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Three-dimensional Mesenchymal Stem Cell Spheroids and Zn-based Biomaterials as Potential Cardiovascular Treatments
Date of Award
Campus Access Dissertation
Doctor of Philosophy in Biomedical Engineering (PhD)
Administrative Home Department
Department of Biomedical Engineering
Committee Member 1
Committee Member 2
Committee Member 3
Mesenchymal stem cells (MSCs) are known for their therapeutic capabilities. In this work, physiologically relevant low oxygen culture is combined with a three-dimensional culture condition to further mimic the in vivo condition and enhance the regenerative properties of the MSCs. MSCs spheroids cultured under low oxygen showed enhanced extracellular matrix (ECM) and growth factor production, as well as stemness, viability and structural integrity. These spheroids can be used for a variety of applications such as injection after a myocardial infarction and acting as model tissues in vitro. Other cardiovascular treatments were explored within this work, including biodegradable stents for coronary arteries. Zinc (Zn) are a potential base metal for biodegradable vascular stents, but a thorough understanding of how these Zn and Zn2+will affect surrounding vascular cell types was currently lacking. This comparative study looked at three vascular cell types- endothelial cells, smooth muscle cells, and fibroblasts. Aqueous and direct cytotoxicity were investigated, as well as attachment, spreading, and migration. Preliminary in vivo data for Zn is also presented. Finally, Zn (2-methylimidazole)2 (ZIF-8) particles were investigated for their effects on cells and drug-releasing characteristics and how these properties can be enhanced with a simple introduction of defects. ZIF-8 particles can be loaded with cardiac therapeutics for treatment after a myocardial infarction for a temporal and spatial release of the drug relevant to the healing phases of the heart tissue.
Shearier, Emily, "Three-dimensional Mesenchymal Stem Cell Spheroids and Zn-based Biomaterials as Potential Cardiovascular Treatments", Campus Access Dissertation, Michigan Technological University, 2015.