In this project, we have made a major breakthrough in cardiac tissue engineering by successfully developing vascularized heart tissue that can form and function without relying on microfluidic forces. This achievement overcomes one of the biggest challenges in the field, the traditional size limits of engineered heart tissues. Because our new tissue model is not confined by these constraints, we can now create larger, more realistic heart tissues to study how contractile forces, matrix stiffness, and extracellular matrix (ECM) composition influence heart function. Importantly, this approach also allows us to explore the role of blood vessels in heart development and disease, something that has been extremely difficult to achieve in laboratory models until now. Building on this innovation, we integrated acoustic manipulation technologies to guide the organization of cells within the tissue. These new vascularized tissues were evaluated beyond the current state of the art, allowing us to identify the key factors that determine tissue quality, alignment, and structure. We also conducted gene expression analysis on acoustically manipulated tissues, providing new molecular insights into how these structures form and mature. Moreover, we demonstrated the ability to generate hollow capillaries within complex co-cultures, a sign of self-organizing vascular networks that assemble naturally without external fluid pressure. Together, these advances represent a significant step forward toward employing these results to fabricate a living heart patch capable of mending human hearts, opening new possibilities for studying heart disease, testing therapies, and developing regenerative treatments for patients with heart failure.
