Bioreactors - Articular Cartilage Tissue Engineering - page 70

70 CHAPTER 4. BIOREACTORS
actively investigating how the unique conditions of this culture environment can be used to exploit
the multi-potentiality of stem/progenitor cells.
Not all bioreactors can accommodate the wide variety of scaffold materials that are present in
the field of tissue engineering. The physical, mechanical, and material characteristics of a scaffold
can prevent its use in devices that apply large forces or require excessive handling. Rotating biore-
actors, however, provide a gentle culture environment that is conducive to many different carriers.
Mesh scaffolds, hydrogels, and microcarrier beads can all be cultured with the same ease. Cells can
even be cultured without a scaffold, with aggregation occurring within days to weeks. This is not
to say that the scaffold-bioreactor compatibility can be totally ignored. In fact, this interaction is
incredibly important when determining the shear forces and nutrient diffusion present in the culture
environment [ 572 ]. Furthermore, the rotating bioreactor cannot overcome disadvantages associated
with certain scaffold types or culture parameters, such as low initial cell densities [ 573 ]. How-
ever, successful experiments have been carried out with a variety of scaffolds. Chondrocyte-seeded
poly(DL-lactic-co-glycolic acid) sponges showed formation of hyaline-like tissue when cultured in
a chondrogenic media for four weeks [ 574 ]. Chitosan scaffolds have also been used in the rotating
bioreactor although tissue growth was shown to be strongly influenced by the microstructure of
the scaffold [ 575 , 576 ]. More recently, a chitosan-hyaluronan hybrid scaffold was investigated in
this culture environment with results showing near-physiological levels for matrix composition and
mechanical properties [ 577 ].
A major concern with rotating bioreactors is the random motion of scaffolds in the culture
vessel. Researchers typically put multiple constructs in a single bioreactor, which results in groups
of tumbling samples that can hit one another or the walls containing them. These unpredictable
contacts can kill cells in localized areas or damage the scaffold during early culture periods. Another
difficulty is identifying the flow patterns within a bioreactor filled with constructs. One attempt to
localize the nutrient flow and keep a more stable culturing environment is the hydrodynamic focusing
bioreactor (HFB), which was created by NASA for use in no-gravity cell culturing [ 543 , 553 , 554 ].
As with other rotating bioreactors, the inner and outer walls rotate to produce a range of shear forces.
However, instead of having a cylindrical shape, the HFB is a dome. This modification is proposed to
focus cells and nutrients together to enhance mass transfer. Another version of the rotating bioreactor
is the “rotating shaft” bioreactor [ 578 ]. This device uses the motion of the inner cylinder to move
attached samples in a continual rotary motion around the central axis. However, the culture vessel is
only half-filled with media, so samples move in and out of liquid and fluid phases. This is proposed
to increase oxygenation as well as provided slightly higher levels of shear. As with other studies
involving rotating bioreactors, experimental results with this device were generally successful for
cartilage tissue engineering [ 559 , 560 ].
4.4 HYBRIDBIOREACTORS
As the field of tissue engineering matures, more complex bioreactors have been developed to more
faithfully replicate the native environment of target tissues. Each bioreactor reviewed in the previ-