Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarang-ro 14-gil 5, Seoungbuk-gu, Seoul 02792, Republic of Korea.
Division of Bio-Medical Science & Technology, University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea.
ACS Appl Bio Mater. 2021 Aug 16;4(8):6381-6393. doi: 10.1021/acsabm.1c00592. Epub 2021 Jul 12.
Engineering an endothelium-mimetic surface has been one of long-lasting topics to develop ideal cardiovascular devices. The aim of the study was to investigate the potential use of a model of lipid bilayers that not only come from membranes extracted from endothelial cells (ECs) but also embedded with a type of organoselenium lipid enabling it to catalyze the generation of nitric oxide (NO). Herein, the titanium-cloaking in lipid bilayers extracted from ECs was prepared to propose a promising idea for the development of endovascular implants. For this purpose, we synthesized and characterized a lipidic molecule containing selenium and verified enough catalytic activity for the NO generation in the presence of S-nitrosothiols (RSNO) as endogenous NO precursors. We demonstrated the fabrication process of tethered lipid bilayers, from membrane extraction to vesicle fusion, and validated the successful formation of the layer and the catalyst insertion. The resulting bilayer presented endothelium-similar properties including the NO generation and cellular interactions. The catalyst inserted into the bilayer provided an unexampled result in the release period and kinetics of NO, likely similar to the native endothelial system. Using three different cells including EC, smooth muscle cell (SMC), and macrophage, it was demonstrated that the membrane responds selectively to each cell in the manner of promotive, suppressive, and nonimmunoreactive, respectively. Taken together, the fundamental study on obtained results not only provides understanding of the kinetics of designed NO catalyst and cellular interactions of reassembled membranes but also suggests very useful data on rational design and development of many vascular implantable devices, even expandable toward to nonvascular biointerfacing devices.
构建内皮细胞仿生表面一直是开发理想心血管设备的长期课题之一。本研究旨在探讨一种脂质双层模型的潜在用途，该模型不仅来源于内皮细胞（EC）提取的膜，而且还嵌入了一种有机硒脂质，使其能够催化一氧化氮（NO）的生成。在此，我们制备了来源于 EC 的脂质双层中的钛包被，以提出一种有前途的用于开发血管内植入物的想法。为此，我们合成并表征了一种含有硒的脂质分子，并验证了其在存在 S-亚硝基硫醇（RSNO）作为内源性 NO 前体的情况下生成 NO 的足够催化活性。我们展示了连接脂质双层的制造过程，从膜提取到囊泡融合，并验证了层和催化剂插入的成功形成。所得双层具有类似于内皮细胞的特性，包括 NO 的生成和细胞相互作用。插入双层的催化剂提供了前所未有的 NO 释放时间和动力学结果，可能类似于天然内皮系统。使用包括 EC、平滑肌细胞（SMC）和巨噬细胞在内的三种不同细胞，证明了该膜以促进、抑制和非免疫反应的方式分别对每种细胞具有选择性响应。总之，获得的结果的基础研究不仅提供了对设计的 NO 催化剂的动力学和重组膜的细胞相互作用的理解，而且还为许多血管植入设备的合理设计和开发提供了非常有用的数据，甚至可以扩展到非血管生物界面设备。
