4.4.3 Hollow fiber bioreactors
In the stirred tank bioreactor systems, cells are taken from high
density environments with little variability in nutrient and oxygen
supply, and they are adapted to low-density suspension growth. While
these systems are widely used, they are not necessarily representative
of the in vivo physiological conditions that many cell types of
interest experience [35]. A more recent innovation that better
mimics in vivo growth conditions are hollow fiber bioreactors
[35]. With this technology, many semipermeable fibers are arranged
in parallel within a generally cylindrical cartridge that is equipped
with inlet and outlet ports. During operation, cells can be grown on the
inside of the fiber, outside, or both and culture medium is pumped
through the hollow fibers, allowing nutrients and other metabolic
products to diffuse both ways.
Mohebbi-Kalhori et al. [36] models hollow-fiber membrane bioreactors
intended to grow human bone tissue, in part motivated by the fact that
these systems are difficult to sample in real-time during cell and
tissue growth. The model developed treats the hollow-fiber scaffold as a
porous domain consisting of two interpenetrating porous regions
separated by a membrane through which nutrients and waste products pass.
In this conception, the hollow-fiber membrane scaffold is perfused with
culture medium on the lumen side and cells are grown at the exterior of
the fibers. The model was used to show how nutrient gradients impact the
cell volume fraction distribution as cells proliferate inside the
bioreactor. Predictions agreed with experimental results from the
literature. Notably, recent work by Allan et al. [37] presented at
the 5th International Conference on Cultured Meat explored the
applicability of hollow fiber bioreactors for largeāscale production of
skeletal muscle stem cells. This represents an excellent collaboration
opportunity to apply computational modeling methods.