The influence of biomimetic topographic features and the extracellular matrix peptide RGD on human corneal epithelial contact guidance

摘要

A major focus in the field of tissue engineering is the regulation of essential cell behaviors through biophysical and biochemical cues from the local extracellular environment. The impact of nanotopographic cues on human corneal epithelial cell (HCEC) contact guidance, proliferation, migration and adhesion have previously been demonstrated. In the current report, we have expanded our study of HCEC response to include both biophysical and controlled biochemical extracellular cues. By exploiting methods for the layer-by-layer coating of substrates with reactive poly(ethylene imine) and poly(2-vinyl-4,4-dimethylazlactone) (PEI/PVDMA)-based multilayer thin films, we have incorporated a single adhesion peptide motif, Arg-Gly-Asp (RGD), onto topographically patterned substrates. This strategy eliminates protein adsorption onto the surface, thus decoupling the effects of the HCEC response to topographic cues from adsorbed proteins and the soluble media proteins. The direction of cell alignment was dependent on the scale of the topographic cues, and, to less of an extent, the culture medium. In EpiLife® medium, cell alignment to unmodified-NOA81 topographic features, which allowed for protein adsorption, differed significantly from cell alignment on RGD-modified features. These results demonstrate that the surface chemical composition affects significantly how HCECs respond to topographic cues. In summary, we demonstrate the modulation of the HCEC response to environmental cues through critical substrate and soluble parameters.