Engineered Development: Directed Morphogenesis of an Embryonic Heart Tube

Morphogenesis is a major developmental process that shapes organs in utero through coordinated structural deformations. Outside of simple cellular or animal models, limited models of morphogenesis exist due to the complexity of hierarchical structural change. In development, the embryonic heart undergoes a complex morphogenesis process involving looping, chamber growth, and septation, transforming the primordial tube to an adult four-chambered organ. An in vitro model of looping could provide unique insights into this phase of development and improve understanding of congenital defect generation. In this study, we combined tissue engineering with developmental biology in an approach called directed morphogenesis to build a humanized tissue model of looping. To build such a model, embryonic heart tubes (EHT) mimicking native anatomy were fabricated. A perfusion bioreactor was designed to direct EHT's through a looping-like process. EHTs looped in the bioreactor fused into chamber-like structures with ventricular-like geometry resembling early cardiac morphology. Furthermore, there was an upregulation in morphogenic genes in looped constructs after 1 week in culture, indicating biological effects from directed morphogenesis. In conclusion, a controllable in vitro model of mechanically induced cardiac morphogenetic reorganization was established, which has the potential to be translated to other organ types that undergo complex spatial reorganization.