Recent vascular mechanobiology studies find that endothelial cells (ECs) convert multiple mechanical forces into functional responses in a nonadditive way, suggesting that signaling pathways such as those regulating cytoskeleton may be shared among the processes of converting individual forces. However, previous in vitro EC-culture platforms are inherent with extraneous mechanical components, which may saturate or insufficiently activate the shared signaling pathways and accordingly, may misguide EC mechanobiological responses being investigated. Here, a more physiologically relevant model artery is reported that accurately reproduces most of the mechanical forces found in vivo, which can be individually varied in any combination to pathological levels to achieve diseased states. Arterial geometries of normal and diseased states are also realized. By mimicking mechanical microenvironments of early-stage atherosclerosis, it is demonstrated that the elevated levels of the different types of stress experienced by ECs strongly correlate with the disruption of barrier integrity, suggesting that boundaries of an initial lesion could be sites for efficient disease progression.
Keywords: artery models; barrier disruption; endothelial cells; hydrogels; microfluidics.
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