Hydrodynamics in Porous Media with Applications to Tissue Engineering - Porous Media: Applications in Biological Systems and Biotechnology - page 81

or less solid-phase substratum. The feedback between the physicochemical
properties of this phase and the cell metabolism is strongly implied in their
development, differentiation, disease, and regeneration states (Discher et al.
2005). In tissue engineering, new bioactive, degradable and porous, composite
substrates associated with bone marrow stem cells may serve as basic mate-
rials for preparing synthetic tissue. Indeed, such porous media are generally
offering large-pore open space, enabling tissue progenitor and endothelial cells
to migrate into the overall structure and hence contribute to the long-term
development and irrigation of the newly formed tissue.
Flow perfusion culture within three-dimensional porous scaffolds is an e-
cient way of fostering cell population growth and matrix production through-
out these seeded media owing to the enhancement of nutrient delivery and
mechanical action genesis (Bancroft et al . 2003). In this framework, three-
dimensional porous media with suciently high porosity promoting tissue
formation are required to have specific internal microarchitectural features.
These features characterizing highly porous interconnected structures include
large surface-to-volume ratios of the pore network favoring cell in growth and
cell distribution throughout the matrix. A very important parameter of these
porous structures is then the specific surface area of the porous medium, S V .
This parameter represents the surface per unit of apparent volume, which
is available for cell attachment and tissue deposition, and can be approx-
imated knowing the pore size and the porosity, owing to the approximate
formula: S V = 2 φ / a . Higher specific surface areas are expected to favor higher
cell attachment and proliferation inside the scaffold structures. In this respect,
the use of porous substrates in tissue engineering is seen as a convenient way
of considerably increasing cell adhesion and exchange surface within a given
volume.
During the culture phase, cells have to proliferate, colonize homogeneously
the porous scaffold, and synthesize extracellular matrix. Nutrient supply of
the cells is a key factor to obtain a successful culture, especially in the case
of “large” implants (with volume around few cubic centimeters). Different
classes of molecules can interact with cells (Lanza et al . 2002). Among the
soluble nutrient elements, a large number of studies were focused on oxygen,
because this chemical element has a major impact on tissue growth, particu-
larly for osteoarticular systems (Tuncay et al . 1994; Arnett et al. 2003). For
instance, in the case of in vitro bone cells culture, osteoblast metabolism is
influenced by the local oxygen concentration, an effect also known for cartilage
and liver cells. Furthermore, the magnitude of cell oxygen local consumption
could be affected by both temperature and cell concentration. Moreover, cell
oxygen need could evolve during culture time and increase during cell division
phase.
For small nutrient components, such as oxygen molecules, that pass
directly across the cell membrane and are subject to enzymatic chemical
reactions, the kinetics of their uptake generally follows a Michaelis-Menten
law considered as fundamental in enzymology. This law stipulates that at
low concentration ( C

≤ K M , K M Michaelis-Menten constant) the chemical