02678nas a2200241 4500000000100000008004100001260001500042653002700057653003100084653003600115653002500151653002500176653002600201100002600227700001500253700001700268245012100285856007200406300001100478490000800489520192500497022001402422 2025 d c2025-09-0110aCardiac drug discovery10aCardiac fibrosis-on-a-chip10aCardiovascular disease modeling10aMicrofluidic devices10aThrombosis-on-a-chip10aVessel-on-chip models1 aVasudeva Reddy Netala1 aTianyu Hou1 aZhijun Zhang00aMicrofluidics in biomedicine: Heart-on-chip platforms for cardiovascular disease modeling and therapeutic innovation uhttps://www.sciencedirect.com/science/article/pii/S177322472500574X a1071710 v1113 aThis study provides a comprehensive overview of microfluidic devices and their transformative potential in biomedicine, with particular emphasis on cardiovascular applications where traditional models often fail to replicate complex physiological conditions. By examining fabrication methods and diverse applications across diagnostics, drug development, cancer research, and tissue engineering, we demonstrate how microfluidics enables precise recreation of critical cardiac parameters including shear stress, oxygen gradients, and endothelial cell behaviour - capabilities that are revolutionizing cardiovascular disease modeling. The review analyzes major advances in microfluidic platforms, beginning with vessel-on-a-chip systems that accurately simulate vascular physiology and atherosclerosis progression. We then detail heart-on-a-chip devices designed for electrophysiological studies and arrhythmia modeling, which have significantly enhanced cardiac drug discovery by better replicating in vivo conditions. The discussion extends to valve-on-a-chip models for studying heart valve disorders, along with specialized platforms for investigating fibrosis, hypertrophy, and thrombosis through controlled recreation of blood flow dynamics and clot formation processes. While these technologies show remarkable promise, we identify key challenges including the complexity of replicating complete hemodynamic conditions, the need for standardized fabrication protocols, and current cost barriers. The study concludes by highlighting how emerging technologies - particularly 3D printing, nanotechnology, and AI integration - are poised to address these limitations. Most importantly, we emphasize how patient-specific microfluidic approaches are paving the way for truly personalized cardiac care solutions, bridging the persistent gap between laboratory research and clinical applications in cardiovascular medicine. a1773-2247