Cell growth as a sheet on three‐dimensional sharp‐tip nanostructures

Cells in vivo encounter with and react to the extracellular matrix materials on a nanometer scale. Recent advances in nanofabrication technologies allowing the precise control of a nanostructure's pattern, periodicity, shape, and height have enabled a systematic study of cell interactions with three‐dimensional nanotopographies. In this report, we examined the behavior of human foreskin fibroblasts on well‐ordered dense arrays (post and grate patterns with a 230‐nm pitch) of sharp‐tip nanostructures with varying three‐dimensionalities (from 50 to 600 nm in structural height) over time—until a cell sheet was formed. Although cells started out smaller and proliferated slower on tall nanostructures (both posts and grates) than on smooth surfaces, they became confluent to form a sheet in 3 weeks. On grate patterns, significant cell elongation in alignment with the underlying pattern was observed and maintained over time. On tall nanostructures, cells grew while raised on sharp tips, resulting in a weak total adherence to the solid surface. A sheet of cells was easily peeled off from such surfaces, suggesting that nanoscale topographies can be used as the basis for cell‐sheet tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009