基于定制化抗凝血重组人源化胶原的心血管植入器械仿生涂层研究

心血管植介入器械临床面临一些共性科学挑战，如凝血、炎症、增生及内皮化困难等。本项目源于对人的III型胶原蛋白序列进行筛选，创新性地提出了定制化重组III型人源化胶原蛋白的设计策略，即着眼于同时规避血小板结合位点（GFOGER片段或含O片段）和携带高细胞粘附位点的序列，进而获得兼具抗凝血及高内皮细胞粘附活性的重组III型人源化胶原蛋白。依托仿生学理念，结合表面改性技术，构建了以重组III型人源化胶原蛋白为主体的细胞外基质仿生涂层材料，赋予了心血管植介入材料及器械表面多功能性，发挥抗凝、抗炎、促内皮及调节平滑肌细胞表型等功能。通过系统的体外生物相容性和动物体内植入实验研究，探究该定制化重组III型人源化胶原蛋白涂层用于心血管植介入材料和器械的潜能，并通过涂层在调节新生内膜重构方面的机制研究，为心血管植介入材料及器械的研究提供新的思路和技术储备。

Implantable cardiovascular devices are facing some common scientific challenges in clinical practice, such as coagulation, inflammation, hyperplasia, and difficulties in endothelialization. This project originated from the screening of human type III collagen sequences, and innovatively proposed a design strategy for customized recombinant human type III collagen, that is, focusing on peptide sequence that avoiding platelet binding sites (GFOGER fragments or O-containing fragments) and carrying sequence of high cell adhesion site, following with obtaining of the recombinant human type III collagen with both anticoagulant and high endothelial cell adhesion activity. Based on the concept of biomimetics, combined with surface modification technology, an extracellular matrix-mimetic coating with recombinant human type III collagen was constructed, which endowed the surface of cardiovascular implants with multifunctionality, in terms of anticoagulation, anti-inflammatory, promoting endothelialization and regulating smooth muscle cell phenotype. Through the systematic in vitro biocompatibility and in vivo implantation experiments, the potential of the tailored recombinant human type III collagen coating for cardiovascular implants was demonstrated. Investigation of the mechanism of regulating the neointima reconstruction process by the coating provides new ideas and technical reserves for implantable cardiovascular materials/devices.