Bioreactors - Articular Cartilage Tissue Engineering - page 56

Figure 4.1: Low shear bioreactors (top), hydrostatic pressure (bottom, left), and direct compression
(bottom, right) bioreactors.
Direct compression has been used successfully to stimulate the chondrocytic phenotype of cells in
vitro . The mechanism for this positive response is not fully known. While the actual mechanical
stimulation is undoubtedly a major factor, enhanced nutrient transfer and removal of waste products
could also contribute to increases in cartilaginous matrix secretion.
Proteoglycan synthesis has often been used in studies as an indicator that a mechanical stimu-
lation is beneficial although some studies also use DNA synthesis, collagen synthesis, or mechanical
properties as gauges. Synthesis is not necessarily a measure of composition, though, and indicates
only which molecules are made and not whether they are integrated into the tissue. The incorpora-
tion of radioisotopes is another measure of macromolecule formation and is an indirect indication
of synthesis. Using the reported values of proteoglycan synthesis, a qualitative comparison can be
made among different loading regimens in different experiments.
The culturing procedure for direct compression is normally a two-step process; the cell-
seeded scaffold is left in medium under normal conditions and, subsequently, moved to a machine
for mechanical stimulation. Alternatively, a media perfusion setup can be implemented that removes
the need for manual feeding, allowing the samples to remain in the bioreactor for the study's duration,
decreasing the possibility for contamination [ 461 , 462 ]. Since native cartilage responds negatively to
static loading, devices have often been designed to load a construct dynamically [ 463 ]. However, for
static loading, it has been postulated that it is not necessarily the mechanical load that is detrimental
but the limited diffusion of wastes and nutrients under such conditions, as well as possibly a decrease
in the local environment's pH [ 464 ]. Whether this is the mechanism or not, static compression has