Microfluidic artery-on-a-chip model with unidirectional gravity-driven flow for high-throughput applications

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide, with a noticeable decline in the approval of new therapeutic interventions. Currently, there is no gold standard for developing new therapies for CVDs, and preclinical models do not translate to clinical efficacy. Therefore, there is an urgent need for in vitro models that more accurately mimic human disease processes. Here we describe a model of the artery consisting of monocultures of human coronary artery endothelial cells (HCAECs) or cocultures of HCAECs with human coronary artery smooth muscle cells (HCASMCs). The model was established in the OrganoPlate® 2-lane-48 UF, a novel microfluidic device, comprised of a microtiter plate footprint with 48 chips. Fluid is circulated in a unidirectional manner by interval rocking. The creation of an air–liquid interface at the inlets at a given inclination is used to select flow paths and establish flow in one direction only, whilst capillary forces ensure the channel remains filled with fluid. We investigated the impact of unidirectional or bidirectional flow conditions. Under unidirectional flow, endothelial cells aligned with the flow direction, decreased fibronectin deposition, and smooth muscle cells presented a non-contractile phenotype, emulating the characteristics of healthy arteries. Contrarily, bidirectional flow mimicked features of early endothelial dysfunction, such as contractile morphology of vessels and increased fibronectin secretion, ICAM-1 staining, and lipid deposits. Vascular inflammation could be induced by the addition of TNFα and IL-1β in both flow conditions. Overall, the OrganoPlate® 2-lane-48 UF is a powerful platform providing both throughput and improved flow control, for creating more physiological models. Its ability to replicate key features of a healthy and diseased artery, its potential use in drug screening, and its compatibility with lab automation make it an invaluable tool for researchers aiming for more accurate and efficient therapeutic development in CVD.