Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

Summer 8-30-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Robert P Mecham

Abstract

Proper arterial function requires a specific composition of extracellular matrix: ECM) proteins to produce a vessel with the right mechanical properties. Closed circulatory systems driven by a beating heart have pulsatile flow, requiring the large elastic arteries to have the ability to distend and recoil to dampen the pulsatile output. This unique ability is made possible by elastin in the ECM that imparts elastic behavior to the artery. Genetic mutations that affect the amount and organization of elastin result in congenital cardiovascular defects that lead to lifelong cardiovascular complications. In order to devise proper treatments we must understand how development is affected due to impaired artery structure and function.

The goal of this dissertation is to test constitutive models against developmental data from genetic mouse models of impaired elastin production to investigate relationships between mechanical function and changes in ECM quantity and identify improvements that could be made in future modeling efforts. A fiber-based microstructural constitutive model was fitted to experimental mechanical data from wild-type: WT) and Eln+/- mice, which have reduced elastin. The model parameters were found to change with age and genotype in a fashion that correlated with protein quantification data for elastin and collagen. The model also predicted collagen fibers would change orientation with age. To investigate this, a new method for visualizing and quantifying collagen fiber reorientation using conventional confocal light microscopy was developed. Collagen fibers were found to be organized largely in two distributions of angles, and differences in fiber orientation were found between WT and Eln+/- mice. A transgenic mouse: hBAC-mNULL) with even less elastin than Eln+/- showed altered arterial development consistent with pathological responses to hypertension. Ascending aortas were found to have increased thickness and were stiffer during mechanical testing. The constitutive model did not fit the hBAC-mNULL data as well, suggesting that improvements are needed to the model to predict the mechanical behavior of arteries subjected to pathological development. To summarize, this dissertation has shown that fiber-based microstructural modeling is a useful tool for identifying structural and mechanical changes in developing arteries with reduced elastin.

DOI

https://doi.org/10.7936/K7V122S7

Comments

This work is not available online per the author’s request. For access information, please contact digital@wumail.wustl.edu or visit http://digital.wustl.edu/publish/etd-search.html.

Permanent URL: http://dx.doi.org/10.7936/K7V122S7

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