Myocardial Infarction (MI) is the partial or complete blockage of blood flow to the myocardial tissue resulting in damage and therefore loss... Show moreMyocardial Infarction (MI) is the partial or complete blockage of blood flow to the myocardial tissue resulting in damage and therefore loss of heart function. In the U.S. every
40 seconds, someone will suffer from MI and the only available treatment is medication to
treat the symptoms of heart function loss, but do not treat the underlying cause. Some
attempts to treat the underlying cause have arisen in the last decades including cell-based
therapies or tissue engineering therapies such as spheroid-based cardiac patches that have
shown to be promising. Improvement in the mechanical properties to create suturable
engineered tissues remain to be improved for ease of implantation purposes. Cell-laden
hydrogel scaffolds can provide improved mechanical properties compared to biomaterial
free cell-based therapies but need to allow for vascularization of the engineered tissue.
Thus, the goal of this thesis is to provide preliminary studies for the use of a cell adhesive,
proteolytically degradable PEG hydrogel scaffold that eventually would be used as an invitro model to evaluate engineered tissue vascularization for cardiac tissue engineering. To
construct this model, important cell spheroid parameters on vascular invasion in 3D culture
were investigated including the total number of cells/spheroid, the supporting cell for
endothelial cells. In order to scale-up scaffolds to size of clinically relevant dimensions, a
multilayered hydrogel construct visible light free-radical polymerization approach
encapsulating vascular spheroids in multiple layers was also investigated. Results indicate
that a total cell number of 5000 cells/spheroid aggregate were feasible due to cell sourcing.
In addition, co-cultures of endothelial and mesenchymal stem cells led to maximized
vascular invasion of the spheroids compared to fibroblast/endothelial co-culture and
endothelial monoculture of spheroids in the hydrogel. Finally, the extent of vascularization
of spheroids in each layer of the multilayered hydrogel constructs varied due to the
observed differences in mechanical properties and swelling ratio of each layer due to
incomplete polymerization of layers. This study demonstrated the importance of support
cells and hydrogel mechanical properties in promoting vascularization of spheroid which
serves as basis for building cell-laden hydrogel scaffolds for vascularization for cardiac
tissues. Show less
