Sanative Patches for Advanced Regenerative Engineering of the Heart

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Cardiovascular diseases are the leading cause of death in the world. Because the human heart has effectively no regenerative capabilities, the damage caused by cardiovascular diseases and heart attacks is both cumulative and progressive. The aim of this project is the development of regenerative tissue-engineered cardiac patches, which will revolutionize healthcare by providing patients with a treatment that seeks not to manage their symptoms, but to correct and reverse the underlying damage to the cardiac muscle. While the theory underpinning regenerative cardiac patches is not novel, reaching TRL5/6 by demonstrating proof-of-concept with 3D-printed, thick, fully vascularized, clinically relevant patches would constitute an extraordinary step forward for the field. In this project, we propose to 3D-print thick, vascularized cardiac tissues comprised of functional cardiomyocytes and blood vessel–forming endothelial cells derived from human induced pluripotent stem cells (iPSCs). The tissues will be between ½ -1 cm thick and will require significant levels of vascularization. Following fabrication, tissues will be matured in custom-designed bioreactors and reinforced, rendering them strong enough to be easily handled by surgeons. We then propose to perform cardiac-regenerative surgery in a large mammal model (pigs). This study will serve as a proof-of-concept that will advance the technology from an academic setting to the biotech industry and ultimately into the clinic.