Enhancement of in vitro capillary tube formation by substrate nanotopography
Tissue engineering scaffolds often aim to control cell behavior using a variety of signaling modalities including chemistry, mechanical properties, and local microenvironmental factors such as oxygen concentration. However, few efforts have explored the use of nanotopography as a means to regulate cell function. Controlling the morphology and function of cells using substrate nanotopography is a phenomenon that can be utilized in a variety of fields including tissue engineering and regenerative medicine. In this work, we explored the possibility of using nanofabricated surfaces to control the function of endothelial cells to ultimately enhance in vitro vasculargenesis. We chose to culture endothelial progenitor cells (EPCs) on poly(dimethylsiloxane) substrates with ridge-groove geometries of approximately 600 nm in width. EPCs cultured on nanotopographic were found to exhibit enhanced morphological alignment and elongation, reduced proliferation, and enhanced migration. Protein-level expression of endothelial cell markers was not significantly affected by topography, as determined by fluorescent microscopy. However, an in vitro capillary tube formation assay induced the formation of larger, more organized vascular structures in EPCs cultured on nanotopographic versus flat substrates. These results suggest substrate nanotopography could function as a tool for controlling EPC function and achieving enhanced vasculargenesis. Furthermore, these nanotopographic substrates could serve as a template for engineering more complex vascularized tissues and organs.