原位血栓应激性血液相容性材料的构建

材料表面血栓的形成是导致血液接触材料应用失败的主要原因之一。多数研究仅通过在材料中引入抗血栓活性分子赋予材料抗血栓功能，但这些材料却很少能效仿生物系统对特定微环境变化做出应激反应和反馈调节，进而实现功能的自我调控。理想的抗血栓材料应能够启动具有原位血栓应激性的抗血栓功能，且血栓被抑制后能够将该信息反馈给材料使其关闭抗血栓功能。基于该构想，本项目针对血栓形成时伴随凝血酶产生的特征性微环境变化，拟构建凝血酶响应性抗血栓材料，使其在血栓形成并产生凝血酶时释放抗凝血分子和纤溶活性分子，同时启动抑制血栓生成和溶解血栓的双重功能，而当血栓被抑制且凝血酶水平恢复正常时及时关闭该功能。本项目最大的特色在于使材料能够感应血栓生成时的分子微环境变化，同时从分子水平上启动特定的血液功能系统，进而调节微环境中的非正常凝血因子水平直至彻底抑制血栓生成反应。该策略将为抗血栓材料的研究开辟一条全新而更有效的途径。

Surface-induced thrombosis has caused the failure of various blood-contacting material applications. Incorporation of antithrombotic molecules into materials is the main strategy to solve this problem. However, the materials modified in this way can seldom mimic biological systems, following the rule of bio-response and feedback regulation under a certain microenvironmental change, thus achieving self-regulation of biofunctions. Ideal antithrombotic materials should be able to in situ promote antithrombotic function in response to local thrombosis, and to shut off the function when the information of thrombus clearance was fed back. Based on this conception, this project is planned to construct thrombin-responsive materials and surface coatings, since thrombin generation is the characteristic event during thrombus formation. The materials or coatings are designed to initiate both antithrombogenic and thrombolytic functions in response to thrombin generation by releasing anticoagulants and thrombolytic molecules at the same time. Once thrombosis is inhibited along with the disappearance of thrombin, both functions are shut off. The main characteristic of this project is to make materials sensing the microenvironmental change caused by thrombosis, then defensing thrombosis by molecularly activating specific functional blood systems. The abnormal level of coagulation factors will be regulated by these functional systems so that thrombotic reaction is inhibited. This strategy will open up a new and more effective way for antithrombotic modification of blood-contacting materials.