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Benjamin Streeter
BME PhD Defense Presentation
Date:2021-11-01
Time: 10:00 AM - 12:00 PM
Location / Meeting Link: https://emory.zoom.us/j/96407155660
Committee Members:
Michael E. Davis, PhD (Advisor)
Younan Xia, PhD
Rebecca Levit, MD
Johnna S. Temenoff, PhD
Josh T. Maxwell, PhD
Title: Electrospun Nanofibrous Patches for the Delivery of Cardiac-derived c-Kit+ Cells
Abstract: Congenital heart disease (CHD) affects 8 in 1000 live births and is the number one cause of birth defect-related deaths. Advances in surgical palliation of CHD have led to improved long-term outcomes, but right ventricular heart failure (RVHF) still often occurs in CHD patients. One promising avenue to restore the contractile function of the RV is autologous cell therapy, but cell injection is hampered by low cell retention following injection and variability in donor cell quality. Therefore, there is a need to enhance cell retention following implantation into the RV and to improve the efficacy of autologous cells in a donor-specific manner. To address these needs, the aim of this study was to combine nanofibrous polycaprolactone (PCL) scaffolds and cardiac-derived c-Kit+ cells (CPCs) isolated from CHD patients to create a biomaterial/cardiac cell patch capable of treating RVHF. We hypothesized that PCL/CPC patches would improve cardiac function in a rat model of RVHF, and that fiber alignment and inclusion of gelatin and fibronectin in PCL scaffolds would affect patch performance by changing CPC function and paracrine release. We characterized the CPC response to culture on eight different types of electrospun PCL scaffolds and found that changes in CPC function on each scaffold were CPC donor-dependent. We then used computational modeling techniques to identify a mechanism of fibronectin-mediated CPC functional improvement and designed a PCL patch to engage this mechanism in a donor-specific manner. Our CPC donor-specific patches were then implanted into a rat model of RVHF and were able to rescue RV function, enhance angiogenesis, and decrease myocyte hypertrophy. In total, this study demonstrated the validity of an electrospun nanofibrous PCL patch as an effective biomaterial for CPC implantation and determined the effects of the patch microenvironment on the reparative function of CPCs from different CHD patients.
