Table 5.

Nanotopographies investigated for corneal tissue regeneration.

Topography	Material used	Size	Cell type	Summary of findings	Ref.
Nanopillar	Tissue culture polystyrene coated with a mixture of fibronectin and collagen	250 and 1000 nm pillars	HCECs	The pillar patterns increased cell proliferation 2–3 folds depending on the seeding density. The tight junction protein ZO-1 production also increased 1.5 times in the 1000 nm pillars than in the unpatterned tissue culture polystyrene. The cells grown on the 250 nm pillars assumed polygonal shape and maintained the shape upon detachment from the patterned surface and reattachment onto other surfaces.	[40]
Nanopillar	Physically and chemically crosslinked gelatin methacrylate hydrogel fabricated by nano-imprinted polyethylene terephthalate	1000 nm pillar with 6 μm spacing	HCECs	Significantly higher expression of functional markers such as Na+/K+-ATPase and a 2-fold increase in ZO-1protein were obtained in cells grown on the nanopillars than on unpatterned films.	[155]
Groove and ridge topography	RGD peptide functionalized poly(ethylene glycol) diacrylate hydrogel fabricated with polydimethylsiloxane	400 nm pitch groove with 200–400 nm depth	HCEC	50% faster wound healing and 2x laminin-332 expression were obtained compared with cells grown on a flat surface.	[156]
Nanopillar and nano well	Nano-patterned polydimethylsiloxane coated with bovine fibronectin and bovine collagen-І as well as laminin and chondroitin sulfate	250 nm pillar and 1000 nm well and pillar	HCEC	Cells grown on the 1000 nm pillars coated with fibronectin-collagen had more regular morphology and expressed 1.2 times higher Na+/K+-ATPase and 2 times more ZO-1 compared with cells grown on the 250 nm fibronectin-collagen-coated pillars. However, on the laminin-chondroitin sulfate coated surfaces the 250 nm pillars exhibited higher ZO-1 expression than the 1000 nm pillars.	[157]
Nanopillar and nanowell	Nano-patterned polydimethylsiloxane substrates coated with poly(methylmethacrylate)	250 and 1000 nm pillars and wells	Bovine corneal endothelial cells	Significantly higher expression of Na+/K+-ATPase and ZO-1 activity were obtained on the 250 nm pillars compared with the nanowell and unpatterned substrates.	[41]

ZO-1, a tight junction protein used as a marker for assessing proper functioning of corneal endothelial cells; Laminin-332, an extracellular matrix protein used as a marker to evaluate the migratory status of cells upon epithelial wound healing; Na+/K+-ATPase, a marker for assessing proper functioning of corneal endothelial cells.