NEURI Center, Hôpital Bicêtre, APHP-Université Paris Sud, Kremlin-Bicêtre, France (J. Cortese, J. Caroff, L.S.).
Laboratory for Vascular Translational Science, Université de Paris, INSERM U1148, France (J. Cortese, C.R., G.E., C.C., J.M., A.N., J.-B.M., G.C.).
Stroke. 2021 Jan;52(2):677-686. doi: 10.1161/STROKEAHA.120.030624. Epub 2021 Jan 8.
Beyond aneurysmal occlusion, metallic flow diverters (FDs) can induce an adverse endovascular reaction due to the foreignness of metal devices, hampering FD endothelialization across the aneurysm neck, and arterial healing of intracranial aneurysms. Here, we evaluated the potential benefits of an FD coating mimicking CD31, a coreceptor critically involved in endothelial function and endovascular homeostasis, on the endothelialization of FDs implanted in vivo.
Nitinol FD (Silk Vista Baby) and flat disks were dip-coated with a CD31-mimetic peptide via an intermediate layer of polydopamine. Disks were used to assess the reaction of endothelial cells and blood elements in vitro. An aneurysm rabbit model was used to compare in vivo effects on the arterial wall of CD31-mimetic-coated (CD31-mimetic, n=6), polydopamine-coated (polydopamine, n=6), and uncoated FDs (bare, n=5) at 4 weeks post-FD implantation. In addition, long-term safety was assessed at 12 weeks.
In vitro, CD31-mimetic coated disks displayed reduced adhesion of blood elements while favoring endothelial cell attachment and confluence, compared to bare and polydopamine disks. Strikingly, in vivo, the neoarterial wall formed over the CD31-mimetic-FD struts at the aneurysm neck was characteristic of an arterial tunica media, with continuous differentiated endothelium covering a significantly thicker layer of collagen and smooth muscle cells as compared to the controls. The rates of angiographic complete occlusion and covered branch arterial patency were similar in all 3 groups.
CD31-mimetic coating favors the colonization of metallic endovascular devices with endothelial cells displaying a physiological phenotype while preventing the adhesion of platelets and leukocytes. These biological properties lead to a rapid and improved endothelialization of the neoarterial wall at the aneurysm neck. CD31-mimetic coating could therefore represent a valuable strategy for FD biocompatibility improvement and aneurysm healing.
除了动脉瘤闭塞之外，由于金属器械的异物性，金属血流导向装置（FD）可引起不良的血管内反应，阻碍 FD 在动脉瘤颈部的内皮化，以及颅内动脉瘤的动脉愈合。在此，我们评估了模仿 CD31 的 FD 涂层的潜在益处，CD31 是内皮功能和血管内稳态的关键核心受体，可促进体内植入的 FD 的内皮化。
通过聚多巴胺中间层，将尼钛 FD（Silk Vista Baby）和平板圆盘浸涂 CD31 模拟肽。使用圆盘评估内皮细胞和血液成分的体外反应。采用兔动脉瘤模型，比较 CD31 模拟涂层（CD31-mimetic，n=6）、聚多巴胺涂层（polydopamine，n=6）和未涂层 FD（bare，n=5）在 FD 植入后 4 周对动脉壁的体内影响。此外，在 12 周时评估长期安全性。
在体外，与裸盘和聚多巴胺盘相比，CD31 模拟涂层的圆盘显示出血液成分黏附减少，同时有利于内皮细胞附着和融合。引人注目的是，在体内，动脉瘤颈部 FD 支柱上形成的新动脉壁具有动脉中膜的特征，连续分化的内皮细胞覆盖着明显较厚的胶原和平滑肌细胞层，与对照组相比。所有 3 组的血管造影完全闭塞率和覆盖分支动脉通畅率相似。
CD31 模拟涂层有利于内皮细胞的内皮化，使金属血管内装置定植，内皮细胞呈现出生理表型，同时阻止血小板和白细胞的黏附。这些生物学特性导致动脉瘤颈部新动脉壁的快速和改善的内皮化。CD31 模拟涂层因此可能代表了改善 FD 生物相容性和动脉瘤愈合的有价值的策略。
