A cardiac stent with repair and monitoring functions and a preparation method thereof

Abstract

The application provides a heart stent with functions of repairing and monitoring and a preparation method thereof, and the steps are as follows: adding PLA powder into a mixed solvent of DMF and acetone to obtain a PLA spinning solution; electrospinning a PLA nanofiber membrane; configuring a drug-loaded P(VDF-TrFE) spinning solution; electrospinning a drug-loaded P(VDF-TrFE) / PLA composite nanofiber; performing plasma treatment on the drug-loaded P(VDF-TrFE) / PLA composite nanofiber stent; coating the drug-loaded P(VDF-TrFE) / PLA composite nanofiber stent with gelatin to obtain a drug-loaded P(VDF-TrFE) / PLA composite nanofiber stent wrapped with gelatin, namely the heart stent with functions of repairing and monitoring; and the electrospinning technology is used to prepare the heart stent with piezoelectric effect and biological activity, so that the heart stent can provide real-time monitoring information while promoting the function of functional tissues, and the heart stent has the dual functions of a biological stent and sensing monitoring.

Description

Technical Field

[0001] This invention belongs to the field of cardiac implant materials technology, specifically relating to a cardiac stent with both repair and monitoring functions and its preparation method. Background Technology

[0002] Cardiovascular disease is a collective term for diseases of the heart and brain vessels, with high morbidity, disability, and mortality rates, seriously threatening human life and health. Myocardial infarction accounts for a significant proportion of cardiovascular diseases. Its main cause is local obstruction of blood flow to the myocardium, leading to myocardial tissue damage, the formation of non-contractile scar tissue, and permanent impairment of the heart's pumping function, further developing into chronic heart failure. Currently, heart transplantation is considered the most effective treatment for end-stage heart failure, helping patients restore heart function. However, donor hearts are scarce, the surgery is costly, and immune rejection can occur between the donor and recipient, causing side effects such as fever, transplant site pain, and organ dysfunction, reducing patient survival rates and limiting its widespread application.

[0003] Cardiac scaffolds, as implantable cardiac materials, can be used to replace damaged areas of an infarcted heart. They possess multi-scale and three-dimensional tissue structures, good mechanical stability, and can promote the orderly arrangement of cardiomyocytes, generating synchronous contraction and anisotropic electromagnetic wave propagation. However, traditional cardiac scaffold materials have poor mechanical properties and lack electrical conductivity, making it impossible to monitor cardiac contractile activity. Furthermore, the fabrication of cardiac scaffolds using integrated sensor monitoring is a time-consuming and complex process. Summary of the Invention

[0004] To address the shortcomings of existing technologies, such as poor mechanical properties, lack of electrical conductivity, inability to monitor cardiac contractile activity, and the time-consuming and complex fabrication process of cardiac stents with integrated sensing monitoring, this invention designs a cardiac stent with both repair and monitoring functions. Using electrospinning technology, a polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE)) copolymer loaded with vascular endothelial growth factor (VEGF) is deposited on a polylactic acid (PLA) nanofiber membrane, which is then coated with gelatin to create a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold material. This scaffold possesses advantages such as good flexibility, low cost, light weight, and good biocompatibility. Its fibrous structure provides a microstructure that supports cell growth and adhesion, while the specific growth factor VEGF promotes further cell maturation and differentiation. High porosity allows cell permeation and promotes cell proliferation. While promoting the function of functional tissues, it also provides real-time monitoring information, fulfilling the dual functions of a biological scaffold and sensing monitoring.

[0005] To achieve the above objectives, this application provides the following technical solution:

[0006] A method for fabricating a cardiac stent with both repair and monitoring functions, comprising the following steps:

[0007] (1) Preparation of PLA spinning solution

[0008] A solvent was prepared by mixing DMF and acetone, PLA powder was added, and the mixture was heated and stirred until completely dissolved to obtain a PLA spinning solution.

[0009] (2) PLA nanofiber membranes were prepared by electrospinning.

[0010] Pour the PLA spinning solution from step (1) into a syringe, and cover the plate collection device with aluminum foil. Set the spinning voltage, spinning distance, and extrusion rate, and electrospin the PLA nanofiber membrane to obtain the PLA nanofiber membrane.

[0011] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0012] A solvent was prepared by mixing DMF and acetone, and P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF was dissolved in an aqueous dextran solution to prepare an aqueous solution. The P(VDF-TrFE) solution was then mixed with the aqueous solution and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0013] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0014] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collecting device. The spinning voltage, spinning distance, extrusion rate, and roller speed were set, and the P(VDF-TrFE) / PLA composite nanofiber scaffold loaded with VEGF was obtained by electrospinning.

[0015] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0016] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber to remove residual organic solvents, and then placed in a plasma treatment machine containing NH3 for surface modification.

[0017] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0018] In step (5), gelatin aqueous solution was added to the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions.

[0019] Preferably, in step (1), the mass ratio of DMF to acetone is 3:2, the stirring temperature is 60-80℃, and the mass fraction of PLA is 2%-10%.

[0020] Preferably, in step (2), the electrospinning needle has an inner diameter of 0.15 mm and an outer diameter of 0.31 mm, and its parameters are: ambient temperature of 18-20℃, spinning voltage of 14-18 kV, spinning distance of 8-16 cm, and extrusion rate of 0.60-0.80 ml / h.

[0021] Preferably, in step (3), the mass ratio of DMF to acetone is 3:2, the mass fraction of P(VDF-TrFE) is 12%-20%, the stirring temperature is 60-80℃, the concentration of the aqueous dextran solution is 3%-7%, the mass fraction of VEGF is 0.32%-0.48%, and the volume ratio of P(VDF-TrFE) solution to aqueous dextran solution is 20:0.8-20:1.2.

[0022] Preferably, in step (4), the electrospinning needle has an inner diameter of 0.15 mm and an outer diameter of 0.31 mm, and its parameters are: ambient temperature of 18-20℃, spinning voltage of 14-18 kV, spinning distance of 8-16 cm, extrusion rate of 0.60-0.80 ml / h, and roller speed of 300-1500 rpm.

[0023] Preferably, in step (5), the drying time is 16-24h, the surface modification is performed, the plasma treatment machine power is 20-60W, and the plasma treatment time is 20-60s.

[0024] Preferably, in step (6), the volume of the added gelatin aqueous solution is 4-12 μL.

[0025] This application also discloses a cardiac stent with both repair and monitoring functions prepared using any of the above-described preparation methods.

[0026] The beneficial effects of this invention are:

[0027] This invention presents a cardiac scaffold with both repair and monitoring functions. It utilizes electrospinning technology to prepare a gelatin-coated, VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold, which mimics the structure and biological functions of the natural extracellular matrix, providing various forms of support for cell adhesion, growth, proliferation, metabolism, and the formation of new tissues and organs. The PTrFE in the polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE)) copolymer increases the β-phase content in PVDF, further enhancing the piezoelectric effect and generating an endogenous electric field, thereby promoting cell adhesion and proliferation. Polylactic acid (PLA) is a novel biodegradable material with good biocompatibility, tensile strength, and ductility. Depositing P(VDF-TrFE) onto a PLA nanofiber membrane improves the mechanical strength of the composite nanofiber scaffold. Vascular endothelial growth factor (VEGF), a cell-produced signaling protein essential to the human body, stimulates angiogenesis and regulates the proliferation, migration, and survival of endothelial cells. Encapsulating VEGF into the P(VDF-TrFE) / PLA nanofiber scaffold promotes cardiac tissue repair; gelatin-encapsulated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold further enhances its hydrophilicity and flexibility. Compared to poly-L-lactic acid (PLLA) electrospun nanofiber scaffolds, the scaffold material of this invention exhibits a relative cell proliferation rate exceeding 100%, with a peak proliferation rate of 182.3 ± 1.76% after 7 days. This demonstrates that the electrospun cardiac scaffold possesses excellent biocompatibility and bioactivity. Furthermore, the cell number increases with increasing relative time and the content of P(VDF-TrFE) and VEGF, indicating that the electrospun cardiac scaffold can significantly promote cell proliferation and growth.

[0028] This invention utilizes electrospinning technology to fabricate a cardiac scaffold with piezoelectric effect and bioactivity. It features good flexibility, high mechanical strength, low manufacturing cost, and good biocompatibility. A roller collection device can further enhance the piezoelectric properties of the fiber scaffold, and the oriented piezoelectric nanoscaffold promotes cell adhesion, growth, and proliferation. Simultaneously, this scaffold can also serve as a sensor for monitoring cardiac tissue contractile activity, with no side effects on cardiac tissue, demonstrating significant application potential and clinical significance. Attached Figure Description

[0029] Figure 1 This is a schematic diagram of the structure of a cardiac stent that combines repair and monitoring functions according to the present invention;

[0030] Figure 2 Voltage response of P(VDF-TrFE) support under different cyclic tensile loads;

[0031] Figure 3 The results of cytotoxicity tests for different scaffold materials;

[0032] Figure 4 The mechanical performance test results are for different support materials.

[0033] Explanation of reference numerals in the attached figures:

[0034] 1. PLA nanofibers; 2. P(VDF-TrFE) nanofibers; 3. Drug VEGF; 4. Gelatin. Detailed Implementation

[0035] The present invention will be further described in detail below with reference to embodiments, but this is not intended to further limit the present invention.

[0036] Example 1:

[0037] A method for fabricating a cardiac stent that combines repair and monitoring functions is as follows:

[0038] (1) Preparation of PLA spinning solution

[0039] A solvent was prepared by mixing 6g DMF and 4g acetone, and 0.23g polylactic acid powder was added. The mixture was heated and stirred at 60°C until completely dissolved to obtain a PLA spinning solution.

[0040] (2) Electrospun PLA nanofiber membrane

[0041] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 14 kV, the spinning distance to 8 cm, and the extrusion rate to 0.60 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0042] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0043] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.36g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.32% was dissolved in a 3% aqueous dextran solution to obtain an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:0.8 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0044] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0045] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 14 kV, the spinning distance to 8 cm, the extrusion rate to 0.60 ml / h, and the roller speed to 300 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0046] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0047] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 16 hours to remove residual organic solvents. Then, it was treated in a 20W NH3 plasma treatment machine for 20 seconds to modify its surface and improve its hydrophilicity.

[0048] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0049] In step (5), 4 μL of gelatin aqueous solution was dropped onto the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification to obtain a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions, further improving the hydrophilicity and flexibility of the scaffold.

[0050] Example 2:

[0051] A cardiac stent with both repair and monitoring functions and its preparation method are as follows:

[0052] (1) Preparation of PLA spinning solution

[0053] A solvent was prepared by mixing 6g DMF and 4g acetone, and 0.48g polylactic acid powder was added. The mixture was heated and stirred at 65°C until completely dissolved to obtain a PLA spinning solution.

[0054] (2) Electrospun PLA nanofiber membrane

[0055] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 15 kV, the spinning distance to 10 cm, and the extrusion rate to 0.65 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0056] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0057] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.63g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.36% was dissolved in a 3% aqueous dextran solution to obtain an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:0.9 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0058] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0059] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 15 kV, the spinning distance to 10 cm, the extrusion rate to 0.65 ml / h, and the roller speed to 600 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0060] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0061] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 18 hours to remove residual organic solvents. Then, it was treated in a 30W NH3 plasma treatment machine for 30 seconds to modify its surface and improve its hydrophilicity.

[0062] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0063] In step (5), 6 μL of gelatin aqueous solution was dropped onto the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions, further improving the hydrophilicity and flexibility of the scaffold.

[0064] Example 3:

[0065] A cardiac stent with both repair and monitoring functions and its preparation method are as follows:

[0066] (1) Preparation of PLA spinning solution

[0067] A solvent was prepared by mixing 6g DMF and 4g acetone, and 0.64g polylactic acid powder was added. The mixture was heated and stirred at 70°C until completely dissolved to obtain a PLA spinning solution.

[0068] (2) Electrospun PLA nanofiber membrane

[0069] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 16 kV, the spinning distance to 12 cm, and the extrusion rate to 0.70 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0070] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0071] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.90g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.40% was dissolved in a 3% aqueous dextran solution to prepare an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:1.0 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0072] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0073] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 16 kV, the spinning distance to 12 cm, the extrusion rate to 0.70 ml / h, and the roller speed to 900 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0074] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0075] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 20 hours to remove residual organic solvents. Then, it was treated in a 40W NH3 plasma treatment machine for 40 seconds to modify its surface and improve its hydrophilicity.

[0076] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0077] In step (5), 8 μL of gelatin aqueous solution was dropped onto the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions, further improving the hydrophilicity and flexibility of the scaffold.

[0078] Example 4:

[0079] A method for fabricating a cardiac stent that combines repair and monitoring functions is as follows:

[0080] (1) Preparation of PLA spinning solution

[0081] A solvent was prepared by mixing 6g DMF and 4g acetone, and 0.86g polylactic acid powder was added. The mixture was heated and stirred at 75°C until completely dissolved to obtain a PLA spinning solution.

[0082] (2) Electrospun PLA nanofiber membrane

[0083] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 17 kV, the spinning distance to 14 cm, and the extrusion rate to 0.75 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0084] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0085] A solvent was prepared by mixing 6g DMF and 4g acetone, and 2.20g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.44% was dissolved in a 3% aqueous dextran solution to obtain an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:1.1 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0086] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0087] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 17 kV, the spinning distance to 14 cm, the extrusion rate to 0.75 ml / h, and the roller speed to 1200 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0088] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0089] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 22 hours to remove residual organic solvents. Then, it was treated in a 50W NH3 plasma treatment machine for 50 seconds to modify its surface and improve its hydrophilicity.

[0090] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0091] 10 μL of gelatin aqueous solution was dropped onto the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification in step (5) to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions, further improving the hydrophilicity and flexibility of the scaffold.

[0092] Example 5:

[0093] A method for fabricating a cardiac stent that combines repair and monitoring functions is as follows:

[0094] (1) Preparation of PLA spinning solution

[0095] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.09g polylactic acid powder was added. The mixture was heated and stirred at 80°C until completely dissolved to obtain a PLA spinning solution.

[0096] (2) Electrospun PLA nanofiber membrane

[0097] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 18 kV, the spinning distance to 16 cm, and the extrusion rate to 0.80 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0098] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0099] A solvent was prepared by mixing 6g DMF and 4g acetone, and 2.50g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.48% was dissolved in a 3% aqueous dextran solution to obtain an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:1.2 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0100] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0101] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 18 kV, the spinning distance to 16 cm, the extrusion rate to 0.80 ml / h, and the roller speed to 1500 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0102] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0103] The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 24 hours to remove residual organic solvents. Then, it was treated in a 60W NH3 plasma treatment machine for 60 seconds to modify its surface and improve its hydrophilicity.

[0104] (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0105] 12 μL of gelatin aqueous solution was dropped onto the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification in step (5) to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions, further improving the hydrophilicity and flexibility of the scaffold.

[0106] Comparative Example 1:

[0107] A method for fabricating a cardiac stent that combines repair and monitoring functions is as follows:

[0108] (1) Preparation of PLA spinning solution

[0109] A solvent was prepared by mixing 6g DMF and 4g acetone, and 0.23g polylactic acid powder was added. The mixture was heated and stirred at 60°C until completely dissolved to obtain a PLA spinning solution.

[0110] (2) Electrospun PLA nanofiber membrane

[0111] The PLA spinning solution from step (1) was poured into a syringe, and aluminum foil was placed on a flat plate collection device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 14 kV, the spinning distance to 8 cm, and the extrusion rate to 0.60 ml / h. The PLA nanofiber membrane was obtained by electrospinning.

[0112] (3) Preparation of P(VDF-TrFE) spinning solution

[0113] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.36g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution.

[0114] (4) Electrospun P(VDF-TrFE) / PLA composite nanofibers

[0115] The spinning solution from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collecting device. A high-voltage electrospinning machine was used, with a spinning needle having an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20°C, the spinning voltage to 14 kV, the spinning distance to 8 cm, the extrusion rate to 0.60 ml / h, and the roller speed to 300 rpm. P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0116] (5) Plasma-treated P(VDF-TrFE) / PLA composite nanofiber scaffold

[0117] The P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 16 hours to remove residual organic solvents. Then, it was treated in a 20W NH3 plasma treatment machine for 20 seconds to modify its surface and improve its hydrophilicity.

[0118] (6) Gelatin-coated P(VDF-TrFE) / PLA composite nanofiber scaffold

[0119] 4 μL of gelatin aqueous solution was dropped onto the surface of the fiber scaffold in step (5) to prepare a gelatin-coated P(VDF-TrFE) / PLA composite nanofiber scaffold, further improving the hydrophilicity and flexibility of the scaffold. Comparative Example 2:

[0120] A method for fabricating a cardiac stent that combines repair and monitoring functions is as follows:

[0121] (1) Preparation of PLA spinning solution

[0122] A solvent was prepared by mixing 6g DMF and 4g acetone, and 1.09g polylactic acid powder was added. The mixture was heated and stirred at 70°C until completely dissolved to obtain a PLA spinning solution.

[0123] (2) Electrospun PLA nanofiber membrane

[0124] Pour the PLA spinning solution from step (1) into a syringe, and cover the plate collection device with aluminum foil. Use a high-voltage electrospinning machine, select a spinning needle with an inner diameter of 0.15 mm and an outer diameter of 0.31 mm, set the ambient temperature to 20℃, the spinning voltage to 18 kV, the spinning distance to 16 cm, and the extrusion rate to 0.80 ml / h to spin PLA nanofiber membrane.

[0125] (3) Preparation of drug-loaded P(VDF-TrFE) spinning solution

[0126] A solvent was prepared by mixing 6g DMF and 4g acetone, and 2.50g P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF with a mass fraction of 0.48% was dissolved in a 3% aqueous dextran solution to obtain an aqueous solution. The P(VDF-TrFE) solution and the aqueous solution were then mixed at a volume ratio of 20:1.2 and stirred overnight to obtain a uniform spinning solution containing VEGF.

[0127] (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers

[0128] The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collecting device. A high-voltage electrospinning machine was used with a spinning needle with an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. The ambient temperature was set to 20℃, the spinning voltage to 18 kV, the distance between the needle and the roller to 16 cm, the extrusion rate to 0.80 ml / h, and the roller speed to 1500 rpm. The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold was obtained by electrospinning.

[0129] (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold

[0130] The drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber for 24 hours to remove residual organic solvents. Then, it was treated in a 60W NH3 plasma treatment machine for 60 seconds to modify its surface and improve its hydrophilicity.

[0131] Example 6:

[0132] Characterization of cardiac stents:

[0133] 1. Piezoelectricity: The scaffold will generate a certain current under the action of external force. The external current and the current generated by the internal electric field of the human body can work together to further promote cell growth and adhesion.

[0134] Table 1 shows the current and voltage values ​​of scaffolds with different P(VDF-TrFE) contents. As can be seen from the table, the higher the P(VDF-TrFE) content, the stronger the piezoelectric properties. This is because the increased PVDF content in the polymer leads to an increased content of the β-phase crystal form during electrospinning, thereby improving the piezoelectric characteristics of the scaffold. The enhanced piezoelectric effect further affects cell growth, adhesion, and the range of measurable shrinkage.

[0135] Table 1 Output voltage at different polyvinylidene fluoride-trifluoroethylene concentrations

[0136]

[0137] A gold pad is further deposited at the end of the P(VDF-TrFE) support to serve as an electrical contact, and the P(VDF-TrFE) support is placed on polydimethylsiloxane. Cyclic loads are applied to measure the voltage response of the support. Figure 2 The voltage response of the P(VDF-TrFE) stent under different cyclic tensile loads is shown in the figure. As shown, the stent exhibits a stable piezoelectric response under 10 cycles of tensile load, which indicates that the P(VDF-TrFE) stent has cardiac contraction monitoring capabilities.

[0138] 2. Cytotoxicity: Normal cells have vigorous metabolism. Succinate dehydrogenase in their mitochondria can reduce tetrazolium salts (such as MTT, XTT, WST-1, etc.) into purple crystalline substances, which are deposited around the cells. The OD value is read using a microplate reader, thereby calculating the relative cell proliferation rate. Relative cell proliferation rate (%) = average absorbance value of the experimental group / average absorbance value of the control group. This invention utilizes the MTT assay to detect cytotoxicity. Samples are seeded in 24-well plates, and 500 μL of cardiomyocytes are injected into each well. The plates are then cultured at 37°C and 5% CO2 for 3, 5, and 7 days. Then, 100 μL of diluted MTT is added to each well, and the plates are cultured for another 4 hours. The drug is then removed, and 100 μL of dimethyl sulfoxide is added to each well. After shaking for 10 minutes, the sample is analyzed.

[0139] Figure 3 The figure shows the effect of scaffolds with different contents of angiogenesis factor (VEGF) on the cytotoxicity of cardiomyocytes. As can be seen from the figure, compared with poly-L-lactic acid (PLLA) electrospun nanofiber scaffolds, the relative cell proliferation rate of drug-loaded P(VDF-TrFE) nanofiber scaffolds exceeded 100%, with the highest proliferation rate reaching 182.3±1.76% after 7 days. This indicates that the electrospun cardiac scaffolds have good biocompatibility and can significantly promote cell proliferation and growth. Comparing scaffolds with different contents of P(VDF-TrFE) and VEGF, cell proliferation increased with increasing relative time and higher contents of P(VDF-TrFE) and VEGF. This is due, firstly, to the improved piezoelectric properties of the scaffold, which effectively promoted cell growth; and secondly, to the increased VEGF content. VEGF, a growth factor, has the effect of inhibiting apoptosis and promoting cell growth, effectively promoting the adhesion, spread, and proliferation of cardiomyocytes on the scaffold.

[0140] 3. Mechanical Properties: Cardiac cell function is highly influenced by extracellular matrix (ECM) fibers. The mechanical properties of the ECM directly affect cardiomyocyte contraction, relaxation, and multiple signal transduction pathways, while highly rigid fibrous scaffolds can limit the function of cardiac scaffolds. Furthermore, for the tissue scaffold to conform properly to healthy myocardium, its mechanical properties should approximate those of the natural heart. This study investigates the effect of gelatin on the flexibility of cardiac scaffolds by analyzing the mechanical properties of uncoated and gelatin-coated fibrous scaffolds. Figure 4 The figure shows the representative yield stress and elastic elongation of different scaffolds. As can be seen from the figure, the yield stress and elastic elongation of the gelatin-coated scaffold are significantly higher than those of the uncoated scaffold. The results indicate that the gelatin-coated fiber scaffold can better resist strain caused by cardiomyocyte adhesion and contraction, and can recover to its initial structure without causing irreparable damage to the morphology or mechanical properties of the fibers.

[0141] This invention utilizes polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE)), polylactic acid (PLA), vascular endothelial growth factor (VEGF), and gelatin as raw materials. Electrospinning is employed to deposit VEGF-loaded P(VDF-TrFE) copolymer onto PLA nanofiber membranes, followed by gelatin coating, to prepare a cardiac scaffold exhibiting piezoelectric effects and bioactivity. This scaffold possesses advantages such as good flexibility, low cost, light weight, and good biocompatibility. Its fibrous structure provides a microstructure supporting cell growth and adhesion, and its high porosity allows for cell permeation and promotes cell diffusion. Previous studies have demonstrated that endogenous electric fields can promote cell migration, growth, and proliferation, and exogenous electric fields can synergistically interact with endogenous electric fields. PTrFE in P(VDF-TrFE) can increase the β-phase content in PVDF, further enhancing the piezoelectric effect and generating an endogenous electric field, thereby promoting cell adhesion and proliferation. Polylactic acid (PLA) is a novel biodegradable material with good biocompatibility and mechanical properties. Depositing P(VDF-TrFE) on PLA nanofiber membranes can improve the mechanical strength of composite nanofibers. VEGF is a cell-produced signaling protein essential to the human body. It can stimulate angiogenesis and regulate the proliferation, migration, and survival of endothelial cells. Loading VEGF into P(VDF-TrFE) nanofibers is beneficial for promoting the repair of cardiac tissue. Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffolds can further improve the hydrophilicity and flexibility of the scaffold.

[0142] Matters not covered in this invention are common knowledge.

[0143] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a cardiac stent with both repair and monitoring functions, characterized in that, Specifically, the steps include the following: (1) Preparation of PLA spinning solution A solvent was prepared by mixing DMF and acetone, PLA powder was added, and the mixture was heated and stirred until completely dissolved to obtain a PLA spinning solution. (2) PLA nanofiber membranes were prepared by electrospinning. Pour the PLA spinning solution from step (1) into a syringe, and cover the plate collection device with aluminum foil. Set the spinning voltage, spinning distance, and extrusion rate, and electrospin the PLA nanofiber membrane to obtain the PLA nanofiber membrane. (3) Prepare a drug-loaded polyvinylidene fluoride-trifluoroethylene [P(VDF-TrFE)] spinning solution A solvent was prepared by mixing DMF and acetone, and P(VDF-TrFE) powder was added. The mixture was heated and stirred until completely dissolved to obtain a P(VDF-TrFE) solution. VEGF was dissolved in an aqueous dextran solution to prepare an aqueous solution. The P(VDF-TrFE) solution was then mixed with the aqueous solution and stirred overnight to obtain a uniform spinning solution containing VEGF. (4) Electrospun drug-loaded P(VDF-TrFE) / PLA composite nanofibers The spinning solution containing VEGF drug from step (3) was poured into a syringe, and the PLA nanofiber membrane obtained in step (2) was placed on a roller collecting device. The spinning voltage, spinning distance, extrusion rate, and roller speed were set, and the P(VDF-TrFE) / PLA composite nanofiber scaffold loaded with VEGF was obtained by electrospinning. (5) Plasma-treated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold The VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold from step (4) was dried in a vacuum chamber to remove residual organic solvents, and then placed in a plasma treatment machine containing NH3 for surface modification. (6) Gelatin-coated drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold In step (5), gelatin aqueous solution was added to the surface of the VEGF-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold after surface modification to prepare a drug-loaded P(VDF-TrFE) / PLA composite nanofiber scaffold coated with gelatin, which is a cardiac scaffold with both repair and monitoring functions.

2. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (1), the mass ratio of DMF to acetone is 3:2, the stirring temperature is 60-80℃, and the mass fraction of PLA is 2%-10%.

3. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (2), the electrospinning needle has an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. Its parameters are: ambient temperature of 18-20℃, spinning voltage of 14-18kV, spinning distance of 8-16cm, and extrusion rate of 0.60-0.80ml / h.

4. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (3), the mass ratio of DMF to acetone is 3:2, the mass fraction of P(VDF-TrFE) is 12%-20%, the stirring temperature is 60-80℃, the concentration of the aqueous dextran solution is 3%-7%, the mass fraction of VEGF is 0.32%-0.48%, and the volume ratio of P(VDF-TrFE) solution to aqueous dextran solution is 20:0.8-20:1.

2.

5. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (4), the electrospinning needle has an inner diameter of 0.15 mm and an outer diameter of 0.31 mm. Its parameters are: ambient temperature of 18-20℃, spinning voltage of 14-18 kV, spinning distance of 8-16 cm, extrusion rate of 0.60-0.80 ml / h, and roller speed of 300-1500 rpm.

6. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (5), the drying time is 16-24h, the surface modification is performed, the plasma treatment machine power is 20-60W, and the plasma treatment time is 20-60s.

7. The method for preparing a cardiac stent with both repair and monitoring functions according to claim 1, characterized in that: In step (6), the volume of the added gelatin aqueous solution is 4-12 μL.

8. A cardiac stent with both repair and monitoring functions, characterized in that: It was prepared using the preparation method described in any one of claims 1-7.

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