Biomedical Engineering Reference
In-Depth Information
stress that the construct can be exposed to is regulated by adjusting the fl ow
parameters. Perfusion systems are usually composed of an oxygenator, a
pump and a medium culture reservoir connected in series with the bioreac-
tor (Bilodeau and Mantovani, 2006).
Another confi guration of the reactors used in tissue engineering is a hol-
low fi ber reactor. In this reactor semi-permeable fi bers are placed inside a
closed vessel. Its principle is based on the
in vivo
vascular system where the
fi bers are responsible for transport of nutrients and waste in and out of the
system. The advantage of these systems is that they allow mass transport to
the center of the construct, unlike fi rst-generation reactors. Although this
confi guration uses intra-capillary medium recirculation based on Starling's
Law, this secondary fl ow is nearly diminished in the 3D scaffolds compared
to oxygen diffusion (Brotherton and Chau, 1995). Coaxial hollow fi ber reac-
tors are a variation on the hollow fi ber reactor. The fi bers in these reactors
contain another set of fi brous membranes within the fi bers, therefore creat-
ing another media compartment in order to further improve mass transfer
in the culture. The large surface-to-volume ratio found in these reactors aids
mass transfer and minimizes the distance between nutrient-rich environ-
ment and cells (Ellis
et al.
, 2005).
The rotating-wall perfused or Couette-Taylor bioreactor has been
widely used in mammalian tissue culture studies. It is also referred to as
a slow-turning lateral vessel reactor. It originated from the viscous pump
bioreactor and was later used in various space missions. It creates a per-
fusion fl ow loop that allows continuous exchange of the medium. In addi-
tion, it permits long-term monitoring and management of culture conditions
such as temperature, pH and oxygen content for up to several months. A
gas exchange membrane in the inner concentric cylinder facilitates gas
exchange. In order to maintain tissues in continuous free-fall condition and
prevent damage to the construct, rotating speeds between 15 and 30 rpm are
predominantly used. Culture in this reactor requires inoculation of cells into
micro-carrier beads that measure about 250 µm in diameter. Once the beads
reach a size of about 100 to 200 cells they fuse together to form larger tissue
constructs. The mechanism for these phenomena is still to be investigated
(Khaoustov
et al.
, 1999). Cartilage tissues grown using this method have
reached 5 mm thickness (Freed
et al.
, 1997) while liver constructs have been
reported to be 3 mm thick (Ellis
et al.
, 2005), unfortunately with necrosis in
the center.
Another bioreactor confi guration using perfusion as a means of mass
transport that has shown promising results is the bed bioreactor. This con-
fi guration allows for tissue development in the stationary matrix, also called
the bed. Various matrices have been implemented into these systems such as
porous ceramic beads (Park and Stephanopoulous, 1993), porous glass beads
(Racher and Griffi ths, 1993), glass fi bers (Rodrigues
et al.
, 1999), polyester
