A Flow-Regulated Endothelial-Smooth Muscle Co-culture Vessel-on-a-Chip for Modeling Vascular Inflammation and Drug Evaluation

Abstract

Vascular inflammation drives vessel injury and cardiovascular disease progression; however, current in vitro models poorly reproduce vascular wall organization under flow. Here, we developed a flow-controlled vessel-on-a-chip (VOC) platform using a tunable collagen matrix, sequential seeding of primary human coronary artery smooth muscle cells (HCASMCs) and human umbilical vein endothelial cells (HUVECs), and an intervening fibronectin layer to establish a biomimetic vascular structure. TNF-α stimulation induced key features of vascular inflammation, including increased VCAM-1, ICAM-1, E-selectin, MCP-1, and IL-6, together with early phenotypic remodeling of HCASMCs. Lovastatin (LS) attenuated these responses, reducing adhesion molecule expression by approximately 60–80%, decreasing cytokine secretion, and helping preserve layered vascular organization. Overall, this VOC provides a controlled and biomimetic platform for studying multilayered vascular inflammation and evaluating cardiovascular therapeutics, with potential applications in mechanistic research and preclinical drug screening.