ABSTRACT: Engineered in vitro cardiovascular systems hold great promise for studying cardiac physiology and development, modeling disease, and screening drugs. To realize this promise, these models must recapitulate key properties of heart tissue, including the dynamic mechanical environment, in which vascular fluid flows and contractile forces regulate cellular phenotype and function. My research centers on the development of cardiovascular organ-on-a-chip systems and engineered heart tissues that incorporate these features of the heart and on their application to the study of cardiac physiology. I will share my work on engineered microvasculature within a microfluidic device that incorporates circulating intravascular flow via an on-chip pump and a flow-responsive genetic reporter. This system, which activates the promoter of KLF2, an integrator of endothelial flow response, was used to study the structural and functional effect of flow in microvessels, with implications for both vascular physiology in the heart and the control of vascular morphology in engineered systems. Further, I will discuss work on vascularizing cardiac organoids-on-a-chip to form fully perfusable systems that enable the study of endothelial cell-cardiomyocyte interactions in the context of a dynamic mechanical environment. Altogether, this suite of engineered models incorporates fundamental features of the heart and represents a toolbox for interrogating the mechanisms by which tissue-specific biophysical forces regulate cardiovascular function in health and disease.

BIO: Adriana Blazeski is a postdoctoral fellow in the Center for Excellence in Vascular Biology at Brigham and Women’s Hospital and Harvard Medical School and the Department of Mechanical Engineering at the Massachusetts Institute of Technology. Her work in the laboratories of Dr. Guillermo García Cardeña and Professor Roger Kamm is focused on the development of microfluidic and vascularized organ-on-a-chip systems to interrogate cardiovascular biology and disease, particularly as they relate to biophysical forces from flow in the vasculature. Dr. Blazeski holds B.S.E. and M.S.E. degrees in Biomedical Engineering from the University of Michigan and a Ph.D. in Biomedical Engineering from the Johns Hopkins University. Her work has been supported by fellowships from the American Heart Association and the NIBIB-funded Organ Design and Engineering Post-doctoral Training Program.