Advances in microfluidic endothelium-on-chip for assessing endothelial function

Vascular interventions can damage the endothelial glycocalyx and disrupt endothelial junction proteins, potentially leading to thrombosis, increased vascular permeability and the transmigration of leukocytes and lipoproteins. Drug-coated endovascular implants are typically evaluated in animal models; however, animals often exhibit exaggerated hyperproliferative responses to vascular injury and more rapid endothelial regeneration than humans. As a result, they may not accurately predict the risk of late vascular complications arising from delayed or incomplete endothelial healing. The development of advanced in vitro systems that incorporate human-derived cells, replicate physiologically relevant blood-flow patterns, and enable intercellular crosstalk could provide a valuable platform for assessing endothelial function. Microfluidic platforms serve as the basis of physiologically relevant in vitro vascular microphysiological systems that recapitulate key aspects of the in vivo vascular environment. Integration of these platforms with functionalized endothelium-on-chip technology creates biologically relevant vascular models, which could provide critical information to bridge data gaps from animal studies. This review highlights recent advances in microfluidic endothelium-on-chip platforms incorporating human-derived cells and discusses their potential applications for evaluating the effects of drug-coated endovascular biomaterial implants on endothelial function and risk assessments of vascular hyperpermeability and thrombogenesis during the early stages of product development.