Heart diseases are a major cause of death in the Western world. No sustainable regenerative therapy is currently available, and cardiac transplantation is the only treatment. However, the scarcity of matching heart donors raises the need to develop new regenerative medicine approaches. Recently, our group has shown the use of patient-specific cells and personalized hydrogels to 3D print vascularized cardiac patches. Moreover, we have developed printing technologies that allow the printing of small-scale, cellularized human hearts with the major blood vessels. Despite these and other advances in the field, premature hearts are very basic, and their ability to pump blood and function in vivo is still considered futuristic, requiring several major breakthroughs. In this project, we plan to go far beyond the current state-of-the-art and overcome some of the remaining challenges in the field. We will develop novel 4D printing approaches, allowing the printing of human cardiac patches and whole functional hearts, including ventricles, atria, pacemakers, conduction system, and extensive vasculature, in high resolution. We will decipher the mechanisms underlying the maturation of the printed tissues and hearts, which are essential for synchronous contraction and heart pumping. The functionality of the printed structures will be compared to that of native cardiac tissues and whole natural hearts by examining their reaction to chronotropic and cardiotoxic drugs, proving their additional potential to serve as reliable, predictive drug testing platforms. The printed tissues and hearts will be then heterotopically transplanted (in parallel to the native heart), and their anastomosis (connection) with the host blood vessels, contraction and blood pumping capabilities in vivo will be tested. Finally, we will demonstrate the ability of the printed, vascularized cardiac patches to improve heart function. Successful completion of this ambitious project will provide a sustainable, regenerative therapy for a myriad of devastating maladies.
