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. 2019 Oct 18;15(4):573–585. doi: 10.4103/1673-5374.266907

Table 1.

Summary of anisotropic topographies influence on neuronal differentiation

Type(s) of topography Material Starting cell type Mechanistic study (Y/N) Major findings Study
Nano-/micro-patterning
Equally space nanogratings (H = 150 nm and 560 nm, W = 500 and 1000 nm).
Hexagonally arranged nanopillars (H = 150 or 560 nm, D = 500 nm)
Poly(dimethylsiloxan) incubate with 1% Geltrex iPSC Y (YAP expression) Gratings with heights of 560 nm showed the best performance, reducing cell proliferation, enhancing cytoplasmic localization of YAP and promoting neuronal differentiation (compared to the flat control). YAP localizations are critical to induce neural differentiation. Song et al. (2016)
Nanogratings (H = 250 nm, W = 250 nm,
1 μm, 10 μm, S = 500 nm, 2 μm, 20 μm)
Poly(dimethylsiloxan) coated with bovine fibronectin MSC Y (focal adhesion kinase) Gratings with 250 nm line widths upregulated neurogenic and myogenic differentiation markers. Focal adhesions on nanogratings were smaller and more elongated than those seem on micro gratings or control. Teo et al. (2013)
Nanogratings (H = 300 nm, W = 350 nm, 2 μm, and 5 μm) Poly(dimethylsiloxan) coated with 1:80 diluted Matrigel iPSC N Neuronal marker expression was inversely proportional to width. Pan et al. (2013)
Nanogratings (H = 350 nm, W = 350 nm, 1 μm, 10 μm; S = 700 nm, 2 μm, 20 μm) Poly(dimethylsiloxan) coated with bovine collagen I MSC N The effect of nanogratings alone was greater than the effect of retinoic acid on flat substrates, regarding upregulation of neuronal markers. Yim et al. (2007)
Nanogratings (H = 500 nm, S = 250 nm) Polyurethane acrylate on glass coverslip ESC N Nanoscale gratings alone can induce the differentiation of ESC into a neuronal lineage without the use of differentiation-inducing agents. Lee et al. (2010)
Nanogratings (H = 625 nm, W = S = 1.5 μm) Nanopores (S = 28 nm, pore size = 10 nm) Hierarchical (combination of nanopores and nanogratings) Polystyrene-poly(methyl methacrylate) random copolymer and polystyrene-poly(methyl methacrylate) block copolymer NSC Y (β1 integrin-mediated binding, intracellular Rho-associated protein kinase pathway Cells have a mechanical memory of the conditions under which neuronal differentiation was induced. Enhanced neuronal differentiation persisted even after the removal of the hierarchical pattern. Yang et al. (2014)
Microgratings (H = W = S = 2 μm) Poly(dimethylsiloxan) coated with Matrigel ESC and iPSC N The effect of topography is additive. An initial exposure to 2 μm increase neural differentiation rate and an additional culture period can improve neural differentiation. Chan et al. (2012)
Microgratings (H = W = S = 2 μm) Micropillars (H = 2 μm, P = 12 μm and D = 2 μm) Poly(dimethylsiloxan) coated with poly-L-ornithine, fibronectin and laminin iPSC N Gratings are beneficial for early stage of differentiation (lineage commitment). Pillars are beneficial for later stages (maturation). Sequential application resulted in significantly increased overall differentiation rate. Tan et al. (2018)
Nanogratings and microgratings:
i. H = W = S = 250 nm
ii. H = 120 nm, S = 1 μm, W = 2 μm
iii. H = 80 nm, S = 2 μm, W = 1 μm
iv. H = W = S = 2 μm Nanopillars:
v. H = 1 μm, P = 6.5 μm, H = 1 μm Nanowells:
vi. H = 2 μm, P = 12 μm, H = 2 μm Hierarchical:
vii. 250 nm gratings with 250 nm space perpendicular to 2 μm gratings.
Poly(dimethylsiloxan) coated with poly-L-ornithine and laminin ESC N High throughput topography screening. Anisotropic patterns promote neuronal differentiation and isotropic patterns promote glial differentiation. Ankam et al. (2013)
Nanogratings and Microgratings (H = 0.35 μm, 0.8 μm, 2 μm and 4 μm, W = 2 μm, S = 2 μm) Poly(dimethylsiloxan) coated with poly-L-ornithine and laminin NPC Y (cytoskeletal bending) Cells can sense the depth of micro-gratings. Neurite elongation, alignment and neuronal differentiation increased with grating depth. Filopodial adhesion in growth cones favour elongation but the neurite cytoskeleton resists it. Chua et al. (2014)
Electrospun fibers
Aligned and random nanofibers, D = 250 nm Electrospun polycaprolactone ESC N Aligned nanofibers enhanced differentiation into neural lineage and directed neurite outgrowth Xie et al. (2008)
Aligned and randomly oriented nanofibers, D = 260 nm, 480 nm and 930 nm Electrospun polycaprolactone coated with poly-L-ornithine and laminin NSC Y (Wnt Signaling) Highest yield of neuronal progenitors on 480 nm aligned fibers, due to selectivity against oligodendrocytes and increase in canonical Wnt signaling. Lim et al. (2010)
Aligned nanofibers, D = 270 nm Electrospun polycaprolactone and gelatin MSC N Aligned fibers up-regulated neural markers at both the protein and mRNA level, compared to the control. Jiang et al. (2011)
Aligned and randomly oriented nanofibers, D = 400 nm and 800 nm Tussah silk fibroin ESC-derived NPCs N Aligned fibers significantly promoted neuronal differentiation and neurite outgrowth. Cells on 400 nm fibers had higher viability, differentiation and neurite outgrowth. Wang et al. (2011)
Randomly oriented nanofibers, D = 283 nm, 749 nm, 153 nm, 1452 nm. Laminin coated electrospun polyether sulfone NSC N Fiber diameter was found to be inversely proportional to proliferation and cell spreading, and directly proportional to degree of cell aggregation. Christopherson et al. (2009)

Stem cell behavior on gratings and electrospun fibers. D: Diameter; ESC: embryonic stem cell; H: height; iPSC: induced pluripotent stem cell; MSC: mesenchymal stem cell; NPC: neural precursor cell; NSC: neural stem cell; P: pitch; S: spacing; W: width; YAP: yes-associated protein.