Hydrodynamics in Porous Media with Applications to Tissue Engineering - Porous Media: Applications in Biological Systems and Biotechnology - page 110

angiogenesis processes. Thus, culturing of cells within a large porous implant
placed in a perfusion bioreactor remains a challenge for tissue engineering.
This challenge can be surmounted only by a multidisciplinary approach where
the modeling analysis, a typical research activity of the engineering sciences,
has to fully play its role.
Nevertheless, it is often useless and indeed not practical to attempt to
reproduce exactly all aspects of cell behavior through a single model. In fact,
the model has to include assumptions neglecting the inappropriate level of
detail for the particular research questions to be answered. As a consequence,
for use in establishing tissue-engineering protocols, a balance between the
predictive eciency of the model, its complexity, and the range of physico-
biological parameters involved has to be reached. Therefore, the model may
either provide a phenomenological description, with its range of applicability
consequently limited to a well-defined experimental system, or include more
mechanistic aspects to actually explain phenomena in tissue regeneration. In
parallel, the biological knowledge of the cell response to physical solicitations
is an avenue worth exploring since this domain remains to be one key limiting
factor of transport phenomena simulation. This is why we adopted a multi-
scale and multiphysics viewpoint with emphasis on the fluid dynamics and
transport phenomena through porous substrates at the mesoscopic scale of
the pore.
Numerical models have been widely used for problems involving fluid
flow through porous media outside the area of biomechanics. Nevertheless,
three-dimensional simulations of cell culture media flowing through a per-
fused three-dimensional construct that estimates local nutrient cell uptake and
shear stresses at the pore scale are not extensively studied. Indeed, transport
phenomena within porous substrate and the resulting threshold in concentra-
tion of nutrient molecules such as oxygen above which cells can survive seems
to be one of the key factors. Thus, an improved understanding of the local
shear stress and nutrient feeding experienced by cells under flow conditions
in three-dimensional scaffolds as a function of flow rate and microarchitecture
is required for identifying culture conditions that would impart appropriate
properties for enhanced cell proliferation and activity.
Given the complexity of cell behavior and the numerous interactions with
the evolving cell and tissue environments, computational approaches, such
as presented here, contribute to a better understanding of the different con-
tributing phenomena and mechanisms involved in the tissue-engineering cul-
ture: effective role of the substrate geometry, culture fluid transport, mechan-
ical stresses induced by the perfusing fluid flow, and possibly in the next
future cell attachment, cell-cell interaction, and population dynamics. Thus,
modeling parametric studies are necessary to determine the effects of diffu-
sion and convection processes on the penetration of cells within the porous
substrate. The models here designed and developed have then brought signif-
icant unpredictable insight, leading to a better knowledge of the cell mechan-
otransduction phenomena taking place in osteoarticular tissue engineering. It