Ultra-thin and ultra-porous nanofiber networks as a basement-membrane mimic
Ultra-thin and ultra-porous nanofiber networks as a basement-membrane mimic
复制标题
DOI：
10.1039/d3lc00304c
复制
发表时间：
2023-09-19
期刊：
影响因子：
6.1
通讯作者：
Davalos，Rafael V.
中科院分区：
文献类型：
--
作者：
Graybill，Philip M.;Jacobs，Edward J.;Davalos，Rafael V.
目前用于体外模拟内皮和上皮屏障的基底膜（BM）模拟物不能忠实地概括关键的体内生理特性，如BM厚度、孔隙率、刚度和纤维组成。在这里，我们使用精确排列的纳米纤维网络来形成超薄（1.3 μm厚）和超多孔（1.90%）BM模拟物，用于血脑屏障建模。我们发现，这些血管内皮细胞网络使内皮细胞单层和周细胞之间的密切接触，跨膜，这是已知的调节屏障的紧密性。细胞骨架染色和跨内皮电阻（TEER）的测量揭示了微流控装置和transwell插入物内集成的生物膜上的屏障形成。此外，显著更高的TEER值表明在超薄隔膜上形成的共培养物的生物学益处。我们的BM模拟物克服了形成接近并促进细胞-细胞接触的共培养物的关键技术挑战，同时仍被限制在各自的侧面。我们预计，我们的神经网络将在药物发现、细胞迁移和屏障功能障碍研究中找到应用。
Current basement membrane (BM) mimics used for modeling endothelial and epithelial barriers in vitro do not faithfully recapitulate key in vivo physiological properties such as BM thickness, porosity, stiffness, and fibrous composition. Here, we use networks of precisely arranged nanofibers to form ultra-thin (∼3 μm thick) and ultra-porous (∼90%) BM mimics for blood–brain barrier modeling. We show that these nanofiber networks enable close contact between endothelial monolayers and pericytes across the membrane, which are known to regulate barrier tightness. Cytoskeletal staining and transendothelial electrical resistance (TEER) measurements reveal barrier formation on nanofiber membranes integrated within microfluidic devices and transwell inserts. Further, significantly higher TEER values indicate a biological benefit for co-cultures formed on the ultra-thin nanofiber membranes. Our BM mimic overcomes critical technological challenges in forming co-cultures that are in proximity and facilitate cell–cell contact, while still being constrained to their respective sides. We anticipate that our nanofiber networks will find applications in drug discovery, cell migration, and barrier dysfunction studies.