Heart-on-Chip for Combined Cellular Dynamics Measurements and Computational Modeling Towards Clinical Applications

Organ-on-chip or micro-engineered three-dimensional cellular or tissue models are increasingly implemented in the study of cardiovascular pathophysiology as alternatives to traditional in vitro cell culture. Drug induced cardiotoxicity is a key issue in drug development pipelines, but the current in vitro and in vivo studies suffer from inter-species differences, high costs, and lack of reliability and accuracy in predicting cardiotoxicity. Microfluidic heart-on-chip devices can impose a paradigm shift to the current tools. They can not only recapitulate cardiac tissue level functionality and the communication between cells and extracellular matrices but also allow higher throughput studies conducive to drug screening especially with their added functionalities or sensors that extract disease-specific phenotypic, genotypic, and electrophysiological information in real-time. Such electrical and mechanical components can tailor the electrophysiology and mechanobiology of the experiment to better mimic the in vivo condition as well. Recent advancements and challenges are reviewed in the fabrication, functionalization and sensor assisted mechanical and electrophysiological measurements, numerical and computational modeling of cardiomyocytes' behavior, and the clinical applications in drug screening and disease modeling. This review concludes with the current challenges and perspectives on the future of such organ-on-chip platforms.