Hydrodynamics in Porous Media with Applications to Tissue Engineering - Porous Media: Applications in Biological Systems and Biotechnology - page 85

tissues, little is known about the specific mechanical forces or regimes of
application (i.e., type of applied stresses, magnitude, frequency, continuous
or intermittent, duty cycle, etc.) that are stimulatory for a particular tis-
sue. In addition, engineered tissues at different stages of development might
require different regimes of mechanical conditioning owing to the increasing
accumulation of extracellular matrix (ECM) and developing structural organi-
zation. In this highly complex field, a comprehensive understanding can only
be achieved through hypothesis-driven experiments aimed at elucidating the
mechanisms of downstream processes of cellular responses to well-defined and
specific mechanical stimuli. In this context, bioreactors can play an important
role since they provide controlled environments for reproducible and accu-
rate application of specific regimes of mechanical forces to three-dimensional
constructs (Demarteau et al . 2003a). This must be coupled with quantitative
analysis and computational modeling of the physical forces experienced by
cells within the engineered tissues, including mechanically induced fluid flows
and changes in mass transport.
The role of bioreactors in applying mechanical forces to three-dimensional
constructs could be broadened beyond the conventional approach of enhancing
cell differentiation and/or ECM deposition in engineered tissues. For exam-
ple, they could also serve as valuable in vitro models to study the pathophys-
iological effects of physical forces on developing tissues and to predict the
responses of an engineered tissue to physiological forces on surgical implan-
tation. Together with biomechanical characterization, bioreactors could thus
help in defining when engineered tissues have a sucient mechanical integrity
and biological responsiveness to be implanted (Demarteau et al . 2003b). More-
over, quantitative analysis and computational modeling of stresses and strains
experienced both by normal tissues in vivo for a variety of activities and by
engineered tissues in bioreactors could lead to more precise comparisons of in
vivo and in vitro mechanical conditioning, and help in determining potential
regimes of physical rehabilitation that are most appropriate for the patient
receiving the tissue.
Despite these results, the mechanisms whereby cells are sensing mechanical
actions produced by their environment have not been well established. This is
particularly true in the case of the viscous shear stresses, τ , generated by slow
interstitial flow within porous tissue (Swartz and Fleury 2007), which can be
evaluated by the following expression:

u 0
a

τ = η × (3.6)

As it is clearly recognized now that the cell biochemical transduction
depends upon its mechanical environment, thorough studies of the flow behav-
ior within three-dimensional matrices in relation with biophysical and bio-
chemical signaling of the cells have to be undertaken.