Biomedical Engineering Reference
In-Depth Information
Figure 12.3
Network analysis, showing involvement of FA, FAK, ERK, actin, sonic hedgehog, and
RhoA signaling in response to 1 kHz nanomechanostimulation:
N
= 3. Note that CP is the canonical
pathway and the lines into the network indicate where these biochemical pathways are involved in the
network. Reproduced from [61] with permission by the American Chemical Society.
real effect. The study also demonstrated that BMP2 was activated by 24 h and RUNX2 by 7
days via nanokicking. This is logical, as RUNX2 activity is mediated by BMP2 signaling
[91, 122], and this would be followed by increased osteocalcin expression by day 14 according
to the Stein and Liano steogenesis time lines [123]. Microarray-based pathway analysis
(Figure 12.3) also implicated purine and nicotinamide metabolism (involved in energy demand)
and sonic hedgehog signaling (involved is stem-cell differentiation) [124] as well as adhesion,
FAK, ERK, and actin-mediated biochemical signaling (all known to be implicated in RUNX2
activation [125-129]) being central to nanomechanotransduction [130, 131].
Bone Bioreactors
Now that we have demonstrated nanoscale mechanotransduction, what is the future direction
for this technique? Use of osteoblasts and stem cells to make bone tissue in the laboratory
(
ex vivo
) is possible [132, 133], but for clinical use (massive bone production), a special device
