I-Corps: In Vitro Cardiac Platform for Drug Discovery and Cardiotoxicity Screens

The broader impact/commercial potential of this I-Corps project is the development of a drug discovery testing platform for potential heart treatments. Currently, most drug discovery testing begins with screening a new drug or therapeutic in traditional cell culture environments (e.g., petri dishes). However, this does not adequately represent the real biological context inside the human body. This is especially true for therapies targeting heart disease, where the cells are normally subjected to dynamic motion from the heart beating every second. The proposed technology aims to advance the next generation of heart disease medications using a cardiac tissue screening platform. The platform is designed to provide a physiologically relevant mechanical environment using electromagnetic controls and automated video tracking in order to expose tissues to the mechanical forces experienced within the body. Such a tool may hold potential for pharmaceutical companies, contract research organizations, and clinical cardiology practices/hospital systems. Ultimately, better discovery tools may lead to better therapies for improving human health and well-being. This I-Corps project is based on the development of heart tissue culture technology designed to mimic the mechanical environment of a beating heart for drug discovery applications. The proposed design of this platform uses computer-controlled electromagnets to subject 3-dimensional cardiac tissues to dynamic force-length relationships. The goal is to match the pressure and volume changes experienced by the heart in various heart disease conditions such as hypertension and aortic valve stenosis. In addition, the platform can produce disease-relevant metrics such as tissue stiffness, contractility, stroke work, and cardiac output curves, which directly translate to clinically relevant diagnostic metrics and outcome measures. The aim is to provide key merits that are not provided with existing approaches by subjecting tissues to full mechanical pressure. A physiologically correct mechanical environment may improve the success of therapy screens while physiologically relevant output metrics may help demonstrate clinical translatability. In addition, a dynamic mechanical environment may provide experimental versatility under desired testing conditions (e.g., normal vs. pressure-overload vs. volume-overload mechanics). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.