炎症条件下抗凝血医用高分子表面构建及其抗凝血机理研究

植介入医疗器械引发的血栓是造成患者发病率、死亡率和治疗成本迅速增加的主要原因，而炎症常常诱发材料表面形成血栓。因而构建炎症环境下抗血栓材料，并揭示其抗凝血原理十分重要。本项目基于炎症产生过量的反应活性氧簇（ROS）和血小板是炎症和血栓内在结合要素的事实，拟在聚氨酯和硅橡胶基底上构建三种抗凝血表面，即，亲水型、亲水释药型和亲水的ROS反应释药型表面，通过调控激活的血小板，同时抑制炎症和凝血，并维持机体的正常功能。首先，在基底材料表面接枝亲水性聚合物；其次，采用静电纺丝方法，在基底材料上制备三种抗凝血表面，研究表面与血小板的作用规律；最后，研究表面在炎症条件下体内、外抗凝血行为，揭示炎症条件下的抗凝血机理，并制备长效、安全的抗凝血材料。本项目的实施，不仅阐明材料表面在炎症环境下的抗凝血机理，而且将为解决介入类医疗器械应用中的血栓问题提供理论指导和技术支持。

Recently, thrombosis induced by blood-contacting devices has led to dramatic increases in morbidity, mortality and increased health care costs. Device-induced thrombosis was complicated with inflammation, so it was necessary to clarify the anti-thrombotic mechanism under the inflammation in the blood. Based on the facts that inflammation induces the excessive reactive oxygen species (ROS) and that platelets are at the interface of thrombosis and inflammation, we will prepare three model surfaces on polyurethane or silicon rubber to obtain hemocompatible surface through platelet pathway in this project. We will firstly graft hydrophilic monomers on substrates to render surface hemocompatible. Secondly, three model surfaces composed of hydrophilic micro/nanofibers, drug-loaded micro/nanofibers and drug-loaded micro/nanofibers with ROS-responsiveness will be fabricated by electrospinning. Thirdly, we will investigate interactions between micro/nanofibers and platelets under inflammatory condition in the blood in vivo and in vitro. Finally, we will prepare long-term anti-thrombotic biomaterials after establishment of anti-thrombotic mechanism of biomaterials surface. The project will not only clarify the anti-thrombotic mechanism of biomaterials surface with inflammation, but pave the new way to design implant and interventional biomedical devices in pathological environment.