支架材料表面免疫调控涂层的构建及免疫调控机制研究

Blood vessel abnormal remodeling caused by vascular inflammatory disorders after stents implantation is the critical factors resulting in the clinical complications. Inflammation is closely related to the vascular remodeling, and it is the necessary process of vascular repair. This project proposes one novel immunoregulatory stent development strategy based on the relationship between immune response and vascular repair. In this project, the angiogenin 1(Ang1) which could regulate inflammation and promote vascular remodeling will be introduced on the stent materials surface. In addition, two different Ang 1 modified surfaces will design to mimic the two states of Ang 1 in vivo, free state and binding state. The effect on inflammatory cells behavior and the regulation mechanism of the Ang1 modified surfaces will be researched. Meanwhile，one microfluidic chip platform will be designed and built for multicellular immune responses evaluation. The regulatory capacity and the regulatory mechanism of the immune cells, which growth on the Ang1 modified surfaces, for the vascular cells will also be evaluated, and it will be looking for the key regulators. The regulating ability of the modified stents on vascular remodeling will be evaluated in vivo, and the regulation mechanism will also be studied. This project will complete the molecular mechanisms of the Ang1-Tie2 signal system regulating vascular immune responses and repair. This project will provide theoretical basis for the novel immunoregulatory stent development strategy, and it also could enrich and complete the inflammatory mechanisms of vascular remodeling process after stents implantation.

血管支架植入后紊乱的炎症应答导致的血管重构异常，是并发症发生的关键因素。炎症应答与血管重构密切相关，是血管修复的必经过程。本项目拟以免疫应答与血管修复之间的联系为切入点，提出一种新颖的免疫调控血管支架开发策略，通过调控血管的炎症应答，快速实现血管重构。本项目将具有调控炎症应答和血管重构的血管生成素1（Ang1）引入支架材料表面，模拟其在体内两种状态构建Ang1固定仿生和Ang1释放仿生表面，研究其对炎症细胞免疫应答的影响和作用机制。建立多细胞免疫应答微流控平台，研究改性表面炎症细胞调控血管细胞生长的能力和调控机制，寻找关键调控因子。体内评价改性支架通过免疫应答调控血管重构的可行性和相关机理。同时完善Ang1-Tie2信号系统对免疫应答和血管重构的调控机制。本项目将为新型免疫调控血管支架开发策略提供理论基础，补充丰富支架植入后血管重建过程中的炎症机制。

动脉粥样硬化是冠心病发生的基础疾病，而针对于严重的冠心病，PCI是目前临床上应用最广泛的治疗手段。PCI术后，血管支架植入病变血管，病变血管组织中紊乱的炎症应答导致血管重构异常，是支架术后并发症发生的关键因素。炎症应答与血管重构密切相关，是血管修复的必经过程。本项目以免疫应答与血管修复之间的联系为切入点，提出一种新颖的免疫调控血管支架开发策略。本项目将具有调控炎症应答和血管重构的血管生成素1（ANG1）引入支架材料表面，模拟其在体内两种状态构建ANG1固定仿生和ANG1多肽仿生表面，研究其对炎症细胞免疫应答的影响和作用机制。体内评价改性支架通过免疫应答调控血管重构的可行性和相关机理。项目还采用没食子酸和己二胺为原料，聚合沉积了一种酚胺交联涂层，通过调控涂层表面的酚羟基、氨基以及醌基等化学活性冠能团，实现了对血管细胞炎症应答的调控，并且通过分子生物学技术初步揭示了酚胺交联涂层通过NF-KB核转录因子调理巨噬细胞以及血管细胞炎症应答的分子机制。本项目将为新型免疫调控血管支架开发策略提供理论基础，补充丰富支架植入后血管重建过程中的炎症机制。