Date of Award

8-9-2014

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Richard L. Goodwin

Abstract

Atherosclerosis is the narrowing of arteries caused by accumulation of cholesterol, calcium and other cellular debris in the inner arterial wall. While extensive studies have been focusing on the inflammatory mechanisms of the disease, pathological and experimental evidence has shown that regions of disturbed flow are susceptible to the atherogenesis. To further understand the relationship between hemodynamics and atherogenesis, this research aims to generate a dynamic, 3D in vitro model of atherogenesis. This will allow for the investigation of specific cellular and molecular mechanisms of plaque formation that will pave the way for new therapies for the disease. A novel fabrication method that produces a 3D vascular construct was developed, which contains the cellular (endothelial cells, smooth muscle cells, and fibroblasts) and extracellular components of native vessels (type I collagen). Briefly, a combination of cells and solubilized collagen are polymerized in a tube mold to create the vascular tissue construct. The resulting tube, or the “cytotube”, contains a radial-symmetric nozzle-like structure in the center of the construct, which was design to generate disturbed flow as fluid passes through the structure. CFD (computational fluid dynamics) modeling indicated an area of recirculating (disturbed) flow downstream the nozzle. Cell viability, morphology and protein expression in the cytotubes were investigated with confocal microscopy. These studies found that all fibroblasts, smooth muscle cells, and endothelial cells remained viable and have expressed various phenotypic morphologies in the cytotubes over 7 days of static culture. The proposed fabrication method and the resulting model not only can serve as an in vitro 3D culture system and pathogenesis monitoring system, but also has the potential to influence vascular tissue-engineering studies.

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