The four one-way valves of the heart open and close to prevent the backflow of blood, and they do this more than three billion times during an average person's lifetime. During pregnancy, the workload of the heart increases, and the total volume of blood in the body rises by 40 percent to accommodate circulation in the placenta. Such an immense increase in cardiac workload has been shown to cause changes in the shape and structure of the heart valves. Currently, it is not clearly understood how changes in the mechanical loads on the heart valve during pregnancy lead to such modifications in shape and structure. It is known that the cells in heart valves (and in other soft tissues) try to maintain a stable equilibrium in their mechanical environment. Any deviations from the normal environment can cause cells to respond in an attempt to restore this balance. For example, cells may produce more proteins to build a stiffer and stronger surrounding structure in order to lower the amount of mechanical strain they experience. In this Faculty Early Career Development Program (CAREER) project, the PI combines experimental measurements and computer simulations to determine how changes in the heart's output and mechanical loading affect the tricuspid valve (the least understood valve in the heart) at the cellular level. The project is expected to widely impact the field of biomechanics, society in general, and engineering education. Specifically, this research project is expected to add knowledge of how mechanical loading affects cells and their surrounding structure, which is useful for future studies of the heart valves and other soft tissue. It will also provide useful information about how valve dysfunctions are brought on by pulmonary hypertension, which is a major cause of tricuspid valve disease in the broader public as well as in pregnant women. The educational goals include engaging K-12 students via hands-on STEM activities involving heart biomechanics during summer camp programs and monthly mentoring sessions at the University of Akron. The PI will also incorporate the research outcomes into courses offered at the University of Akron as well as supplementary educational materials (including relevant homework assignments) in articles submitted to scholarly journals for circulation to the scientific community.
This project has three scientific objectives. First, to measure the effects of cardiac output, loading environment, and extracellular matrix composition on the macroscale mechanical response, microscale extracellular matrix realignment, and cell nuclei of tricuspid valves before and after pregnancy in a bovine model. Second, to develop a mechanistic, multi-scale finite element model to connect the mechanical environment of the organized collagen and elastin components, the disorganized matrix, and the cells to the tissue-level mechanical loading/deformation in tricuspid valves before and after pregnancy. Next, to test the hypothesis that the complex valve geometry and the complex microstructure of the extracellular matrix provide a uniform homeostatic mechanical environment at the cellular/extracellular matrix level in response to the chances in physiological mechanical loading that occurs during and after pregnancy, along with the hypothesis that the alteration in the valves following pregnancy is a mechanobiological remodeling response to restore the tissue towards its pre-pregnancy mechanical state. And finally, to test the hypothesis that to restore the homeostatic mechanical environment, proteins that contribute to the stiffness of the extracellular matrix and nuclei are more prevalent in tricuspid valves during pregnancy. The educational objective is to inspire pre-collegiate students, especially those from underrepresented groups, to pursue higher education and careers in STEM as well as to inspire appreciation of multi-scale biomechanics within a general audience. This will be accomplished by: 1) developing a summer camp outreach program for K12 students that includes hands-on STEM activities; 2) implementing monthly mentorship clinics at the University of Akron for pre-collegiate students; 3) developing YouTube and iTunes videos to show experiments and simulations related to multi-scale biomechanics. In addition, the research results will be integrated into classroom materials that will be used at the University of Akron and disseminated more broadly through publication in engineering education journals.
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.
