Microfluidic organ-on-a-chip for modeling coronary artery disease: Recent applications, limitations and potential

Coronary artery disease (CAD) encompasses a spectrum of pathologies driven by atherosclerosis, trauma, inflammation, or other etiologies that compromise coronary morphology and function, ultimately leading to myocardial ischemia and infarction. While organ-on-a-chip (OOC) technology has emerged as a transformative tool for cardiovascular research, existing reviews have consistently marginalized coronary-specific pathophysiology, treating it merely as a subset of generic vascular biology. This review presents the first dedicated, critical analysis of microphysiological system (MPS) engineered explicitly as CAD-on-a-chip platform. We deliberately depart from generalized vascular models by exclusively evaluating systems designed to recapitulate the unique coronary-specific hallmarks: distinct geometric constraints, pro-inflammatory microenvironments, and dynamic hemodynamic shear stress profiles inherent to human coronary arteries. Following a concise introduction to OOC fabrication materials and techniques, we systematically present vessel-on-a-chip (VOC) models derived from diverse cellular sources. We then emphasize the biomedical applications of VOC in CAD field and analyze key CAD-specific pathological processes, including flow-mediated endothelial dysfunction, atherosclerotic plaque formation, plaque rupture-induced atherothrombosis, and coronary artery aneurysm. Finally, we critically discuss current limitations and outline future directions of OOC technology in CAD research. This review by focusing on the specific pathological features of CAD and the requirements for in vitro modeling, aim to establish a targeted knowledge framework to promote the clinical transformation of VOC technology in CAD diagnosis and treatment.