Date of Award

Summer 7-17-2014

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Advisor

Virginia L. Ferguson

Second Advisor

Mark E. Rentschler

Third Advisor

Karen Jonscher

Abstract

Despite significant advances in medical research, spontaneous preterm birth (SPTB) rates have not changed appreciably in over 100 years. SPTB is a global problem affecting 13 million babies annually and continues to be the leading cause of death among infants. During pregnancy, the cervix and chorioamnion (CA), the sac that surrounds the fetus during pregnancy, provide critical structural support for the growing fetus that requires optimum maintenance of tissue properties for sustaining pregnancy. This dissertation aims to elucidate the events leading to tissue failure in pregnancy by evaluating detrimental alterations in the extracellular matrix (ECM) chemistry and organization and tissue material properties that result in gross structural or functional tissue changes. To study tissue material property losses in the cervix, a novel technique was developed using ultrasound elastography (UE) by coupling ultrasound with a strain dimension to measure applied in vivo strains. A standardized method for UE image collection, using reference standards, image analysis, and an analytical solution that incorporated Hertzian contact mechanics, was developed and validated on tissue phantoms to measure in vivo tissue stiffness. With further validation on the human cervix and other heterogeneous materials, this technique shows promise for monitoring cervical stiffness in vivo to detect premature softening. To elucidate mechanisms that cause preterm rupture of CA, this dissertation characterized material properties and ECM composition and organization of both the amnion and chorion in term membranes with different modes of rupture. Clinically strong membranes (i.e. artificially ruptured CA) demonstrated an increased modulus in the rupture region of chorion and intact CA, but not in the stiff amnion. These results suggest that failure of the chorion to support and integrate with the amnion may play a large role in causing preterm rupture. Overall, the studies included in this dissertation provide novel approaches to measuring material properties and detecting ECM alterations in tissues that are critical for providing structural support during gestation. Thus, the work described in this thesis motivates future studies that could evaluate how the collective influences of cervical and CA gross structure and function link with ECM biochemistry, structure, and organization to ultimately lead to SPTB.

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