An in vitro microfluidic model of the human cardiovascular system for use in pharmaceutical screening applications

MPS World Summit 2025 -- Cardiovascular disease is the leading cause of death worldwide; however, no regulatory in vitro assays are currently available to predict drug/chemical-linked effects on atherosclerosis (an inflammatory process involving a series of progressive cellular events, including monocyte adhesion to the luminal endothelial surface). We have developed an in vitro cardiovascular adhesion assay using commercially available BioFlux™ microfluidic technology to model monocyte adhesion to primary human aortic endothelial cells (HAECs), mimicking an important early stage of atherosclerosis to predict in vivo inflammatory outcomes. We validated the approach using a panel of 20 blinded pharmaceutical and reference compounds. Monocyte adhesion to HAECs was evaluated and mechanistically linked to modulation of cytokine release in response to known inflammatory mediators. This work demonstrates an in vitro endpoint for screening and preclinical assessment as a predictor of atherosclerotic risk. Using this technology, we have completed validation of an in vitro assay with physiological relevance that creates a bridge between in vitro and in vivo experiments for the screening of pharmaceutical compounds.