A high-throughput microtissue platform to probe endothelial function in vitro

Integrative Biology : Quantitative Biosciences From Nano to Macro
Alexandra L CramptonDavid K Wood

Abstract

A critical role of vascular endothelium is as a semi-permeable barrier, dynamically regulating the flux of solutes between blood and the surrounding tissue. Existing platforms that quantify endothelial function in vitro are either significantly throughput limited or overlook physiologically relevant extracellular matrix (ECM) interactions and thus do not recapitulate in vivo function. Leveraging droplet microfluidics, we developed a scalable platform to measure endothelial function in nanoliter-volume, ECM-based microtissues. In this study, we describe our high-throughput method for fabricating endothelial-coated collagen microtissues that incorporate physiologically relevant cell-ECM interactions. We showed that the endothelial cells had characteristic morphology, expressed tight junction proteins, and remodeled the ECM via compaction and deposition of basement membrane. We also measured macromolecular permeability using two optical modalities, and found the cell layers: (1) had permeability values comparable to in vivo measurements and (2) were responsive to physiologically-relevant modulators of endothelial permeability (TNF-α and TGF-β). This is the first demonstration, to the authors' knowledge, of high-throughput assessme...Continue Reading

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Citations

Nov 16, 2018·Tissue Engineering. Part C, Methods·Katherine A CumminsDavid K Wood
Mar 16, 2021·Acta Biomaterialia·Mackenzie L Grubb, Steven R Caliari
May 29, 2021·Journal of Cellular Physiology·Kyoung Moo ChoiDaniel J Tschumperlin
Jun 18, 2021·Seminars in Liver Disease·David A Kukla, Salman R Khetani

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