Cryogel bioreactor for therapeutic protein production

Disposable bioreactors are becoming popular for small-scale therapeutic development and initial clinical trials due to their low cost and high efficiency. Our group has developed disposable cryogel bioreactor matrices for therapeutic protein production. A distinguishing feature of these cryogel bioreactor matrices is their low cost, a high surface-to-volume ratio and effective nutrient transport. Polyacrylamide coupled with gelatin or as a semi-interpenetrating network with chitosan (polyacrylamide-chitosan) has been used to formulate these cryogel bioreactor matrices. Both matrices are synthesized by free radical polymerization at -12°C in various formats such as monolith, beads and discs. Both adherent and nonadherent cells can be immobilized over a cryogel surface in high density for therapeutics production. The packed-bed, closed, continuous bioreactor configuration has been used to produce therapeutically important proteins like urokinase or monoclonal antibodies (mAb). The bioreactor can also be run as an integrated setup where protein purification can be done online with production using an affinity cryogel. The efficiency of these bioreactors has been found to be four times that of T-flask. Furthermore, the cryogels have also been used successfully to culture primary hepatocytes and hepatocarcinoma cell lines to be used in a bioreactor matrix in bioartificial liver devices (BAL).