All ETDs from UAB

Advisory Committee Chair

Jianyi Jz Zhang

Advisory Committee Members

Joel Jlb Berry

Alan Awe Eberhardt

Palaniappan Ps Sethu

Chao Cz Zhao

Wuqiang Wz Zhu

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

The human heart is an exceptionally complex muscular organ that is vital for survival. Electrical impulses signal activation of mechanical contractions, pumping blood through the entire body and allowing for oxygen-exchange to occur. Unfortunately, certain disease states or traumatic injuries such as myocardial infarctions hamper the heart’s efficiency and function by damaging its structure. Ideal treatment would allow for the replacement or regeneration of the damaged tissue with cells and material harvested from the patient, thus avoiding the potential for immune rejection. Engineered cardiac tissues fabricated from human induced pluripotent stem cells have shown great promise for restoring function in infarcted left ventricular myocardium, and since these induced pluripotent stem cells originate from reprogrammed somatic cells, they also skirt the ethical issues associated with the use of embryonic stem cells. For engineered cardiac tissue constructs to reach their translational potential, they need to be of a clinically relevant volume and thickness, while also being capable of generating synchronous and forceful contraction to assist the pumping action of the recipient heart. Design requirements necessitate a thickness sufficient to produce a useful contractile force, prevascularization to overcome diffusion limitations and sufficient structural development to allow for optimal cell communication. Previous attempts to meet these requirements have been hampered by diffusion limits of oxygen and nutrients, which occur within 100-200 µm of the boundary conditions, resulting in necrosis. Herein we develop a viable three dimensional engineered cardiac tissue model of the left ventricular myocardium fabricated from multi-lineage human induced pluripotent stem cell-derived cells. A novel layer-by-layer fabrication method will be employed to mimic the native myocardium in both form and function, while also minimizing the potential for necrosis. The engineered constructs will be evaluated and characterized in terms of cell fate and migration, extracellular matrix development, viscoelastic properties, ultrastructure development as well as their electrophysiological properties.

Included in

Engineering Commons

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