Control of stem cell fate by engineering their micro and nanoenvironment

Table 1 Examples of studies, which have demonstrated surface topographies can direct stem cell differentiation

Stem cell source	Scaffold type	Description of topographical feature	Differentiation outcome	Ref.
hMSC	PDMS	Islands	Large 10000 μm2 islands promoted osteogenesis. Small 1024 μm2 island promoted adipogenesis	McBeath et al[25]
hMSC	TiO2 nanotubes	30-, 50, -70 and 100 nm nanotubes	70-100 nm nanotubes promoted osteogenesis	Oh et al[28]
hMSC	PMMA	Ordered and disordered square or hexagonal pattern and Nanopits	Disordered squared promoted osteogenesis	Dalby et al[31]
hBMDSC	Hydrogenated amorphous carbon	Grooves	Neurogenesis	D’Angelo et al[37]
mESC	PLLA	Grating	Osteogensis	Smith et al[38]
hMSC	PDMS	Grating	Neurogenesis	Yim et al[39]
hESC	PDMS	Micropatterned fibronectin with square shape surrounded by Pluronic F127	Myogenesis and chondrogenesis	Gao et al[49]
hMSC	PDMS	Micropatterned with striped groove morphology coated with collagen type I.	Myogenesis	Kurpinski et al[50]
hNSC	PDMS	Micropatterned with striped groove morphology coated with PLL and laminin.	Neuronal	Béduer et al[51]
hMSC	PDMS	Micropatterned with striped groove morphology coated with collagen type I	Neuronal	Biehl et al[52]
hESC	PDMS	Groove	Neuronal	Lu et al[53]
hMSC	PCL	Nanopillar, nanohole and nanogrill	Nanopillar and nanohole topography enhanced	Wu et al[54]
hNSC	PUA	Groove and Pillar	MSC chondrogenesis and facilitated hyaline cartilage. Neuronal	Yang et al[55]
rMSCs	Polystyrene	Groove	Myogenesis and adipogenesis	Wang et al[56]

hESC: Human embryonic stem cell; hMSC: Human mesenchymal stem cell; rMSCs: Rat mesenchymal stem cell; hNSC: Human neural stem cell; hBMDSC: Human bone marrow derived stem cell; mESC: Mouse embryonic stem cell; PMMA: Polymethyl methacrylate; PDMS: Polydimethylsiloxane; PCL: Polycaprolactone; PUA: Polyurethane acrylate; PLL: Poly-l-lysine; PLLA: Poly(L-lactide).

Table 2 Example of studies, which have demonstrated that the use of different chemical inductors can direct stem cell differentiation

Immobilisedchemical inductor	Scaffold type	Functional group	Differentiation outcome	Ref
Chemical group
	Silk fibroin	-COO-	hMSC osteogenic differentiation	Murphy et al[59]
	Silk fibroin	=C=O	hMSC osteogenic differentiation	Murphy et al[59]
	Silk fibroin	SO3H	hMSC osteogenic differentiation	Murphy et al[59]
	PEG	PO3	Increase in hMSC osteogenic markers at gene and protein level	Benoit et al[60], Nuttelman et al[61], Nuttelman et al[62], Gandavarapu et al[63]
	Silk fibroin	NH2	hMSC osteogenic differentiation	Murphy et al[59]
	Silk fibroin	CH3	hMSC osteogenic differentiation	Murphy et al[59]
	Glass	COOH, CH3, OH, NH2	-NH2 support hMSC osteogenic differentiation	Liu et al[64]
	Glass	OH, SO3H, NH2, COOH, SH and CH3	-NH2 support hNSC differentiation	Ren et al[65]
	Glass	CH3, NH2, SH, OH and COOH	NH2 and -SH- promoted and maintained hMSC Osteogenesis, -OH and -COOH- promoted and maintained chondrogenesis	Curran et al[66]
Peptide sequence
	Alginate	Osteopontin peptide	Increase in hMSC osteogenic markers	Lee et al[67]
	HA-PLG	Osteocalcin peptide	Increase hMSC osteogenic markers	Lee et al[68]
	PLGA	BMP-2 peptide	Increase rMSC ALP expression in osteogenic medium and promotion of ectopic bone formation in vivo	Lin et al[15]
	RGD	BCP/PLA	hMSC osteogenic differentiation	Shin et al[70]
Molecule
	PLGA	BMP-2	hMSC osteogenic differentiation	Ko et al[71]
	PLLA	BMP-2	hMSC osteogenic differentiation	Beazley et al[16]
	Collagen-PLGA hybrid	Collagen-binding domain derived from fibronectin (CBD-BMP4)	hMSC osteogenic differentiation	Lu et al[72]
	Methacrylamide chitosan hydrogel coated glass substrates	Laminin and collagen	Supported hNSC differentiation	Wilkinson et al[73]
	PMMA-g-PEG	EGF	MSC osteogenic differentiation	Platt et al[74]
	Agarose	PDGF-AA	MSC neural differentiation	Aizawa et al[75]
	PCL/PCL-PEG	NGF	MSC neural differentiation	Cho et al[76]
	Chitosan/collagen IV	VEGF	Endothelial differentiation	Chiang et al[77], Poh et al[78], Rahman et al[79]

hESC: Human embryonic stem cell; hMSC: Human mesenchymal stem cell; rMSCs: Rat mesenchymal stem cell; hNSC: Human neural stem cell; PEG: Polyethylene glycol; HA-PLG: Hydroxyapatite (HA)/poly(lactic-co-glycolic acid); BMP: Bone morphogenetic protein; PLGA: Poly(lactic- co –g lycolic acid); PLA: Poly(lactic acid); PLLA: Poly(L-lactide); PCL: Polycaprolactone; PMMA-g-PEG: Poly(methyl methacrylate)-graft-poly(ethylene glycol; BCP: Biphasic calcium phosphate; EGF: Epidermal growth factor; NGF: Nerve growth factor; PDGF-AA: Platelet-derived Growth Factor AA; VEGF: Vascular endothelial growth factor.