Alginate-chitosan core-shell microcapsule cultures of hepatic cells in a small scale stirred bioreactor: impact of shear forces and microcapsule core composition

A small scale stirred bioreactor was designed and the effect of different agitation rates (30, 60 and 100 rpm) was investigated on HepG2 cells cultured in alginate-chitosan (AC) core-shell microcapsule in terms of the cell proliferation and liver-specific function. The microencapsulated hepatic cells could proliferate well when they were cultured for 10 days at 30 rpm while the cell-laden microcapsules showed no cell proliferation at 100 rpm in the bioreactor system. Albumin production rate, as an important liver function, increased also 1.8- and 1.5- fold under stirring rate of 30 rpm compared to the static culture and 60 rpm of agitation, respectively. Moreover, In comparison with the static culture, about 1.5-fold increment in urea production was observed at 30 rpm. Similarly, the highest expressions of albumin and P450 genes were found at 30 rpm stirring rate, which were 4.9- and 19.2-fold of the static culture. Addition of collagen to the microcapsule core composition (ACol/C) could improve the cell proliferation and functionality at 60 rpm in comparison with the cell-laden microcapsules without collagen. The study demonstrated the hepatic cell-laden ACol/C microcapsule hydrogel cultured in the small scale stirred bioreactor at low mixing rate has a great potential for mass production of the hepatic cells while maintaining liver-specific functions.