Application of a bionic electroactive implant membrane

Abstract

The present invention discloses an application of a bionic electroactive implant membrane, belonging to the field of biomedical technology. The bionic electroactive implant membrane is used to prepare or be used as a medical consumable for inducing regeneration of tissue defects; the bionic electroactive implant membrane includes a basement membrane and an active coating located on the surface of the basement membrane, and the basement membrane is made of a piezoelectric polymer and an electroactive material. The bionic electroactive implant membrane can adapt to the physiological potential of the defect area and can continuously exert an anti-oxidative stress effect for a long time. In response to the active oxygen continuously produced in the body of diabetic patients, the above-mentioned bionic electroactive implant membrane can be combined with in vitro ultrasound, an external field intervention method with strong penetration, non-invasiveness and no side effects, after being implanted in the patient's body, to produce cyclic anti-oxidative stress efficacy, continuously eliminate the adverse effects of oxidation products in the bone defect area, thereby regulating diabetic bone immunity and promoting bone regeneration.

Description

Technical Field

[0001] The invention relates to the field of biomedical technology, and in particular to the application of a bionic electroactive implant membrane. Background Art

[0002] Diabetes is a metabolic disease characterized by high blood sugar levels, affecting more than 430 million people worldwide and has become a global problem that endangers the health of residents. After suffering from diabetes, patients have an increased incidence of fractures, prolonged healing time after fractures, and increased failure rates of bone transplantation surgery. Multiple mechanisms leading to diabetes-related bone repair abnormalities have been widely recognized, including that high blood sugar levels in diabetic patients can activate the AGEs receptor (RAGE) expressed in human osteogenic cells, leading to the production of inflammatory cytokines and reactive oxygen species (ROS), and causing the body's oxidative stress response and chronic inflammatory response, leading to a vicious cycle of chronic inflammation and bone non-union.

[0003] Using implanted membrane materials to induce regeneration of tissue defects is currently a common clinical treatment method. Electroactive implant materials can restore the electrical microenvironment of the damaged area and accelerate the repair of defects to a certain extent. However, for patients with bone defects who have poor blood sugar control, the process of tissue defect repair is complicated, and the existing electroactive materials are not effective in removing reactive oxygen species, and ultimately have limited effects.

[0004] Currently, commonly used intervention methods to promote diabetic bone healing include local application of anti-inflammatory cytokines, hyperbaric oxygen therapy, and drug therapy. However, the existing treatment options have very poor clinical efficacy for diabetic bone defect patients with long-term oxidative stress response.

[0005] In view of this, the present invention is proposed. Summary of the invention

[0006] The purpose of the present invention is to provide an application of a bionic electroactive implant membrane, which is used to prepare or serve as a medical consumable for inducing regeneration of tissue defects, can adapt to the physiological potential of the defect area, and can exert an anti-oxidative stress effect for a long time.

[0007] This application can be implemented as follows:

[0008] The present application provides an application of a bionic electroactive implant membrane, for example, using it to prepare or use it as a medical consumable for inducing regeneration of tissue defects;

[0009] The bionic electroactive implant membrane comprises a base membrane and an active coating located on the surface of the base membrane. The base membrane is made of piezoelectric polymer and electroactive material.

[0010] In an optional embodiment, the medical consumable is a material that promotes the repair and regeneration of bone tissue in diabetic patients.

[0011] In an optional embodiment, the medical consumables are materials that promote bone healing or repair bone defects in diabetic patients.

[0012] In an optional embodiment, the medical consumable is a material that promotes macrophage M2 polarization and / or promotes osteogenic differentiation of stem cells.

[0013] In an optional embodiment, the medical consumable is a material for removing active oxygen in the body.

[0014] In an optional embodiment, the medical consumable is a material for removing oxidation products from tissue defect sites.

[0015] In an optional embodiment, the piezoelectric polymer includes polyvinylidene fluoride-trifluoroethylene, and / or the electroactive material includes graphene oxide, and / or the active coating is a polydopamine coating.

[0016] In an alternative embodiment, the base film has a thickness of 50-80 μm, and / or the active coating has a thickness of 100-500 nm.

[0017] In an optional embodiment, the bionic electroactive implant membrane is prepared by the following method:

[0018] The base film is reacted with a dopamine hydrochloride solution to form a polydopamine coating by in-situ polymerization on the surface of the base film.

[0019] In an alternative embodiment, the reaction is carried out at 30-50° C. for 12-24 h.

[0020] In an optional embodiment, the pH value of the dopamine hydrochloride solution is 8.5.

[0021] In an optional embodiment, the basement membrane is prepared by the following method:

[0022] The mixed solution of graphene oxide and polyvinylidene fluoride-trifluoroethylene is cast, dried, annealed and polarized.

[0023] In an alternative embodiment, the casting is to attach the mixed solution to the surface of the substrate.

[0024] In an alternative embodiment, drying is performed under vacuum conditions at 50-120° C. for 12-24 h.

[0025] In an alternative embodiment, the annealing is performed under vacuum conditions at 100-140° C. for 0.5-2 h.

[0026] In an alternative embodiment, the polarization is performed at a polarization voltage of 10-24 kV and a polarization distance of 5-30 cm for 10-30 min.

[0027] In an optional embodiment, the mixed solution is obtained by mixing a graphene oxide dispersion with a polyvinylidene fluoride-trifluoroethylene solution.

[0028] In an optional embodiment, the graphene oxide dispersion is obtained by dispersing 10-40 mg of graphene oxide in 5-20 mL of N,N-dimethylformamide.

[0029] In an optional embodiment, the particle size of graphene oxide is 0.5-2 μm.

[0030] In an optional embodiment, the polyvinylidene fluoride-trifluoroethylene solution is obtained by dissolving 0.5-2 g of polyvinylidene fluoride-trifluoroethylene in 5-8.5 mL of N,N-dimethylformamide.

[0031] In an optional embodiment, every 0.5-2 g of polyvinylidene fluoride-trifluoroethylene corresponds to 1.5-5 mL of graphene oxide dispersion.

[0032] In an optional embodiment, N,N-dimethylformamide is a powder with a particle size of 1-10 μm.

[0033] The beneficial effects of this application include:

[0034] The bionic electroactive implant membrane provided in the present application can adapt to the physiological potential of the defect area, can continuously exert an anti-oxidative stress effect for a long time, and can be used to prepare or be used as a medical consumable for inducing regeneration of tissue defects. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0036] Figure 1 This is an AFM electron microscope image of the surface of the bionic electroactive implant membrane provided in Example 1 of the present application;

[0037] Figure 2 This is a DPPH free radical scavenging detection diagram of the bionic electroactive implant membrane provided in Example 1 of the present application;

[0038] Figure 3 This is the flow cytometric detection result of reactive oxygen species generated in human macrophages under oxidative stress after the bionic electroactive implant membrane provided in Example 1 of the present application acts on the cells for 48 hours;

[0039] Figure 4Micro-CT photos of the experimental group and the control group of the traditional charged repair material in the experiment of repairing the skull defect of diabetic rats with the bionic electroactive implant membrane provided in Example 1 of the present application;

[0040] Figure 5 These are micro-CT photos of the ultrasound stimulation group and the non-ultrasound stimulation group in the experiment of repairing skull defects in diabetic rats with the bionic electroactive implant membrane provided in Example 1 of the present application. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0042] The application of the bionic electroactive implant membrane provided in the present application is described in detail below.

[0043] The inventors proposed that the key to promoting diabetic bone healing is to effectively and continuously remove oxidation products from bone defects, reduce inflammation levels, and activate bone regeneration and repair. The main reason why existing treatment options have extremely poor clinical efficacy for diabetic bone defect patients with long-term oxidative stress is that existing treatment options can only react with oxidation products once and lose their effectiveness after the reaction, that is, they can produce effects in a short time, but cannot achieve long-term and sustained anti-oxidative stress function.

[0044] In view of this, the present application creatively proposes an application of a bionic electroactive implant membrane. Specifically, the bionic electroactive implant membrane is used to prepare or serve as a medical consumable for inducing regeneration of tissue defects.

[0045] It can be understood that the above-mentioned bionic electroactive implant membrane can be directly used as a medical consumable for inducing regeneration of tissue defects, or it can be used as a medical consumable for inducing regeneration of tissue defects after further processing (for example, combining with other materials, or adjusting its shape, size, etc.).

[0046] The bionic electroactive implant membrane provided by the present application comprises a base membrane and an active coating located on the surface of the base membrane, and the base membrane is made of a piezoelectric polymer and an electroactive material.

[0047] The functional coating mainly plays the role of inducing regeneration of tissue defects.

[0048] After the bionic electroactive implant membrane is placed in the patient's body, it can induce continuous bone regeneration through electrical signals generated by external forces such as muscle squeezing or external ultrasound stimulation. Specifically, the basement membrane can be continuously charged under the action of the electrical signal, so that the active coating on the surface of the basement membrane is continuously charged and continuously active, thereby inducing continuous bone regeneration.

[0049] For reference, the medical consumables mentioned in this application are mainly materials that promote the repair and regeneration of bone tissue in diabetic patients. In addition, it is not excluded that the medical consumables are materials that promote the repair and regeneration of bone tissue in non-diabetic patients.

[0050] Illustratively, the medical consumables mentioned in the present application may be materials that promote bone healing or repair bone defects in patients, especially materials that promote bone healing or repair bone defects in diabetic patients.

[0051] For reference, the medical consumables mentioned in the present application may be materials that promote macrophage M2 polarization and / or promote osteogenic differentiation of stem cells.

[0052] In addition, the medical consumables mentioned in the present application can also be materials for removing active oxygen in the body. Further, they can be materials for removing oxidation products at tissue defect sites.

[0053] As mentioned above, the bionic electroactive implant membrane provided by the present application can adapt to the physiological potential of the defect area and can exert the anti-oxidative stress effect for a long time. In view of the active oxygen continuously produced in the body of diabetic patients, the above-mentioned bionic electroactive implant membrane can be combined with in vitro ultrasound, a highly penetrating, non-invasive, and side-effect-free external field intervention method, to produce cyclic anti-oxidative stress efficacy, continuously eliminate the adverse effects of oxidation products in the bone defect area, thereby regulating diabetic bone immunity and promoting bone regeneration.

[0054] For reference, the piezoelectric polymer in the bionic electroactive implant film includes (is) polyvinylidene fluoride-trifluoroethylene. The electroactive material includes (is) graphene oxide. The active coating is a polydopamine coating.

[0055] The base film (piezoelectric film) is prepared by using polyvinylidene fluoride, graphene-based electroactive materials and polydopamine as raw materials. It has the characteristics of easy industrial production, low cost, containing bionic biological tissue structure and being able to provide various electrochemical environments required for tissue repair.

[0056] It should be noted that the piezoelectric polymer mentioned above may also be other commonly used substances of the same type, and the point-active material may also be other commonly used substances of the same type.

[0057] Illustratively, the thickness of the base film may be 50-80 μm, such as 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm or 80 μm, etc., or any other value within the range of 50-80 μm.

[0058] The thickness of the active coating may be 100-500 nm, such as 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm or 500 nm, or any other value within the range of 100-500 nm.

[0059] In some embodiments, the bionic electroactive implant membrane can be prepared by the following method:

[0060] The base film is reacted with a dopamine hydrochloride solution to form a polydopamine coating by in-situ polymerization on the surface of the base film.

[0061] The reaction can be carried out at 30-50°C (such as 30°C, 35°C, 37°C, 40°C, 45°C or 50°C) for 12-24h (such as 12h, 15h, 18h, 20h or 24h). The pH value of the dopamine hydrochloride solution used can be 8.5.

[0062] Furthermore, the base film can be prepared by the following method:

[0063] The mixed solution of graphene oxide and polyvinylidene fluoride-trifluoroethylene is cast, dried, annealed and polarized.

[0064] The casting process is to attach the mixed solution to the surface of a substrate, which may be a glass plate.

[0065] Drying can be carried out under vacuum conditions (such as in a vacuum box) at 50-120°C (such as 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C or 120°C, etc.) for 12-24h (such as 12h, 18h, 22h or 24h, etc.).

[0066] Annealing can be performed under vacuum conditions (such as in a vacuum box) at 100-140°C (such as 100°C, 110°C, 120°C, 130°C or 140°C, etc.) for 0.5-2h (such as 0.5h, 1h, 1.5h or 2h, etc.).

[0067] Polarization can be carried out for 10-30 min (such as 10 min, 15 min, 20 min, 25 min or 30 min) under the conditions of a polarization voltage of 10-24 kV (such as 10 kV, 15 kV, 18 kV, 20 kV or 24 kV, etc.) and a polarization distance of 5-30 cm (such as 5 cm, 10 cm, 15 cm, 20 cm, 25 cm or 30 cm, etc.). The process is to peel off the annealed film from the substrate surface and place the film in a corona polarization device.

[0068] The mixed solution can be obtained by mixing a graphene oxide dispersion with a polyvinylidene fluoride-trifluoroethylene solution.

[0069] Illustratively, the graphene oxide dispersion can be obtained by dispersing 10-40 mg (such as 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg or 40 mg, etc.) of graphene oxide in 5-20 mL (such as 5 mL, 10 mL, 15 mL or 20 mL, etc.) of N,N-dimethylformamide.

[0070] Preferably, after graphene oxide is dissolved in N,N-dimethylformamide, the mixed solution may be ultrasonicated and stirred to make the two mixed evenly.

[0071] The particle size of the graphene oxide used may be 0.5-2 μm (eg, 0.5 μm, 1 μm, 1.5 μm or 2 μm, etc.).

[0072] Illustratively, the polyvinylidene fluoride-trifluoroethylene solution can be obtained by dissolving 0.5-2 g (e.g., 0.5 g, 1 g, 1.5 g, or 2 g, etc.) of polyvinylidene fluoride-trifluoroethylene in 5-8.5 mL (e.g., 5 mL, 5.5 mL, 6 mL, 6.5 mL, 7 mL, 7.5 mL, 8 mL, or 8.5 mL, etc.) of N,N-dimethylformamide.

[0073] The N,N-dimethylformamide used may be, for example, N,N-dimethylformamide powder having a particle size of 1-10 μm (eg, 1 μm, 2 μm, 5 μm, 8 μm or 10 μm, etc.).

[0074] Preferably, during the preparation process, every 0.5-2 g (such as 0.5 g, 1 g, 1.5 g or 2 g, etc.) of polyvinylidene fluoride-trifluoroethylene preferably corresponds to 1.5-5 mL (such as 1.5 mL, 2 mL, 2.5 mL, 3 mL, 3.5 mL, 4 mL, 4.5 mL or 5 mL, etc.) of graphene oxide dispersion.

[0075] It should be noted that in the process of preparing the graphene oxide dispersion, N,N-dimethylformamide can be replaced by other reagents that can dissolve graphene oxide. Similarly, in the process of preparing the polyvinylidene fluoride-trifluoroethylene solution, N,N-dimethylformamide can be replaced by other reagents that can dissolve polyvinylidene fluoride-trifluoroethylene.

[0076] As mentioned above, this application uses piezoelectric polymers and electroactive materials as substrates, and prepares composite piezoelectric films (i.e., base films) through static casting and other processes. The film material has good flexibility and improves clinical operability. At the same time, dopamine is self-polymerized in situ on the surface of the base film to prepare a polydopamine coating, which gives the film material excellent biocompatibility and is more conducive to in vivo implantation.

[0077] The prepared electroactive film composite material (bionic electroactive implant film) matches the physiological potential due to annealing and corona polarization treatment, and has higher charge storage efficiency and good electrical stability; at the same time, since polydopamine is used as a coating, it can undergo redox reaction with the reactive oxygen produced by cells under oxidative stress, and the catechol group of the polydopamine coating is converted into a quinone group and then the reaction fails. Based on the charge transfer ability of graphene, the electrical signal released by the composite piezoelectric film after mechanical stimulation can provide charge to the oxidized dopamine, reducing it, and thus circulate and remove reactive oxygen in the body. In addition, graphene oxide itself has the function of promoting bone repair, which can further play the role of the film in promoting bone repair.

[0078] The electroactive film composite material can be placed in various bone defects, and the electrical signals generated by the squeeze of external forces such as muscles or external ultrasound stimulation play a role in inducing continuous bone regeneration. The electroactive film composite material is used in bone defect repair, and has the characteristics of excellent electrical properties, controllable electrical activity, and can meet clinical needs.

[0079] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0080] Example 1

[0081] Step (1): 20 mg of graphene oxide was dissolved in 10 mL of N,N-dimethylformamide, and then ultrasonicated for 30 min and magnetically stirred until the dispersion was uniform to obtain a graphene oxide dispersion.

[0082] Step (2): Dissolve 1 g of polyvinylidene fluoride-trifluoroethylene powder in 8.5 mL of N,N-dimethylformamide, and stir to dissolve to obtain a uniform solution. Then, add 1.5 mL of the above graphene oxide dispersion, stir and disperse evenly to obtain a mixed casting solution.

[0083] Step (3): Cast the mixed casting solution onto a glass plate, place it in a vacuum drying oven, and vacuum dry it at 60° C. for 12 h to obtain a thin film; then place it in a vacuum drying oven at 110° C. for annealing for 2 h.

[0084] Step (4): peel off the annealed film from the glass plate and place it in a corona polarization device, polarize it for 15 minutes under the conditions of a polarization voltage of 15 kV and a polarization distance of 20 cm to obtain a polarized base film.

[0085] Step (5): prepare 100 mL of dopamine hydrochloride solution with a pH of 8.5, add the polarized basement membrane, place in a shaker at 37°C for reaction for 24 hours, take out and dry to obtain the electroactive thin film composite material (bionic electroactive implant membrane).

[0086] The AFM electron microscope image of the bionic electroactive implant membrane surface is shown in Figure 1 shown.

[0087] Example 2

[0088] The difference between this embodiment and embodiment 1 is that:

[0089] Step (2): Dissolve 1 g of polyvinylidene fluoride-trifluoroethylene powder in 7.5 mL of N,N-dimethylformamide, and stir to dissolve to obtain a uniform solution. Then, add 2.5 mL of the above graphene oxide dispersion, stir and disperse evenly to obtain a mixed casting solution.

[0090] Example 3

[0091] The difference between this embodiment and embodiment 1 is that:

[0092] Step (2): Dissolve 1 g of polyvinylidene fluoride-trifluoroethylene powder in 5 mL of N,N-dimethylformamide, and stir to dissolve to obtain a uniform solution. Then, add 5 mL of the above graphene oxide dispersion, stir and disperse evenly to obtain a mixed casting solution.

[0093] Example 4

[0094] Step (1): 10 mg of graphene oxide was dissolved in 5 mL of N,N-dimethylformamide, and then ultrasonicated for 30 min and magnetically stirred until the dispersion was uniform to obtain a graphene oxide dispersion.

[0095] Step (2): Dissolve 0.5 g of polyvinylidene fluoride-trifluoroethylene powder in 8.5 mL of N,N-dimethylformamide, and stir to dissolve to obtain a uniform solution. Then, add 1.5 mL of the above graphene oxide dispersion, stir and disperse evenly to obtain a mixed casting solution.

[0096] Step (3): Cast the mixed casting solution onto a glass plate, place it in a vacuum drying oven, and vacuum dry it at 50° C. for 24 hours to obtain a thin film; then place it in a vacuum drying oven at 100° C. for annealing for 1 hour.

[0097] Step (4): peel off the annealed film from the glass plate and place it in a corona polarization device, and polarize it for 30 minutes under the conditions of a polarization voltage of 10 kV and a polarization distance of 5 cm to obtain a polarized base film.

[0098] Step (5): prepare 100 mL of dopamine hydrochloride solution with a pH of 8.5, add the polarized basement membrane, place in a shaker at 30° C. to react for 16 h, take out and dry to obtain the electroactive thin film composite material (bionic electroactive implant membrane).

[0099] Example 5

[0100] Step (1): 40 mg of graphene oxide was dissolved in 20 mL of N,N-dimethylformamide, and then ultrasonicated for 30 min and magnetically stirred until the dispersion was uniform to obtain a graphene oxide dispersion.

[0101] Step (2): Dissolve 2 g of polyvinylidene fluoride-trifluoroethylene powder in 8.5 mL of N,N-dimethylformamide, and stir to dissolve to obtain a uniform solution. Then, add 1.5 mL of the above graphene oxide dispersion, stir and disperse evenly to obtain a mixed casting solution.

[0102] Step (3): Cast the mixed casting solution onto a glass plate, place it in a vacuum drying oven, and vacuum dry it at 120° C. for 15 h to obtain a thin film; then place it in a vacuum drying oven at 140° C. for annealing for 0.5 h.

[0103] Step (4): peel off the annealed film from the glass plate and place it in a corona polarization device, polarize it for 10 minutes under the conditions of a polarization voltage of 24 kV and a polarization distance of 30 cm to obtain a polarized base film.

[0104] Step (5): prepare 100 mL of dopamine hydrochloride solution with a pH of 8.5, add the polarized basement membrane, place in a 50° C. shaker for reaction for 12 h, take out and dry to obtain the electroactive thin film composite material (bionic electroactive implant membrane).

[0105] Test example

[0106] ①. Provide 10N mechanical force to the sample through periodic impact of the linear motor. The electrical signal generated by the sample is connected to the signal acquisition system through a wire and amplified by a low-noise current preamplifier to obtain the output voltage. Place a 1MHz ultrasonic probe 5cm above the bionic electroactive implant membrane for continuous ultrasonic stimulation for 15min. The electrical signal generated by the sample is connected to the signal acquisition system through a wire and amplified by a low-noise current preamplifier to obtain the ultrasonic-piezoelectric output voltage. The bionic electroactive implant membrane prepared in the above embodiments 1-5 was subjected to performance testing. The piezoelectric performance test was carried out in accordance with the test standard "GB / T3389.2-1999". The piezoelectric output capacity of the bionic electroactive implant membrane was tested by the Materials Testing Center of Wuhan University of Technology. The test performance results are shown in Table 1.

[0107] Table 1 Performance test results of bionic electroactive implant membrane

[0108]

[0109] ②, using DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging method to detect the free radical scavenging rate of the bionic electroactive implant membrane provided in Examples 1-5, the test performance results are shown in Table 1. The free radical scavenging rate before ultrasound and the free radical scavenging rate after ultrasound of the bionic electroactive implant membrane provided in Example 1 were also detected, and the test results are shown in Figure 2 .

[0110] The results showed that after the bionic electroactive implant membrane reacted with DPPH free radicals, its free radical scavenging efficiency dropped to 40% of the initial state of the implant membrane. After external field ultrasound stimulation, the free radical scavenging efficiency of the implant membrane could be restored to 80% of the initial value.

[0111] ③ After the bionic electroactive implant membrane prepared in Example 1 was sterilized by ultraviolet radiation, the density of inoculation was 5×10 5 The number of cells / mL of human macrophages was 240 cells / mL, and hydrogen peroxide was used to put the cells in an oxidative stress state. The ultrasound group was stimulated with ultrasound every day, and the non-ultrasound group was not stimulated. The control group was treated with the traditional charged repair material P (VDF-TrFE) in the same way. After 48 hours, the cells were collected for flow cytometry detection of intracellular reactive oxygen species. The test results are shown in Figure 3 .

[0112] The results show that after stimulation with hydrogen peroxide, the bionic electroactive implant membrane prepared in Example 1 can significantly reduce the reactive oxygen species produced by macrophages compared with traditional charged repair materials; and the reactive oxygen species production of macrophages can be further reduced by external field ultrasonic reactivation.

[0113] ④. After ultraviolet sterilization, the bionic electroactive implant membrane prepared in Example 1 was cut into 7 mm circular membrane pieces and covered on the skull defect of diabetic rats with a diameter of 5 mm. The defect was covered with the traditional charged repair material P (VDF-TrFE) as the control group. The rats were killed after 4 weeks, and the skull specimens were scanned and observed by micro-CT after the membrane material was completely removed. The test results are shown in Figure 4 The left side shows the micro-CT scan of the conventional charged repair material, and the right side shows the micro-CT scan of the bionic electroactive implant membrane of Example 1.

[0114] The results showed that compared with traditional charged repair materials, the diabetic skull defect covered with the bionic electroactive implant membrane described in Example 1 produced more new bone, and the bionic electroactive implant membrane showed a better repair effect in the repair and regeneration of diabetic bone defects.

[0115] ⑤. After ultraviolet sterilization, the bionic electroactive implant membrane prepared in Example 1 was cut into 7 mm circular membrane sheets, which were respectively covered on both sides of the skull defect of diabetic rats with a diameter of 5 mm. Every day after the operation, the skull defect of the experimental group of rats was subjected to in vitro ultrasonic stimulation, while the skull defect of the control group was not subjected to ultrasonic stimulation. After 4 weeks, the rats were killed, and the skull specimens were subjected to micro-CT scanning and observation after the membrane material was completely removed. The test results are shown in Figure 5 The left side shows the micro-CT scan of the biomimetic electroactive implant membrane of Example 1 without in vitro ultrasonic stimulation, and the right side shows the micro-CT scan of the biomimetic electroactive implant membrane of Example 1 with ultrasonic stimulation.

[0116] The results showed that after in vitro ultrasound stimulation, more new bone was generated in the diabetic skull defect covered with the bionic electroactive implant membrane.

[0117] As mentioned above, it can be seen from the product performance test that compared with traditional electrical repair materials, the bionic electroactive implant membrane prepared in Example 1 resists environmental oxidative stress through the self-assembled polydopamine coating on the surface, and at the same time utilizes ultrasound to stimulate charge output, giving the surface coating the ability to cyclically remove reactive oxygen, so that the implant membrane material has the function of cyclic anti-oxidative stress regulated by external field ultrasound, which can achieve long-lasting and lasting ROS removal in the regenerative microenvironment, and thus effectively promote the polarization of macrophages M2 and osteogenic differentiation of stem cells in the bone regeneration microenvironment under the conditions of diabetic oxidative stress, and ultimately promote the repair and regeneration of diabetic bone tissue.

[0118] In summary, the bionic electroactive implant membrane provided by the present application is different from traditional electroactive materials. By introducing graphene electroactive materials and polydopamine, the electrical properties of the implant membrane are improved, and the implant membrane is endowed with the ability to circulate and remove reactive oxygen. The implant membrane can effectively regulate the release of electrical signals of the material in vivo under the stimulation of in vitro ultrasound, solving the problems of uncontrolled and weakened potential after long-term implantation of traditional electroactive materials. Under the stimulation of in vitro ultrasound, the implant membrane exhibits a circulatory and continuous free radical scavenging ability, showing excellent therapeutic effects in the repair of diabetic bone defects, and has the potential to become a favorable way to treat bone defects in vitro in the future.

[0119] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A bionic electroactive implant membrane combined with an electrical signal generated by in vitro ultrasonic stimulation in the preparation or use of a medical consumable for inducing regeneration of tissue defects, characterized in that: The medical consumable is a medical consumable for inducing continuous bone regeneration, which is prepared for diabetic bone defect patients with long-term oxidative stress response; The bionic electroactive implant membrane comprises a base membrane and an active coating located on the surface of the base membrane, wherein the base membrane is made of a piezoelectric polymer and an electroactive material; The piezoelectric polymer includes polyvinylidene fluoride-trifluoroethylene, the electroactive material includes graphene oxide, and the active coating is a polydopamine coating; The bionic electroactive implant membrane is prepared by the following method: reacting a basement membrane with a dopamine hydrochloride solution to form a polydopamine coating by in-situ polymerization on the surface of the basement membrane; The reaction is carried out at 30-50° C. for 12-24 hours; the pH value of the dopamine hydrochloride solution is 8.5; The base film is prepared by the following method: casting, drying, annealing and polarizing a mixed solution of graphene oxide and polyvinylidene fluoride-trifluoroethylene; casting is to attach the mixed solution to the surface of the substrate; drying is carried out under vacuum conditions of 50-120° C. for 12-24 hours; annealing is carried out under vacuum conditions of 100-140° C. for 0.5-2 hours; polarization is carried out under the conditions of a polarization voltage of 10-24 kV and a polarization distance of 5-30 cm for 10-30 minutes.

2. The use according to claim 1, characterized in that: The medical consumables are materials that promote macrophage M2 polarization and / or promote osteogenic differentiation of stem cells.

3. The use according to claim 1, characterized in that: The medical consumables are materials for removing active oxygen in the body.

4. The use according to claim 3, characterized in that: The medical consumables are materials for removing oxidation products from tissue defect sites.

5. The use according to claim 1, characterized in that: The base film has a thickness of 50-80 μm, and / or the active coating has a thickness of 100-500 nm.

6. The use according to claim 1, characterized in that: The mixed solution is obtained by mixing a graphene oxide dispersion with a polyvinylidene fluoride-trifluoroethylene solution.

7. The use according to claim 6, characterized in that: The graphene oxide dispersion is obtained by dispersing 10-40 mg of graphene oxide in 5-20 mL of N,N-dimethylformamide.

8. The use according to claim 7, characterized in that: The particle size of the graphene oxide is 0.5-2 μm.

9. The use according to claim 6, characterized in that: The polyvinylidene fluoride-trifluoroethylene solution is obtained by dissolving 0.5-2 g of polyvinylidene fluoride-trifluoroethylene in 5-8.5 mL of N,N-dimethylformamide.

10. The use according to claim 9, characterized in that: Every 0.5-2 g of the polyvinylidene fluoride-trifluoroethylene corresponds to 1.5-5 mL of graphene oxide dispersion.

11. The use according to claim 9, characterized in that: The N,N-dimethylformamide is a powder with a particle size of 1-10 μm.

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