CN115737907A - Application of bionic electroactive implant film - Google Patents
Application of bionic electroactive implant film Download PDFInfo
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- CN115737907A CN115737907A CN202211472256.3A CN202211472256A CN115737907A CN 115737907 A CN115737907 A CN 115737907A CN 202211472256 A CN202211472256 A CN 202211472256A CN 115737907 A CN115737907 A CN 115737907A
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Abstract
The invention discloses an application of a bionic electroactive implant film, belonging to the technical field of biological medical treatment. The bionic electroactive implant film is used for preparing or serving as a medical consumable for inducing and regenerating tissue defects; the bionic electroactive implant film comprises a base film and an action coating positioned on the surface of the base film, wherein the base film is prepared from a piezoelectric polymer and an electroactive material. The bionic electroactive implant film can be matched with the physiological potential of a defect area, and can continuously exert the effect of resisting oxidative stress for a long time. Aiming at active oxygen continuously generated in the body of a diabetic patient, after the bionic electroactive implant film is implanted into the body of the patient, the bionic electroactive implant film can generate cyclic antioxidant stress efficiency by combining external ultrasound, an external field intervention means with strong penetrability, non-invasive type and no side effect, and continuously eliminate the adverse effect of oxidation products in a bone defect area, thereby regulating the bone immunity of the diabetes and promoting bone regeneration.
Description
Technical Field
The invention relates to the technical field of biological medical treatment, in particular to application of a bionic electroactive implant film.
Background
Diabetes is a metabolic disease characterized by hyperglycemia, affects more than 4.3 million people worldwide, and has become a global problem harming the health of residents. After diabetes, the incidence of bone fracture increases, healing time after fracture is prolonged, and the failure rate of bone graft surgery increases. Various mechanisms leading to diabetes-related bone repair abnormalities are well established, including that elevated blood glucose levels in diabetic patients activate AGEs Receptors (RAGE) expressed in human bone-derived cells, leading to the production of inflammatory cytokines and Reactive Oxygen Species (ROS), and causing oxidative stress and chronic inflammatory responses in the body, resulting in a vicious circle of chronic inflammation and bone nonunion.
The induced regeneration of tissue defect by using implant membrane material is the current clinical common treatment means, and the electroactive implant material can restore the electric microenvironment of the damaged area and accelerate the repair of defect to a certain extent. However, for bone defect patients with poor blood sugar control, the process of repairing tissue defects is complicated, the active oxygen scavenging effect of the existing electroactive materials is poor, and the final effect is limited.
The currently common intervention methods for promoting diabetic bone healing include topical application of anti-inflammatory cytokines, hyperbaric oxygen therapy, drug therapy, and the like. However, the current treatment regimens are extremely poor in clinical efficacy for patients with diabetic bone defects with chronic oxidative stress.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide application of a bionic electroactive implant film, wherein the bionic electroactive implant film is used for preparing or serving as a medical consumable for inducing and regenerating tissue defects, can be matched with physiological potential of defect areas, and can continuously exert an anti-oxidative stress effect for a long time.
The application can be realized as follows:
the application provides an application of the bionic electroactive implant film, such as the application of the bionic electroactive implant film in preparation or serving as a medical consumable for inducing and regenerating tissue defects;
the bionic electroactive implant film comprises a base film and an action coating positioned on the surface of the base film, wherein the base film is prepared from a piezoelectric polymer and an electroactive material.
In an alternative embodiment, the medical consumable is a material that promotes bone tissue repair and regeneration in a diabetic patient.
In an alternative embodiment, the medical consumable is a material that promotes healing of a bone of a diabetic patient or repairs a bone defect of a diabetic patient.
In an alternative embodiment, the medical consumable is a material that promotes macrophage M2 polarization and/or promotes osteogenic differentiation of stem cells.
In an alternative embodiment, the medical consumable is a material that scavenges reactive oxygen species in the body.
In an alternative embodiment, the medical consumable is a material that removes oxidation products from the tissue defect site.
In an alternative embodiment, the piezoelectric polymer comprises polyvinylidene fluoride-trifluoroethylene, and/or the electroactive material comprises graphene oxide, and/or the active coating is a polydopamine coating.
In an alternative embodiment, the base film has a thickness of 50 to 80 μm and/or the active coating has a thickness of 100 to 500nm.
In an alternative embodiment, the biomimetic electroactive implant film is prepared by the following method:
the basement membrane is reacted with a dopamine hydrochloride solution to form a polydopamine coating in situ on the surface of the basement membrane.
In an alternative embodiment, the reaction is carried out at 30-50 ℃ for 12-24h.
In an alternative embodiment, the pH of the dopamine hydrochloride solution is 8.5.
In an alternative embodiment, the base film is prepared by:
and carrying out tape casting, drying, annealing and polarization on the mixed solution of the graphene oxide and the polyvinylidene fluoride-trifluoroethylene.
In an alternative embodiment, the casting is to attach the mixed solution to the surface of the substrate.
In an alternative embodiment, the drying is carried out under vacuum at 50-120 ℃ for 12-24h.
In an alternative embodiment, the annealing is performed at 100-140 ℃ under vacuum for 0.5-2h.
In an alternative embodiment, the poling is performed at a poling voltage of 10-24kV for 10-30min at a poling distance of 5-30 cm.
In an alternative embodiment, the mixed solution is obtained by mixing the graphene oxide dispersion liquid and the polyvinylidene fluoride-trifluoroethylene solution.
In an alternative embodiment, the graphene oxide dispersion is prepared by dispersing 10-40mg of graphene oxide in 5-20mL of N, N-dimethylformamide.
In an alternative embodiment, the graphene oxide has a particle size of 0.5 to 2 μm.
In an alternative embodiment, the polyvinylidene fluoride-trifluoroethylene solution is prepared by dissolving 0.5 to 2g of polyvinylidene fluoride-trifluoroethylene in 5 to 8.5mL of N, N-dimethylformamide.
In an alternative embodiment, 1.5-5mL of the graphene oxide dispersion is used per 0.5-2g of polyvinylidene fluoride-trifluoroethylene.
In an alternative embodiment, the N, N-dimethylformamide is a powder with a particle size of 1 to 10 μm.
The beneficial effect of this application includes:
the application provides a bionical electroactive implant membrane can with defect regional physiological potential looks adaptation, can continuously exert anti-oxidative stress effect for a long time, can be used to prepare or be used as the medical consumables that carry out induction regeneration to the tissue defect.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and those skilled in the art can also obtain other related drawings based on the drawings without inventive efforts.
Fig. 1 is an AFM electron microscope picture of the surface of the biomimetic electroactive implant film provided in example 1 of the present application;
FIG. 2 is a DPPH free radical scavenging assay graph of a biomimetic electroactive implant film provided in example 1 of the present application;
FIG. 3 is a flow-based assay result of reactive oxygen species generated in cells 48 hours after human macrophages are exposed to oxidative stress by the bionic electroactive implant membrane provided in example 1 of the present application;
FIG. 4 is a micro-CT photograph of an experimental group in an experiment for repairing skull defect of diabetic rat by using a bionic electroactive implant membrane provided in example 1 of the present application and a control group of a conventional charged repairing material;
fig. 5 is a micro-CT photograph of an ultrasound stimulation group and a non-ultrasound stimulation group in a experiment for repairing a skull defect of a diabetic rat by using a biomimetic electroactive implant film provided in example 1 of the present application.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The application of the biomimetic electroactive implant film provided by the present application is specifically described below.
The inventor proposes that: effectively and continuously removing oxidation products at the bone defect part, reducing the inflammation level and activating the regeneration and repair of bones, which is the key for promoting the healing of the diabetic bones. The reason why the existing treatment scheme has extremely poor clinical curative effect on patients with the diabetic bone defects accompanied with long-term oxidative stress reaction mainly lies in that: the existing treatment scheme can only react with the oxidation products for one time, and the effect is lost after the reaction, namely, the treatment scheme can generate the effect in a short time, but cannot realize long-term and continuous anti-oxidative stress function.
In view of the above, the present application creatively proposes an application of a bionic electroactive implant film, and particularly, the bionic electroactive implant film is used for preparing or serving as a medical consumable for inducing and regenerating tissue defects.
Understandably, the bionic electroactive implant membrane can be directly used as a medical consumable for inducing and regenerating tissue defects, and can also be further processed (for example, matched with other materials, or adjusted in shape, size and the like) to be used as a medical consumable for inducing and regenerating tissue defects.
The bionic electroactive implant film comprises a base film and an action coating located on the surface of the base film, wherein the base film is made of piezoelectric polymers and electroactive materials.
The active coating mainly plays a role in inducing regeneration of the tissue defect.
After the bionic electroactive implant membrane is arranged in a plant patient, the bionic electroactive implant membrane can play a role in inducing continuous regeneration of bones through electric signals generated by external force extrusion of muscles and the like or external ultrasonic stimulation. Specifically, the basement membrane can be continuously charged under the action of the electric signal, so that the action coating on the surface of the basement membrane can be continuously charged and continuously has activity, and further the function of inducing continuous regeneration of bones is achieved.
For reference, the medical consumables mentioned in the present application are mainly materials that promote bone tissue repair and regeneration in diabetic patients. In addition, it is not excluded that the medical consumable is a material that promotes bone tissue repair and regeneration in non-diabetic patients.
Illustratively, the medical consumables mentioned in the present application may be a material for promoting healing of a bone or repairing a bone defect of a patient, in particular a material for promoting healing of a bone or repairing a bone defect of a diabetic patient.
For reference, the medical consumables mentioned in the present application may be a material that promotes macrophage M2 polarization and/or promotes osteogenic differentiation of stem cells.
In addition, the medical consumables mentioned in the present application may also be a material for scavenging active oxygen in the body. Further, it may be a material that removes oxidation products from the tissue defect site.
Bearing, the bionic electroactive implant film provided by the application can be matched with the physiological potential of a defect area, and can continuously exert an anti-oxidative stress effect for a long time. Aiming at active oxygen continuously generated in the body of a diabetic patient, after the bionic electroactive implant film is implanted into the body of the patient, the bionic electroactive implant film can generate cyclic antioxidant stress efficiency by combining external ultrasound, an external field intervention means with strong penetrability, non-invasive type and no side effect, and continuously eliminate the adverse effect of oxidation products in a bone defect area, thereby regulating the bone immunity of the diabetes and promoting bone regeneration.
For reference, the piezoelectric polymer in the biomimetic electroactive implant film comprises (is) polyvinylidene fluoride-trifluoroethylene. The electroactive material comprises (is) graphene oxide. The action coating is a polydopamine coating.
The base membrane (piezoelectric film) is prepared by taking polyvinylidene fluoride, graphene type electroactive materials and polydopamine as raw materials, and has the characteristics of easiness in industrial production, low cost, bionic tissue structure, capability of providing various electrochemical environments required by tissue repair and the like.
It should be noted that the piezoelectric polymer can be other commonly used materials of this type, and the point-active material can also be other commonly used materials of this type.
Illustratively, the thickness of the base film may be 50 to 80 μm, such as 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, or 80 μm, or any other value in the range of 50 to 80 μm.
The thickness of the active coating may be 100-500nm, such as 100nm, 150nm, 200nm, 250nm, 300nm, 350nm, 400nm, 450nm or 500nm, etc., or any other value within the range of 100-500nm.
In some embodiments, the biomimetic electroactive implant film can be prepared by the following method:
and reacting the basement membrane with a dopamine hydrochloride solution to form the polydopamine coating by in-situ polymerization on the surface of the basement membrane.
The reaction can be carried out at 30-50 deg.C (such as 30 deg.C, 35 deg.C, 37 deg.C, 40 deg.C, 45 deg.C or 50 deg.C) for 12-24h (such as 12h, 15h, 18h, 20h or 24 h). The pH of the dopamine hydrochloride solution used can be 8.5.
Further, the above base film may be prepared by:
carrying out tape casting, drying, annealing and polarization on the mixed solution of the graphene oxide and the polyvinylidene fluoride-trifluoroethylene.
Wherein, the casting is to attach the mixed solution to the surface of a substrate. The substrate may be a glass plate.
The drying can be carried out under vacuum (such as vacuum box) at 50-120 deg.C (such as 50 deg.C, 60 deg.C, 70 deg.C, 80 deg.C, 90 deg.C, 100 deg.C, 110 deg.C or 120 deg.C) for 12-24h (such as 12h, 18h, 22h or 24 h).
The annealing can be performed under vacuum (e.g., in a vacuum chamber) at 100-140 deg.C (e.g., 100 deg.C, 110 deg.C, 120 deg.C, 130 deg.C, or 140 deg.C) for 0.5-2h (e.g., 0.5h, 1h, 1.5h, or 2h, etc.).
The polarization may be carried out at a polarization voltage of 10-24kV (e.g., 10kV, 15kV, 18kV, 20kV, 24kV, etc.) and a polarization distance of 5-30cm (e.g., 5cm, 10cm, 15cm, 20cm, 25cm, 30cm, etc.) for 10-30min (e.g., 10min, 15min, 20min, 25min, 30min, etc.). The process is that the film after annealing treatment is taken off from the surface of the substrate and the film is put into a corona polarization device for carrying out the process.
The mixed solution can be obtained by mixing the graphene oxide dispersion liquid and a polyvinylidene fluoride-trifluoroethylene solution.
Illustratively, the graphene oxide dispersion may be prepared by dispersing 10-40mg (e.g., 10mg, 15mg, 20mg, 25mg, 30mg, 35mg, or 40mg, etc.) of graphene oxide in 5-20mL (e.g., 5mL, 10mL, 15mL, or 20mL, etc.) of N, N-dimethylformamide.
Preferably, after the graphene oxide is dissolved in the N, N-dimethylformamide, the mixed solution can be subjected to ultrasonic treatment and stirring, so that the graphene oxide and the N, N-dimethylformamide are uniformly mixed.
The particle size of the graphene oxide used may be 0.5-2 μm (e.g., 0.5 μm, 1 μm, 1.5 μm, or 2 μm).
Illustratively, the polyvinylidene fluoride-trifluoroethylene solution can be prepared by dissolving 0.5-2g (e.g., 0.5g, 1g, 1.5g, or 2g, etc.) of polyvinylidene fluoride-trifluoroethylene in 5-8.5mL (e.g., 5mL, 5.5mL, 6mL, 6.5mL, 7mL, 7.5mL, 8mL, or 8.5mL, etc.) of N, N-dimethylformamide.
The N, N-dimethylformamide used may be, for example, N-dimethylformamide powder having a particle diameter of 1 to 10 μm (e.g., 1 μm, 2 μm, 5 μm, 8 μm, 10 μm or the like).
Preferably, during the preparation process, every 0.5-2g (e.g., 0.5g, 1g, 1.5g, 2g, etc.) of the polyvinylidene fluoride-trifluoroethylene preferably corresponds to 1.5-5mL (e.g., 1.5mL, 2mL, 2.5mL, 3mL, 3.5mL, 4mL, 4.5mL, 5mL, etc.) of the graphene oxide dispersion.
It should be noted that, in the preparation process of the graphene oxide dispersion liquid, N-dimethylformamide may be replaced by other reagents capable of dissolving graphene oxide. Similarly, in the above-mentioned process for preparing the polyvinylidene fluoride-trifluoroethylene solution, the N, N-dimethylformamide may be replaced by other reagents which can be used for preparing the polyvinylidene fluoride-trifluoroethylene solution.
Bearing, this application adopts piezoelectric polymer and electroactive material as the substrate, has made compound piezoelectric film (being the basement membrane) through technologies such as curtain coating of stewing, and this film material flexibility is good, has promoted clinical maneuverability. Meanwhile, the polydopamine coating is prepared by in-situ self-polymerization of dopamine on the surface of the basement membrane, so that the film material is endowed with excellent biocompatibility and is more beneficial to in-vivo implantation.
The prepared electroactive thin film composite material (bionic electroactive implant film) is matched with physiological potential due to annealing treatment and corona polarization treatment, so that the electroactive thin film composite material has higher charge storage efficiency and good electrical stability; meanwhile, polydopamine is treated as a coating, so that the polydopamine can generate oxidation-reduction reaction with active oxygen generated by cells under an oxidative stress state, and a catechol group of the polydopamine coating fails to react after being converted into a quinone group. Based on the charge transmission capability of graphene, an electric signal released by the composite piezoelectric film after mechanical stimulation can provide charges for oxidized dopamine to reduce the oxidized dopamine, so that active oxygen in a body can be removed circularly. In addition, the graphene oxide has the function of promoting bone, and can further play the role of promoting bone repair of the film.
The electroactive film composite material can be placed at various bone defects, and electric signals generated after the electroactive film composite material is extruded by external forces such as muscles or subjected to in-vitro ultrasonic stimulation play a role in inducing continuous regeneration of bones. The electroactive film composite material is applied to bone defect repair, and has the characteristics of excellent electrical property, controllable electrical activity and capability of meeting clinical requirements.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
Step (1): and (3) dissolving 20mg of graphene oxide in 10mL of N, N-dimethylformamide, performing ultrasonic stirring for 30min, and performing magnetic stirring until the graphene oxide is uniformly dispersed to obtain a graphene oxide dispersion liquid.
Step (2): 1g of polyvinylidene fluoride-trifluoroethylene powder was dissolved in 8.5mL of N, N-dimethylformamide, and the resulting solution was dissolved with stirring to obtain a uniform solution. Then, 1.5mL of the graphene oxide dispersion was added thereto, and the mixture was uniformly stirred and dispersed to obtain a mixed casting solution.
And (3): casting the mixed casting solution on a glass plate, putting the glass plate into a vacuum drying oven, and performing vacuum drying for 12 hours at the temperature of 60 ℃ to obtain a film; then the mixture is placed in a vacuum drying oven at 110 ℃ for annealing treatment for 2h.
And (4): and (3) taking off the annealed film from the glass plate, placing the film in corona polarization equipment, and polarizing for 15min under the conditions of 15kV polarization voltage and 20cm polarization distance to obtain a polarized base film.
And (5): preparing 100mL of dopamine hydrochloride solution with the pH value of =8.5, adding the polarized base membrane into the solution, putting the base membrane into a shaking table at 37 ℃ for reaction for 24 hours, taking out the base membrane and drying the base membrane to obtain the electroactive thin film composite material (bionic electroactive implanted membrane).
An AFM electron microscope image of the surface of the bionic electroactive implant film is shown in figure 1.
Example 2
The present example differs from example 1 in that:
step (2): 1g of polyvinylidene fluoride-trifluoroethylene powder was dissolved in 7.5mL of N, N-dimethylformamide, and the resulting solution was dissolved with stirring to obtain a uniform solution. Then, 2.5mL of the graphene oxide dispersion liquid is added thereto, and the mixture is uniformly stirred and dispersed to obtain a mixed casting solution.
Example 3
This example differs from example 1 in that:
step (2): 1g of polyvinylidene fluoride-trifluoroethylene powder was dissolved in 5mL of N, N-dimethylformamide, and the resulting solution was dissolved with stirring to obtain a uniform solution. And then, adding 5mL of the graphene oxide dispersion liquid, and uniformly stirring and dispersing to obtain a mixed casting solution.
Example 4
Step (1): dissolving 10mg of graphene oxide in 5mL of N, N-dimethylformamide, performing ultrasonic stirring for 30min, and performing magnetic stirring until the graphene oxide is uniformly dispersed to obtain a graphene oxide dispersion liquid.
Step (2): 0.5g of polyvinylidene fluoride-trifluoroethylene powder was dissolved in 8.5mL of N, N-dimethylformamide, and dissolved by stirring to obtain a uniform solution. Then, 1.5mL of the graphene oxide dispersion liquid is added thereto, and the mixture is uniformly stirred and dispersed to obtain a mixed casting solution.
And (3): casting the mixed casting solution on a glass plate, putting the glass plate into a vacuum drying oven, and performing vacuum drying at 50 ℃ for 24 hours to obtain a film; then the mixture is placed in a vacuum drying oven at 100 ℃ for annealing treatment for 1h.
And (4): and (3) taking off the annealed film from the glass plate, placing the annealed film in corona polarization equipment, and polarizing for 30min under the conditions of 10kV polarization voltage and 5cm polarization distance to obtain a polarized base film.
And (5): preparing 100mL of dopamine hydrochloride solution with the pH value of =8.5, adding the polarized base membrane into the solution, putting the base membrane into a shaking table at the temperature of 30 ℃ for reaction for 16 hours, taking out the base membrane and drying the base membrane to obtain the electroactive thin film composite material (bionic electroactive implanted membrane).
Example 5
Step (1): and (3) dissolving 40mg of graphene oxide in 20mL of N, N-dimethylformamide, performing ultrasonic stirring for 30min, and performing magnetic stirring until the graphene oxide is uniformly dispersed to obtain a graphene oxide dispersion liquid.
Step (2): 2g of polyvinylidene fluoride-trifluoroethylene powder was dissolved in 8.5mL of N, N-dimethylformamide, and the resulting solution was dissolved with stirring to obtain a uniform solution. Then, 1.5mL of the graphene oxide dispersion was added thereto, and the mixture was uniformly stirred and dispersed to obtain a mixed casting solution.
And (3): casting the mixed casting solution on a glass plate, putting the glass plate into a vacuum drying oven, and performing vacuum drying for 15 hours at 120 ℃ to obtain a film; then the mixture is placed in a vacuum drying oven at 140 ℃ for annealing treatment for 0.5h.
And (4): and (3) removing the annealed film from the glass plate, placing the film in corona polarization equipment, and polarizing for 10min under the conditions of 24kV polarization voltage and 30cm polarization distance to obtain a polarized base film.
And (5): preparing 100mL of dopamine hydrochloride solution with the pH value of =8.5, adding the polarized base membrane into the solution, putting the base membrane into a shaking table at 50 ℃ for reaction for 12 hours, taking out the base membrane and drying the base membrane to obtain the electroactive thin film composite material (bionic electroactive implanted membrane).
Test examples
(1) The sample is periodically impacted by a linear motor to provide 10N mechanical force for the sample, and an electric signal generated by the sample is connected into a signal acquisition system through a lead and is amplified by a low-noise current preamplifier to obtain an output voltage. And (3) placing a 1MHz ultrasonic probe above the bionic electroactive implant film for continuous ultrasonic stimulation for 15min, connecting an electric signal generated by a sample into a signal acquisition system through a lead, and amplifying by using a low-noise current preamplifier to obtain the voltage output by ultrasonic-piezoelectric. The bionic electroactive implant membranes prepared in the above examples 1 to 5 were subjected to performance tests, and the piezoelectric performance tests were carried out according to the test standards of GB/T3389.2-1999, and the piezoelectric output capabilities of the bionic electroactive implant membranes were tested by the material test center of the university of wuhan's science and technology, and the test performance results are shown in table 1.
TABLE 1 Performance test results of bionic electroactive implanted membranes
(2) The radical scavenging rate of the biomimetic electroactive implant films provided in examples 1-5 was determined by DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method, and the performance results are shown in table 1. And the removal rate of the free radicals before the ultrasound and the removal rate of the free radicals after the ultrasound of the bionic electroactive implant film provided by the embodiment 1 are respectively detected, and the detection result is shown in figure 2.
The results show that: after the bionic electroactive implant film reacts with DPPH free radicals, the free radical scavenging efficiency of the bionic electroactive implant film is reduced to 40% of the initial state of the implant film, and the free radical scavenging efficiency of the implant film can be restored to 80% of the initial value after external field ultrasonic stimulation.
(3) The bionic electroactive implant film prepared in example 1 was sterilized by ultraviolet radiation, and then was inoculated on the surface thereof at a density of 5 × 10 5 Cells/ml human-derived macrophages and hydrogen peroxide were used to place the cells in an oxidative stress state, with the ultrasound group being ultrasonically stimulated daily and the non-ultrasound group not being stimulated. The control group was subjected to the same treatment using a conventional charged repair material P (VDF-TrFE). After 48 hours, the cells were collected and subjected to intracellular reactive oxygen species flow assay, and the assay results are shown in FIG. 3.
The results show that: after the stimulation of hydrogen peroxide is carried out, compared with the traditional charged repairing material, the bionic electroactive implant membrane prepared in the embodiment 1 can obviously reduce active oxygen generated by macrophages; by external field ultrasonic reactivation, the active oxygen yield of macrophages can be further reduced.
(4) The bionic electroactive implant membrane prepared in the example 1 is subjected to ultraviolet sterilization, then cut into a 7mm circular membrane, covered on a skull defect part of a diabetic rat with the diameter of 5mm, and the defect is covered with a traditional charged repairing material P (VDF-TrFE) to serve as a control group. The rats are sacrificed after 4 weeks, and after the membrane material is completely taken out, the skull specimens are subjected to micro-CT scanning observation. The test results are shown in FIG. 4. Wherein the left is the micro-CT scan of the traditional charged repair material, and the right is the micro-CT scan of the bionic electroactive implant film of the embodiment 1.
The results show that: compared with the traditional charged repair material, the diabetic skull defect part covered with the bionic electroactive implant film disclosed in the embodiment 1 generates more new bones, and the bionic electroactive implant film has a better repair effect in the repair and regeneration of the diabetic skull defect.
(5) The bionic electroactive implant membrane prepared in the example 1 is subjected to ultraviolet sterilization, then cut into 7mm circular membranes, and the circular membranes are respectively covered on skull defects at two sides of a diabetic rat with the diameter of 5 mm. After operation, the rat experimental group was subjected to ultrasonic stimulation in vitro at the skull defect site, and the control group was not subjected to ultrasonic stimulation. After 4 weeks, the rats were sacrificed and the membrane material was completely removed and the skull specimens were observed by micro-CT scanning. The test results are shown in FIG. 5. Wherein the left side is the micro-CT scan of the bionic electroactive implant film of the embodiment 1 without external ultrasonic stimulation, and the right side is the micro-CT scan of the bionic electroactive implant film of the embodiment 1 with ultrasonic stimulation.
The results show that: after the external ultrasonic stimulation, more new bones are generated at the diabetic skull defect part covered with the bionic electroactive implant film.
In summary, it can be seen from product performance detection that, compared with the conventional electrical repair material, the bionic electroactive implant film prepared in example 1 resists environmental oxidative stress through the surface self-assembly polydopamine coating, and simultaneously utilizes ultrasound to excite charge output, so that the surface coating is endowed with the capability of circularly removing active oxygen, the implant film material has the function of circularly adjusting and controlling the cyclic antioxidant stress through external field ultrasound, and can remove ROS in a long-acting and lasting regeneration microenvironment, thereby effectively promoting macrophage M2 polarization and stem cell osteogenic differentiation in a bone regeneration microenvironment under the condition of diabetic oxidative stress, and finally promoting the repair and regeneration of diabetic bone tissues.
To sum up, the bionic electroactive implant membrane provided by the application is different from the traditional electroactive material, and the graphene electroactive material and the polydopamine are introduced, so that the electrical property of the implant membrane is improved, and the capability of circularly removing active oxygen is endowed to the implant membrane. The implanted membrane can effectively regulate and control the release of electric signals of materials in vivo under the stimulation of in vitro ultrasound, and solves the problems of uncontrolled potential, weakened potential and the like of the traditional electroactive materials after long-term implantation. Under the stimulation effect of in vitro ultrasound, the implant membrane shows a circulating and continuous free radical scavenging capacity, shows an excellent treatment effect in the repair of the diabetic bone defect, and has the potential to become a favorable way for treating the bone defect in vitro in the future.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The application of the bionic electroactive implant film is characterized in that the bionic electroactive implant film is used for preparing or serving as a medical consumable for inducing and regenerating tissue defects;
the bionic electroactive implant film comprises a base film and an action coating located on the surface of the base film, wherein the base film is made of piezoelectric polymers and electroactive materials.
2. The use according to claim 1, wherein the medical consumable is a material that promotes bone tissue repair and regeneration in diabetic patients;
preferably, the medical consumable is a material that promotes bone healing or repair of a bone defect in a diabetic patient.
3. Use according to claim 1, wherein the medical consumable is a material promoting macrophage M2 polarization and/or promoting osteogenic differentiation of stem cells.
4. The use according to claim 1, wherein the medical consumable is a material that scavenges reactive oxygen species in the body;
preferably, the medical consumable is a material that removes oxidation products from the tissue defect site.
5. The use according to any one of claims 1 to 4, wherein the piezoelectric polymer comprises polyvinylidene fluoride-trifluoroethylene, and/or the electroactive material comprises graphene oxide, and/or the active coating is a polydopamine coating.
6. Use according to claim 5, wherein the base film has a thickness of 50-80 μm and/or the effect coating has a thickness of 100-500nm.
7. The use of claim 5, wherein the biomimetic electroactive implant film is prepared by:
reacting a basement membrane with a dopamine hydrochloride solution to form a polydopamine coating in situ on the surface of the basement membrane;
preferably, the reaction is carried out at 30-50 ℃ for 12-24h;
preferably, the pH of the dopamine hydrochloride solution is 8.5.
8. Use according to claim 7, characterized in that the base film is prepared by:
carrying out tape casting, drying, annealing and polarization on the mixed solution of the graphene oxide and the polyvinylidene fluoride-trifluoroethylene;
preferably, the casting is to attach the mixed solution to the surface of a substrate;
preferably, the drying is carried out for 12-24h under the vacuum condition of 50-120 ℃;
preferably, the annealing is carried out for 0.5 to 2 hours under the vacuum condition of 100 to 140 ℃;
preferably, the polarization is carried out at a polarization voltage of 10-24kV and a polarization distance of 5-30cm for 10-30min.
9. The use according to claim 8, wherein the mixed solution is obtained by mixing the graphene oxide dispersion liquid and a polyvinylidene fluoride-trifluoroethylene solution;
preferably, the graphene oxide dispersion liquid is obtained by dispersing 10-40mg of graphene oxide in 5-20mL of N, N-dimethylformamide;
preferably, the particle size of the graphene oxide is 0.5-2 μm.
10. The use according to claim 9, wherein the polyvinylidene fluoride-trifluoroethylene solution is prepared by dissolving 0.5 to 2g of polyvinylidene fluoride-trifluoroethylene in 5 to 8.5mL of N, N-dimethylformamide;
preferably, 1.5-5mL of graphene oxide dispersion per 0.5-2g of the polyvinylidene fluoride-trifluoroethylene;
preferably, the N, N-dimethylformamide is a powder having a particle size of 1 to 10 μm.
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| CN114796601A (en) * | 2022-05-20 | 2022-07-29 | 武汉理工大学 | Composite piezoelectric film for inducing bone regeneration and preparation method and application thereof |
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| CN114796601A (en) * | 2022-05-20 | 2022-07-29 | 武汉理工大学 | Composite piezoelectric film for inducing bone regeneration and preparation method and application thereof |
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