene copolymer (PVDF) and mixed for 4 hours at a temperature of 60°C and a stirring speed of 300 rpm to form a uniform electrospinning precursor solution. The precursor solution is transferred to a 10 mL syringe and electrospun at room temperature through a 21G metal needle. The electrospinning parameters are set as follows: applied voltage of 18 kV, collection distance of 15 cm, and propulsion rate of 0.8 mL / h. The spun fibers are collected on a rotating aluminum foil substrate to prepare a fiber membrane.

[0064] S2. The fiber membrane obtained in step S1 was vacuum dried at 60°C for 14 hours, and then heated at 130°C for 2 hours for annealing; the annealed fiber membrane was immersed in a 2 mg / mL dopamine hydrochloride aqueous solution (using Tris-HCl buffer, pH about 8.5), gently stirred at room temperature for 12 hours to allow self-assembled dopamine polymerization reaction to occur on the surface of the fiber membrane, and then vacuum dried at 60°C for 14 hours to obtain a nanocomposite membrane (PVDF+BaTiO3+PDA).

[0065] Example 2

[0066] S1. 0.2 g of barium titanate (BaTiO3, particle size <100 nm) was dispersed in 5 mL of a solvent consisting of N,N-dimethylformamide and acetone, with a volume ratio of N,N-dimethylformamide to acetone of 1:0.3. The mixture was ultrasonically treated for 35 minutes to ensure that the barium titanate was uniformly dispersed in the solvent. The mixture was then mixed with 0.8 g of polyvinylidene fluoride-trifluoroethylene copolymer (PVDF) and stirred at 50°C and 400 rpm for 3 hours to form a uniform electrospinning precursor solution. The precursor solution was transferred to a 10 mL syringe and electrospun at room temperature using a 21G metal needle. The electrospinning parameters were set as follows: applied voltage of 16 kV, collection distance of 13 cm, and propulsion rate of 0.7 mL / h. The spun fibers were collected on a rotating aluminum foil substrate to prepare a fiber membrane.

[0067] S2. The fiber membrane obtained in step S1 was vacuum dried at 70°C for 13 hours, and then heated at 120°C for 3 hours for annealing; the annealed fiber membrane was immersed in a 4 mg / mL dopamine hydrochloride aqueous solution (using Tris-HCl buffer, pH about 8.5), gently stirred at room temperature for 11 hours to allow self-assembled dopamine polymerization reaction to occur on the surface of the fiber membrane, and then vacuum dried at 70°C for 13 hours to obtain a nanocomposite membrane (PVDF+BaTiO3+PDA).

[0068] Example 3

[0069] S1. Disperse 0.2 g of barium titanate (BaTiO3, particle size <100 nm) in 6 mL of N,N-dimethylformamide and acetone solvent, with the volume ratio of N,N-dimethylformamide to acetone in the solvent being 1:0.5. Ultrasonic treatment is performed for 40 minutes to ensure that the barium titanate is uniformly dispersed in the solvent. Then, the mixture is mixed with 1.2 g of polyvinylidene fluoride-trifluoroethylene copolymer (PVDF) and mixed at a temperature of 70°C and a stirring speed of 500 rpm for 5 hours to form a uniform electrospinning precursor solution. The precursor solution is transferred to a 10 mL syringe and electrospun at room temperature through a 21G metal needle. The electrospinning parameters are set as follows: applied voltage of 20 kV, collection distance of 18 cm, and propulsion rate of 0.9 mL / h. The spun fibers are collected on a rotating aluminum foil substrate to prepare a fiber membrane.

[0070] S2. The fiber membrane obtained in step S1 was vacuum dried at 80°C for 12 hours, and then heated at 140°C for 1 hour for annealing; the annealed fiber membrane was immersed in a 4 mg / mL dopamine hydrochloride aqueous solution (using Tris-HCl buffer, pH about 9), gently stirred at room temperature for 13 hours to allow self-assembled dopamine polymerization reaction to occur on the surface of the fiber membrane, and then vacuum dried at 80°C for 12 hours to obtain a nanocomposite membrane (PVDF+BaTiO3+PDA).

[0071] Example 4

[0072] A nanocomposite membrane was prepared according to the method of Example 1, except that in step S1 1 g of polyvinylidene fluoride-trifluoroethylene copolymer was replaced with 2 g of polyvinylidene fluoride-trifluoroethylene copolymer.

[0073] Example 5

[0074] A nanocomposite film was prepared according to the method of Example 1, except that in step S1, the volume ratio of N,N-dimethylformamide to acetone was replaced with 1:1.

[0075] Example 6

[0076] A nanocomposite membrane was prepared according to the method of Example 1, except that in step S1, 5 mL of N,N-dimethylformamide and acetone were replaced by 5 mL of N,N-dimethylformamide.

[0077] Example 7

[0078] The nanocomposite membrane was prepared according to the method of Example 1, except that the temperature for forming a uniform electrospinning precursor solution was changed to 40° C. in step S1.

[0079] Example 8

[0080] The nanocomposite membrane was prepared according to the method of Example 1, except that the propulsion rate of electrospinning in step S1 was set to 1.2 mL / h.

[0081] Example 9

[0082] The nanocomposite film was prepared according to the method of Example 1, except that the annealing temperature in step S2 was replaced with 160°C.

[0083] Example 10

[0084] A nanocomposite film was prepared according to the method of Example 1, except that in step S1, barium titanate (BaTiO3, particle size <100 nm) was replaced with an equal amount of barium titanate (BaTiO3, particle size 300-500 nm, purchased from Qinghe County Ruijiang Metal Materials Co., Ltd.).

[0085] Comparative Example 1

[0086] PVDF membrane (purchased from Shanghai Laidig Biotechnology Co., Ltd., product model: 20 cm long, 10 cm wide, and 1 mm thick) was used as the membrane sample.

[0087] Comparative Example 2

[0088] The PVDF membrane was vacuum dried at 60°C for 12 h and then heated at 130°C for 2 h for annealing. The annealed fiber membrane was immersed in a 2 mg / mL dopamine hydrochloride aqueous solution (using Tris-HCl buffer, pH about 8.5) and gently stirred at room temperature for 12 h to allow self-assembled dopamine polymerization reaction to occur on the surface of the PVDF membrane. The membrane was then vacuum dried at 60°C for 12 h to obtain a membrane sample (PVDF+PDA).

[0089] Comparative Example 3

[0090] 0.2 g of barium titanate (BaTiO3, particle size <100 nm) was dispersed in 5 mL of a solvent consisting of N,N-dimethylformamide and acetone in a volume ratio of 1:0.4. The mixture was ultrasonically treated for 30 minutes to ensure uniform dispersion of the barium titanate in the solvent. The mixture was then mixed with 1 g of polyvinylidene fluoride-trifluoroethylene copolymer (PVDF) and stirred at 60°C and 300 rpm for 4 hours to form a uniform electrospinning precursor solution. The precursor solution was transferred to a 10 mL syringe and electrospun at room temperature using a 21G metal needle. The electrospinning parameters were set as follows: applied voltage of 18 kV, collection distance of 15 cm, and propulsion rate of 0.8 mL / h. The spun fibers were collected on a rotating aluminum foil substrate to prepare a membrane sample (PVDF+BaTiO3).

[0091] Comparative Example 4

[0092] A. Preparation of polyvinylidene fluoride / dopamine solution:

[0093] Dimethylacetamide and acetone were prepared into a mixed solvent in a volume ratio of 1:1, and polyvinylidene fluoride was added to the mixed solvent. The mixture was heated to 45°C and stirred for 5 hours to obtain a dimethylacetamide-acetone solution of polyvinylidene fluoride, wherein the mass percentage of polyvinylidene fluoride in the solution was 20%. Dopamine monomer was then added to the dimethylacetamide-acetone solution of polyvinylidene fluoride, and the mixture was stirred for 1.5 hours. The mixture was then ultrasonically treated for 1 hour at an intensity of 5×10 4 W / m 3 The mass ratio of polyvinylidene fluoride to dopamine monomer is 100:50;

[0094] B. Preparation of polyvinylidene fluoride / polydopamine composite film:

[0095] The polyvinylidene fluoride / dopamine solution was electrospun at a spinning speed of 0.01 ml / min, a spinning voltage of 18 kV, a curing distance of 18 cm, and an aluminum foil was coated on the receiving plate to obtain a polyvinylidene fluoride / dopamine composite film;

[0096] The obtained polyvinylidene fluoride / dopamine composite film was placed in a 0.1 mol / L tris(hydroxymethyl)aminomethane (Tris) solution with a pH value of 8.5, and then sealed and placed in an oven at 30°C for reaction for 18 hours before being taken out. After being taken out, it was washed with distilled water until the pH value was neutral to obtain a polyvinylidene fluoride / dopamine composite film. Finally, the film was placed in an oven at 60°C for drying.

[0097] Test Example 1 Mechanical properties test of nanocomposite film

[0098] Nanocomposite film samples prepared in each example and the comparative example were cut into standard "dog-bone" test strips (25 mm in length, 5 mm in width, and approximately 100 μm in thickness). Tensile tests were performed using an electronic universal testing machine (Instron 3343, USA) at a tensile speed of 10 mm / min at room temperature. Each sample was tested at least five times to ensure data reproducibility and reliability.

[0099] The measured stress-strain curves were used to calculate the tensile strength, fracture strain and Young's modulus of the nanocomposite film to evaluate the flexibility and mechanical stability of the nanocomposite film. The test results are shown in Table 1 and Figure 1 shown.

[0100] Table 1

[0101] Example No. Tensile strength (MPa) fracture strain Young's modulus (GPa) Example 1 54.8 2.33 2.29 Example 2 53.2 2.24 2.33 Example 3 55.8 2.45 2.34 Example 4 53.4 2.38 2.38 Example 5 54.5 2.23 2.36 Example 6 53.4 2.24 2.28 Example 7 52.2 2.46 2.40 Example 8 52.9 2.22 2.37 Example 9 53.8 2.23 2.31 Example 10 52.6 2.29 2.38 Comparative Example 1 50.8 2.19 2.27 Comparative Example 2 51.1 2.22 2.39 Comparative Example 3 53.4 2.38 2.40 Comparative Example 4 52.9 2.29 2.43

[0102] The data comparison of the nanocomposite film sample prepared in Example 1 and the film samples prepared in Comparative Examples 1-3 is shown in the figure below. Figure 1 As shown, Figure 1 Figure A is a statistical graph of the tensile strength of four nanocomposite membrane materials (PVDF, PVDF+PDA, PVDF+BaTiO3, PVDF+PDA+BaTiO3). It can be clearly seen in the figure that the tensile strength values of the four membrane materials are similar, with no significant difference, and the "ns" marked above indicates that through statistical analysis, there is no significant difference between the tensile strengths of these four membrane materials. Figure 1 Figure B is a statistical graph of the fracture strain of the four membrane materials mentioned above. It can be seen that the fracture strain values of the four membrane materials are relatively close, with no significant differences. The "ns" marked above indicates that after statistical analysis, there is no significant difference in the fracture strain of the membrane materials. Figure 1 Figure C shows the Young's modulus of the four membrane materials. The Young's modulus values for the four membrane materials are relatively close, with no significant differences. The "ns" notation above indicates that statistical analysis revealed no significant differences between the Young's moduli. This suggests that the addition of a dopamine (PDA) coating to a PVDF / BaTiO3 composite membrane has no significant effect on the tensile strength, fracture strain, or Young's modulus of the nanocomposite membrane.

[0103] Test Example 2: Testing of the piezoelectric properties of nanocomposite films

[0104] The nanocomposite film samples prepared in each embodiment and the film samples prepared in the comparative example were subjected to ultrasonic equipment as the piezoelectric excitation source, and the output voltage signal was collected by a low-noise voltage amplifier (Keithley 6517B). The obtained voltage-time and current-time curves were used to evaluate their transient piezoelectric response and stable output capability. The test results are shown in Table 2 and Figure 2 shown.

[0105] Table 2

[0106]

[0107]

[0108] The open circuit voltages of the nanocomposite film samples prepared in Example 1 and the film samples prepared in Comparative Examples 1-3 under mechanical loading are as follows: Figure 2 shown. Figure 2 Figure A is the voltage-current diagram of comparative example 1 (pure PVDF membrane). In the current-time diagram, the current fluctuates between -20nA and 20nA, and the fluctuation is relatively frequent and large in amplitude; in the voltage-time diagram, the voltage fluctuates between -0.5V and 0.5V, and the relative current fluctuation amplitude is small, indicating that the electrical signal of the pure PVDF membrane is unstable over time under test. Figure 2 Figure B is the voltage-current diagram of comparative example 3 (PVDF+BaTiO3 membrane). In the current-time diagram, the current fluctuation range is from -30nA to 30nA, which is slightly larger than that of the pure PVDF membrane. In the voltage-time diagram, the voltage fluctuation range is similar to that of the pure PVDF membrane, between -0.5V and 0.5V, indicating that the addition of BaTiO3 has a greater impact on the current change and a relatively smaller impact on the voltage fluctuation. Figure 2 Figure C in the middle is the voltage-current diagram of comparative example 2 (PVDF+PDA membrane). In the current-time diagram, the current fluctuation range is about -30nA to 30nA, which is similar to the case of adding BaTiO3; in the voltage-time diagram, the voltage fluctuation amplitude is increased compared with the previous two, between -0.5V and 1.0V. Figure 2 Figure D is the voltage-current diagram of Example 1 (PVDF+PDA+BaTiO3 film). In the current-time diagram, the current fluctuation range increases significantly, reaching -150nA to 150nA; in the voltage-time diagram, the voltage fluctuation range also increases to between -1.0V and 1.0V, which indicates that the simultaneous addition of PDA and BaTiO3 will have a significant effect on the piezoelectric properties of the nanocomposite film.

[0109] Test Example 3 Macrophage Polarization Detection

[0110] This test case is used to evaluate the regulatory effect of the nanocomposite membrane on macrophage polarization in an inflammatory microenvironment. The specific test method is as follows:

[0111] The nanocomposite membrane samples prepared in each example and the membrane samples prepared in the comparative example were co-cultured with RAW264.7 mouse macrophages (purchased from Zhejiang Baidi Biotechnology Co., Ltd.) in vitro, and the expression of M1 / M2 phenotype markers was detected by immunofluorescence staining. The specific process was as follows: the membrane material was cut into circular sheets with a diameter of 14 mm, placed in a 24-well cell culture plate, sterilized with 75% ethanol for 30 minutes, and then washed three times with sterile PBS; then, RAW264.7 cells were inoculated into each well at a density of 1×10 5 Cells were plated at 4% paraformaldehyde for 15 minutes and cultured for 24 hours to promote cell adhesion and interaction with the membrane surface. Ultrasound was used as a piezoelectric excitation source for 20 minutes. After 24 hours of culture, cells were fixed with 4% paraformaldehyde for 15 minutes, lysed with 0.1% Triton X-100 for 5 minutes to permeabilize the cell membrane, and washed three times with PBS. Subsequently, 5% BSA was added for 1 hour to reduce nonspecific binding. Primary antibodies against iNOS and CD206 were added and incubated for 12 hours. Subsequently, the cells were washed three times with PBS and the corresponding fluorescently labeled secondary antibodies were added and incubated for 1 hour at room temperature in the dark. Cell nuclei were stained with DAPI, and immunofluorescence images were acquired using a confocal laser scanning microscope (Leica TCS SP8). The fluorescence signal intensity and expression position of iNOS and CD206 were analyzed, and the fluorescence intensity was quantified by Image J software to calculate the M1 / M2 polarization ratio; RAW264.7 cells co-cultured with the membrane material were collected, washed with sterile PBS three times, lysed and centrifuged to obtain the supernatant, and catalase (Cat) and superoxide dismutase (Sod1) detection kits were used respectively. Standards, samples and blank wells were set in 24-well plates. After adding the corresponding reagents for reaction, the absorbance was measured with an enzyme reader, and the relevant mRNA (Cat) and (Sod1) activities were calculated according to the standard curve; the collected cells were washed with PBS, and the lysis solution was added to the ice bath homogenate, reacted in a 95℃ water bath, cooled and centrifuged to obtain the supernatant, and the MDA detection kit was used. The relevant wells were also set in the 24-well plate, the detection reagent was added for incubation, the absorbance was measured with an enzyme reader, and the MDA content was calculated according to the standard curve. The test results are shown in Table 3 and Figure 3 shown.

[0112] Table 3

[0113]

[0114] The immunofluorescence staining images of the nanocomposite membrane samples prepared in Example 1 and the membrane samples prepared in Comparative Examples 1-3 when co-cultured with RAW264.7 mouse macrophages are shown in FIG. Figure 3 shown. Figure 3Middle A is an immunofluorescence staining image of breast tissue; green represents the macrophage M1 phenotype marker (iNOS), red represents the macrophage M2 phenotype marker (CD206), and blue represents the macrophage nucleus (DAPI staining); Figure 3 Middle B is the percentage of macrophage M1 phenotype marker iNOS positive in breast tissue; Figure 3 Middle C is the percentage of macrophage M2 phenotype marker CD206 positive in breast tissue; Figure 3 Middle D is the quantitative analysis of Cat expression in breast tissue; Figure 3 Middle E is the quantitative analysis of Sod1 expression in breast tissue; Figure 3 Middle F is the quantitative analysis of MDA in breast tissue; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 in the figure.

[0115] from Figure 3 As can be seen in Figure A, the expression of surface markers (iNOS positive) of M1 macrophages in the surrounding tissues of the nanocomposite membrane samples prepared in Example 1 and the membrane samples prepared in Comparative Examples 1-3 decreased in sequence, among which the membrane material of Comparative Example 1 (pure PVDF) had the highest expression, and the nanocomposite membrane of Example 1 (PVDF+PDA+BaTiO3) had the lowest expression. However, the expression of surface markers (CD206 positive) of M2 macrophages in the surrounding tissues of the four membrane materials (PVDF, PVDF+PDA, PVDF+BaTiO3, PVDF+PDA+BaTiO3) increased in sequence, and the expression of the nanocomposite membrane material of Example 1 (PVDF+PDA+BaTiO3) was the highest, and the expression of the membrane material of Comparative Example 1 (pure PVDF membrane) was the lowest.

[0116] Figure 3 The quantitative analysis results of the positive percentage of M1 macrophage surface marker (iNOS) in Figure B showed that Comparative Example 1 (pure PVDF membrane) was higher than Comparative Example 2 (PVDF+PDA), higher than Comparative Example 3 (PVDF+BaTiO3), and higher than Example 1 (PVDF+PDA+BaTiO3), among which PVDF was the highest and PVDF+PDA+BaTiO3 was the lowest, indicating that PVDF+PDA+BaTiO3 membrane had the best anti-inflammatory effect after implantation into breast tissue. Figure 3 The quantitative analysis results of the biomarker MDA content in Figure F showed that Comparative Example 1 (pure PVDF membrane) was higher than Comparative Example 2 (PVDF+PDA), higher than Comparative Example 3 (PVDF+BaTiO3), and higher than Example 1 (PVDF+PDA+BaTiO3), among which PVDF content was the highest and PVDF+PDA+BaTiO3 content was the lowest, indicating that PVDF+PDA+BaTiO3 membrane had the best antioxidant effect after implantation into tissue and could reduce oxidative stress response.

[0117] also, Figure 3 Quantitative analysis of the positive percentage of the surface marker (CD206) of M2 macrophages in Figure C shows that Comparative Example 1 (pure PVDF membrane) is lower than Comparative Example 2 (PVDF + PDA), lower than Comparative Example 3 (PVDF + BaTiO membrane), and lower than Example 1 (PVDF + PDA + BaTiO3). Among them, Example 1 (PVDF + PDA + BaTiO3) is the highest, indicating that the PVDF + PDA + BaTiO3 membrane is beneficial for promoting anti-inflammatory response and tissue repair after implantation into tissues. Figure 3 Figures D and E are quantitative analyses of mRNA (Cat) and mRNA (Sod1) expression, respectively. The test results show that Example 1 (PVDF+PDA+BaTiO3) is the highest, indicating that the antioxidant capacity of cells is enhanced after the PVDF+PDA+BaTiO3 membrane is implanted into the tissue, which is beneficial to tissue repair.

[0118] Test Example 4: Reactive Oxygen Species (ROS) Scavenging Detection

[0119] This test case was used to further verify the mitigation capability of the nanocomposite membrane in a microscopic oxidative environment.

[0120] Human bone marrow mesenchymal stem cells (BMSCs, purchased from Zhejiang Baidi Biotechnology Co., Ltd.) were co-cultured with the nanocomposite membrane samples prepared in Example 1 and the membrane samples prepared in Comparative Examples 1-3, and the level of reactive oxygen species in the cells was detected by a fluorescent probe method to evaluate the ROS scavenging ability of the nanocomposite membrane material.

[0121] The specific process was as follows: a pre-sterilized nanocomposite membrane sample (circular piece, 14 mm in diameter) was placed in a 24-well plate and pre-equilibrated with α-MEM complete medium containing 10% FBS and 1% P / S for 2 h; then BMSCs were seeded at a density of 5 × 10 4cells / well, placed in a 37°C, 5% CO2 incubator for 24 hours; to induce oxidative stress, hydrogen peroxide (H2O2) solution was added at the 24th hour to a final concentration of 200 μM, and incubation was continued for 4 hours to simulate the inflammatory damage environment and observe the intervention effect of the nanocomposite membrane material on the ROS level; 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA, Beyotime) was used as a fluorescent probe to quantitatively detect intracellular ROS; after H2O2 stimulation, the culture medium was discarded, washed twice with PBS, and then 10 μM DCFH-DA working solution (prepared in serum-free culture medium) was added and incubated at 37°C for 30 minutes; after staining, the cells were washed thoroughly with PBS to remove the probes that did not enter the cells; fluorescence images were collected using a confocal microscope; and semi-quantitative analysis of the images was performed using ImageJ software. The test results are shown in Table 4 and Figure 4 shown.

[0122] Table 4

[0123]

[0124]

[0125] The intracellular reactive oxygen species detection images of the nanocomposite membrane sample prepared in Example 1 and the membrane samples prepared in Comparative Examples 1-3 when co-cultured with human bone marrow mesenchymal stem cells (BMSC) are shown in FIG. Figure 4 shown. Figure 4Figure A shows the green fluorescence staining of intracellular reactive oxygen species (ROS) after four membrane materials (PVDF, PVDF+PDA, PVDF+BaTiO3, PVDF+PDA+BaTiO3) were implanted into breast tissue and cultured for 1 day and 7 days. The green fluorescence intensity of different membrane materials was different, indicating that the ROS levels were different. The fluorescence intensity of pure PVDF membrane was higher in both tests, indicating that pure PVDF membrane material stimulated the cells to produce more ROS. In the test on the first day, PVDF+PDA membrane had a higher fluorescence intensity. The number of green fluorescent spots was significantly less than that in the PVDF group, and the fluorescence intensity was also weaker, indicating that the addition of polydopamine (PDA) can reduce the production of intracellular ROS and has a certain antioxidant capacity. The fluorescence intensity on the 7th day increased compared to the 1st day, indicating that ROS levels increased. After the polyphenol groups of PDA undergo redox reactions with ROS in the environment to generate quinone groups, they cannot switch back to polyphenol groups on their own, resulting in increased ROS levels. The fluorescence intensity of the PVDF+BaTiO3 membrane was not significantly different from that of the pure PVDF group. In the fluorescence intensity test on the PVDF+PDA+BaTiO3 membrane on the first day, the number of green fluorescent spots was very small and the fluorescence intensity was extremely weak, indicating that the combined action of PDA and BaTiO3 can greatly inhibit the production of intracellular ROS. The fluorescence intensity on the 7th day was lower than that on the 1st day, indicating that this membrane material combination can effectively scavenge ROS over a long period of time and play a therapeutic and repairing role in tissues.

[0126] Figure 4 Middle B is a bar graph of quantitative analysis of intracellular reactive oxygen species (ROS) after 1 day of culture. As can be seen from the figure, the ROS level of the pure PVDF membrane group is the highest, about 22%, followed by the PVDF+BaTiO3 membrane group, about 21%, the PVDF+PDA membrane group is relatively low, about 14%, and the PVDF+PDA+BaTiO3 membrane group has the lowest ROS level, about 8%; the levels of the PVDF membrane group and the PVDF+BaTiO3 membrane group are similar, indicating that the addition of BaTiO3 has no significant effect on the clearance of ROS; the PVDF+PDA membrane group is significantly lower than the PVDF group, indicating that the addition of PDA can effectively clear ROS; the PVDF+PDA+BaTiO3 membrane group has the lowest ROS level, indicating that the simultaneous addition of PDA and BaTiO3 is better than the addition of PDA alone in clearing ROS. Figure 4Middle C is a bar graph of quantitative analysis of intracellular reactive oxygen species (ROS) after 7 days of culture. Similar to the data trend on the first day, the ROS levels of the pure PVDF membrane, PVDF+PDA membrane, and PVDF+BaTiO3 membrane groups did not change much, while the ROS levels of the PVDF+PDA+BaTiO3 membrane group still decreased by about 3% compared with the first day, indicating that the synergistic effect of PDA and BaTiO3 on reducing intracellular ROS levels is sustained and more prominent, indicating that it is the most excellent.

[0127] It can be seen from the results in Tables 1-4 that the nanocomposite membranes prepared in the examples of the present invention have significantly better effects when applied to prostheses in breast reconstruction surgery compared with the membrane samples prepared in the comparative examples.

[0128] In response to the capsular contracture problem of breast prostheses, the present invention successfully designed a nanocomposite membrane that combines barium titanate and PVDF and is modified with a polydopamine coating (PDA). This membrane material has shown significant effectiveness in suppressing the capsular contracture problem. In terms of membrane material performance, the tensile strength, fracture strain, and Young's modulus of the nanocomposite membrane are less affected by the composition and coating modification, and can maintain stable mechanical properties to meet the mechanical requirements of breast prosthesis fixation devices in actual use. In terms of piezoelectric properties, after adding BaTiO3 and PDA, the open-circuit voltage fluctuation range of the membrane material is significantly increased, and it has better force-to-electricity conversion capabilities, laying the foundation for subsequent regulation of the tissue microenvironment. In terms of biocompatibility, the membrane material device has obvious advantages.

[0129] In the detection of inflammatory response, the breast tissue using PVDF+PDA+BaTiO3 membrane material showed a decrease in the positive percentage of M1 macrophage marker iNOS and an increase in the positive percentage of M2 macrophage marker CD206. At the same time, the expression of Cat and Sod1 increased and the MDA content decreased, indicating that the material effectively regulated the inflammatory response and inhibited the inflammation-mediated fibrosis process, which is the key link in the occurrence of capsular contracture.

[0130] The PVDF+PDA+BaTiO3 membrane material demonstrated superior ROS scavenging capabilities. After one and seven days of co-culture, intracellular ROS levels were significantly lower than those in the other material groups, with the scavenging effect being even more pronounced on the seventh day. This is attributed to the antioxidant properties of the PDA coating and the built-in electric field, which enhances the efficiency of carrier separation and migration, thus enhancing its antioxidant properties. This allows for sustained and efficient ROS scavenging, effectively inhibiting oxidative stress and further reducing the factors that induce capsular contracture.

[0131] In summary, the nanocomposite membrane material provided by the present invention effectively and actively inhibits prosthesis capsular contracture in the long term through electromechanical coupling and "self-cleaning" antioxidant strategy, providing a new and effective solution for the stable use of prostheses in breast reconstruction surgery, and is expected to improve the quality of life of breast cancer patients after surgery, and has broad prospects in clinical applications.

[0132] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A nanocomposite film, characterized in that: The nano composite membrane comprises a fiber membrane and polydopamine modified on the surface of the fiber membrane. The fiber membrane contains polyvinylidene fluoride copolymer and barium titanate.

2. The nanocomposite film according to claim 1, characterized in that The polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer; Preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6.

3. A method for preparing a nanocomposite film, characterized in that: The preparation method comprises the following steps: S1. In the presence of a solvent, barium titanate and polyvinylidene fluoride copolymer are mixed and electrospun to obtain a fiber membrane; S2. Contacting dopamine with the fiber membrane to react, so that the surface of the fiber membrane is modified with polydopamine.

4. The method according to claim 3, characterized in that The solvent is N,N-dimethylformamide and / or acetone; Preferably, the solvent is N,N-dimethylformamide and acetone; Preferably, the volume ratio of the N,N-dimethylformamide to the acetone is 1:0.3-0.

5.

5. The method according to claim 3, characterized in that In step S1, the polyvinylidene fluoride copolymer is a polyvinylidene fluoride-trifluoroethylene copolymer; Preferably, the mass ratio of the barium titanate to the polyvinylidene fluoride-trifluoroethylene copolymer is 1:4-6.

6. The method according to any one of claims 3 to 5, characterized in that In step S1, the mixing conditions include at least: a temperature of 50-70°C, a stirring speed of 300-500 rpm, and a time of 3-5 hours.

7. The method according to any one of claims 3 to 5, characterized in that In step S1 , the electrospinning conditions include at least: a temperature of 20-35° C., an applied voltage of 16-20 kV, a collection distance of 13-18 cm, and a propulsion rate of 0.7-0.9 mL / h.

8. The method according to any one of claims 3 to 5, characterized in that Step S2 further includes: performing an annealing treatment on the fiber membrane before the contact reaction; Preferably, the annealing treatment conditions at least include: a temperature of 120-140° C. and a time of 1-3 hours.

9. The method according to any one of claims 3 to 5, characterized in that: The contact reaction conditions at least include: temperature of 20-35° C., pH of 8-9, and time of 11-13 hours.

10. Use of the nanocomposite film according to any one of claims 1 to 2 or the nanocomposite film prepared by the method according to any one of claims 3 to 9 in the preparation of breast prosthesis.

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