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 large‐scale production of skeletal muscle stem cells. This represents an excellent collaboration opportunity to apply computational modeling methods.