Preparation method of piezoelectric-driven adaptive drug-release electrospun film-coated tracheal stent

Abstract

The present invention provides a preparation method of a piezoelectric-driven self-adaptive drug-release electrospun film-covered tracheal stent, belonging to the technical field of medical devices. First, an anti-inflammatory drug is encapsulated in poly(3,4-ethylenedioxythiophene) nanoparticles by emulsion polymerization; PVDF is dissolved in a DMF / acetone mixture to prepare a spinning solution, and a piezoelectric film is formed on the surface of a metal stent by electrospinning; subsequently, Au nanoparticles are coated on both sides of the PVDF fiber membrane as electrodes, and a PDMS film is covered for insulation encapsulation; finally, the drug-loaded nanoparticles are dispersed in a PVA hydrogel, adhered to the easily proliferated parts of the stent, and the hydrogel is connected to the electrodes on both sides through a bioconductive adhesive, thereby obtaining a piezoelectric-driven self-adaptive drug-release electrospun film-covered tracheal stent. The present invention solves the technical problems of many complications in traditional tracheal stent treatment, uncontrollable drug release, and difficulties in optimizing drug binding and piezoelectric properties of PVDF in the application of tracheal stents.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and particularly to a preparation method of a piezoelectric-driven adaptive drug-release electrospun film-coated tracheal stent. Background Art

[0002] Tracheal stenosis is a serious respiratory disease, often caused by tumors, trauma or inflammation, leading to airway stenosis and dyspnea. Currently, tracheal stent implantation is one of the main methods for treating tracheal stenosis, but this method is accompanied by a series of complications, especially granulation tissue hyperplasia, stent displacement or mucus retention, etc. These complications may lead to restenosis or stent detachment, seriously affecting the treatment effect and the quality of life of patients. To inhibit granulation tissue hyperplasia, researchers have developed drug-eluting stents, which achieve local treatment by depositing drugs on the surface of the stent. However, these stents usually rely on passive drug release mechanisms, making it difficult to precisely control the rate and dose of drug release, resulting in limited treatment effects and may cause problems of drug overdose or insufficiency.

[0003] Although the application of stimulus-responsive materials in drug-eluting stents provides a certain degree of possibility for controlling drug release, in the field of tracheal stents, the application of these materials is still limited. In particular, for such a special application scenario as tracheal stents, a material that can adaptively adjust drug release according to changes in the pathological environment in the airway is needed, and the existing technology has not fully met this requirement. At the same time, polyvinylidene fluoride (PVDF), as a material with piezoelectric effect, can theoretically control drug release by sensing changes in external forces. However, the technology of applying PVDF to tracheal stents and achieving effective drug release is not yet mature, especially there are challenges in realizing the effective binding of drugs to the PVDF electrospun membrane and optimizing the piezoelectric properties. Summary of the Invention

[0004] In order to overcome the deficiencies of the prior art, the purpose of the present invention is to provide a preparation method of a piezoelectric-driven adaptive drug-release electrospun film-coated tracheal stent, which solves the technical problems of many complications in traditional tracheal stent treatment, uncontrollable drug release, and difficulties in drug binding and piezoelectric property optimization of PVDF in the application of tracheal stents.

[0005] To achieve the above purpose, the present invention provides the following solution:

[0006] A preparation method of a piezoelectric-driven adaptive drug-release electrospun film-coated tracheal stent, comprising the following steps:

[0007] Oxidatively polymerize 3,4-ethylenedioxythiophene monomers by emulsion polymerization method, and add an anti-inflammatory drug during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating the anti-inflammatory drug;

[0008] Mix polyvinylidene fluoride (PVDF) powder in a mixed solution of N,N-dimethylformamide (DMF) and acetone, and stir magnetically until the PVDF is completely dissolved to form a homogeneous spinning solution. Subsequently, based on an electrospinning device, evenly electrospin the spinning solution onto the surface of a bare metal self-expanding metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent.

[0009] Evenly coat Au nanoparticles on both sides of the PVDF fiber membrane of the PVDF piezoelectric film-coated metal tracheal stent. Subsequently, evenly coat a PDMS thin film on the surface of the PVDF fiber membrane coated with Au nanoparticles for insulation encapsulation.

[0010] Disperse the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs in a polyvinyl alcohol (PVA) hydrogel. Subsequently, evenly and firmly adhere the PVA hydrogel containing the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs to the part of the outer side of the PVDF fiber membrane where granulation tissue is likely to occur. Finally, use a biocompatible conductive adhesive to connect the PVA hydrogel to the Au electrodes on both sides respectively to construct a piezoelectric-driven self-adaptive drug-release electrospun film-coated tracheal stent.

[0011] Preferably, in the step of oxidatively polymerizing 3,4-ethylenedioxythiophene monomers by an emulsion polymerization method and adding anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs, the specific process is as follows: First, dissolve the stabilizer in deionized water and form a stable colloid by magnetic stirring. Subsequently, add 3,4-ethylenedioxythiophene monomers and an anti-inflammatory drug solution dissolved in absolute ethanol to the stable colloid, and stir magnetically to obtain a homogeneous mixed solution. Subsequently, dissolve the oxidant in deionized water and add it to the mixed solution, and continuously stir overnight to oxidatively polymerize the 3,4-ethylenedioxythiophene monomers and incorporate anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs. Finally, remove impurities by centrifugation and vacuum freeze-dry to obtain dry poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs.

[0012] Preferably, the concentration range of the 3,4-ethylenedioxythiophene monomers in the reaction system is 30 - 35 mM.

[0013] Preferably, the stabilizer is sodium dodecylbenzenesulfonate (SDBS), and the concentration of the sodium dodecylbenzenesulfonate (SDBS) in the reaction system is 9.0 - 9.5 mM.

[0014] Preferably, the oxidant is ammonium persulfate (APS), and the concentration of the ammonium persulfate (APS) in the reaction system is 0.7 - 0.9 M.

[0015] Preferably, the proportion of the anti-inflammatory drug solution in the total volume of the solution in the reaction system ranges from 1:9 to 1:11. The anti-inflammatory drug is curcumin or a small molecule anti-inflammatory drug glucocorticoid, and the glucocorticoid includes methylprednisolone and triamcinolone acetonide.

[0016] Preferably, in the step of mixing polyvinylidene fluoride (PVDF) powder in a mixed solution of N,N-dimethylformamide (DMF) and acetone and magnetically stirring until the PVDF is completely dissolved to form a uniform spinning solution, it includes: the volume ratio of DMF to acetone is 3:2, and the mass concentration of PVDF in the spinning solution is 20-25%.

[0017] Preferably, the stirring speed of the magnetic stirring is 100-500 rpm / min, and the stirring time is 1-2 h.

[0018] Preferably, in the step of uniformly electrospinning the spinning solution onto the surface of a bare metal self-expanding metal stent based on an electrospinning device to obtain a PVDF piezoelectric film-coated metal tracheal stent, the specific process is as follows: firmly install the bare metal stent on the receiving device of the electrospinning device, and then load the PVDF spinning solution into the syringe of the electrospinning device; secondly, set the working parameters of the electrospinning device, start the device and continuously electrospin to make the spinning solution uniformly cover the surface of the bare metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent.

[0019] Preferably, the working parameters of the electrospinning device are: the electrospinning voltage is 10-30 kV, the nozzle diameter of the syringe used during the electrospinning process is 0.5-1.0 mm, the spinning distance is 10-20 cm, the solution flow rate is 0.1-1.0 ml / h, the spinning time is 1-2 h, the environmental temperature during the electrospinning process is 20-25 °C, and the relative humidity is 30-60%.

[0020] According to the specific embodiments provided by the present invention, the following technical effects of the present invention are disclosed:

[0021] (1) By utilizing the piezoelectric effect, the stent of the present invention can accurately release anti-inflammatory drugs according to the magnitude of the force between the airway and the stent. When the airway pressure changes due to granulation tissue hyperplasia, the PVDF piezoelectric film generates a pulsed current, promoting the release of drugs from the nanoparticles encapsulating the anti-inflammatory drugs, effectively inhibiting granulation tissue hyperplasia, reducing complications in traditional tracheal stent treatment, and improving the treatment effect and quality of life of patients.

[0022] (2) Through the emulsion polymerization method, the present invention realizes the effective combination of anti-inflammatory drugs and poly(3,4-ethylenedioxythiophene) nanoparticles, improving the drug loading and stability. At the same time, the application of PVDF in the tracheal stent is optimized, and it is made into an electrospun membrane with good piezoelectric properties, enhancing the overall piezoelectric properties of the stent and ensuring the close correlation between drug release and pressure changes.

[0023] (3) During the preparation process of the present invention, a stable drug-loading and conductive structure is constructed. The nanoparticles encapsulating the anti-inflammatory drug are dispersed in the PVA hydrogel and adhered to the site prone to granulation tissue, and the Au electrodes are connected through a bio-conductive adhesive to form a stable conductive path, ensuring the stability and persistence of piezoelectric-driven drug release, and improving the therapeutic effect and biocompatibility of the stent. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0025] Figure 1 It is a flowchart of a preparation method of a piezoelectric-driven adaptive drug-release electrospun film-covered tracheal stent according to the present invention;

[0026] Figure 2 It is a schematic diagram of a drug-loading electrospun film-covered metal tracheal stent provided in Embodiment 1 of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the drawings in the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, rather than all embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0028] To make the above objects, features, and advantages of the present invention more obvious and understandable, the present invention will be further described in detail below with reference to the drawings and specific embodiments.

[0029] As Figure 1 shown, the present invention provides a preparation method of a piezoelectric-driven adaptive drug-release electrospun film-covered tracheal stent, including the following steps:

[0030] Step 100: Oxidatively polymerize 3,4-ethylenedioxythiophene monomers by emulsion polymerization method, and add anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs;

[0031] Step 200: Mix polyvinylidene fluoride (PVDF) powder in a mixed solution of N,N-dimethylformamide (DMF) and acetone, and stir magnetically until the PVDF is completely dissolved to form a uniform spinning solution. Subsequently, based on an electrospinning device, electrospin the spinning solution uniformly onto the surface of a bare metal self-expanding metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent;

[0032] Step 300: Uniformly coat Au nanoparticles on both sides of the PVDF fiber membrane of the PVDF piezoelectric film-coated metal tracheal stent as electrodes. Subsequently, uniformly coat a PDMS thin film on the surface of the PVDF fiber membrane coated with Au nanoparticles for insulation encapsulation;

[0033] Step 400: Disperse the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulated with anti-inflammatory drugs in a polyvinyl alcohol (PVA) hydrogel. Subsequently, firmly and uniformly adhere the PVA hydrogel containing the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulated with anti-inflammatory drugs to the site prone to granulation tissue on the outer side of the PVDF fiber membrane. Finally, use a biocompatible conductive adhesive to connect the PVA hydrogel to the Au electrodes on both sides respectively, to construct a piezoelectric-driven self-adaptive drug-release electrospun film-coated tracheal stent.

[0034] According to the above content, in Step 100, the specific process is as follows: First, dissolve the stabilizer in deionized water, and stir magnetically to form a stable colloid. Subsequently, add 3,4-ethylenedioxythiophene monomer and an anti-inflammatory drug solution dissolved in absolute ethanol to the stable colloid, and stir magnetically to obtain a uniform mixed solution; Subsequently, dissolve the oxidant in deionized water and add it to the mixed solution, and continuously stir overnight to oxidize and polymerize the 3,4-ethylenedioxythiophene monomer, and combine the anti-inflammatory drug during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulated with anti-inflammatory drugs; Finally, remove impurities by centrifugation and perform vacuum freeze-drying to obtain dry poly(3,4-ethylenedioxythiophene) nanoparticles encapsulated with anti-inflammatory drugs.

[0035] Among them, the concentration range of the 3,4-ethylenedioxythiophene monomer in the reaction system is 30 - 35 mM. The stabilizer is sodium dodecylbenzenesulfonate (SDBS), and the concentration of sodium dodecylbenzenesulfonate (SDBS) in the reaction system is 9.0 - 9.5 mM. The oxidant is ammonium persulfate (APS), and the concentration of ammonium persulfate (APS) in the reaction system is 0.7 - 0.9 M. The proportion of the anti-inflammatory drug solution in the total volume of the solution in the reaction system ranges from 1:9 to 1:11. The anti-inflammatory drug is curcumin or a small molecule anti-inflammatory glucocorticoid, and the glucocorticoid includes methylprednisolone and triamcinolone acetonide.

[0036] In the above content, 3,4-ethylenedioxythiophene (EDOT) monomers can be oxidized and polymerized into positively charged poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) under the action of the stabilizer dodecylbenzenesulfonic acid (DBSA) and the oxidant ammonium persulfate (APS). Additionally, since curcumin (CUR) itself is a hydrophobic and neutral drug, PEDOT NPs can encapsulate CUR through the hydrophobic interior. At the same time, in order to further bind CUR to PEDOT NPs through electrostatic interactions to increase the CUR loading amount. And because sodium dodecylbenzenesulfonate (SDBS) can make the solution weakly alkaline (the DBSA solution is acidic), in an alkaline environment, the hydroxyl group of CUR undergoes deprotonation to make it have a negative potential, and it further binds to the positively charged PEDOT NPs through electrostatic interactions to increase the drug loading amount. Therefore, on the basis of DBSA, the pH value of the mixed solution is adjusted to be alkaline by using sodium hydroxide (NaOH) to optimize the drug loading amount of CUR.

[0037] According to the above content, in the step of mixing polyvinylidene fluoride PVDF powder in a mixed solution of DMF and acetone and magnetically stirring until PVDF is completely dissolved to form a uniform spinning solution, it includes: the volume ratio of DMF to acetone is 3:2, and the mass concentration of PVDF in the spinning solution is 20 - 25%. And, the stirring speed of the magnetic stirring is 100 - 500 rpm / min, and the stirring time is 1 - 2 h.

[0038] In the step of uniformly electrospinning the spinning solution onto the surface of a bare metal self-expanding metal stent based on an electrospinning device to obtain a PVDF piezoelectric film-coated metal tracheal stent, the specific process is as follows: firmly install the bare metal stent on the receiving device of the electrospinning device, and then load the PVDF spinning solution into the syringe of the electrospinning device; secondly, set the working parameters of the electrospinning device, start the device and continuously electrospin, so that the spinning solution uniformly covers the surface of the bare metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent.

[0039] Among them, the working parameters of the electrospinning device are: the electrospinning voltage is 10 - 30 kV, and the nozzle diameter of the syringe used during the electrospinning process is 0.5 - 1.0 mm, the spinning distance is 10 - 20 cm, the solution flow rate is 0.1 - 1.0 ml / h, the spinning time is 1 - 2 h, the environmental temperature during the electrospinning process is 20 - 25 °C, and the relative humidity is 30 - 60%. In this way, a PVDF nanofiber membrane with excellent properties such as high piezoelectric performance, high mechanical properties, high drug loading rate, and excellent biocompatibility is prepared.

[0040] Example 1

[0041] In this embodiment, poly(3,4-ethylenedioxythiophene) conductive nanoparticles encapsulating curcumin (PEDOT / CURNPs) were first prepared, and the experimental procedure is as follows: First, 32.6 mg of sodium dodecylbenzenesulfonate (SDBS) was weighed and dissolved in 8 ml of deionized water. Under the condition of 40 °C, it was magnetically stirred at a speed of 750 rpm / min for 1 hour to fully dissolve SDBS to form a stable colloid. At this time, the concentration of SDBS in the reaction system was approximately 9.3 mM. Subsequently, 40.6 mg of 3,4-ethylenedioxythiophene (EDOT) monomer was weighed, and 1 ml of CUR solution (10 mg / ml dissolved in absolute ethanol) was measured and added to the SDBS colloid solution together. At this time, the concentration of EDOT in the reaction system was approximately 32.2 mM, and the proportion of the CUR ethanol solution in the total volume of the reaction system was 1:10. Under the condition of 40 °C, it was magnetically stirred at a speed of 750 rpm / min for 1 hour. Subsequently, 182.4 mg of ammonium persulfate (APS) was weighed, dissolved in 1 ml of deionized water, and then slowly added to the above mixed solution. At this time, the concentration of APS in the reaction system was approximately 0.8 M. At 40 °C, continuous stirring was carried out overnight to promote the oxidative polymerization of EDOT monomer under the action of SDBS and APS, and curcumin (CUR) was combined during the polymerization process. After the overnight reaction was completed, centrifugation was carried out 3 times at 4 °C and 9000 rpm / min for a total of 40 min to remove impurities and supernatant, and poly(3,4-ethylenedioxythiophene) conductive nanoparticles encapsulating curcumin (PEDOT / CURNPs) were obtained. Subsequently, after vacuum freeze-drying, dry PEDOT / CURNPs were obtained.

[0042] Secondly, a polyvinylidene fluoride (PVDF) electrospun scaffold film was prepared, and the specific process is as follows: 1.6 g of PVDF (Mw ∼ 400000) powder was weighed and added to a mixed solution of 5 ml of N,N-dimethylformamide (DMF) and acetone, where the volume ratio of DMF to acetone was 3:2. Under the conditions of 70 °C and 200 rpm / min, magnetic stirring was carried out for 2 h until PVDF was completely dissolved to form a uniform spinning solution, where the mass concentration of PVDF was 24 wt%.

[0043] Thirdly, a bare metal stent was selected and firmly installed on the receiving device of the electrospinning equipment. The above-prepared PVDF spinning solution was filled into a syringe equipped with a nozzle diameter of 0.9 mm. Set the parameters of the electrospinning equipment: the electrospinning voltage was adjusted to 18 kV, the spinning distance was controlled at 15 cm, the solution flow rate was set at 0.5 ml / h, the ambient temperature was maintained at 23 °C, and the relative humidity was maintained at 37%. Start the electrospinning equipment and continuously electrospin for 1 - 2 h to uniformly cover the surface of the bare metal stent with the spinning solution, and a PVDF piezoelectric film-coated metal tracheal stent was obtained.

[0044] Refer toFigure 2 , take the prepared PVDF-coated metal tracheal stent, and evenly coat Au nanoparticles on both sides of its PVDF fiber membrane. Ensure the uniform distribution of Au nanoparticles during the coating process to serve as electrodes. Subsequently, evenly coat a PDMS thin film on the surface of the PVDF fiber membrane coated with Au nanoparticles for insulation encapsulation. The thickness of the PDMS thin film needs to be controlled evenly to ensure the insulation effect without affecting the overall performance. Then disperse the prepared PEDOT / CUR NPs in polyvinyl alcohol PVA hydrogel and stir well to make it evenly dispersed. Uniformly and firmly adhere the PVA hydrogel containing PEDOT / CUR NPs to the upper and lower edges on the outside of the PVDF fiber membrane. This position is where granulation tissue is likely to occur after the tracheal stent is implanted. Finally, use a bioconductive adhesive to connect the drug-loaded PVA hydrogel to the Au electrodes on both sides respectively, ensuring a tight connection to form a stable conductive path, and complete the preparation of the piezoelectric-driven adaptive drug release electrospun-coated tracheal stent as shown in Figure 2 .

[0045] To further explore the performance of drug release driven by the piezoelectric effect in this embodiment, relevant tests are required. Since the normal adult breathing frequency is 0.2 - 0.4 Hz and the pressure of the trachea on the stent coating is 0.7 - 1.2 N, when granulation tissue occurs, the PVDF piezoelectric coating can convert the mechanical force received by the stent during tracheal movement into pulsed current (when exhaling, the tracheal diameter decreases, the stent coating is compressed, generating a negative electric potential; when inhaling, the pressure is released), thereby electrically stimulating the release of anti-inflammatory drugs encapsulated in conductive nanoparticles. Moreover, the drug release dose is positively correlated with the pressure magnitude received by the PVDF stent coating. Therefore, after the tracheal stent of this embodiment is implanted into the trachea, with the formation of granulation tissue as a complication, the force exerted by the airway tissue on the tracheal stent will increase significantly, and the piezoelectric effect of the PVDF fiber membrane will also be enhanced. The generated electrical stimulation induces the PEDOT conductive nanoparticles to be in a reduced state and undergo volume contraction, promoting the desorption and release of the drug CUR from the PEDOT / CUR nanoparticles. This further illustrates that this embodiment can achieve adaptive drug release by utilizing human breathing and pathological pressure changes, effectively deal with granulation tissue hyperplasia, and improve the treatment effect of tracheal stents.

[0046] Therefore, by adopting the above preparation method of a piezoelectric-driven adaptive drug release electrospun-coated tracheal stent, the following technical effects are achieved:

[0047] (1) The present invention utilizes the piezoelectric effect to enable the stent to accurately release anti-inflammatory drugs according to the magnitude of the force between the airway and the stent. When granulation tissue hyperplasia causes airway pressure changes, the PVDF piezoelectric coating generates pulsed current, prompting the nanoparticles encapsulating anti-inflammatory drugs to release the drugs, effectively inhibiting granulation tissue hyperplasia, reducing complications in traditional tracheal stent treatment, and improving the treatment effect and quality of life of patients.

[0048] (2) Through the emulsion polymerization method, the present invention realizes the effective combination of anti-inflammatory drugs and poly(3,4-ethylenedioxythiophene) nanoparticles, improving the drug loading and stability. At the same time, the application of PVDF in the tracheal stent is optimized, and it is made into an electrospun membrane with good piezoelectric properties, enhancing the overall piezoelectric properties of the stent and ensuring that the drug release is closely related to the pressure change.

[0049] (3) During the preparation process of the present invention, a stable drug-loading and conductive structure is constructed. The nanoparticles encapsulating anti-inflammatory drugs are dispersed in the PVA hydrogel and adhered to the parts prone to granulation tissue, and the Au electrodes are connected through a bio-conductive adhesive to form a stable conductive path, ensuring the stability and persistence of piezoelectric-driven drug release, and improving the therapeutic effect and biocompatibility of the stent.

[0050] Specific examples are used in this article to elaborate on the principle and implementation mode of the present invention. The description of the above embodiments is only used to help understand the method and its core idea of the present invention; at the same time, for those of ordinary skill in the art, according to the idea of the present invention, there will be changes in the specific implementation mode and application scope. In summary, the content of this specification should not be construed as a limitation to the present invention.

Claims

1. A preparation method of a piezoelectric-driven adaptive drug-release electrospun film-covered tracheal stent, characterized in that, It includes the following steps: Oxidatively polymerize 3,4-ethylenedioxythiophene monomers by emulsion polymerization method, and add anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs; Mix polyvinylidene fluoride PVDF powder in a mixed solution of DMF and acetone, and stir magnetically until PVDF is completely dissolved to form a uniform spinning solution. Subsequently, based on an electrospinning device, electrospin the spinning solution uniformly onto the surface of a bare metal self-expanding metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent; Uniformly coat Au nanoparticles on both sides of the PVDF fiber membrane of the PVDF piezoelectric film-coated metal tracheal stent as electrodes, and then uniformly coat a PDMS film on the surface of the PVDF fiber membrane coated with Au nanoparticles for insulation encapsulation; Disperse the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs in a polyvinyl alcohol PVA hydrogel, and then uniformly and firmly adhere the PVA hydrogel containing the poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs to the part of the outer side of the PVDF fiber membrane where granulation tissue is likely to occur. Finally, use a bioconductive adhesive to connect the PVA hydrogel to the Au electrodes on both sides respectively to construct a piezoelectric-driven self-adaptive drug-release electrospun film-coated tracheal stent.

2. The preparation method of an electrospun coated tracheal stent with piezoelectric-driven adaptive drug release according to claim 1, wherein, In the step of oxidatively polymerizing 3,4-ethylenedioxythiophene monomers by emulsion polymerization method and adding anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs, the specific process is as follows: First, dissolve the stabilizer in deionized water and stir magnetically to form a stable colloid. Subsequently, add 3,4-ethylenedioxythiophene monomers and an anti-inflammatory drug solution dissolved in absolute ethanol to the stable colloid, and stir magnetically to obtain a uniform mixed solution; Then dissolve the oxidant in deionized water and add it to the mixed solution, and continuously stir overnight to oxidatively polymerize 3,4-ethylenedioxythiophene monomers and combine anti-inflammatory drugs during the polymerization process to obtain poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs; Finally, remove impurities by centrifugation and vacuum freeze-dry to obtain dry poly(3,4-ethylenedioxythiophene) nanoparticles encapsulating anti-inflammatory drugs.

3. The preparation method of an electrospun film tracheal stent with piezoelectric-driven adaptive drug release according to claim 2, characterized in that, The concentration range of the 3,4-ethylenedioxythiophene monomers in the reaction system is 30 - 35 mM.

4. The preparation method of an electrospun film-coated tracheal stent with piezoelectric-driven self-adaptive drug release according to claim 2, wherein, The stabilizer is sodium dodecylbenzenesulfonate SDBS, and the concentration of the sodium dodecylbenzenesulfonate SDBS in the reaction system is 9.0 - 9.5 mM.

5. The preparation method of an electrospun coated tracheal stent with piezoelectric-driven self-adaptive drug release according to claim 2, characterized in that, The oxidant is ammonium persulfate APS, and the concentration of the ammonium persulfate APS in the reaction system is 0.7 - 0.9 M.

6. The preparation method of an electrospun coated tracheal stent with piezoelectric-driven adaptive drug release according to claim 2, characterized in that The proportion of the anti-inflammatory drug solution in the total volume of the solution in the reaction system ranges from 1:9 to 1:

11. The anti-inflammatory drug is curcumin or a small molecule anti-inflammatory drug glucocorticoid, and the glucocorticoids include methylprednisolone and triamcinolone acetonide.

7. The preparation method of a piezoelectric-driven adaptive drug-release electrospun film-covered tracheal stent according to claim 1, characterized in that, In the step of mixing polyvinylidene fluoride (PVDF) powder in a mixed solution of N,N-dimethylformamide (DMF) and acetone and magnetically stirring until PVDF is completely dissolved to form a uniform spinning solution, it includes: the volume ratio of DMF to acetone is 3:2, and the mass concentration of PVDF in the spinning solution is 20-25%.

8. The preparation method of an electrospun film-covered tracheal stent with piezoelectric-driven self-adaptive drug release according to claim 7, characterized in that, The stirring speed of the magnetic stirring is 100-500 rpm / min, and the stirring time is 1-2 h.

9. The preparation method of an electrospun film-covered tracheal stent based on piezoelectric drive according to claim 1, wherein, In the step of uniformly electrospinning the spinning solution onto the surface of a bare metal self-expanding metal stent based on an electrospinning device to obtain a PVDF piezoelectric film-coated metal tracheal stent, the specific process is as follows: firmly install the bare metal stent on the receiving device of the electrospinning device, and then load the PVDF spinning solution into the syringe of the electrospinning device; Secondly, set the working parameters of the electrospinning device, start the device and continuously electrospin to make the spinning solution uniformly cover the surface of the bare metal stent to obtain a PVDF piezoelectric film-coated metal tracheal stent.

10. The preparation method of an electrospun film tracheal stent with piezoelectric-driven adaptive drug release according to claim 9, wherein, The working parameters of the electrospinning device are: the electrospinning voltage is 10-30 kV, the nozzle diameter of the syringe used in the electrospinning process is 0.5-1.0 mm, the spinning distance is 10-20 cm, the solution flow rate is 0.1-1.0 ml / h, the spinning time is 1-2 h, the ambient temperature during the electrospinning process is 20-25 °C, and the relative humidity is 30-60%.

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