Disturbed Flow Promotes Atherosclerotic Plaque Development in Human 3D Tissue-Engineered Vessels On-a-Chip

Atherosclerosis is an arterial disease characterized by intravascular plaques. Disease hallmarks are vessel stenosis and hyperplasia, eventually escalating into plaque rupture and acute clinical presentations. Innate immune cells and local flow variations are core players in the pathology, but their combined effects have never been investigated before in human vessel replicas due to the lack of modeling systems with adequate degree of complexity. Here, we combined computational fluid dynamics and tissue-engineering to achieve full human atherosclerotic plaque development on-a-chip. Our model incorporates induced pluripotent stem cell-derived populations into small-caliber arteries that are cultured in atheroprone conditions. Using machine-learning-aided immunophenotyping, as well as molecular and nanoprobe-based tensile analyses, we found that immune cells and extracellular matrix were comparable between in vitro and ex vivo human plaques. Our results provide further insights into the relation between disturbed flow dynamics and vascular inflammation, introducing a versatile, scalable modeling tool to study atherosclerosis onset and progression.