Heart valve disease is a major global health problem that affects about 25% of the population over age 65 in developed countries. Approximately 300,000 valve replacement/repair surgeries are performed every year to replace the diseased valve with a bioprosthetic or mechanical valve. While these valves are an effective option, they lack long-term functionality. A dire need thus exists for better treatment options for heart valve disease.
The long-term goal of this BRIGE (Broadening Participation Research Initiation Grants in Engineering) proposal is to design functional tissue-engineered heart valves (TEHVs) with similar composition to the native tissue. Current tissue engineering strategies for heart valves utilize cell source, substrate, chemical, and mechanical cues to modify their physical properties. In spite of recent progress, existing functional TEHVs are limited by their low mechanical strength and resilience. This lack of desirable mechanical properties hinders their successful operation in the complex mechanical environment of the heart. The extracellular matrix (ECM) composition and alignment significantly contributes to the mechanical properties of native and TEHVs. For example, aortic valves contain a bi-directional network of ECM, which assists in their differential stretching during the opening and closing cycles. A critical need exists for ways to modulate cell-mediated ECM synthesis and organization to improve mechanical properties of TEHVs. Functional TEHV design also requires an improved understanding of valvular cells, since they are primarily responsible for developing and maintaining ECM; unfortunately, they also differentiate to produce abnormal amounts of ECM in diseases. Therefore, the proposed two-year project will: 1) design a culture device to mimic the stretch environment of heart valves in vitro to measure the contribution of cellular and environmental factors in creating TEHVs; and 2) determine the ideal culture conditions for valvular cells to generate favorable ECM in TEHVs and avoid excessive ECM remodeling observed in diseases. This will be accomplished by modulating ECM signaling, directional stretch magnitudes, and cell phenotypes.
The proposed project will develop a state-of-the-art stretch device for mechanobiology studies of heart valve. The research outcomes will be incorporated into a newly developed graduate course in the area of Biomechanics in Tissue Engineering.
Broadening Participation of Underrepresented Groups in Engineering:
The PI will engage in university-wide activities to attract bright and talented undergraduate students who are from populations that are underrepresented in engineering. Yearly laboratory tours will be organized to foster higher education in pre-collegiate students and expose them to the interdisciplinary research happening at the University of Tennessee, Knoxville. Finally, opportunities will be created for female students to share and learn from the experience of successful women in academia. Completing this BRIGE proposal will thus advance tissue engineering, engage students of all backgrounds in pioneering research, and lead to a deeper understanding of the biology, pathology, and tissue engineering of heart valves.
This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.
The research is also funded through the Experimental Program to Stimulate Competitive Research (EPSCoR), which is part of the Office of International and Integrative Activities.
