Ultrathin Dual-Scale Nano- and Microporous Membranes for Vascular Transmigration Models.
Ultrathin Dual-Scale Nano- and Microporous Membranes for Vascular Transmigration Models.
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DOI：
10.1002/smll.201804111
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发表时间：
2019-01
期刊：
影响因子：
13.3
通讯作者：
Alec T. Salminen;Jingkai Zhang;G. Madejski;T. Khire;R. Waugh;J. McGrath;T. Gaborski
中科院分区：
文献类型：
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作者：
Alec T. Salminen;Jingkai Zhang;G. Madejski;T. Khire;R. Waugh;J. McGrath;T. Gaborski
穿过微血管内皮的选择性细胞迁移调节先天性和适应性免疫反应、干细胞定位和癌细胞转移。将传统微孔膜整合到微流体血管模型中可以快速测定迁移事件，但存在细胞渗透性基底膜复制不良的问题。这些系统中当前的微孔膜在微孔之间具有大的无孔区域，抑制基底外侧表面上的细胞通讯和营养物质交换，从而降低其生理相关性。在这里，提出了使用 100 nm 厚的连续纳米多孔氮化硅膜作为 3 µm 孔的光刻制造的基础基底，从而产生高孔隙度（约 30%）、双尺度纳米和微孔膜，用于改进的血管迁移模型。使用精密激光刻录机对超薄膜进行图案化，以实现经济高效、快速的微孔设计迭代。光学透明的双尺度膜能够完整观察各种孔隙密度的白细胞排出情况。发现每个细胞的最大密度为约 14 个微孔，超过该密度，细胞-基质相互作用就会受到损害，导致流动下内皮细胞损失。添加腔内细胞外基质可以挽救细胞粘附，从而可以在近 30% 的连续多孔基质上创建剪切引发的内皮屏障模型。
Selective cellular transmigration across the microvascular endothelium regulates innate and adaptive immune responses, stem cell localization, and cancer cell metastasis. Integration of traditional microporous membranes into microfluidic vascular models permits the rapid assay of transmigration events but suffers from poor reproduction of the cell permeable basement membrane. Current microporous membranes in these systems have large nonporous regions between micropores that inhibit cell communication and nutrient exchange on the basolateral surface reducing their physiological relevance. Here, the use of 100 nm thick continuously nanoporous silicon nitride membranes as a base substrate for lithographic fabrication of 3 µm pores is presented, resulting in a highly porous (≈30%), dual-scale nano- and microporous membrane for use in an improved vascular transmigration model. Ultrathin membranes are patterned using a precision laser writer for cost-effective, rapid micropore design iterations. The optically transparent dual-scale membranes enable complete observation of leukocyte egress across a variety of pore densities. A maximal density of ≈14 micropores per cell is discovered beyond which cell-substrate interactions are compromised giving rise to endothelial cell losses under flow. Addition of a subluminal extracellular matrix rescues cell adhesion, allowing for the creation of shear-primed endothelial barrier models on nearly 30% continuously porous substrates.