Laboratory for Biomaterials and Bioengineering (CRC-I) Department of Min-Met-Mat Engineering and the CHU de Québec Research Center, Laval University, PLT-1745G, Québec, QC G1V 0A6, Canada.
Laboratory for Vascular Translational Science, Université de Paris, Inserm U1148, 46 rue Henri HUCHARD, Paris 75018, France.
Eur Heart J. 2021 May 7;42(18):1760-1769. doi: 10.1093/eurheartj/ehab027.
The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leukocyte activation but impair endothelialization, delaying effective device integration into arterial walls. Previously, we have shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leukocyte homeostasis and arterial healing. Furthermore, we have shown that a soluble synthetic peptide (known as P8RI) acts like a CD31 agonist. The aim of this study was to evaluate the effect of CD31-mimetic metal stent coating on the in vitro adherence of endothelial cells (ECs) and blood elements and the in vivo strut coverage and neointimal growth.
We produced Cobalt Chromium discs and stents coated with a CD31-mimetic peptide through two procedures, plasma amination or dip-coating, both yielding comparable results. We found that CD31-mimetic discs significantly reduced the extent of primary human coronary artery EC and blood platelet/leukocyte activation in vitro. In vivo, CD31-mimetic stent properties were compared with those of DES and BMS by coronarography and microscopy at 7 and 28 days post-implantation in pig coronary arteries (n = 9 stents/group/timepoint). Seven days post-implantation, only CD31-mimetic struts were fully endothelialized with no activated platelets/leukocytes. At day 28, neointima development over CD31-mimetic stents was significantly reduced compared to BMS, appearing as a normal arterial media with the absence of thrombosis contrary to DES.
CD31-mimetic coating favours vascular homeostasis and arterial wall healing, preventing in-stent stenosis and thrombosis. Hence, such coatings seem to improve the metal stent biocompatibility.
裸金属支架（BMS）的快速内皮化被炎症诱导的新生内膜生长所抵消。药物洗脱支架（DES）可防止白细胞激活，但会损害内皮化，从而延迟器械有效整合到动脉壁中。先前，我们已经表明，血管 CD31 共受体的参与对于内皮细胞和白细胞的稳态以及动脉愈合至关重要。此外，我们已经表明，一种可溶性合成肽（称为 P8RI）的作用类似于 CD31 激动剂。本研究的目的是评估 CD31 模拟金属支架涂层对体外内皮细胞（EC）和血液元素黏附以及体内支架覆盖率和新生内膜生长的影响。
我们通过两种程序（等离子体氨化或浸涂）生产了涂有 CD31 模拟肽的钴铬圆盘和支架，这两种程序都产生了类似的结果。我们发现 CD31 模拟盘在体外显著降低了原代人冠状动脉 EC 和血小板/白细胞的激活程度。在体内，通过血管造影术和显微镜检查将 CD31 模拟支架的特性与 DES 和 BMS 进行了比较，分别在猪冠状动脉植入后 7 天和 28 天（每组/时间点 n=9 个支架）。植入后 7 天，只有 CD31 模拟支架完全内皮化，没有激活的血小板/白细胞。在第 28 天，与 BMS 相比，CD31 模拟支架上的新生内膜发展明显减少，表现为正常的动脉中层，没有血栓形成，而 DES 则相反。
CD31 模拟涂层有利于血管稳态和动脉壁愈合，防止支架内狭窄和血栓形成。因此，这种涂层似乎可以提高金属支架的生物相容性。
