磁场与纳米体系介导的铁基可降解血管支架与生物体的相互作用

Based on the recongnition of the interaction of vascular stent with surround vascular tissue environment and the complications such as thrumbus and restenosis caused by stent intervention, a new strategy which can adjust the interactions of the stent with biological environments to realize regeneration of the blood vessel is proposed. Nanopaticles on which CD34 antibody and vascular endotheliail cell growth factor (VEGF)immobilized are injected into blood vessel to cupture endotheliail progentor cells in circulate blood and finally settled down on degradable iron stent surface under the effect of magnetic field applied, and differentiated as endotheliail cells induced by VEGF. the stent will treated by surface modification to improve biocompatibility and coated with biodegradable polymer drug eluting coating on the outside surface of the stent so that to prevent restenosis. By means of regulating the interactions of magnetic field, nanopaticles and stent with biological environment to regulate the coagulation reaction, inflammation reaction etc histopathological processes to finally realize fast endothelialization and biodegradation. it will provide the basic knownledge of the new tpye of the stent with regeneration functions.

针对血管支架与组织相互作用过程中创伤、凝血、组织增生反应、内皮化的时序性特点和存在血栓形成、再狭窄等并发症问题，提出主动调控血管支架与生物体相互作用，实现血管组织再生的研究策略。将具有捕获血液中的内皮祖细胞（EPC）功能，及具有诱导EPC向内皮细胞分化的血管内皮细胞生长因子（VEGF）修饰的表面的超顺磁氧化铁纳米粒子注入血管，在循环血液中与EPC结合，通过磁场介导实现EPC、VEGF与磁响应的可降解铁血管支架的靶向结合，诱导EPC向内皮细胞分化, 通过干细胞"归巢"和分化诱导的调控，实现快速内皮化；同时在支架血液接触表面进行表面改性，在与血管组织接触面进行抗增生设计，调控凝血反应、炎症反应等组织修复过程的组织病理变化。最后，随着支架降解,完成天然生理功能的血管组织和血流动力学的重建，通过对外场、纳米物质、支架材料对生物体环境相互作用的研究与调控，为发展出新的具有再生功能的血管支架奠定基础

冠心病患者血管病灶部位缺乏完整的血管内膜组织，导致炎症、增生、血栓从而导致心肌梗死。用于冠心病治疗的血管支架介入后实现完整的内膜化是降低临床并发症（再狭窄与血栓形成）的关键措施。本项目研究了负载磁性纳米粒子的内皮祖细胞在磁场作用下归巢到血管支架表面，以实现内膜修复的技术。通过对磁性纳米粒子表面修饰，使其带有可以特异性捕获内皮祖细胞的功能分子，注入血管内使其与内皮祖细胞靶向结合而成为可带磁性的细胞，使用纳米粒子的临界浓度和安全剂量为100 ug/mL。在血管病变部位植入铁基血管支架，在磁场强度250mT外磁场引导下，带磁性的内皮祖细胞将定向吸引到具有磁性的血管支架表面，从而促进血管支架表面快速内膜化。