一种新型介孔miRNA21控释纳米微球/肝素复合修饰小口径聚氨酯人工血管的实验研究

项目名称： 一种新型介孔miRNA21控释纳米微球/肝素复合修饰小口径聚氨酯人工血管的实验研究

项目编号： No.81501595

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陆树洋

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 小口径人工血管（<6 mm）移植后再狭窄和血栓形成是限制其临床广泛应用的瓶颈，目前尚未得到有效解决。本课题在前期研究的基础上，从制备小口径人工血管的材料工艺和调节血管移植后局部微环境两方面加以改进，采用同轴静电纺丝法制备双层膜小口径人工血管，外层采用顺应性、韧性及弹性更加优越的聚氨酯作为血管材料底物，内层采用可降解材料己内酯-丙交酯共聚物制备载miRNA21控释纳米微球及肝素的功能性涂层对管腔进行覆膜修饰。既往研究提示miRNA21具有显著的促进内皮细胞增殖分化和调节炎性因子表达的作用，且肝素抗凝效果确切。随后从新型材料表征的测试、体外血液相容性及生物相容性测试、植入动物体内后血管局部的血流动力学变化和内皮化成分及效果等方面对载miRNA21控释纳米微球及肝素复合修饰小口径人工血管进行综合研究。本研究可以为构建一种有望能够临床应用的小口径人工血管提供理论和实验依据。

中文关键词： 人工血管；小口径；表面处理；同轴静电纺丝技术；药物缓释

英文摘要： Post-transplantational restenosis and thrombosis are the main problems which limit the application of small-caliber artificial vessels in clinical widly and have not been resolved effectively. On our original researching basis, we intend to improve the performance of small-caliber artificial vessels from two aspects, preparing materials and post-transplantational local micorenvironment. We will prepare double membrane small-caliber vascular graft through a coaxial electrospinning technique. The inner layer will be prepared by electrospinning poly(L lactide-co-ε-caprolactone) (P(LLA-CL)) , miRNA21-loaded controlling-delivery nanoparticles and heparin, and the outer layer will be prepared by electrospinning polyurethane which has better compliance, toughness and elasticity. Original studies have shown that miRNA21 could promote the proliferation of endothelial cells and regulate the expression of inflammatory factors, and heparin has definite antithrombotic effect. Then we will do a comprehensive research for miRNA21-loaded controlling-delivery nanoparticles/heparin modified small-caliber artificial vessels from the following aspects, test of modifed material properties, hemocompatibility and biocompatibility evaluation, computer-based local hemodynamic situation and in vivo animal experiments. Our work will provide new theoretical and experimental basis for the research and clinical application of small-caliber artificial vessels.

英文关键词： artificial vessels;small-caliber;surface modification;coaxial electrospinning technique;sustained drug release