关键词: Anti-thrombotic coating Endothelialization Intracranial aneurysm Neurovascular stent Silane coupling Surface modification

Mesh : Silanes / chemistry pharmacology Animals Cell Adhesion / drug effects Humans Stents / adverse effects Swine Coated Materials, Biocompatible / chemistry pharmacology Propylamines / pharmacology chemistry Adsorption Thrombosis / prevention & control Fibrinolytic Agents / pharmacology chemistry Blood Platelets / drug effects metabolism Human Umbilical Vein Endothelial Cells / drug effects Endothelial Cells / drug effects metabolism

来  源:   DOI:10.1038/s41598-024-65832-5   PDF(Pubmed)

Abstract:
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.
摘要:
血管内治疗的发展,特别是在颅内动脉瘤治疗领域,已经真正引人注目,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对此类支架的更广泛临床应用提出了挑战.尽管表面改性技术取得了进步,满足所有期望要求的理想涂层,包括抗血栓形成和迅速内皮化,尚未可用。为了解决这些问题,我们研究了一种包含3-氨基丙基三乙氧基硅烷(APTES)的新型涂层,该涂层具有抗血栓形成和细胞粘附特性。我们使用体外血液循环模型通过评估血小板计数和凝血酶-抗凝血酶(TAT)复合物的水平来评估涂层的抗血栓形成特性,并使用扫描电子显微镜(SEM)研究表面上的血栓形成。然后我们评估了内皮细胞在金属表面上的粘附。体外血液测试显示,与裸支架相比,涂层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粘附在涂层表面以阻断血液中的血栓形成活化。细胞粘附测试还表明,与粘附到裸支架或涂覆有防污磷脂聚合物的支架的数量相比,粘附到APTES涂覆表面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,随后在1周内通过血管造影评估动脉的健康状况和血管通畅性。我们发现,在使用APTES涂层支架的组中,对猪没有不利影响,并且其血管的管腔保持得很好。因此,我们的新涂层具有高抗血栓形成和细胞粘附性能,满足可植入支架的要求。
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