Date(s) - 04/02/2013
One of the largest problems facing the field of regenerative medicine is the delivery of nutrients to cells seeded deep within engineered tissues and organs. Improving nutrient delivery in ex vivo derived tissue scaffolds is especially complicated because they have pre-existing extracellular matrix architectures. However, the use of ex vivo derived tissue scaffolds remains popular because of their biochemical makeup. In these studies, we analyze and modulate nutrient deficiencies present in the model ex vivo derived human umbilical vein (HUV) scaffold, which has potential applications as a vascular graft. To better develop the HUV as a vascular graft, its physical barriers and other tissue specific mass transfer limitations were analyzed so that conditions such as decellularization and nutrient delivery could be optimized. Next, controlled oxygen gradients were used to increase the migration of smooth muscle cells into oxygen deprived regions of the HUV bioscaffold. Finally, we attempted to provide a long-term mechanism for the delivery of nutrients by inducing the formation of a nutrient rich microvessel system. Overall, our goal was to overcome the mass transfer limitations that have historically impeded attempts to densely populate the HUV with cells, and then to provide a long-term solution to sustain these high-cell densities. These investigations have shown that the creation of engineered tissues from ex vivo derived scaffolds can be aided by selective decellularization to optimize mass transfer and cellular integration characteristics. Additionally, the use of controlled and directed oxygen gradients in vitro was shown to significantly enhance the initial stages of construct maturation and cell migration. Finally, after deriving a pro-angiogenic extract, it was shown that we can induce and modulate the initial stages of microvessel formation within the HUV bioscaffold.