ORCID Identifier(s)

0000-0001-6712-3353

Graduation Semester and Year

2020

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Michael Cho

Abstract

Elastin is an essential structural protein responsible for the elasticity of many tissues, including skin, lungs, blood vessels, and other highly dynamic tissues and organs in the body. In the heart, cardiac elastin has been largely ignored as one of the key players in heart health and functionality. In this study, we will fill the knowledge gap with novel experiments and biomechanical investigations that will allow us to understand the roles of elastin in cardiac biomechanics, as well as explore the bioengineering applications of elastin-rich cardiac tissues. For Aim 1, we performed a biomechanical and ultrastructural comparison of the elastin-rich porcine neonatal aorta (AA) and pulmonary artery (PA) as compared to these same tissues in adult specimens. We showed the differences in mechanical properties and ultrastructural elastin between neonatal AA/PA and adult AA/PA, and demonstrated that the biomechanical variations were caused by the differences in tissue structural compassions and organization. Uniaxial stress-strain behavior, tissue stress relaxation, tissue creep, biaxial property, and open angle residual stress characterization were reported and thoroughly compared among neonatal AA, neonatal PA, adult AA, and adult PA. Histological images showed that the neonatal AA/PA consisted of dominantly elastin fibers and the elastin network was lack of smooth muscles, which apparently would add the needed cell functionality and alter the tissue mechanical properties along with the developmental process. In Aim 2, we investigated the biomechanics of the elastin-rich epicardium and endocardium and correlated the biomechanical properties to their unique elastin ultrastructure. Our group has recently reported that heart epicardial layer, rich in elastin, acts like a prestrained ‘balloon’ that wraps around the heart and functions as an extra confinement and protective interface for the heart ventricle. In this Aim, we investigated the elastin-rich endocardium, an important interface on the inside of the heart ventricular wall. Uniaxial stress-strain behavior, stress relaxation, and creep behavior of the endocardium were assessed and compared with the epicardium. Prestrains of the endocardium were also qualified using marker technique to fill the missing knowledge gap. Together with previously reported epicardial prestrains, our understanding of heart ventricular wall interfaces will be more completed. Lastly, we designed and fabricated a simple uniaxial stretcher that could be mounted onto a Laser Scanning Confocal Microscope (LSCM). With this stretcher, we were able to perform real time imaging to reveal the elastin fiber kinematic in fresh epicardium. This proof-of-concept study established a protocol to study elastin fiber kinematics in epicardium and endocardium by using the autofluorescent property of elastin and a miniature tissue stretcher fitting to LSCM. In Aim 3, we explored the bioengineering application of the acellular, elastin-rich epicardium as a potential tissue-derived patch material for myocardial infarction (MI) treatment. Epicardium had the needed elastin structural composition and mechanical properties, serving as a protective interface in cardiac biomechanics. A major challenge in in vivo application would be the fast degradation of elastin fibers after implantation. We hence proposed a treatment to slow down the degradation of the acellular epicardium using a novel cross-linking technique. Pentagalloyl glucose (PGG) cross-linked acellular epicardium was hence fabricated and assessed its readiness in structural integrity, biomechanical properties, and biocompatibility. We performed biaxial and uniaxial mechanical characterizations and compared the properties among decellularized (DEC) epicardium, PGG cross-linked decellularized (PGG-DEC) epicardium, and glutaraldehyde cross-linked decellularized (glut-DEC) epicardium. We also performed cell viability study and degradation assessment of these three types of scaffolds to compare their cytotoxicity, cell biocompatibility, degradation under the treatment of elastase, a protease that specifically targets elastin in degradation. We found that that PGG-DEC epicardium preserved structural integrity and optimal mechanical properties, as well as demonstrated desirable biocompatibility and scaffold degradation rate, rendering it a promising scaffold material for cardiac patch tissue engineering.

Keywords

Cardiac biomechanics, Cardiac elastin, Epicardium, Endocardium, Neonatal aorta, Neonatal pulmonary artery, Scaffold, Cardiac patch

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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