ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

present study, such values were phenomenological and depended on factors such as
diffusivities of solutes in agarose, and fitted exponential decays over time. Although the
critical values for glucose and pH are in the range that emerges from the in vitro studies
(Bibby and Urban, 2004) and other computational investigations (Sirazi-Adl et al.,
2010), other phenomena, such as oxygen-dependent cell death, cell proliferation and
migration could eventually be considered in the future, to explain the differences
between in vitro cell viability profiles and results from our phenomenological model.
By implementing such criteria in the whole-IVD FE model the effect of biphasic
mechanics coupled with diffusion and transient responses of external loads on cell
viability were studied. In the central nucleus, the delay predicted for cell death due to
mechanical effect that increases glucose concentration (Fig. 2) seems a general effect:
We believe that this does not depend from little variations around the critical glucose
value that we obtained in our calibration - 0.5 mM -, which is a realistic value when
compared to the in vitro results of Horner and Urban (2001). Long-term steady-state
deformations have been indicated either as a possible enhancement for nutritional
processes, due to shortening of transport routes (Malandrino et al., 2011; Galbusera et
al., 2011) or as detrimental for cell viability in other recent metabolic-coupled IVD FE
studies (Jackson et al., 2011). Although loads were applied statically over 16 h in our
study, transient mechanical dependency of the cell viability could occur, for instance
due to strain-dependent diffusivity and shortening of diffusion distances in an organ of
non-negligible dimensions. Our methodology was able to model such phenomena,
which are most likely physiologically relevant.
Moreover, our study also predicted locally cell viability based on a spatial and temporal
variations of porosities, volume changes and metabolism-related nutrient
concentrations: In the inner annulus fibrosus, due to the combination of all these factors,
cell viability was affected negatively by mechanical loads. This points out on the
importance of realistic geometrical models and regional material parameters to increase
the ability of the models in predicting local features which could be missed otherwise.
However, the mechanical effect considered here and in other FE studies (Malandrino et
al., 2011; Galbusera et al., 2011; Jackson et al., 2011) did not address the issue of
chemical signals (e.g. inflammatory factors) which could arise due to sustained loads
and that could explain the detrimental effect of sustained loads on in vitro cell cultures
(Miyamoto et al., 2006). Thus, future studies should integrate such concerns towards a
more comprehensive understanding of mechanobiological phenomena within the IVD.
In conclusion, deformability of healthy IVDs was found to be positive for the
maintaining of cell viability in the disc centre. Moreover, in degenerated discs cell death
acceleration may occur due to the loss of compliance that hinders proper metabolic
transport. Our novel mechanobiological study of the intervertebral disc points out on the
restoration of mechanical properties as a potentially beneficial regenerative treatment
for cells in those cases where a reduced nutritional balance at the disc boundaries can
occur.
6. ACKNOWLEDGLEMENTS
Funding from the European Commission (DISC REGENERATION-NMP3-LA-2008-
213904) is acknowledged.