Biomedical Engineering Reference
In-Depth Information
was found that both osteogenic and adipogenic inductions showed increased
differentiation on patterns of large RGD nanospacings relative to those of small
nanospacings. However, under co-induction using the mixed differentiation media
catering to both adipogenesis and osteogenesis, osteogenesis was greater than
adipogenesis on patterns of larger RGD nanospacings (Fig.
8
). Since cell
spreading area was smaller on larger nanospacings in their study, the data on MSC
fates cannot be interpreted via the changes in cell spreading area (if you recall that
smaller cell size tends to be beneficial to adipogenesis but not osteogenesis,
Fig.
6
). Thus, there may be inherent role of cell-adhesive ligand spacing to control
the MSC fate other than affecting cell spreading and cytoskeletal tension.
The control of MSC differentiation behavior by substrate topographies, espe-
cially by nanoscale topographies, has been blooming but mostly for the purpose of
enhancing MSC osteogenesis. This approach has been pursued for bone implant
surface modification or bone tissue engineering scaffold fabrication. Obtained data
strongly suggest that nanotopographic substrate modification to have specific
shape or scale has a potential to stimulate the MSC osteogenesis. For example, our
study showed that nanoisland topographies with specific scale nanoisland height
(10-20 nm) induced greater expression of AP activity and bone-like mineral
staining from MSCs [
30
]. Importantly, such regulation by nanotopography may be
accomplished by the static mechanical signal that influences cellular mechanical
compartments such as focal adhesion, cytoskeleton, and related cell signaling such
as FAK [
29
]. Furthermore, cytosolic calcium triggering by fluid flow was signif-
icantly greater if MSCs were seeded on specific nanotopographies, suggesting that
mechanical sensitivity of MSCs may be governed by cell-nanotopography inter-
action [
40
]. Therefore, it may be concluded that nanotopographic cell culture may
provide synergistic effects with flow shear in inducing MSC osteogenesis via
upregulating cellular mechanical responsiveness. On the other hand, it is true there
is almost no study on the effects of cell culture substrate topography, for both
micro and nanoscale, on the adipogenesis of MSCs.
Substrate rigidity is another important static mechanical signal formed by the
substrate. A pioneering study revealed that the elastic modulus of the cell culture
surface can direct MSC fate even in the absence of soluble signals [
11
]. They
showed using polyacrylamide gels with varying modulus/stiffness that MSC dif-
ferentiation into neuronal, muscle, and bone cells was each stimulated on the
substrate having elastic modulus that resembles that of the corresponding in vivo
tissue. MSCs cultured on soft gels (1 kPa modulus mimicking neuronal tissue)
differentiated to neuronal cells, while those on stiffer gels (10 and 100 kPa) to
muscle and bone cells, respectively. Similar data were observed for MSCs cultured
on a substrate with gradient stiffness such that the areas with the highest con-
centration of bone cell formation were on the higher stiffness regions of the
mechanical gradient substrate [
46
]. They also observed some parts of the substrate
did not experience as much osteogenesis as other areas depending on the species of
functionalized FN or collagen, which was attributed to that the paracrine signaling
from tenogenic cell fate may have interfered with osteogenic differentiation. Thus,
substrate rigidity control of cell fate may be co-mediated by biochemical signal
Search WWH ::
Custom Search