Biomechanics and modeling methods for quantifying mechanically-mediated disease progression in neglected populations
Caulk, Alexander Wilson
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It is well known that biological tissue grows and remodels in response to changes in mechanical loading. Arteries and lymphatic vessels share many similar mechanical loads including luminal pressure, axial force, and fluid shear force on the endothelium. Diseases of vascular systems have previously been associated with deviations from a hypothesized “preferred” homeostatic mechanical environment and maladaptive growth and remodeling. Mechanically-mediated disease development affects many populations, but developing nations face challenges that are unique due to disease burdens that are region-specific. Treatment strategies for HIV have resulted in HIV-positive patients living longer lives, but these patients also suffer from non-AIDS-related comorbidities including vascular remodeling and accelerated progression of cardiovascular disease. Similarly, lymphatic filariasis often leads to lymphedema, a condition characterized by tissue swelling and fibrosis as well as remodeling of the lymphatic vasculature. Disease burden in sub-Saharan Africa is due in large part to pathologies such as these; yet, studies investigating the role of biomechanics in disease development in these populations are limited. Thus, the purpose of this dissertation is to develop novel experimental and theoretical frameworks for the study of mechanically-mediated diseases of the arterial and lymphatic vasculature that are commonly seen in developing nations with the ultimate intention of identifying key parameters that contribute to tissue growth and remodeling leading to disease progression.