DOI

10.17077/etd.ly701oxu

Document Type

Dissertation

Date of Degree

Summer 2016

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biomedical Engineering

First Advisor

Edward A. Sander

First Committee Member

Madhavan L. Raghavan

Second Committee Member

Nicole M. Grosland

Third Committee Member

H.S. Udaykumar

Fourth Committee Member

Sarah C. Vigmostad

Abstract

The formation of organized, functional tissues, and later in life, their limited regeneration in response to injury, or disease, are governed by cell-matrix interactions. Directing and optimizing tissue self-structuring and remodeling in these processes are progressing, but there is still a lack of understanding how these interactions are coordinated across various scales, especially in terms of the role of cell’s mechanical environment. This environment is affected by the organization, and the properties of the local extracellular matrix (ECM) in which physical forces are communicated at the cellular and fiber levels. Thus, mechanical cues along with biochemical and electrical cues contribute to a complex process of self-structuring and remodeling that necessitates the development of computational frameworks which can incorporate a large number of experiments into a comprehensive whole.

Theoretical development of the mechanics of ECM substrates has relied on making many simplifying assumptions. Continuum-based models are commonly used for these purposes, but they mostly do not consider the fiber-fiber interactions and non-affine microstructural reorganization of fibrous materials. Another limitation of these models is that they generally do not include autonomous mechanoresponsive cells. These cells generate forces that reorganize the ECM and alter their activity in response to forces from the ECM. The purpose of this work is to develop such a fiber-based computational model and to account for active cellular component to help understand the dynamics and reciprocal nature of the cell’s mechanical environment.

Pages

xii, 91 pages

Bibliography

Includes bibliographical references (pages 73-78).

Copyright

Copyright © 2016 Maziar Aghvami

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