The development of in vitro human model systems that more accurately represent in vivo biology may provide an additional model system for studying biological mechanisms. We have recently developed a high-throughput bioengineered human cardiac organoid (hCO) platform, which provides functional contractile tissue with biological properties similar to native heart tissue. We have developed functional and omics assays to tease apart mechanisms of action for a wide variety of perturbations. This approach may be useful to uncover holistic mechanisms of action of a wide variety of perturbations. in this presentation I will summarize how we have used these approaches to study maturation and regeneration of the heart, which has also opened up new questions to be answered.