R&D Department, Japan Medical Device Startup Incubation Program, 3-7-2 Nihonbashihon-cho, Chuo-ku, Tokyo, 103-0023, Japan.
R&D Department, N.B. Medical Inc., 3-7-2 Nihonbashihon-cho, Chuo-ku, Tokyo, 103-0023, Japan.
Sci Rep. 2024 Jul 10;14(1):15178. doi: 10.1038/s41598-024-65832-5.
The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.
血管内治疗的发展,特别是在颅内动脉瘤治疗领域,取得了显著的进步,其特点是各种支架的发展。然而,与血栓形成或下游栓塞相关的缺血性并发症给这些支架的更广泛临床应用带来了挑战。尽管表面改性技术取得了进步,但仍没有一种理想的涂层能够满足所有期望的要求,包括抗血栓形成和快速内皮化。为了解决这些问题,我们研究了一种新的涂层,该涂层由具有抗血栓形成和细胞黏附特性的 3-氨基丙基三乙氧基硅烷(APTES)组成。我们使用体外血液回路模型评估了涂层的抗血栓形成特性,通过评估血小板计数和凝血酶-抗凝血酶(TAT)复合物的水平,并通过扫描电子显微镜(SEM)研究表面血栓形成。然后,我们评估了金属表面上的内皮细胞黏附。体外血液测试表明,与裸支架相比,该涂层可显著抑制血小板减少和血栓形成;更多的人血清白蛋白自发黏附在涂层表面,以阻止血液中的血栓形成激活。细胞黏附测试还表明,与裸支架或涂有抗污磷脂聚合物的支架相比,黏附在 APTES 涂层表面上的细胞数量显著增加。最后,我们通过将涂层支架植入小型猪的胸内动脉和咽升动脉,进行了体内安全性测试,然后通过血管造影术在 1 周内评估了动脉的健康状况和血管通畅性。我们发现,在 APTES 涂层支架组中,对猪没有不良影响,并且其血管的血管腔保持良好。因此,我们的新型涂层具有高抗血栓形成和细胞黏附特性,满足可植入支架的要求。