CAREER: Congenital Heart on a Chip: Investigating Mechanical, Biomolecular, Cellular and Tissue-Level Mechanisms in Cardiac Fibrosis

Cardiac fibrosis is the formation of scar tissue in the heart. This scar tissue leads to impairment in heart function. The heart is composed of several types of cells including cardiomyocytes, fibroblasts, and endothelial cells. Each type plays a critical role in heart function and tissue maintenance. During heart disease, these cells undergo transitions in response to environmental stressors. The ultimate objective of this Faculty Early Career Development Program (CAREER) award is to investigate how different cells in the heart respond to chemical and mechanical signals that cause cardiac fibrosis. The research will focus on developing a 3D tissue model that mimics the dynamics of chemical and mechanical cues in cardiac function. This project will determine how these different cells contribute to scar tissue formation and ultimately to heart dysfunction. The proposed integration of research and education will support the recruitment of graduate and undergraduate researchers from diverse and historically excluded groups into Science, Technology, Engineering, and Mathematics (STEM) careers. A specific focus will be the training of current and pre-service middle and high school teachers from the Houston metropolitan area in developing teaching modules for 7-12th graders based on tissue engineering for cardiac health. The central goal of this CAREER project is to leverage mechanically tunable hydrogel-based heart tissue models to investigate cellular, biomolecular, and mechanical cues in the onset and progression of cardiac fibrosis. This project seeks to evaluate the role of maternal autoantibodies in concert with cytokines in fibroblast and endothelial activation. The specific research objectives are to: 1) determine the role of the endothelial mesenchymal transition in cardiac fibrosis, and 2) develop a 3D cardiac fibrosis model and microfabrication techniques to investigate tissue remodeling cascades. The heart chip will support the interrogation of endothelial transition that may facilitate autoantibody translocation into the heart as well as fibroblast transdifferentiation in autoantibody mediated cardiac fibrosis. Additionally, studies will probe the impact of mechanical cues on heart tissue remodeling during disease. The integration of research and education will aim to: 1) develop the HeartChips_Teach initiative that will introduce pre-service STEM teachers to tissue engineering concepts and develop effective teaching modules for 7-12th grade students, and 2) plan ChipSquad Teaching Workshops that will train teachers from middle and high schools located in the Third Ward and Houston metro area that have a high percentage of students belonging to historically excluded groups. Teachers will be trained to develop tissue engineering modules inspired by the proposed research and suitable for executing in their classroom. The modules will be broadly disseminated and integrated into an education plan that supports 7-12th graders and K-12 STEM teachers. An industrial partner will be engaged to enhance the research and education experience by providing a more applied scientific perspective in the investigation and training process. The award will support graduate and undergraduate researchers at the University of Houston, a minority serving institution, and foster learning experiences that broaden exposure to the field of tissue engineering, thus training the next generation of diverse scientists and engineers. 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.