Cody Crosby, M.S.E.
Department of Biomedical Engineering
The University of Texas at Austin
Ph.D. dissertation defense will take place virtually on July 28th, 2020
***The data contained within the last section of the summary will be posted to a preprint server soon.
Summary: Induced pluripotent stem cell-derived endothelial progenitors (iPSC-EPs) have emerged as a promising candidate cell source for patient-specific ischemic therapies. Therefore, it is imperative to study the mechanisms of CD34+ iPSC-EP-driven vascular network assembly in extracellular matrix (ECM)-mimicking, three-dimensional microenvironments. We quantified the vasculogenic potential of iPSC-EPs with a novel computational pipeline and found that the addition of a ROCK pathway inhibitor and exogenous vascular endothelial growth factor were imperative for inducing robust iPSC-EP vasculogenesis; in contrast, increasing the concentration of collagen in the hydrogels abrogated network formation and encouraged the formation of disconnected, large-diameter lumens. Notably, physically crosslinked collagen hydrogels compacted rapidly and exhibited limited strength. To address these limitations, we synthesized a hybrid interpenetrating polymer network (IPN) hydrogel comprised of collagen and norbornene-modified hyaluronic acid (NorHA). We modulated the stiffness and degradability, respectively, of this novel IPN hydrogel by varying the concentration and sequence of the peptide crosslinker. Our results suggested that an IPN hydrogel consisting of collagen and NorHA was highly tunable, resisted compaction, and stimulated angiogenesis. Our two studies underscore the importance of understanding the role of mechano-regulation on vasculogenesis so that ECM-mimicking angiogenic biomaterials can be effectively deployed in the clinic and ultimately improve vascular health.