The PI's long-term research goal is to develop a fundamental understanding of the mechanisms by which biomimetic materials can drive electrophysiological maturation of stem cell-derived cardiomyocytes (SC-CMs). This CAREER research plan uses a novel hydrogel microsphere encapsulation system to provide pluripotent stem cells with specific cues to direct their differentiation into cardiomyocytes and assesses the functional electrophysiological properties of resulting SC-CMs at the single cell and tissue levels. Using current differentiation methods, SC-CM maturation typically does not progress beyond a prenatal phenotype and overall electrophysiological properties vary greatly. Therefore, the objective of the PI?s research plan is to test the following hypotheses: (1) biomimetic scaffolds can be used to increase the homogeneity of SC-CMs and decrease variability in electrophysiological properties both within and between differentiation batches; (2) localized release of signaling molecules, including nitric oxide, can be used to enhance SC-CM maturity; (3) electrophysiological properties of SC-CMs will depend on the differentiation environment they are provided including variations in copolymer formulation, culture time, and initial stem cell concentration; and (4) SC-CMs will enhance electrical propagation through engineered cardiac tissues by directly coupling with more mature neonatal ventricular-derived cardiomyocytes. The following educational goals are integrated with the PI's research objective: (1) maintain a 1:1 ratio of undergraduate to graduate student researchers in her laboratory; (2) engage cardiac nursing students in learning about stem cell and cardiac regeneration research so they are better prepared to educate patients; (3) incorporate cardiovascular research-related content and projects into her coursework; (4) inspire K-12 students to pursue science and engineering careers through conducting K-12 outreach (5) support women and minority retention in science and engineering through organizational activities and one-on-one mentoring.
Intellectual Merit: The PI's focus on characterizing and directing SC-CM electrophysiology is unique, particularly for SC-CMs differentiated in scalable systems or encapsulated in biomaterial scaffolds, and the anticipated results will provide a valuable foundation for others in the field. Knowledge gained from these studies will be applied to the design of injectable biomaterial scaffolds and engineered cardiac tissues to improve electrophysiological integration, which is essential for cardiac regeneration. Establishing a fundamental understanding of how to uniformly progress SC-CM electrophysiological maturity and using this information to develop differentiation systems that control batch-to-batch variability is critical to reducing SC-CM's potential to cause deadly arrhythmias. In addition, obtaining sufficient numbers of homogeneous cells to form tissues is challenging. The interdisciplinary nature of this research draws on and furthers our knowledge of fundamentals in several fields including transport phenomena and thermodynamics, electrical signal processing, and developmental biology.
Broader Impacts: Heart disease is the number one cause of death in the United States each year for both men and women. Improving the ability to repair damaged or diseased hearts will provide patients the opportunity for both a longer and potentially better quality of life. The results of the PI's research will provide the foundation for educational materials that will be integrated into her core undergraduate courses and upper level cell and tissue engineering course. Cardiac nursing students, who in their careers will be important health educators, will also come to the PI's lab to learn about stem cell and cardiac regeneration research. Mentoring undergraduate researchers will continue to be a priority the PI, and she will expand her efforts to engage students from underrepresented groups. To engage K-12 students in this research and foster their interest in pursuing a career in science and engineering, the PI will use existing, successful frameworks including Auburn University's Youth Experience in Science (YES) camps and Getting Under the Surface (GUTS) program.
