Effects of nanotopography on stem cell phenotypes

Table 1 Different types of stem cells, their properties, and functions

Stem cell type	Properties	Functions
MSCs	Multipotent and pluripotent. Bone marrow is the major source of MSC	MSCs are capable of differentiating into bone, cartilage, fat, muscle, marrow stroma, and other tissue types
ESCs	Derived from an early stage embryo and can differentiate into derivatives of all three primary germ layers. ESCs are multipotent and pluripotent	Can differentiate into brain and nervous system cells, insulin producing cells of the pancreas, bone cells, hematopoietic cells, endothelial cells, cardiomyocytes
ASCs	Multipotent, oligopotent, or unipotent progenitor cells. Derived from a more mature tissue, such as the umbilical cord, bone marrow, or skin	To treat leukemia and related bone/blood cancers through bone marrow transplants
HSCs	Found in the bone marrow. Multipotent	All types of blood cells
iPS	Derived from epithelial cells. Pluripotent	The iPS cell lines could be differentiated into heart muscle and neuronal cells, in addition to basic cell types (ectoderm, mesoderm, and endoderm)
Mammary stem cells	Isolated from human and mouse tissue	Growth of mammary glands
Endothelial stem cells	Multipotent cells found in the bone marrow	Can differentiate into endothelial cells, the cells that make up the lining of blood vessels

Table 2 Various fabrication techniques to achieve nanotopography

Fabrication technique	Advantages	Drawbacks
Laser deposition	Uniform distribution of pore size, simple and fast	Reduced resolution and poor surface finish
Self assembly	Can generate fibrous networks capable of supporting cells in three dimensions. Cell-seeding problems associated with using prefabricated nanofibrous scaffolds eliminated owing to spontaneous assembly	Lack mechanical strength, Limited amphiphilic materials, random and very short nanofibers
Lithography	Relatively good resolution	Time consuming and expensive.
Electrospinning	The properties of electrospun nanofibers, such as fiber diameter, can be controlled readily via manipulation of spinning parameters. Capable of mimicking the stem cell niche	Electrospinning yields a flat mat that has limited three dimensionality and suffers from cell infiltration problems because of the small pore size of the mats
Phase separation	A nanofibrous (fibers with diameters of 50-500 nm) three-dimensional scaffold can be constructed. Has controllable high porosity, surface-to- volume ratios, and well as defined mechanical properties	Nanofiber distribution and uniformity is subject to the controllability of the processing

Table 3 Various cell types and the nanotopographies on which they are cultured

Cell type	Nanotopography	Advantages	Ref.
Chondrocytes	(a) PCL nanofibrous scaffold (200-800 nm) in the presence of TGF-β1; (b) Collagen nanofibers of diameter 110 nm-1.8 μm	The differentiation of the stem cells into chondrocytes in the nanofibrous scaffold was comparable to an established cell pellet culture. Nanotopography supports chondrocyte growth and infiltration	[82,90]
Osteoblasts	(a) Ceramics like HA, alumina and titania having nanostructures of grain sizes less than 100 nm and nanophase zinc oxide (23 nm); (b) PLGA, PLLA and PCL nanofibers (diameter 200-800 nm); (c) Nanotubes of diameter less than 100 nm	Enhanced proliferation and differentiation of MSC to osteoblasts	[67,77-79,105-113]
Smooth muscle cells (SMC)	(a) PLGA and PCL, PLLA-CL nanofibers (diameter 200-800 nm); (b) Nanogratings of 350 nm in width, spacing, and depth imprinted on PMMA or PDMS	SMC adhesion was enhanced on the nanostructured substrates compared to the conventional submicron substrates	[114-118]
Fibroblasts	(a) PLGA (85:15 ratio) nanofibers of diameter 500-800 nm; (b) Nanocolumns	Increased endocytic activity. Nanotopography can be used to improve hemocompatibility of blood-contacting biomaterials	[82]
Nerve cells	(a) Silicon wafer in the range of 20-70 nm; (b) PLLA or PCL scaffolds via electrospinning and phase separation	The cell adhesion and viability significantly improved on the nanofeatured surface	[70,91]

PCL: Polycaprolactone; TGF-β: Transforming growth factor-β; HA: Hydroxyapatite; PLGA: Poly-lactide-co-glycolide; PLLA: Poly-L-lactide acid; MSC: Mesenchymal stem cell; PMMA: Poly-methylmethacrylate; PDMS: Polydimethylsiloxane.