Table 1.

Summary of the substrates properties and the cellular responses they evoked.

Grooves/Channels
Material	Dimension		Cell/tissue	Remarks	Ref.
Width/Diameter	Depth/Height
PMMA	10, 25, 100 μm	330 nm	HOBs	Decreased nanogroove widths led to increased contact guidance, decreased adhesion and increased angiogenic gene expressions	78,79
	2, 3, 6, 12 μm	0.2, 0.5, 1.1, 1.9 μm	Baby hamster kidney cells,	Increased alignment with increased depth and decreased with increased width.	21,80
PDMS	5, 10, 20, 60 μm	25 μm	Human neural stem cell	Increased alignment and induced neurite growth with decreased micropattern dimensions. Increased neuron density but altered neurite alignment with increased micropattern dimesions.	81
	30 μm	10 μm	VEC	Orientation along grooves; changes in gene expression	82,83
	20–60 μm	11 μm	VSMC	Enhanced alignment of cell/nuclei on narrow grooves	83,84
	20, 50, 80 μm	5, 12 μm	VSMC	Enhanced cell/nuclei aspect ratio and cell alignment	83,85
	3.5 μm	0.2–5 μm	VEC	Orientation along grooves; no change in proliferation	83,86
	2–10 μm	50–200 nm	VSMC or VEC	Cell orientation and migration along grooves; enhanced cell elongation	19,83
	1200 nm	600 nm	VEC	Increased cell elongation, alignment and migration along grooves and reduced cell proliferation	83,87
	600 nm	600 nm	Human embryonic stem cells	Reduced cell proliferation	21,87
PS	10 μm	3 μm	Rat astrocytes	Low adhesion, strong alignment	21,88
	1–10 μm	0.5–1.5 μm	Rat bone marrow cells	On large grooves, focal adhesions cover the surface, On narrow grooves, focal adhesions are only on edges	21,89
	1, 2, 5, 10 μm	0.5, 1, 1.5 μm	Rat bone marrow cells	Better mineralization with 1 μm depth and 1–2 μm width	89
	20–1000 nm	5–530 nm	Fibroblasts	No alignment for depths ˂ 35 nm or widths ˂ 100 nm	21,90
Polyimide	4 μm	5 μm	Osteoblasts	Strong alignment, no change in adhesion	9,21
PDLA	10 μm	3 μm	Schwann cells (nerve cells)	Strong alignment	21,91
PHBV	1–10 μm	5–30 μm	Rat mesenchymal stem cell-derived osteoblasts	Increased osteoblast adhesion and alignment	79,92
PLGA	350, 700, 1050 nm	500 nm	VEC	Enhanced adhesion strength, Increased cell alignment along grooves	83,93
Ti	750 nm- 100 μm	200 nm	VEC	Increased cell alignment along grooves and higher cell density on grooves with width < 10 μm	83,94
Quartz	0.5,5,10, 25 μm	0.5, 5 μm	Murine macrophage	Increased orientation	21,95
	12.5 μm	5 μm	Fibroblasts	Change in gene expression profile	21,96
	1, 4 μm	1.1 μm	MSC	Alignment better in the wider grooves	21,97
	2–10 μm	30–280 nm	Murine macrophage	Higher phagocytotic activity when topography size is equal to collagen fiber size	21,98
TCPS	5, 45 μm	5 μm	Primary (glioma) and metastatic (lung and colon) tumors	Induced migration of primary and metastatic brain, lung and colon cancer cells	99
HA on PET	5, 25 μm	–	Articular knee chondrocytes	Induced adhesion, migration, alignment, and differentiation of chondrocytes	79,100
Collagen	27 μm	12 μm	Mesenchymal osteoprogenitor cells	Cell alignment and enhanced bone formation	53
	10 μm	30 μm	Human corneal keratocytes and D407	Higher mechanical properties on patterned collagen films	101
	650, 500, 332.5 nm	300, 250, 200 nm	HMEC	No change in proliferation and has a minimal effect on cell alignment, enhanced cell retention under flow-shear conditions	67
Collagen coated with fibrinogen	27 μm	12 μm	Rat bone marrow osteoblast cells	Enhanced cell orientation and bone formation	102
Ti— coated Si	15 μm	200 nm	T24	Less round and smaller cell shape	21,103
Pillars
Material	Dimension		Cell/tissue	Remarks	Ref.
	Width/Diameter	Depth/Height
PMMA	4, 8, 16 μm	8 μm	DPSC	Control of fate of the stem cells	60
	100 nm	160 nm	Fibroblasts	Smaller, less organized actin cytoskeleton	21,104
	100 nm	160 nm	Fibroblasts	Less spreading	21,105
PLGA	4, 8, 16 μm	8 μm	Saos-2, L929, SH-SY5Y, MCF7, hOB	Nuclear deformation in cancer cells (Saos-2, MCF-7, SH-SY5Y) not in noncancerous cells (hOB, L929)	58
	3 μm	7 μm	MSC	Geometry of cell nuclei responds to the micropillar array	106
	3 μm	5 μm	BMSC	Severe nucleus deformation, no change in proliferation and differentiation	107
PLGA and PDMS	30 μm	4, 9 μm	NIH 3T3 fibroblasts	On PDMS, 3T3 cells on stiffer (longer) pillar area. No such effect on PLGA.	108
PDMS	1–5.6 μm	1–8 μm	VEC	Enhanced cell alignment and elongation on PDMS pillars	109
PDMS coated with fibronectin	10 μm	10 μm	MCF-10 A, MDA-MB-231	Epithelial to mesenchymal transition of the breast cancer cells within enclosed micropillar arrays	110
PLLA	2–20 μm with interpillar spaces 2–20 μm	5–6 μm	Saos-2, MG-63, OHS4	Nuclear deformation in cancer cells (Saos-2) higher than in healthy counterparts (OHS-4 and MG-63). Saos-2 cells deformed severely on pillars with 5–10 μm spacing.	111
PLLA, PLLA: PLGA blend	200 nm	900 nm	Saos-2, BMSC	Saos-2 cells populated fields with pillars 1 μm apart but not on pillar-free surfaces. BMSCs avoided fields with interpillar distances <2 μm.	112
Collagen and PLGA	8, 16 μm	8 μm	Saos-2	Increased proliferation and ALP production on collagen micropillars. Increased nuclear deformation on PLGA micropillars	113
Ti	21 nm	15 nm	BMSC and hBMHCs	Improved bone deposition on nanopillars	114
Alumina	110 nm	–	Mouse bone marrow stem cells	Increased proliferation and differentiation	21,115
Wells/Pits
Material	Dimension		Cell/tissue	Remarks	Ref.
	Width/Diameter	Depth/Height
PMMA	120 nm	100 nm	MSC	Stimulated differentiation and production of bone mineral in vitro	21,116
	35, 75, 120 nm	–	Fibroblasts	Reduced adhesion, orientation and distinction of symmetries	21,[117], [118], [119]
PDMS	2, 5, 10 μm	–	Human fibroblasts	2 and 5 μm showed better proliferation 10 μm showed no effect	21,120
PC	7, 25, 50 μm	0.5, 1.5, 2.5 μm	Fibroblasts	No orientation	21,121
Titanium	100, 30, 10 μm	–	MG63	Cell attachment, growth, aggregation and morphology depends on the presence and dimension of the micropatterns	79,122
PCL	30 μm	80, 220, 333 nm	BMSC	Optimal adhesion on 80 nm deep pits, inductive capability on 220 nm deep pits	123
	150 nm	80 nm	Fibroblasts	Less focal contacts and vinculin F-actin cytoskeleton less developed	21,124

*Cells (hOB: primary human osteoblasts, MSC: mesenchymal stem cells, VEC: vascular endothelial cells, VSMC: vascular smooth muscle cells, DPSC: human dental pulp mesenchymal stem cells, HMEC: human microvascular endothelial cells, BMSC: bone marrow stem cells, Saos-2: osteosarcoma cells, MCF-10 A: mammary epithelial cells, MDA-MB-231: breast adenocarcinoma cells, MG63: osteoblast like cells, OHS4: human osteosarcoma cells, L929: mouse fibroblast cell, SH-SY5Y: human neuroblastoma cells, T24: human bladder carcinoma, D407: retinal pigment epithelial cells, hBMHCs: human bone marrow hematopoietic cells).

**Polymers (HA: hyaluronic acid, PET: polyethylene terephthalate, PLLA: poly(l-lactic acid), PMMA: poly(methylmethacrylate), PDMS: polydimethyl siloxane, PLGA: polylactic acid-co-glycolic acid, PCL: polycaprolactone, PC: polycarbonate, PS: polystyrene, PDLA: poly(D,l-lactic acid), PHBV: poly(hydroxybutyrate-co-hydroxyvalerate), TCPS: tissue culture polystyrene).