Integration of cell programming and tissue engineering for in-vitro modeling of a cardiac stimulation patch: a game-changer in the clinical scenario

Cardiac implantable electronic devices (CIEDs) are currently used in the clinic to address arrhythmias. The main limitations and complications associated with CIEDs are mostly related to the mechanical (synthetic) structure of the device components (e.g., lead infection and rupture) and are potentially life-threatening for patients, with a significant impact on healthcare costs. A “no-mechanical device solution” would be desirable. In literature, biological pacemakers have been, recently, developed using gene- and cell-based research strategies, but to date, those technologies are far from clinical translation due to several clinical implications (e.g., cell migration, potential teratogenic effects). Furthermore, mechanoelectrical and automaticity pathways have been, newly, employed to reproduce biological features of the heart into biohybrid platforms. This thesis project aims to overcome such limitations by combining cell-based strategies with principles of regenerative medicine. Our engineered contractile patch will be constituted by induced pluripotent stem cells, programmed to acquire a myocardial phenotype. Cells will be seeded upon a biological scaffold, derived from swine cardiac decellularized extracellular matrix. The patch, so generated, will serve not only as an implantable stimulating device but also, prospectively, as a diagnostic tool for patients’ disease characterization.