The influence of different cultivation conditions on the metabolic functionality of encapsulated primary hepatocytes

The clinical application of bioartificial liver support systems (BALS) is still limited because of technical problems associated with the storage, transport and scale-up of common systems. The encapsulation of primary hepatocytes could solve these problems since the scale-up depends only on the number of the beads and encapsulation leads to protection of the cells during the process of freezing and thawing. Many efforts have been made to find an appropriate material for the encapsulation of primary hepatocytes in terms of mechanical resistance as well as appropriate bio- and hemo-compatibility. This study focuses on the improvement of the metabolic functionality of encapsulated primary hepatocytes. A comparison between two different cultivation models showed that dynamic cultivation conditions lead to a 20.4-fold increase in the albumin production and a 5.21-fold increase in the urea synthesis of encapsulated hepatocytes. Furthermore, the influence of different ratios of the number of the cells to the volume of the media was analyzed. Encapsulated hepatocytes cultured with a high amount of medium were characterized by a significantly higher metabolic activity compared to encapsulated hepatocytes cultured with a low level of medium. Interestingly, the cell concentration per mL alginate has no significant influence on the metabolic activity of encapsulated hepatocytes. In conclusion, different optimization strategies are discussed and, finally, the functionality of encapsulated hepatocytes is compared to the standard model of hepatocyte culture, the collagen sandwich.