Electrostatic spinning core-shell structure tubular stent as well as preparation method and application thereof

Abstract

The invention relates to an electrostatic spinning core-shell structure tubular stent, the electrostatic spinning core-shell structure tubular stent comprises a core and a shell, the core comprises polyvinylidene fluoride and colestimine, the shell comprises polyvinyl butyral and ademetionine, and the shell wraps the surface of the core. The preparation method of the tubular stent with the electrostatic spinning core-shell structure comprises the following steps: preparing a core solution; preparing a shell solution; and preparing the tubular stent with the core-shell structure. According to the tubular stent with the electrostatic spinning core-shell structure, the core layer loaded with the colestyramine is chelated with bile acid in a bile duct, absorption of a human body to the bile acid is reduced, the adenosyl methionine loaded on the shell layer adjusts the immune environment and enhances the antioxidant capacity of hepatocytes, and the colestyramine and the adenosyl methionine have a synergistic effect, so that the bile duct environment is comprehensively improved, and the treatment effect is improved; the core-shell structure solves the time-space sequential release of drugs, enhances the drug delivery efficiency and repair effect, and can be used for bile duct repair products.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to an electrospun core-shell tubular scaffold, its preparation method, and its application. Background Technology

[0002] Biliary duct diseases, including bile duct strictures, obstructions, inflammation, and cholangiocarcinoma, are common digestive system disorders in clinical practice. These diseases often lead to obstructive jaundice, liver dysfunction, and infection, severely impacting patients' quality of life and survival. Cholangiocarcinoma, as an aggressive tumor, is often diagnosed at an advanced stage. Surgery is the only potentially curative treatment, but the recurrence rate is high. The estimated incidence of new intrahepatic cholangiocarcinoma cases in 2025 is approximately 9.4 per 100,000. For patients who are not candidates for resection or do not wish to undergo surgery, biliary stent placement has become the preferred palliative treatment, effectively relieving obstruction, improving jaundice, and prolonging survival.

[0003] Current biliary stents mainly include plastic stents, self-expanding metallic stents (SEMS), covered metallic stents, anti-reflux stents, drug-eluting stents, and radial stents. Plastic stents are low-cost and easy to place, but they are prone to obstruction and migration, requiring multiple endoscopic retrograde cholangiopancreatography (ERCP) interventions, increasing patient risk and hospitalization time. Metal stents have a longer patency period (median survival >3 months) and are suitable for patients with a longer expected survival, but there are problems such as intratumoral growth, restenosis, and stent failure. Covered stents are designed to prevent tumor embedding, but multiple studies have shown no significant advantage in long-term patency rates and may increase the risk of migration. Although anti-reflux stents and drug-eluting stents can partially improve patency and survival, clinical trial sample sizes are small, structural advantages are not fully validated, and the incidence of complications such as late cholangitis remains as high as 36.7%. Radial stents combined with chemotherapy have shown positive effects, but safety data are limited, and core issues such as stent obstruction, migration, and tumor growth have not been completely resolved. In addition, while existing self-detaching stents can avoid the need for secondary stent removal, they are only suitable for short-term treatment and have insufficient mechanical properties and biocompatibility.

[0004] Electrospinning, as an emerging method for preparing nanofibers, has been widely applied in tissue engineering. It can fabricate fibrous scaffolds with high surface area, high porosity, and biomimetic structures, promoting cell attachment, proliferation, and tissue regeneration. Core-shell nanofibers, achieved through coaxial electrospinning, can load drugs, growth factors, or bioactive molecules, enabling controlled release, such as pulsed or sustained release, suitable for drug delivery and local therapy. This technology has proven effective in myocardial, bone, vascular, and skin tissue engineering; however, its application in bile duct scaffolds remains exploratory, lacking dedicated core-shell structure designs to address bile duct-specific issues such as anti-inflammation, anti-fibrosis, and promotion of epithelial regeneration.

[0005] Existing bile duct stents have limitations, including poor biocompatibility, uncontrollable degradation rates, uneven drug release, and an inability to effectively promote tissue regeneration, leading to high restenosis rates and limited survival. Therefore, there is an urgent need to develop a novel stent that combines the advantages of electrospun nanostructures with the core-shell design for controlled drug release, providing better mechanical support, biodegradability, and regeneration promotion to improve treatment outcomes for bile duct diseases.

[0006] In summary, biliary stents require multi-target intervention that addresses inflammation, fibrosis, and promotes epithelial regeneration. Based on core-shell electrospinning technology, cholestyramine (core layer, chelating bile acids) and S-adenosylmethionine (outer shell, regulating inflammation and enhancing antioxidant capacity) are functionally integrated. This approach leverages the core-shell structure to achieve sequential functional release and improves the biliary environment through the synergistic effects of multiple components. This design provides a new research direction for biliary stent development and has significant clinical translational value. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides an electrospun core-shell tubular scaffold, comprising a core and a shell. The core comprises polyvinylidene fluoride (PVDF) and cholestyramine (Cho), and the shell comprises polyvinyl butyral (PVB) and S-adenosylmethionine (SAMe). The shell is wrapped around the surface of the core.

[0008] A second aspect of the present invention also provides a method for preparing the above-mentioned electrospun core-shell tubular scaffold, comprising the following steps:

[0009] Preparation of the nucleus solution: Polyvinylidene fluoride was dissolved in an organic solvent, cooled, and then cholestyramine was added. The mixture was stirred and degassed under vacuum to obtain the nucleus solution. Preparation of shell solution: Polyvinyl butyral was dissolved in an organic solvent, S-adenosylmethionine was added, and the mixture was ultrasonically dispersed and degassed under vacuum to obtain the shell solution. Preparation of core-shell tubular scaffold: Using the core solution and shell solution as raw materials, electrospinning is performed to obtain a tubular scaffold, which is then vacuum dried to obtain an electrospun core-shell tubular scaffold.

[0010] In one embodiment, the organic solvent used in the preparation of the core solution includes a mixture of dichloromethane and N,N-dimethylformamide; and the organic solvent used in the preparation of the shell solution includes anhydrous ethanol.

[0011] In one embodiment, in the preparation of the nuclear solution, the stirring is magnetic stirring, the stirring time is 1-3 hours, and the vacuum degassing time is 20-40 minutes.

[0012] In one embodiment, during the preparation of the shell solution, the ultrasonic dispersion time is 20-40 min; the vacuum degassing time is 20-40 min.

[0013] In one embodiment, during the preparation of the core-shell tubular scaffold, the electrospinning time is 2-10 hours; the vacuum drying temperature is 38-45°C, and the time is 20-26 hours.

[0014] In one embodiment, in the fabrication of the core-shell tubular scaffold, the electrospinning is achieved by a coaxial electrospinning device. The electrospinning step includes: injecting the core solution into an inner syringe, injecting the shell solution into an outer syringe, installing the device into the coaxial electrospinning device, and spinning under working conditions. The operating conditions include: voltage: 10~20kV, receiving distance: 10~20cm, core flow rate: 0.1~0.5mL / h, shell flow rate: 0.3~1.5mL / h, and receiving drum diameter: 3~10mm.

[0015] In one embodiment, during the fabrication of the core-shell tubular scaffold, the inner syringe is a 21G needle and the outer syringe is an 18G needle.

[0016] In one embodiment, in the preparation of the core solution, the polyvinylidene fluoride (PVDF) has a dissolved mass fraction concentration of 5% to 20%, and the cholestyramine has a dissolved mass fraction concentration of 0.1% to 1% before being added to the PVDF solution. In the core solution, the mass ratio of PVDF to cholestyramine is (10 to 150): 1. In the preparation of the shell solution, the polyvinyl butyral has a dissolved mass fraction concentration of 8% to 20%, and the S-adenosylmethionine has a dissolved mass fraction concentration of 0.1% to 5% before being added to the PVDF solution. In the shell solution, the mass ratio of PVDF to S-adenosylmethionine is (1 to 100): 1.

[0017] A third aspect of the present invention also provides the application of the above-described electrospun core-shell tubular stent or the electrospun core-shell tubular stent obtained by the above preparation method in the preparation of products for repairing bile duct injuries.

[0018] In a fourth aspect, the present invention also provides a product for repairing bile duct injuries, comprising the above-described electrospun core-shell tubular stent or the electrospun core-shell tubular stent obtained by the above-described preparation method.

[0019] Compared with the prior art, the present invention has the following beneficial effects: The electrospun core-shell tubular scaffold of this invention features a core-shell structure that enables functional stratification. The core layer, loaded with Cho, chelates with bile acids in the bile duct, reducing the body's absorption of bile acids. The outer shell, loaded with SAMe, regulates the immune environment and enhances the antioxidant capacity of hepatocytes. Through synergistic effects, these two components comprehensively improve the bile duct environment and enhance therapeutic efficacy. Finally, the electrospun core-shell tubular scaffold offers significant advantages. It utilizes biocompatible materials such as PVDF and PVB, ensuring excellent safety and biodegradability. The core-shell structure addresses the temporal and spatial release of drugs, enhancing drug delivery efficiency and repair effects, making it suitable for use in bile duct repair products. Attached Figure Description

[0020] Figure 1 The diagram shows a bile duct stent. The first and second images from left to right are actual images of the bile duct stent prepared by this invention from different angles. The third image is a SEM image of the bile duct stent. Figure 2 This is a TEM image of the core-shell structure. Detailed Implementation

[0021] This invention provides an electrospun core-shell tubular scaffold, wherein the core layer is loaded with cholestyramine (Cho) to chelate bile acids in the bile duct, preventing reabsorption and reducing their accumulation in the body. The outer shell layer is loaded with S-adenosylmethionine (SAMe), which has anti-inflammatory properties and enhances the antioxidant capacity of hepatocytes. Both layers integrate the functions of reducing bile acid absorption and regulating inflammation. The Cho in the core layer of this electrospun core-shell tubular scaffold chelates bile acids in the bile duct, reducing their accumulation in the body and decreasing the inducing factors of inflammation. The SAMe in the outer shell layer regulates the inflammatory environment, enhances the antioxidant capacity of hepatocytes, and provides a better immune microenvironment for bile acid chelation. Through this synergistic effect, both layers comprehensively improve the bile duct environment and enhance therapeutic efficacy.

[0022] To facilitate understanding of the present invention, a more complete description will be given below with reference to the accompanying drawings. Preferred embodiments of the invention are shown in the drawings. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the invention.

[0023] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0024] Unless otherwise specified, all reagents, materials, and equipment used in this embodiment are commercially available; unless otherwise specified, all test methods are conventional test methods in this field.

[0025] Example This invention provides a method for preparing an electrospun core-shell tubular scaffold, comprising the following steps: Preparation of the core solution: Polyvinylidene fluoride (PVDF) was completely dissolved in a mixed solvent of dichloromethane / N,N-dimethylformamide, cooled to room temperature, Cho was added, magnetic stirring was carried out for 2 hours, and vacuum degassing was carried out for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: Polyvinyl butyral (PVB) was completely dissolved in anhydrous ethanol solution, and then SAMe was added to the PVB solution. The mixture was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core solution was injected into the inner syringe (21G needle) and the shell solution was injected into the outer syringe (18G needle). The syringes were then installed in a coaxial spinning device. The spinning parameters were adjusted and the scaffolds were spun for 8 hours. The tubular scaffolds were collected and vacuum dried for 24 hours (40℃) to remove residual solvent, thus obtaining core-shell tubular scaffolds.

[0026] To further understand the present invention, the present invention will be described in more detail below with reference to specific embodiments and comparative examples.

[0027] Example 1 Preparation of the nucleus solution: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.5% Cho was added to make the mass ratio of PVDF to Cho in the nucleus solution 30:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution. The solution was stirred until completely dissolved. Then, 3% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 10:3. The solution was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the outer shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0028] Example 2 Preparation of Solution A: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.5% Cho was added to make the mass ratio of PVDF to Cho in Solution A 30:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of solution B: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution. The solution was stirred until completely dissolved. Then, 3% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in solution B 10:3. The solution was ultrasonically dispersed for 30 min and vacuum degassed for 30 min. Preparation of tubular scaffolds: Solution A was injected into a syringe (21G needle), and solution B was injected into another syringe (18G needle). At the same time, high voltage power was started for blending. The diameter of the receiving roller was 5mm, the spinning voltage was adjusted to 15kV, the receiving distance was 15cm, the core flow rate was 0.2mL / h, the shell flow rate was 0.6mL / h, and spinning was carried out for 8h. The tubular scaffolds were collected and vacuum dried for 24h (40℃) to remove residual solvent, thus obtaining the tubular scaffolds.

[0029] Comparative Example 1 Preparation of the core solution: PVDF was added to a 15% PVDF solution in a mixed solvent of dichloromethane / N,N-dimethylformamide, stirred at 50°C for 2 hours until completely dissolved, and then degassed under vacuum for 30 minutes to obtain the PVDF solution for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution, stirred until completely dissolved, and vacuum degassed for 30 min to obtain the PVB solution for later use; Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0030] Comparative Example 2 Preparation of the nucleus solution: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.5% Cho was added to make the mass ratio of PVDF to Cho in the nucleus solution 30:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution, stirred until completely dissolved, and vacuum degassed for 30 min to obtain the PVB solution for later use; Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0031] Comparative Example 3 Preparation of the core solution: PVDF was added to a 15% PVDF solution in a mixed solvent of dichloromethane / N,N-dimethylformamide, stirred at 50°C for 2 hours until completely dissolved, and then degassed under vacuum for 30 minutes to obtain the PVDF solution for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution. The solution was stirred until completely dissolved. Then, 3% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 10:3. The solution was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0032] Comparative Example 4 Preparation of the nucleus solution: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.5% Cho was added to make the mass ratio of PVDF to Cho in the nucleus solution 30:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution, and stirred until completely dissolved. Then, 0.1% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 100:1. The mixture was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0033] Comparative Example 5 Preparation of the core solution: PVDF was added to a 15% PLA solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.5% Cho was added to make the mass ratio of PVDF to Cho in the core solution 30:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution. The solution was stirred until completely dissolved. Then, 5% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 2:1. The solution was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0034] Comparative Example 6 Preparation of the core solution: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 0.1% Cho was added to make the mass ratio of PVDF to Cho in the core solution 150:1. The solution was magnetically stirred for 2 hours and then vacuum degassed for 30 minutes to obtain a PVDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol to prepare a 10% PVB solution and stirred until completely dissolved. Then, 3% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 10:3. The mixture was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0035] Comparative Example 7 Preparation of the core solution: PVDF was added to a 15% PVDF solution in a dichloromethane / N,N-dimethylformamide mixed solvent. The solution was stirred at 50°C for 2 hours until completely dissolved. After cooling to room temperature, 1% Cho was added to make the mass ratio of PVDF to Cho in the core solution 15:1. The solution was magnetically stirred for 2 hours and then degassed under vacuum for 30 minutes to obtain a PCDF / Cho mixture for later use. Preparation of shell solution: PVB was dissolved in anhydrous ethanol solution to prepare a 10% PVB solution. The solution was stirred until completely dissolved. Then, 3% SAMe was added to the PVB solution to make the mass ratio of PVB to SAMe in the shell solution 10:3. The solution was ultrasonically dispersed for 30 min and vacuum degassed for 30 min to obtain a PVB / SAMe mixture for later use. Preparation of core-shell tubular scaffolds: The core layer solution was injected into an inner syringe (21G needle), and the shell layer solution was injected into an outer syringe (18G needle). The syringes were then installed in a coaxial spinning device with a receiving roller diameter of 5 mm, a spinning voltage of 15 kV, a receiving distance of 15 cm, a core layer flow rate of 0.2 mL / h, a shell layer flow rate of 0.6 mL / h, and spinning was carried out for 2 h. The scaffolds were then vacuum dried for 24 h (40 °C) to remove residual solvent, resulting in core-shell tubular scaffolds.

[0036] Test effect evaluation 1. Cytological evaluation Test method: Cultured bile duct epithelial cells, HUVEC cells, and macrophages were digested and suspended using trypsin, then seeded into 48-well plates. After 12 hours of culture, the original culture medium was removed, and a core-shell bile duct scaffold was added for further culture for 24 hours. The culture medium was then aspirated, and the cells were washed three times with PBS. CCK-8 staining agent was added, followed by washing with PBS. Cell viability was then determined by measuring the absorbance of different examples and comparative examples using a microplate reader.

[0037] Table 1. Survival rates of different cells in the examples and comparative examples

[0038] Test results: As shown in Table 1, it can be seen that the electrospun core-shell tubular scaffold prepared in the embodiments of the present invention has good biocompatibility, and the survival rate of the above three types of cells is above 75%, indicating that the above materials do not have obvious biotoxicity and have excellent biocompatibility.

[0039] 2. Immune regulation properties Test method: RAW264.7 was 1×10 6 Cells were seeded at a density of 1 cell per well in 6-well plates that had been coated with cell spreaders. After being cultured overnight, the cells were induced overnight with 5 μg / mL lipopolysaccharide (LPS). Then, a core-shell bile duct scaffold was added and the cells were cultured for another 24 hours. The cell culture medium was collected and the expression levels of different inflammatory factors were detected by qPCR.

[0040] Table 2. Immunomodulatory effects of the examples and comparative examples

[0041] Test results: As shown in Table 2, it can be seen that the core-shell tubular scaffold prepared in this invention has good biocompatibility, promotes macrophage polarization towards M2, exhibits good immunomodulatory effects in vitro, promotes the release of anti-inflammatory factors TGF-β1 and IL-4, and inhibits the secretion of pro-inflammatory factors TNF-α and IFN-γ.

[0042] 3. Mechanical properties Test method: Fix both ends of the tubular support to the upper and lower clamps of the universal testing machine, ensuring that the clamps are aligned and the clamping force is appropriate. Adjust the initial gauge length, then set the test parameters and apply axial tension at a constant rate of 2 mm / min. Simultaneously record the tension value and displacement data in real time until the support shows obvious fracture. Calculate the fracture strength and elongation at break using data analysis software.

[0043] Table 3 Mechanical properties of the examples and comparative examples

[0044] Test results: As shown in Table 3, it can be seen that the core-shell tubular scaffold prepared by the present invention has good fracture strength and elongation at break, which can meet the tensile stress caused by organ peristalsis after implantation.

[0045] 4. Scanning electron microscope (SEM) Test method: After cutting a flat slit in the tubular support, it is attached to the sample stage with conductive adhesive, sputtered with gold, and then observed using SEM.

[0046] Test results: like Figure 1 As shown in the figure, it is clear from the figure that the core-shell tubular scaffold prepared by the present invention exhibits a tubular structure and is basically composed of fibers.

[0047] 5. TEM Test method: During the spinning process, a copper sheet is placed in a receiver and the voltage is turned on. A small amount of fiber is sprayed onto the copper sheet, and after gold is sprayed on, the core-shell structure is observed using TEM.

[0048] Test results: like Figure 2 As shown in the figure, it is clear from the figure that the single fiber of the core-shell structured tubular scaffold prepared by the present invention exhibits a distinct core-shell structure, which provides an effective load space for the spatiotemporal sequential release of drugs.

[0049] This invention provides an electrospun core-shell tubular scaffold for bile duct injury repair. It uses polyvinylidene fluoride (PVDF) and cholestyramine (Cho) as the core layer of the tubular scaffold, and polyvinyl butyral (PVB) as the outer shell of nanofibers, loaded with S-adenosylmethionine (SAMe) to form the core-shell tubular scaffold. This electrospun core-shell tubular scaffold exhibits spatiotemporally synergistic release characteristics. The PVB shell layer rapidly releases SAMe, reducing inflammation levels and enhancing the antioxidant capacity of hepatocytes. The released Cho core layer chelates with bile acids, preventing their reabsorption and reducing bile acid accumulation in the body. It not only possesses excellent mechanical properties, providing radial support for the bile duct, but also integrates the functions of reducing bile acid absorption and regulating inflammation.

[0050] The core-shell tubular scaffold of this invention has excellent biocompatibility, immunomodulatory effects, and bile duct repair capabilities. Its active ingredients are released spatiotemporally in a coordinated manner, effectively regulating the microenvironment of bile duct injury, and are suitable for the treatment of bile duct repair.

[0051] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0052] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. An electrospun core-shell structure tubular scaffold, characterized in that, It includes a core and a shell, wherein the core comprises polyvinylidene fluoride and cholestyramine, and the shell comprises polyvinyl butyral and S-adenosylmethionine, and the shell surrounds the surface of the core.

2. The method of claim 1, wherein the electrospinning of the tubular scaffold of core-shell structure is performed by using a solution of the polymer of the core and a solution of the polymer of the shell. Includes the following steps: Preparation of the nucleus solution: Polyvinylidene fluoride was dissolved in an organic solvent, cooled, and then cholestyramine was added. The mixture was stirred and degassed under vacuum to obtain the nucleus solution. Preparation of shell solution: Polyvinyl butyral was dissolved in an organic solvent, S-adenosylmethionine was added, and the mixture was ultrasonically dispersed and degassed under vacuum to obtain the shell solution. Preparation of core-shell tubular scaffold: Using the core solution and shell solution as raw materials, electrospinning is performed to obtain a tubular scaffold, which is then vacuum dried to obtain an electrospun core-shell tubular scaffold.

3. The production method according to claim 2, characterized by, In the preparation of the core solution, the organic solvent includes dichloromethane and N,N-dimethylformamide; in the preparation of the shell solution, the organic solvent includes anhydrous ethanol.

4. The production method according to claim 2, characterized by, In the preparation of the nuclear solution, the stirring is magnetic stirring, the stirring time is 1~3h; the vacuum degassing time is 20~40min.

5. The preparation method according to claim 2, characterized in that, In the preparation of the shell solution, the ultrasonic dispersion time is 20-40 min; the vacuum degassing time is 20-40 min.

6. The preparation method according to claim 2, characterized in that, In the preparation of the core-shell tubular scaffold, the electrospinning time is 2~10h; the vacuum drying temperature is 38~45℃, and the time is 20~26h.

7. The preparation method according to claim 2, characterized in that, In the preparation of the core-shell tubular scaffold, the electrospinning is achieved by a coaxial electrospinning device. The electrospinning steps include: injecting the core solution into an inner syringe, injecting the shell solution into an outer syringe, installing the device into the coaxial electrospinning device, and spinning under working conditions. The operating conditions include: voltage: 10~20kV, receiving distance: 10~20cm, core flow rate: 0.1~0.5mL / h, shell flow rate: 0.3~1.5mL / h, and receiving drum diameter: 3~10mm.

8. The method of any one of claims 2-7, wherein, In the preparation of the core solution, the mass fraction concentration of the polyvinylidene fluoride after dissolution is 5%~20%, and the mass fraction concentration of the cholestyramine after dissolution before being added to the polyvinylidene fluoride solution is 0.1%~1%. In the core solution, the mass ratio of polyvinylidene fluoride to cholestyramine is (10~150):

1. In the preparation of the shell solution, the mass fraction concentration of polyvinyl butyral after dissolution is 8%~20%, and the mass fraction concentration of adenosylmethionine after dissolution before adding the polyvinyl butyral solution is 0.1%~5%. In the shell solution, the mass ratio of polyvinyl butyral to adenosylmethionine is (1~100):

1.

9. The application of the electrospun core-shell tubular stent as described in claim 1, or the electrospun core-shell tubular stent obtained by the preparation method described in claims 2-8, in the preparation of products for repairing bile duct injuries.

10. A product for repairing a bile duct injury, characterized by, Includes the electrospun core-shell tubular scaffold as described in claim 1, or the electrospun core-shell tubular scaffold obtained by the preparation method described in claims 2-8.

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