Date of Award

8-26-2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering

Advisor(s)

Zhen Ma

Subject Categories

Biomedical Engineering and Bioengineering | Engineering

Abstract

Temporal and spatial mechanical cues play an important role in heart development, function, and disease manifestation. A deeper understanding of cardiac mechanobiology is especially important for fundamental biology and clinical diagnosis or heart disease treatment. Currently, human induced pluripotent stem cells (hiPSCs) are widely used to build human cell or tissue models, but culturing them in a petri dish fail to recapitulate the mechanical complexity in the native heart. To create a mechanical environment with better pathophysiological relevance, biomaterial scaffolds are usually employed to mimic the mechanical cues originated from extracellular matrix (ECM) remodeling. The goal of this dissertation is to introduce both spatial and temporal mechanical complexity in the biomaterial scaffolds to produce more in vivo like models or guide the organization of cardiac cells.Shape memory polymers (SMPs) are stimuli-responsive materials that can change their shape triggered by specific stimuli. This on-demand shape transformation property enables them to provide a temporal mechanical modulation to the cultured cells. By combining the SMP, microcontact patterning and hiPSCs, we developed a dynamic model under single cell level to mimic the eccentric remodeling in a diseased heart. hiPSC derived cardiomyocytes (hiPSC-CMs) showed significant sarcomere damage and contractile dysfunction during their remodeling. hiPSC-CMs carrying different mutations demonstrated distinct abnormality to the eccentric remodeling. Two photon polymerization (TPP) is featured by its high-resolution printing capability in 3D scaffolds, and it was used to introduce the spatial mechanical difference. A nonuniform scaffold fabricated by TPP induced hypercontractile behaviors of the cardiac tissue. Metamaterials with different unit geometries printed by TPP guided different ways of mesenchymal tissue organization, which could direct the scaffold optimization for cardiac tissue engineering.

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Open Access

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