In Silico Electrophysiological Evaluation of Scaffold Geometries for Cardiac Tissue Engineering

Abstract

Human induced pluripotent stem cell-derived car-diomyocytes (hiPSC-CMs) cultured on bio-printed scaffolds have shown promising results for cardiac function restoration in regenerative medicine. Nevertheless, pro-arrhythmicity favored by reduced conduction velocity of the transplanted constructs as compared to native tissue has been poorly assessed. Here, we investigate the impact of the scaffold geometry on the electrical activation properties of hiPSC-CMs cultures. Electrophysiological models of hiPSC-CMs and the Finite Element Method were employed for computational simulation of hiPSC-CMs cultures. The models were calibrated to replicate experimentally measured activation time maps by adjusting parameters representative of fiber alignment and cell-to-cell coupling. Scaffolds with rectangular, auxetic and elongated hexagonal pore shapes were studied to determine the most biomimetic structure in terms of electrical propagation characteristics. Our results showed that the geometry with elongated hexagonal pores led to faster activation of hiPSC-CMs cultures by facilitating the alignment of cardiac fibers in the longitudinal direction. These pore shapes mimic cardiac anisotropy, therefore would be the preferred geometry for experimental culture.