Biomedical Engineering Reference
In-Depth Information
72 CHAPTER 4. BIOREACTORS
spread adaptation. While combining two or more established mechanical stimuli seems straight-
forward, the biological response of an engineered construct could be totally unpredictable.
4.5 CHAPTER CONCEPTS
Bioreactors can be used to apply chemical and nutrient gradients in the culture of articular
cartilage constructs; it can also be used to apply mechanical forces to the developing cartilage.
Direct compression, hydrostatic pressure, high and low shear, and hybrid bioreactors have all
been examined, oftentimes in an effort to replicate physiological loading regimens.
Cyclic direct compression has been shown to be more beneficial than static compression. For
hydrostatic pressure, however, it has been shown that both static and dynamic applications can
result in functional improvements.
For hydrostatic pressure, it has also been shown that an optimal window in time exists in the
application of this force.
In self-assembly of articular cartilage, 10 MPa of hydrostatic pressure, applied statically for
one hour a day, five days total, has been shown to increase functional properties, both com-
pressive and tensile.
Direct compression and hydrostatic pressure have both been applied in combination with
growth factors to show enhanced effects.
Shear can be applied as either contact or as fluid shear in bioreactors. Translation or rotation
shear can be applied directly to constructs. It is hypothesized that chondrocytes experience
shear as the tissue is deformed during loading.
Direct fluid perfusion is another way to apply shear to chondrocytes while increasing nutri-
ent/waste transport.
As proinflammatory mediators have been seen with the application of shear on chondro-
cytes, low shear bioreactors have been developed to aid in nutrient transfer without eliciting
inflammatory and catabolic factors.
Several bioreactors can be used at once and at different times. For instance, a spinner flask
bioreactor can be used for seeding cells onto a scaffold, and then the construct can be trans-
ferred to a rotating wall bioreactor to experience minimal fluid shear with increased nutrient
transportation, and, finally, the construct can experience direct compression or hydrostatic
pressure in separate bioreactors.
