Date of Award

Summer 2021

Document Type

Open Access Thesis

Department

Biomedical Engineering

First Advisor

John F. Eberth

Abstract

Aortopathies refer to a broad class of pathological conditions affecting the aorta and are a major cause of morbidity and mortality in the US. Specifically, aortic aneurysms and aortic dissections have diverse etiologies that are initiated by alterations in the tissue’s extracellular-matrix (ECM) proteins, namely collagen and elastin, thereby predisposing the aortic wall to weaken and rupture. Pentagalloyl glucose (PGG) has recently emerged as a non-surgical treatment to reduce the risk of dissection or rupture. PGG is a known antioxidant and anti-inflammatory which has been shown to have ECM-restorative qualities that enhance collagen and elastin’s functional properties. Prior studies using PGG were largely performed in vivo or acutely in vitro; here, we aim to create a controllable, repeatable, fast, and inexpensive in vitro experimental platform to allow testing of this and other vascular therapeutics. To that end, we first created and validated the in vitro platform by ensuring that cultured aortas maintained viability and mechanical properties for up to 2 weeks using multiple freely floating and stress-free configurations within a nutating mixer bioreactor. Next, we used this platform to investigate the effect of PGG on otherwise healthy thoracic aortas. Finally, we used tissues taken from a genetic mouse model of elastin damage, Marfan Syndrome (Fbn1C1041G/+), to test PGG’s restorative capability on diseased aortas.

Rights

© 2021, Shahd Ali Hasanain

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