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CN-122005957-A - Electrostatic spinning-photocuring composite tubular stent and preparation method and application thereof

CN122005957ACN 122005957 ACN122005957 ACN 122005957ACN-122005957-A

Abstract

The invention relates to an electrostatic spinning-photo-curing composite tubular stent which comprises a core, a shell and a coating layer, wherein the core comprises polylactic acid and valeric acid, the shell comprises polyvinyl butyral and a YAP (gamma-valeric acid) agonist, the coating layer comprises methacryloyl hyaluronic acid and geniposide, the shell is wrapped on the surface of the core, the coating layer is wrapped on the surface of the shell, and the YAP agonist comprises C381. The preparation method comprises the following steps of preparing the core-shell tubular stent and wrapping the core-shell tubular stent by a coating layer. The electrostatic spinning-photo-curing composite tubular stent provided by the invention realizes a bile duct repair integrated platform with no acidification degradation, high encapsulation efficiency, bionic surface and three-medicine space-time cooperation for the first time, and provides a breakthrough tissue engineering solution which can be sutured, degraded and actively regenerated for refractory bile diseases such as PSC, bile duct locking and the like.

Inventors

  • XIANG YANG
  • GAO YUANHUI
  • LEI ZHONGWEN

Assignees

  • 海口市人民医院(中南大学湘雅医学院附属海口医院、海口市人民医院医疗集团总院)

Dates

Publication Date
20260512
Application Date
20260211

Claims (10)

  1. 1. An electrostatic spinning-photo-curing composite tubular stent, which is characterized by comprising a core, a shell and a coating layer; The core comprises polylactic acid and valeric acid, the shell comprises polyvinyl butyral and a YAP agonist, and the coating comprises methacryloylated hyaluronic acid and geniposide; the shell is wrapped on the surface of the core, and the cladding layer is wrapped on the surface of the shell; The YAP agonist comprises C381.
  2. 2. The method for preparing the electrostatic spinning-photo-curing composite tubular stent according to claim 1, comprising the following steps: preparing a core-shell tubular stent, namely dissolving polylactic acid in an organic solvent, adding valeric acid, stirring to obtain a core solution, dissolving polyvinyl butyral in the organic solvent, adding a YAP agonist, performing ultrasonic dispersion to obtain a shell solution, and performing electrostatic spinning by taking the core solution and the shell solution as raw materials to obtain the core-shell tubular stent; Coating, namely dissolving the methacryloyl hyaluronic acid in water, adding the jasminoidin and the photoinitiator, stirring to obtain a bionic spray liquid of the methacryloyl hyaluronic acid, performing electrospray deposition of the microspheres of the methacryloyl hyaluronic acid on the surface of the core-shell tubular stent, photo-curing, washing, vacuum drying and sterilizing to obtain the electrostatic spinning-photo-curing composite tubular stent.
  3. 3. The method of claim 2, wherein the polylactic acid-soluble organic solvent comprises methylene chloride, the polyvinyl butyral-soluble organic solvent comprises absolute ethanol, and the photoinitiator comprises Irgacure2959.
  4. 4. The preparation method of the core-shell tubular stent according to claim 2, wherein in the preparation of the core-shell tubular stent, the stirring time is 20-40 min, and the ultrasonic dispersion time is 10-20 min.
  5. 5. The method according to claim 2, wherein the stirring time is 20-40 min and the photo-curing time is 20-40 s in the wrapping of the coating layer.
  6. 6. The production method according to claim 2, wherein the electrospinning is achieved by a coaxial electrospinning device comprising a rotary drum electrospinning device; The electrostatic spinning working conditions comprise 10-20 kV voltage, 10-20 cm receiving distance, 0.1-0.5 mL/h nuclear layer flow rate, 0.3-1.5 mL/h shell flow rate and 3-10 mm receiving roller diameter.
  7. 7. The method according to claim 2, wherein the electrospray deposition is performed by an electrostatic spray gun device, and the electrostatic spray gun voltage is 5-10 kv.
  8. 8. The method according to any one of claims 2 to 7, wherein the mass ratio of polylactic acid, valeric acid, polyvinyl butyral, YAP agonist, methacryloylated hyaluronic acid and geniposide in the electrospinning-photocuring composite tubular stent is (10-30) 1 (20-40) 1-5) 3-8 (3-8).
  9. 9. Use of an electrospun-photocurable composite tubular scaffold according to claim 1, or obtained by a method according to any one of claims 2-8, for the preparation of a product for repairing bile duct injury.
  10. 10. A product for repairing bile duct injury, comprising the electrospun-photocurable composite tubular stent of claim 1 or the electrospun-photocurable composite tubular stent obtained by the method of any one of claims 2-8.

Description

Electrostatic spinning-photocuring composite tubular stent and preparation method and application thereof Technical Field The invention relates to the technical field of biomedicine, in particular to an electrostatic spinning-photo-curing composite tubular stent, and a preparation method and application thereof. Background The biliary tract system is a key pipeline structure for transporting bile between the liver and the duodenum, and mainly consists of bile duct epithelial cells (BECs), and BECs is not only responsible for concentration, modification and transportation of bile, but also plays a core role in maintaining the steady state of the liver, regulating immunity and repairing injury. However, a variety of pathological factors may lead to bile duct injury, including congenital bile duct Blockage (BA), primary Sclerosing Cholangitis (PSC), primary cholangitis (PBC), ischemia reperfusion injury, drug bile duct injury, and bile duct stenosis after liver transplantation, etc. Common pathological features of these diseases are insufficient proliferation of bile duct epithelial cells, abnormal differentiation, progressive fibrosis, and lumen stenosis or occlusion, ultimately leading to cholestasis, secondary hepatocyte injury, cirrhosis and even liver failure. Clinical data show that biliary tract occlusion is the most common biliary tract disease of newborns, the incidence rate is about 1/8000-1/18000, the Kasai operation can temporarily relieve symptoms, but the 5-year survival rate after the operation is only about 50%, and most infants finally need liver transplantation. PSC is a chronic progressive disease, the incidence rate of adults is about 1/10000, the characteristic bead-like bile duct stenosis and fibrosis currently lack specific treatment means, about 10% -15% of patients progress to liver cirrhosis within 5 years, and the risk of bile duct cancer is obviously increased. Traditional treatment strategies include endoscopic expansion, stent implantation and ursodeoxycholic acid (UDCA) drug treatment, but none of them can fundamentally reverse the regeneration disorder and fibrosis progression of bile duct epithelium. From a tissue repair perspective, the ideal repair process after bile duct injury should include three key phases, namely an acute inflammatory phase, a proliferation differentiation phase and a remodeling stabilization phase. The method comprises the steps of rapidly clearing necrotic tissues in an acute inflammatory phase, inhibiting excessive inflammation, starting the transdifferentiation of liver cells to bile duct-like cells, expanding and directionally differentiating bile duct progenitor cell pools in a proliferation and differentiation phase to mature BECs and form a lumen structure, and reasonably remodelling extracellular matrix (ECM) in a remodelling stable phase, preventing scarring and maintaining bile duct barrier function and polarity. However, current tissue engineering scaffold materials have difficulty achieving the above-described space-time precise regulation. For example, although pure collagen membranes or acellular matrixes (dECM) have good biocompatibility, but lack active drug release capability, cannot interfere with key signal paths such as NOTCH, YAP and the like, electrospun nanofiber membranes are widely studied due to high specific surface area, controllable porosity and bionic structure, but the prior art is mostly focused on single drug loading, such as VEGF loading to promote vascularization or dexamethasone loading to inhibit inflammation, and is difficult to meet multi-stage and multi-target requirements of bile duct repair. In recent years, the central role of NOTCH signaling pathways in bile duct development and regeneration has been deeply elucidated. During embryonic stage, NOTCH2-Hes1 axis inhibits hepatic progenitors from differentiating to BECs, and after birth, continuous activation of NOTCH maintains bile duct plate structure. It was found that Valeric Acid (VA) as an HDAC inhibitor down-regulates Hes1 expression, up-regulates Atoh1/Math1, promotes cholangiocellular maturation and luminal. However, VA has a short half-life and requires long-term low dose release to maintain NOTCH inhibition, otherwise it is prone to induce proliferation-apoptosis imbalance. At the same time, YAP acts as a downstream effector of the Hippo pathway, being activated early in liver injury, driving hepatocyte dedifferentiation and switching to the cholangioid phenotype. C381 is a novel YAP small molecule agonist, and can rapidly induce YAP nuclear translocation and activate bile duct marker gene expression of Sox9, K19 and the like. However, C381 has poor water solubility and low bioavailability, and requires burst release within 48 hours after injury to capture the "plasticity window" of hepatocytes. The regulation of inflammatory microenvironment is the key to the success or failure of bile duct repair. After injury, ROS burst, TGF- β1 hypersecretion drives