Key Laboratory of Biorheological Science and Technology, Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Chongqing University, Chongqing, 400030, People's Republic of China.
Nanoscience Centre, Department of Engineering, University of Cambridge, Cambridge, CB3 0FF, UK.
J Biomed Mater Res B Appl Biomater. 2020 Jan;108(1):94-103. doi: 10.1002/jbm.b.34369. Epub 2019 Apr 11.
Improving the surface properties of vascular stents to accelerate endothelialization in vivo could play an important role in minimizing the risk of late thrombosis. We previously showed that mussel adhesive protein fused with VE-cadherin extracellular domain (VE-M) specifically triggered endothelial cell adhesion in vitro. In this study, using stent implants coated with VE-M, we evaluated the clinical applicability of VE-M in endothelialization recovery in vivo. First, we explored the effect of VE-M on hemocompatibility and tight junctions between endothelial cells (ECs) in vitro. VE-M significantly inhibited platelet adhesion and promoted EC proliferation. Furthermore, VE-M drastically increased the centralization of F-actin in human umbilical vein endothelial cells (HUVECs) along the cell contacts, reduced fluorescein isothiocyanate (FITC)-dextran transport across the HUVECs, and elevated expression levels of tight junction proteins (TJPs) in ECs. We then evaluated the effect of VE-M on endothelialization recovery in vivo through implantation of vascular stents. At 1 day after implantation, stents coated with VE-M recruited more endothelial progenitor cells (EPCs) than bare stents. At 7 days after implantation, VE-M stents had a greater coverage of ECs than bare stents. At 1 month after implantation, ECs on VE-M stents were appropriately elliptical in morphology and closely resembled physiological morphology. Hematoxylin-eosin (HE) staining revealed little in-stent neointima formation on VE-M stents, and SEM images revealed that smooth endothelium had formed on VE-M stents without adherent platelets. Taken together, these findings indicate that VE-M accelerates in vivo endothelialization of vascular stents via recruitment of EPCs and promotes endothelium formation and could be explored as a potential bioactive coating for vascular implant. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:94-103, 2020.
提高血管支架的表面性能，以加速体内的内皮化，这在最大限度地降低迟发性血栓形成的风险方面可能发挥重要作用。我们之前已经表明，与 VE-钙黏蛋白细胞外域（VE-M）融合的贻贝类黏蛋白可特异性地触发体外内皮细胞黏附。在这项研究中，我们使用涂覆有 VE-M 的支架植入物，评估了 VE-M 在体内内皮化恢复中的临床适用性。首先，我们在体外探索了 VE-M 对血液相容性和内皮细胞（ECs）之间紧密连接的影响。VE-M 显著抑制血小板黏附，并促进 EC 增殖。此外，VE-M 极大地增加了人脐静脉内皮细胞（HUVECs）中 F-肌动蛋白的中心化，沿细胞接触减少 FITC-葡聚糖穿过 HUVECs 的转运，并提高了 EC 中紧密连接蛋白（TJPs）的表达水平。然后，我们通过植入血管支架来评估 VE-M 对体内内皮化恢复的影响。植入后 1 天，涂覆有 VE-M 的支架比裸支架招募了更多的内皮祖细胞（EPCs）。植入后 7 天，VE-M 支架的 EC 覆盖面积大于裸支架。植入后 1 个月，VE-M 支架上的 EC 呈适当的椭圆形，形态与生理形态非常相似。苏木精-伊红（HE）染色显示 VE-M 支架上的支架内新生内膜形成较少，SEM 图像显示 VE-M 支架上已形成光滑的内皮，没有黏附的血小板。综上所述，这些发现表明，VE-M 通过募集 EPCs 加速血管支架的体内内皮化，并促进内皮形成，可作为血管植入物的潜在生物活性涂层进行探索。 © 2019 Wiley 期刊，公司。J 生物医学材料研究 B：应用生物材料 108B：94-103，2020。
