Biomedical Engineering Reference
In-Depth Information
incorporated the technique, was performed by Brekelmans et al. (
1972
). The popu-
larity of the application grew exponentially ever since, many of the prominent pub-
lications of the first decade of its existence being reviewed in Huiskes and Chao
(
1983
).
Micro-computed tomography (micro-CT), introduced several years later (Feld-
kamp et al.,
1989
), allowed not only three-dimensional (3D) visualization of bone
architecture, but also a more reliable image-based validation method for the com-
putational models. However, the first validation of an
in silico
model against the
corresponding biological data was reported only in 1997, in a study that compared
FE models of trabecular bone with contact radiographs both quantitatively and qual-
itatively (Silva and Gibson,
1997
).
In the meantime, both computational and visualization advances have provided
a framework for accurate simulations of bone remodeling and mechanobiology
throughout the hierarchical levels of its complexity, while algorithm validation with
experimental data collected within the same study was deemed 'gold standard' for
model confirmation (Anderson et al.,
2007
). This review focuses on different ap-
proaches of
in vivo
validation across multiscale modeling of bone remodeling and
mechanobiology from cell to tissue and on to the organ level.
27.2 Cell Level
Bone is a tissue subject to frequent remodeling due to various mechanically trig-
gered remodeling processes as well as micro- and macro-fractures. The study of
bone mechanobiology, thus, remains relevant throughout the lifetime of the organ-
ism. However, understanding and prediction of the cell mechanics is particularly
significant for the multiscale applications, such as implant selection and fixation,
and fracture healing (Van der Meulen and Huiskes,
2002
). Nevertheless, even with
the focus of research narrowed down to the single cell level,
in silico
studies range
from the simulations of cellular interactions, to signaling pathway modeling, and all
the way to the intracellular predictions of cytoskeletal reorganization.
The first validated model in mechanobiology described osteocyte excitation by
mechanical stresses in mathematical terms (Weinbaum et al.,
1994
). The model was
based on the experimental observations, and attempted to quantify mechanical stim-
uli sensed by osteocytes within the bone tissue. For validation purposes, the calcula-
tions were compared to experimentally measured results, reported by a collaborating
group (Fritton et al.,
2000
).
Incorporation of the FE analysis into the mechanobiological models was initially
an attempt to provide analytical perspectives on observed
in vivo
events; this trend
later developed quantification and even prediction of the mechanical changes on the
local level. Nevertheless, comparison with literature remained a preferred method of
validation in the field (Carter et al.,
1998
; Knothe Tate and Niederer,
1998
; Bonivtch
et al.,
2007
).
