Continuous contractile force and electrical signal recordings of 3D cardiac tissue utilizing conductive hydrogel pillars on a chip.

Abstract

Heart-on-chip emerged as a potential tool for cardiac tissue engineering, recapitulating key physiological cues in cardiac pathophysiology. Controlled electrical stimulation and the ability to provide directly analyzed functional readouts are essential to evaluate the physiology of cardiac tissues in the heart-on-chip platforms. In this scenario, a novel heart-on-chip platform integrating two soft conductive hydrogel pillar electrodes was presented here. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts were seeded into the apparatus to create 3D human cardiac tissues. The application of electrical stimulation improved functional performance by altering the dynamics of tissue structure and contractile development. The contractile forces that cardiac tissues contract was accurately measured through optical tracking of hydrogel pillar displacement. Furthermore, the conductive properties of hydrogel pillars allowed direct and non-invasive electrophysiology studies, enabling continuous monitoring of signal changes in real-time while dynamically administering drugs to the cardiac tissues, as shown by a chronotropic reaction to isoprenaline and verapamil. Overall, the platform for acquiring contractile force and electrophysiological signals in situ allowed monitoring the tissue development trend without interrupting the culture process and could have diverse applications in preclinical drug testing, disease modeling, and therapeutic discovery.