Design and fabrication of an integrated heart-on-a-chip platform for construction of cardiac tissue from human iPSC-derived cardiomyocytes and in situ evaluation of physiological function

Abstract

In vitro model of the human cardiac tissues generated from human induced pluripotent stem cells (hiPSCs) could facilitate drug discovery and patient-specific studies of physiology and disease. However, the immature state of hiPSC-derived cardiomyocytes (hiPSC-CMs) compared to adult myocardium is a key defect that must be overcome to enable the potential applications of hiPSC-CMs in drug testing. For this purpose, we developed a heart-on-a-chip device that contains microfluidic channels for long-term dynamic culture of cells, platinum wire electrodes for electrical stimulation of hiPSC-CMs, and gold electrode arrays as acquisition electrodes for real-time recording electrophysiological signals of cardiac tissues. Human iPSC-CMs cultured on biocompatible hydrogels in the chip chamber can be electrically stimulated to prompt the maturation of cardiomyocytes (CMs) and generate functional cardiac tissues. Drug tests were performed with calcium transient measurements to evaluate drug responsiveness of electrical stimulated and unstimulated cardiac tissues. The results show that only the electrical-stimulated cardiac tissues respond correctly to drug treatment of verapamil and isoprenaline, indicating the reliability of this engineered cardiac tissues for drug testing. The above integrated heart-on-a-chip device provides a promising platform for drug efficacy testing and cardiactoxicity.

Keywords: Cardiac tissue engineering; Heart-on-a-chip; Local field potentials; Stimulation and recording; hiPSC-CMs.