There is high potential for current technologies to be used to recapitulate heart development in vitro by focusing on its earliest stage of morphogenesis: the embryonic heart tube. Recent advances in stem cell biology have enabled the production of cardiac progenitor lineages for bioengineering approaches. Biofabrication techniques can create structures and features of the heart tube at the appropriate scale. Biochemical cues that govern cardiac morphogenesis can be controlled and studied through techniques such as engineered diffusion gradients, functionalized hydrogels, and optogenetics.
Mechanical cues that influence cardiac growth and remodeling can be applied to engineered heart tubes using hemodynamic flow and direct or field-based micromanipulation techniques.
Recent advances in stem cell biology and tissue engineering have laid the groundwork for building complex tissues in a dish. We propose that these technologies are ready for a new challenge: recapitulating cardiac morphogenesis in vitro. In development, the heart transforms from a simple linear tube to a four-chambered organ through a complex process called looping. Here, we re-examine heart tube looping through the lens of an engineer and argue that the linear heart tube is an advantageous starting point for tissue engineering. We summarize the structures, signaling pathways, and stresses in the looping heart, and evaluate approaches that could be used to build a linear heart tube and guide it through the process of looping.
