4.4 Bioreactor process optimization
Producing large numbers of cells efficiently is a key step in the
process of creating cultivated meat. Several bioreactor configurations
have been suggested [10], but the jury is out as to whether any of
them will be practical at the much larger scale and lower cost required
to support commercial production. Building out large-scale bioreactor
prototypes is an expensive and time-consuming proposition, so making a
judgement by empirical means is hampered by cost. Developing a single
model specific to one configuration is also likely to be expensive and
time-consuming; however, once created, a model can be iteratively
refined and tested at a far lower cost than redesigning and testing
physical bioreactors. In addition, the methodology used to model any one
bioreactor configuration is likely applicable to others with incremental
modifications. Indeed, computational modeling approaches have been
applied to bioreactor use in cell therapy development [23-28], and
these approaches should translate to cultivated meat production.
Here, we briefly detail five bioreactor configurations that have
potential utility in cultivated meat - i) suspension growth (w/o
microcarriers) in a stirred tank bioreactor, ii) adherent growth (w/
microcarriers) in a stirred tank bioreactor, iii) hollow fiber
bioreactors, iv) a continuous flow bioreactor design relying on coated
surface and v) a rocking bioreactor design. We also describe instances
where computational modeling has been applied to study these reactors.
In the future, novel and more holistic modeling of these systems must
combine simulation of the cell biology with modeling of
physio-mechanical properties (e.g. adherence, elasticity, susceptibility
to shear forces) and computational fluid dynamics to get a better
understanding of which reactor design is best-suited to achieve the high
output requirements of cultivated meat production.