User-friendly and parallelized generation of Human Induced Pluripotent Stem Cell-Derived Microtissues in a Centrifugal Heart-on-a-Chip

The persistence of cardiovascular diseases as leading global causes of death has spurred attempts to develop microphysiological systems integrating engineered cardiac tissue. These novel platforms enable investigation of mechanisms underlying myocardial pathology as well as in vitro screening of candidate drugs for possible cardiotoxicity. However, most of the developed systems rely on manual cell injection protocols, resulting in nonstandardized tissue creation and requiring excessive amounts of cells. To address these issues, we present a novel integrated device enabling the parallelized generation of cardiac microtissues based on human induced pluripotent stem cells as well as rat primary cardiomyocytes in an especially designed multichamber system that provides a precisely controlled physiological environment. The next-generation device utilizes a centrifugally assisted cell loading procedure, which enables robust generation of tissues devoid of air bubbles. It requires solely a minimal amount of cells to create uniaxially aligned cardiac muscle fibers, displaying well-aligned collections of sarcomeres. The viability and functionality of myocardial tissues can be maintained for long time periods, while detailed spatial and temporal beating kinetics can be examined by optical means. As proof of concept, the applicability of the system for drug testing was demonstrated, highlighting the potential of this user-friendly and economical centrifugal heart-on-a-chip for future applications in pharmaceutical industry and mechanistic research.