Stem-Cell Responses to Surface Nanotopographies - Stem-Cell Nanoengineering - page 180

Table 11.1 Stem-cell response on nanoporous substrates

Attachment/
adhesion Cell type Substrate Feature size Proliferation Differentiation Reference

Human BMSCs PMMA 120 nm

(disordered)

Osteogenic (+) 39

Human BMSCs PMMA 120 nm (ordered) (−) Osteogenic (−) 42

C57 BJ mice
BMSCs

Alumina ~79 nm (+) (+) Osteogenic (+) 45

Human BMSCs PC 120 nm (−) 40

Rat BMSCs TiO 2 15-100 nm < 30 nm(+);

> 50 nm (−)

< 30 nm (+);
> 50 nm (−)

< 30 nm (+);
> 50 nm (−)

44

Human BMSCs TiO 2 30-300 nm 30 nm (+) Osteogenic:

30 nm (+)

29

Rat BMSCs Silicon 20-30 nm 0 89

Rat BMSCs Silicon Few nm to 1 µ m 0 48

Rat BMSCs/
human BMSCs/
human ASCs

Silicon Few nm to 2 µ m (−) 49

Rat BMSCs Silicon Few nm to

230 nm

(−) (−) Osteogenic/

adipogenic (+)

46

Human BMSCs Alumina 50 nm to 3 µ m (−) 0 Osteogenic (+) 35

BMSCs, bone-marrow mesenchymal stem cells; ASCs, adipocyte-derived mesenchymal stem cells;
PMMA, polymethyl methacrylate; (+), positive effect; (−), negative effect; 0, no significant effect.

Several recent reviews have summarized the effects of engineered nanopits on the fates of
mammalian cells [37, 38]. Dalby and his colleagues have carried out a series of studies on
stem-cell responses to nanopits [39-42]. They used electron-beam lithography to precisely
create defined nanopits (120 nm diameter, 100 nm deep) of different symmetry and with
varying degrees of disorder on polymethylmethacrylate substrates. They found that
osteogenesis of human MSCs is stimulated by disordered nanopits in the absence of chemical
induction, with similar efficiency to the osteogenesis of cells cultured with osteogenic media
[39]. They proposed that topographical modification could modulate cellular differentiation
in multipotent stem-cell populations [42] through the ERK/MAPK (extracellular signal-
regulated kinase/mitogen activated protein kinase) signalling pathway via integrin-mediated
cellular adhesion [43]. They showed that nanopit arrays disrupt cellular adhesion and
spreading, which prevents osteogenesis indicated by the downregulation of several osteospe-
cific genes (Ets and Stat1) in skeletal stem cells. The results imply that the formation of focal
adhesions and the cytoskeleton has an impact on directing cell differentiation.
The responses of stem cells to nanoporous topography vary with cell type/source,
topographic feature, and material types. It is difficult to infer a general conclusion from the
studies regarding nanoporous surfaces. Some results are contradictory to each other. For
example, Park et al . showed that the adhesion, proliferation, and osteogenesis of rat MSCs on
nanoporous TiO 2 were reduced on a surface with pore size larger than 50 nm compared with
a plane TiO 2 surface or a surface with smaller pore size (~15 nm) [44], while some studies
showed that larger pore sizes (79 and 150 nm) stimulate osteogenesis [29, 45]. The diversity in
cell type/source, culture condition, material chemistry, and topographic feature may be the
reason for the difficulty in making a conclusion on nanoporous effects. It should be noted that
most of the porous studies focus only on the size of pores and porosity. However, the architecture