Abstract Body: Introduction
Cardiotoxicity resulting from the side effects of the drugs leads to serious adverse events. Engineered heart tissues (EHTs) using human induced pluripotent stem cells provide a valuable in vitro platform for assessing pharmacologic and toxicologic effects on cardiac functions. Although EHT devices offer a feasible approach to readily evaluate drug responses on contractile properties, including contractile force and relaxation time, by measuring the moving distance of pillars attached to EHTs, the absorption of small molecules by poly (dimethylpolysiloxane) (PDMS), a commonly used material for ECT devices, can be a serious issue to precisely evaluate drug effect on contraction properties.
Hypothesis
This study aimed to develop a low-absorption EHT device and evaluate the impct of PDMS absorption on the sensitivity of EHTs to cardiotoxicity.
Method and results
In this study, we developed a low-absorption EHT device using polystyrene (PS) to address this issue. Moreover, we generated an original Python-based analysis program to avoid analytical bias when tracking pillar positions and analyzing the contractile waveform drawn from EHT movements. This analytic platform enables the detection of increased contractile force during EHT maturation and the negative inotropic effects of Diltiazem and Blebbistatin on EHT contractile functions. Moreover, EHTs with PS-based devices suppressed the absorption of a cardiotoxic drug, doxorubicin, thus allowing the detection of cardiotoxic effects even at low concentrations compared to EHTs grown on PDMS-based devices. In summary, Our results indicated that small-molecule absorption by device materials impairs low-concentration measurements, while our PS-based EHT devices enhance sensitivity.