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Title page for ETD etd-07252014-110513


Type of Document Master's Thesis
Author Rath, Rutwik
URN etd-07252014-110513
Title Cardiac ECM Structure-Mimetic Electrospun Scaffolds Reinstate Healthy Cardiomyocyte Phenotype
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Hak-Joon Sung, Ph.D. Committee Chair
Douglas B. Sawyer, M.D., Ph.D. Committee Member
Keywords
  • electrospun scaffold
  • cardiomyocyte phenotype
  • extracellular matrix
Date of Defense 2014-07-24
Availability unrestricted
Abstract
Although extracellular matrix (ECM) composition and organization are considered important regulators of cardiomyocyte phenotype in vitro and in vivo, a causal relationship between the ECM structure and effect on maintenance of cardiomyocyte (CM) phenotype has not been established. In this study, we investigated how key structural characteristics of electrospun scaffolds (fiber alignment, spacing, and diameter) regulated CM phenotype – specifically cell morphology, actin/myosin patterning, and cardiac gene expression. We found that aligned fiber scaffolds resulted in a longer, more rod shaped morphology in both neonatal and adult CMs. Along with better morphology, CMs were also found to have better-organized cell actin/myosin bands and cardiac specific gene expressions of β-MYH7 and SCN5A.1 and SCN5A.2 in both neonatal and adult cells. Additionally, upon exposure to variously spaced aligned fibers, adult CM action/myosin structure and morphology did not change but the overall orientation of the cells, relative to the fibers, increased from 45° to parallel as fiber spacing increased from 2 µm to 15µm. These findings provide critical insights into ECM-CM interactions that are responsible for maintenance/loss of neonatal and adult cardiomyocyte phenotype, and highlight the importance of developing more relevant cardiomyocyte culture substrates for in vitro studies.
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