Grant: China-Canada Joint Health Research Initiative

Myocardial infarction (MI), commonly known as heart attack, is one leading cause of death worldwide, including both Canada and China. The myocardium has extremely limited regeneration potential. With advances in tissue engineering, implantation or injection of tissue engineering cardiac constructs made from biomaterials and/or living cells into the affected myocardium shows promise for improving MI repair. This therapy is still being conducted in animal trials, and we believe significant advances can be made by creating cardiac scaffolds or constructs with carefully controlled composition and properties. In this project, we will develop novel injectable cardiac scaffolds that encapsulate living cells for use in MI repair. Our central hypothesis is that alginate hydrogels can be engineered with controlled composition (including living cells and locally-delivered molecular agents) and properties for optimal cardiomyocyte regeneration and functional recovery after MI. Our specific objectives are to: (1) synthesize self-cross-linked alginate hydrogels to optimize cell viability during cell injection; (2) examine the ability of hydrogels encapsulating living cells to promote cardiomyocyte regeneration in vitro; (3) integrate strategies for promoting cardiomyocyte regeneration and antagonizing the effects of matrix metalproteases to achieve combined or synergistic effects for MI repair in vivo; and (4) develop synchrotron biomedical imaging technologies to track the success of the strategies developed. This work will significantly advance the theoretical and practical basis of developing injectable hydrogels encapsulating living cells to foster MI repair in animal models, and eventually in humans. As such, this project is well aligned with research on "treatment and ultimate cure of cardiovascular diseases, including MI" within the "cardiovascular system" research area of the 2013 China-Canada Joint Health Research Initiative funding opportunity announcement.