Table 1. Summary of cell response to nanotopographies.

Technique	Materials used	Pattern and dimension	Cell type	Cell responses	Ref.
Polymer demixing	PS/PBrS	Nanoislands with an average height of 11, 38 and 85 nm respectively	hFOB	Higher cell adhesion and larger cell size on 11 nm nanoislands.	[42]
				Similar ALP activity on 85 nm nanoislands and TCPS
Polymer demixing	PMMA	3:1000 imprint (height:45 nm, diameter: 2.2 μm, center-to-center distance: 4.3 μm)	HMSCs	Increased cell spreading, enhanced expression of stress fibers, tubulin and vimentin networks and higher OCN and OPN expression on nanotopographies compared to control	[47]
		3:3000 imprint (height: 33 nm, diameter: 1.7 μm, center-to-center distance: 2.9 μm)		Cells extending filopodia on hemispheres and curling around imprints
		Hemispheres (height:10 ± 1 nm, diameter: 144 ± 11 nm, spacing:184 ± 24 nm)
Polymer demixing	PLLA/PS	Pit-shaped topography of 14 nm, 29 nm, 45 nm deep respectively	hFOB	Higher cell coverage, αv integrin and paxillin expression on 14 nm and 29 nm	[46]
				Greatest cell attachment on 14 nm followed by 29 nm and 45 nm pits
				Invariant vinculin expression on pits
Photolithography	PMMA	Pit diameter to depth ratio: 30:310 nm (denoted as 30:300P) 40:362 nm (denoted as 40:400P)	hBMCs	hBMCs conformed, formed filopodial contact and exhibited increased cell spreading, increased tubulin and vimentin networks as well as OCN and OPN expressions on the pit patterns	[54]
				Larger hBMCs cell area, more defined stress fibers and mature nodule formation (after 21 days) on 40:400P
		Groove width to depth ratio: 5:510 nm (denoted as 5:500G) 50:327 nm (denoted as 50:300G)		Better contact guidance, significant reduction of cell area, highly aligned stress fibers along the groove direction and tubulin condensing along the ridges on 5:500G
				Aligned vimentin and increased areas of OCN and OPN production on groove patterns
EBL	PMMA	100 nm deep (D: 120 nm) PMMA imprints arranged:	MSC	Elongated, and aligned morphology with fibroblastic appearance on SQ and planar control	[49]
		SQ: in square array with center-to-center spacing of 300 nm		Decreased osteoprogenitor density on HEX
		HEX: hexagonal array		Increased level of OPN, OCN and mineralization on DSQ50 after 28 days
		DSQ50: randomly up to 50 nm on both axes from their position in a true square		Osteoblastic morphology and expressed foci of OPN on DSQ20
		DSQ20: randomly up to 20 nm on both axes from their position in a true square		Denser cell growth on RAND compared with planar PMMA
		RAND: randomly over a 150 μm by 150 μm field, repeated to fill a 1 cm2 area		Polygonal, osteoblastic morphology on RAND after 21 days
EBL	PC	PC imprints comprised of 120 nm diameter pits with 300 nm center-to-center spacing in SQ and HEX arrangements	Osteoprogenitor cell	Stellate cell structure, higher number of filopodia per μm of membrane and presence of cortical actin on PC imprints	[52]
				Higher cell spread on hexagonal arrangement and planar control Stress fibers on planar control
EBL	Polycaprolactone (PCL)	SQ: PCL imprints comprised of 120 nm deep pits in square arrangement with center-center spacing of 300 nm	MSC	SQ induced a switch from osteogenic stimulation to a surface conducive to MSC growth and permitted prolonged retention to MSC markers and multipotency	[50]
		NSQ50: PCL imprints comprised of 120 nm deep pits with ±50 nm offset in both x- and y- axes		MSC differentiated into osteogenic cells on NSQ50 and OGM controls after four and eight weeks
				STRO-1, ALCAM, OPN and OCN markers expressed by cells on NSQ50 and OGM
				Increased OPN expression on NSQ50 and OGM after a few weeks
				Cells exhibited raised/similar metabolomic profiles on NSQ50 and OGM compared to SQ

Abbreviation: OGM, osteogenic media.