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DRUG ELUTING TISSUE ENGINEERED VASCULAR GRAFTS

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abstract
Electrospun Tissue Engineered Vascular Grafts (TEVG) have been synthesized with variable success. TEVG ≤5mm in diameter have had limited success due to poor patency outcomes with high rates of restenosis secondary to a phenomenon called Intimal Hyperplasia (IH). We have performed previous animal studies using 2mm TEVG in rabbits and 5mm TEVG in sheep which had restenosis rates secondary to IH of 70% and 60% respectively. IH is secondary to an inflammatory response after implantation resulting in occlusion of the lumen of TEVG at the anastomotic site. This inflammatory process occurs in arterial stents and synthetic grafts as well; however restenosis rates in stents have been significantly reduced through the use of Drug eluting stents (DES), which contain antiproliferative agents that suppress the inflammatory process after implantation reducing the incidence of IH. This study evaluates the efficacy of using and synthesizing Drug Eluting Tissue Engineered Vascular Grafts (DETEVG) using a murine model with 1.5mm trilayer constructs comprised of a macrofiber diameter poly(ε-caprolactone) (PCL) type I collagen outer layer that promotes vascular smooth muscle integration and media layer formation, a nanofiber diameter PCL type I collagen middle layer that promotes endothelial monolayer formation, and a microfiber poly(lactic-co-glycolic acid) (PLGA) inner layer loaded with an antiproliferative agent. PCL typically takes 1-2 years to degenerate, where as PLGA takes approximately weeks to months depending on the ratio of Poly Lactic Acid (PLA) to Poly Glycolic Acid (PGA) present. The purpose of this study is to evaluate the ability of DETEVG with an antiproliferative agent loaded PLGA layer to decrease IH formation and prevent graft restenosis. To accomplish this task, parameters that affect the drug release kinetics of PLGA were evaluated to determine if drug release can be controlled by controlling the fiber diameter of fibers in Electrospun PLGA scaffolds. The antiproliferative effects of drugs loaded to PLGA scaffolds were also evaluated against proliferation dominant macrophages. Current literature suggests that local proliferation of macrophages precipitates the conversion of vascular smooth muscle cells from a contractile type to a synthetic myofibroblast type which is believed to secrete the extracellular proteins that result in IH.
subject
Engineered
Graft
Hyperplasia
Intimal
Tissue
Vascular
contributor
Woods, Ian (author)
Lee, Sang Jin (committee chair)
Hoth, Jason (committee member)
Ju, Young Min (committee member)
date
2017-06-15T08:35:31Z (accessioned)
2017-06-15T08:35:31Z (available)
2017 (issued)
degree
Molecular Medicine and Translational Science (discipline)
identifier
http://hdl.handle.net/10339/82166 (uri)
language
en (iso)
publisher
Wake Forest University
title
DRUG ELUTING TISSUE ENGINEERED VASCULAR GRAFTS
type
Thesis

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