Three-dimensional 10% cyclic strain reduces bovine aortic endothelial cell angiogenic sprout length and augments tubulogenesis in tubular fibrin hydrogels

The development of a functional microvasculature is critical to the long-term survival of implanted tissue-engineered constructs. Dynamic culture conditions have been shown to significantly modulate phenotypic characteristics and stimulate proliferation of cells within hydrogel-based tissue engineered blood vessels. Although prior work has described the effects uniaxial or equibiaxial mechanical stimulation has on endothelial cells, no work has outlined effects of three-dimensional mechanical stimulation on endothelial cells within tubular vessel analogues. We demonstrate here that 7 days of 10% cyclic volumetric distension has a deleterious effect on the average length and density of angiogenic sprouts derived from pellets of bovine aortic endothelial cells. Although both groups demonstrated lumen formation, the sprouts grown under dynamic culture conditions typically had wider, less-branching sprout patterns. These results suggest that prolonged mechanical stimulation could represent a cue for angiogenic sprouts to preferentially develop larger lumens over cellular migration and subsequent sprout length.