A Flow-Regulated Endothelial-Smooth Muscle Co-culture Vessel-on-a-Chip for Modeling Vascular Inflammation and Drug Evaluation
Yanke Wang, Changmin Shao, Xuting Zhang, Andong Liu, Jing Lin, Xing Rong, Chao Niu, Chang Jia, Jia Sun, Hao Zhang, Weiting Yu, Rongzhou Wu, Peiyu Chen, Fangfu Ye, Maoping ChuAbstract
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.