Biomimetic materials replicating Schwann cell topography enhance neuronal adhesion and neurite alignment in vitro

It is well established that Schwann cells (SCs) promote and enhance axon guidance and nerve regeneration by providing multiple cues, including extracellular matrix, cell surface molecules, neurotrophic factors and cellular topography. Which of the elements of the complex environment associated with SCs provides the essential information for directed nerve growth is unclear, because, until now, it has been impossible to investigate their contributions individually. Our development of biomimetic materials that replicate the micro- and nanoscale topography of SCs has allowed us to investigate for the first time the role of cellular topography in directing nerve growth. Dorsal root ganglion (DRG) neurons were cultured on flat poly(dimethyl siloxane) (PDMS) and on PDMS replicas with protruding SC topography. Image analysis showed that more neurons adhered to the replicas than to the flat substrates, and that neurite growth on the replicas followed the underlying SC pattern. Neuronal alignment was dependent on cell density. Live SCs derived from the DRG also grew along the replica SC pattern. These results suggest that the combination of micro- and nanoscale topographical cues provided by SCs can influence nerve growth and point toward design parameters for future nerve guidance channels.