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Modular Design of Stent Polymers Regulates Human Coronary Artery Cell Type-Specific Oxidative Response and Phenotype

dc.creatorCrowder, Spencer William
dc.date.accessioned2020-08-22T00:25:04Z
dc.date.available2011-10-12
dc.date.issued2011-04-15
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-04042011-144148
dc.identifier.urihttp://hdl.handle.net/1803/11996
dc.description.abstractPolymer 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.
dc.format.mimetypeapplication/pdf
dc.subjectcoronary stent
dc.subjectCopolymerization
dc.subjectbiomaterials
dc.subjectoxidative stress
dc.titleModular Design of Stent Polymers Regulates Human Coronary Artery Cell Type-Specific Oxidative Response and Phenotype
dc.typethesis
dc.contributor.committeeMemberCraig L. Duvall
dc.contributor.committeeMemberHak-Joon Sung
dc.type.materialtext
thesis.degree.nameMS
thesis.degree.levelthesis
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorVanderbilt University
local.embargo.terms2011-10-12
local.embargo.lift2011-10-12


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