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Advisory Committee Chair

Jianyi Zhang

Advisory Committee Members

Joel L Berry

Lee G Moradi

Palaniappan Sethu

Abidin Yildirim

Wuqiang Zhu

Document Type

Dissertation

Date of Award

2020

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

The human heart is one of the more complex organs in the body to study and understand given the structural and functional characteristics it possesses. These characteristics work in synchrony to transfer oxygen-rich blood to vital organs throughout the body and oxygen-deficient blood back to the lungs for oxygenation. Furthermore, it can be reasoned that when these complexities are compounded with disease states which negatively affect the structure and function of the heart, determining the best treatments while also limiting adverse side effects becomes increasingly more challenging. While the goal of having patient-specific therapies has not completely been realized, the discovery of induced pluripotent stem cells has started to help bridge the gap. Given the patient specific origins of the cells, their projected potential use in cardiac specific therapies has grown significantly. However, the cardiomyocytes that can be derived from these stem cells are not adult-like in structure or function. The maturity of cells that are used in certain therapies is vital to understand exactly how the patient’s cells will respond. In addition, cardiomyocytes interact in vivo in a three dimensional manner so a true tissue surrogate for testing of therapeutic approaches should be as close to the three dimensional cardiac tissue environment as possible, but currently there are no proven in vitro models or techniques to efficiently generate these three dimensional, mature tissue equivalents. Given these limitations, we aim to improve the maturation of human induced pluripotent stem cell derived cardiomyocytes in a three dimensional tissue construct using novel techniques and devices. Three dimensional constructs known as spheroids will be generated and exposed to electrical and mechanical stimuli to enhance the maturity of the cardiomyocytes and to better understand how the cells respond three dimensionally to these regimes. The innate ability of these spheroids to fuse together will be used in conjunction with a novel bioprinter to construct three dimensional tissues. To effectively culture and mature these bioprinted tissues, a bioreactor platform will be designed to provide simultaneous electrical and mechanical stimuli to be used in the elucidation of the proper regimens needed to engineer adult-like cardiac tissues.

Video S1. Layer-by-layer bioprinting process..wmv (48607 kB)
Video - S1 bioprinting process

Video S2. Alginate bead synthesis..wmv (26824 kB)
Video - S2 alginate bead synthesis

Video S3. Printing of alginate beads onto the needle array..wmv (20604 kB)
Video - S3 printing beads onto needle array

Video S4. Printing of two layers of alginate beads onto the needle array..wmv (50107 kB)
Video - S4 printing 2 layers of beads onto needle array

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