# Biomedical Applications of Polymeric Cryogels
## 3 Cryogels in Medical Applications
### Cryogels for Tissue Engineering
#### 3.4.1 Bioreactors  
Bioreactors are defined as devices which support biological reactions. They have a great importance in the cell cultivation providing control and monitoring of pH, temperature, oxygen and nutrient dissociation in microbiology. When tissue engineering was taken into consideration, bioreactors can be applied to develop new functional tissue in vitro with the production of regulatory signals in an appropriate physical environment. By this way, they stimulate cell proliferation, modification with the advantage of uniform cell distribution on 3D matrices and ECM generation before implantation step. Scaffolds are particularly well-designed candidates to store and deliver of the cells. Cryogels have an important role in the development of bioreactor matrix enabling high amount of mass transfer and have been attractive alternatives as bioreactors. There have been several research publications highlighting the vital roles of cryogels in bioreactor platforms. A previous study regarding with the storage and transportation ability of the cells reported the application of both HEMA-agarose (HA) and gelatin cryogels for this purpose. Firstly, HA cryogel matrices seeded with C\({}_{2}\)C\({}_{12}\) cells, after five days, it was indicated that C\({}_{2}\)C\({}_{12}\) cells were successfully protected with high viability. In terms of gelatin cryogels, it was shown that C\({}_{2}\)C\({}_{12}\) cells, human hepatocellular liver carcinoma cell line (HepG2), human umbilical vein endothelial cells (HUVECs) were sustained by cryopreservation [58]. [PERSON], [PERSON], et al. were examined the capability of PVA cryogels in the storage of both gram-positive and gram-negative bacteria, yeasts, and filamentous fungi. This study revealed that the viability and effective reproductive potential of the microbial cells were kept at \(-18\)\({}^{\circ}\)C for two years [59]. Polymeric cryogel matrices have been prominent tools for the cultivation of a large number of cells as well. In a previous study, copolymer of acrylonitrile and \(N\)-vinyl-2-pyrrolidone and interpenetrated polymer networks of chitosan and NIPA were prepared as cryogel matrices. These two types of cryogels with supermacropores the size of 20-100 \(\upmu\)m provided operative transportation; besides that, they were triggered in vitro cultivation of fibroblasts and HepG2. On the other hand, both hemocompatibility and biocompatibility of these cryogels were proved. Consequently, cryogels as efficient bioreactor matrices enable hepatocyte immobilization and their ability for detoxification of plasma was clinically demonstrated in acute on chronic liver failure [60]. In another study, it was aimed to establish cryogels and use them as bioreactor systems to hydrolyze starch. For this purpose, the immobilization of alpha-amylase from _Aspergillus oryzae_ was performed by cryopolymerization of AAm monomers. The effect of different experimental conditions (pH, temperature, concentration of starch solution) on starch hydrolysis were investigated. The results obtained in this study supports that the alpha-amylase immobilized cryogels are applicable for industrial processes [61]. In a study carried out by [PERSON], [PERSON] et al., different cryogels consist of polyacrylamide-chitosan (PAAC), poly(NIPA)-chitosan, polyacrylamide, and poly(NIPA) were investigated for hybridoma cell (6A4D7, B7B10, and H9E10) growth and monoclonal antibody (mAb) production. PAAC was demonstrated better activity on mAb production and cell growth. PAAC cryogel was also prepared as monolith, disks, beads and was applied for continuous packed-bed bioreactor. The monolith one has a good performance on antibody production with markedly high concentration. The data reported by this study suggests that the productivity of these systems may be broadened by different polymeric blends [62]. Cryogels have been represented to withstand cell behavior modification and stimulation of molecule generation.