Hydrodynamics in Porous Media with Applications to Tissue Engineering - Porous Media: Applications in Biological Systems and Biotechnology - page 89

3.4.1 Different Types of Bioreactors
Bioreactors are classically used in the food-processing industry (fermenta-
tion and water treatment) as well as in the pharmaceutical industry (proteins
manufacturing). They are generally defined as devices in which biological or
biochemical processes occur in a well-controlled environment (pH tempera-
ture, pressure, nutrient supply, etc., [Martin et al . 2004]). As regards tissue
engineering, bioreactors are used to obtain a culture environment adapted to
the implant development.
As summarized by Martin and Vermette (2005), the bioreactor functions
should be ideally the same as those performed by the uterus during embryo
development. Even if this objective is still unreachable in the near future, a few
researchers use the human body as a bioreactor (those applications are based
on the body's self regeneration, [Service 2005]). For in vitro tissue-engineering
applications, different kind of bioreactors are classically used (see Figure 3.4)
not only to cultivate implants but also to seed biomaterials with living cells.
However, “traditional” cell cultures within Petri dishes or wells seem to be
unsuitable when the implant volume is too large because the diffusion flux car-
rying oxygen or nutrient is too weak compared to the nutrient requirements of
cells. To obtain a tissue volume of clinical interest, the use of a flowing culture
media could be beneficial to the cell culture, as shown by numerous experimen-
tal and also numerical experiments. In this case, the flow induces an increase
of the nutrient flux, of the oxygen supply, and of the waste removal by sup-
plementing diffusion transport processes with convection transport processes
(generally more intense). Moreover, the flow generates a mechanical loading
on the cells, which can be beneficial to the implant development under definite
conditions (Nauman et al . 2001; Bancroft et al . 2002; Raimondi et al . 2002;
Cartmell et al . 2003; Sikavitsas et al . 2003; Healy et al . 2005; Gemmiti and
Guldberg 2006; Leclerc et al . 2006; Zhao et al . 2007).
In contrast to the “static” feature of the traditional cell cultures (culture
media without movement), “dynamic” culture processes using a flowing cul-
ture media have been widely developed. Depending on the bioreactor charac-
teristics and the biomaterial's geometry, the culture media flows at the implant
periphery or flows throughout the implant. For example, in a “hollow fiber
bioreactor” (Dulong and Legallais 2005) cells are confined within the fiber
where no flow occurs (the culture media flows around the fiber). Convection
allows transporting a large amount of oxygen or nutrient to the outer surface
of the fiber, but the transport between the outer surface of the fiber and the
cells is only achieved by diffusion.
At the opposite, in a perfusion bioreactor (Goldstein et al . 2001; Raimondi
et al . 2002; Cartmell et al . 2003; Sikavitsas et al . 2003) due to the imposed
perfusion flow rate, convection occurs within the pores of the implant.
Between these two last configurations are placed the “stirring flask biore-
actors” (Malda et al . 2004; Sucosky et al . 2004; Lewis et al . 2005; Bilgen et al .