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Title page for ETD etd-04042011-144148

Type of Document Master's Thesis
Author Crowder, Spencer William
Author's Email Address spencer.w.crowder@vanderbilt.edu
URN etd-04042011-144148
Title Modular Design of Stent Polymers Regulates Human Coronary Artery Cell Type-Specific Oxidative Response and Phenotype
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Craig L. Duvall Committee Member
Hak-Joon Sung Committee Member
  • coronary stent
  • Copolymerization
  • biomaterials
  • oxidative stress
Date of Defense 2011-05-13
Availability unrestricted
Polymer properties can be altered by copolymerizing subunits with specific physicochemical characteristics. Vascular stent materials require biocompatibility, mechanical strength, and prevention of restenosis. Here we copolymerized poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), and carboxyl-PCL (cPCL) at varying molar ratios and characterized the resulting effects on physicochemical and mechanical properties. We then evaluated these polymers for their applicability as coronary stent materials using two primary human coronary artery cell types: smooth muscle cells (HCASMCs) and endothelial cells (HCAECs). Changes of their proliferation and phenotype were dependent upon intracellular reactive oxygen species (ROS) levels, and 4%PEG-96%PCL was identified as the most appropriate material for this application. On this substrate, HCASMCs maintained a contractile phenotype identified by arrested proliferation, moderate oxidative activity, up-regulated expression of smooth muscle myosin heavy chain (smMHC), and healthy spindle morphology. HCAECs on 4%PEG-96%PCL maintained a physiologically-relevant proliferation rate and a balanced redox state. Other test substrates promoted a pathological, synthetic phenotype in HCASMCs and/or hyperproliferation in HCAECs. The cellular responses related to the phenotypic change were modulated by Young’s modulus and surface charge of test substrates, indicating a structure-function relationship that can be exploited for intricate control over vascular cell functions.
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