Biomedical Engineering Reference
In-Depth Information
MSCs play a crucial role in bone regeneration and bony fixation of implanted biomaterials. Most
of the osteoblastic cells that colonize the implant surface to induce bone growth originate from MSCs
and hence, in order to accomplish good osseointegration, it is critical to induce the differentiation of
MSCs preferentially toward osteogenitor cells and then into osteoblasts in lieu of other cell lineages.
We find that the NTs significantly promote MSC attachment and spreading (
Figure 17.8
), collagen
secretion and ECM mineralization (
Figure 17.9
), as well as osteogenesis-related gene expression in
the absence of extra OS
[2]
. The osteogenesis-inducing ability of the 80 nm NTs is higher than that
of the 25 nm ones. Oh et al.
[37]
have also observed that small 30 nm NTs promote MSC adhesion
without noticeable differentiation whereas larger ones of 70
100 nm elicit selective MSC differentia-
tion to osteoblasts. Moon et al.
[38]
have recently assessed the size effect of NTs on the behavior and
osteogenic functionality of human MSCs. After incubation for 2 weeks, expression of ALP, osteopon-
tin, integrin-
, and protein kinase R-like endoplasmic reticulum kinase genes are significantly higher
in cells cultured on 70 nm NTs than those cultured on 30, 50, and 100 nm NTs and Ti. The evidence
demonstrates that NTs with a suitable tube size have osteogenesis-inducing ability.
The osteogenesis-inducing ability of the NTs arises from their modulating effect on cell shape and
focal adhesion. This will lead to changes in the mechanotransduction including the indirect one, that
is integrin-dependent signal pathways, and the direct one that is gene expression originating from the
cell nucleus distortion by force transferred via the cytoskeleton
[39,40]
. The shape of stem cells
on biomaterials is closely related to the high cytoskeletal tension such as the well-spread stem cell
and that with the proper aspect ratio undergoing osteogenesis with the poorly spread stem cell becom-
ing adipocytes
[41]
. Therefore, the effects of the NTs on promoting MSC spreading constitute an
important mechanism for the osteogenesis-inducing ability. The higher osteogenesis-inducing ability
rendered by the 80 nm NTs than the 25 nm ones can be explained by the influence of the nanotopo-
graphy on the cell focal adhesion size, distribution, and related mechanotransduction. The presenta-
tion of integrin ligation sites at a distance larger than a certain value (about 50
β
70 nm) perturbs
integrin clustering, focal adhesion assembly, and organization of the actin stress fiber anchored to the
focal adhesion
[42]
. Accordingly, the 25 nm NTs do not, or slightly, influence the integrin clustering
and focal adhesion formation. Instead, the 80 nm NTs constrain the cell focal adhesion to the inter-
tubular area. In this way, the 80 nm NTs modulate the size, shape, and distribution of focal adhesion
to a nanoscale periodic occurrence. On one hand, it triggers more integrin-related signals, and on the
other hand, it induces a nanoscale periodic distribution of the cytoskeletal actin and stress leading to
extensive nucleus distortion and related direct mechanotransduction signals.
17.4.2
In vivo osseointegration of the NTs
The good bone-favoring properties of the NTs with suitable size have also been verified by
various in vivo studies. Bjursten et al.
[13]
have investigated the in vivo bone bonding between
80 nm NTs and grit-blasted TiO
2
. Four weeks after implantation into rabbit tibias, the NTs improve
the bone bonding strength by as much as ninefolds compared to the grit-blasted TiO
2
surface. The
histological analysis confirms greater BIC areas, new bone formation, and calcium and phosphorus
levels on the NTs. Von Wilmowsky et al.
[14]
have reported that a NT structured implant surface
with a diameter of 30 nm can influence bone formation and bone development by enhancing the
osteoblast functionalities and the NT coatings resist shearing forces evoked by implant insertion.
They have recently reported a significantly higher value of the BIC for the 50, 70, and 100 nm NTs
