Biomedical Engineering Reference
In-Depth Information
[133-137]
. Stem cells normally remain in their mitotic cycle unless they are guided by an external cue
which would then cause them to differentiate into more specialized cells
[132]
. One main factor that
has been observed to guide stem cell differentiation is the presence and composition of extracellulat
matrix (ECM) components. Presence of collagen fibrils of diameter ranging from 15 to 300 nm pro-
vides cellular anchorage and presents cues for stem cell differentiation
[135]
. Cells attach to the ECM
through attachment points such as integrins (transmembrane proteins) which form bonds with specific
amino acid sequences found within the ECM network. These linkages cause a cascade of signaling
pathways that affect different cellular processes such as migration, proliferation, and differentiation
[137]
. Several substrate characteristics such as size
[138]
, lateral spacing
[138]
, surface chemistry
[139]
, and geometry
[140]
of the nanofeatures play an important role in integrin clustering and activa-
tion. For instance, it was shown that rat mesenchymal stem cells had maximum adhesion, spreading,
and differentiation on TiO
2
nanotubes vertically aligned with a diameter of 15 nm (which is similar to
the theoretical spacing of the integrin receptors on the cell surface). A change in the nanotube diame-
ter showed a significant alteration in the cell behavior
[138]
, e.g., focal adhesion kinase (FAK) activity
was maximum on 15-nm diameter TiO
2
tubes in comparison to 100-nm diameter tubes.
8.5.1
Effects of Nanotopography on Endothelial Progenitor Cells
Endothelial progenitor cells (EPCs) have been observed to differentiate into endothelial cells
[141]
,
a major type of cells responsible for vasculature within the bone tissue, and to behave according to
nanoscale features of a substrate
[142-147]
. For example, growth and differentiation of EPCs can be
controlled by a ridge-groove type nanotopography generated within 1,200 nm intervals and 600 nm
in depth
[141]
. Although endothelial cellular biochemistry was not altered, EPCs cultured on sub-
strate nanotopography formed aligned band structures after 6 days
[141]
. The study also showed
that formation of long, thin-walled capillary tubes was much more prominent on nanostructured sur-
faces than unstructured surfaces. While reduced proliferation has been observed in cell types such
as smooth muscle cells and human embryonic stem cells (hESCs)
[144,148]
, EPCs have shown to
express increased migration velocity and adhesion on linear substrate nanotopography
[149]
. The
presence of nanotopographical features such as linear and long grooves in the substrate has also been
shown to aid in maintaining morphology of elongated EPCs over a long period without causing any
decrease in cell growth and to enhance the rate of capillary formation as compared to EPCs grown on
flat surfaces. While nanotopography has been shown to affect cells at the protein level
[150]
, which
suggests a genetic level change in response to the nanoscale substrate features, it has been observed
that no change in the characteristic endothelial-specific markers occurs in the EPCs grown on nanos-
tructured surfaces
[141]
.
8.5.2
Effects of Nanotopography on Bone Marrow Stem Cells
Several studies have observed an obvious response from bone-marrow-derived stem cells to the
topography of materials, and these cells elicit a large range of responses such as changes in adhesion,
spreading, proliferation, and genomic responses
[86,151-157]
. For instance, nanotopography has a
noticeable effect on the interactions between the human mesenchymal stem cells (hMSCs or bone-
marrow-derived stem cells) and the substrate by influencing the focal adhesion formation, organiza-
tion of the cytoskeleton and cellular mechanical properties
[158]
. In addition, Berry et al.
[159]
have
