A human engineered mini-heart platform for mimicking ventricular pump function

Abstract

Engineered cardiac tissue models for in vitro physiological studies often fail to replicate the pump function of the heart. Despite promising advancements, the use of engineered cardiac chambers is often hindered by complex fabrication processes and invasive characterization techniques. Here, we engineered a human cardiac chamber, referred to as a mini-heart, by employing a novel sacrificial molding approach within a customized bioreactor. The mini-hearts pumping capability was confirmed through optical recording of fluid displacement at the engineered tissue inlet, enabling the non-invasive acquisition of hemodynamic parameters such as stroke volume, stroke work, ejection fraction, and developed pressure. Morphological analysis of the engineered tissues revealed organized sarcomeres and extracellular matrix self-determination, highlighting the advantage of our degradable mold technology. Additionally, we have measured calcium transients during both spontaneous and electrically-paced beating, and observed a positive inotropic response to the {beta}-adrenergic agonist drug isoproterenol. Altogether, our biomimicking engineered tissue platform provides a robust tool for exploring cardiac pressure-volume dynamics, thereby facilitating complex disease modelling and drug screening applications in vitro.