Microfabrication of a tunable collagen/alginate-chitosan hydrogel membrane for controlling cell-cell interactions

Indirect cell contact co-culture system is increasingly becoming more attractable owing to their advantages of easy cell separation and desirable outcomes for cell-cell interactions. However, how to precisely control the spatial position of cells within multicellular co-cultures is still experimentally challenging due to the incapability of the conventional methods in vitro. In the present study, a tunable collagen/alginate-chitosan (Col/Alg-Chi) membrane was established, which was capable of controlling intercellular distance between the neighboring cells at a level of micrometer resolution. It was showed that intercellular distance between the hepatocytes and the fibroblasts exerted significant influence on hepatic function in vitro. In particular, maintenance of the functionality of primary hepatocytes requires direct contact between the hepatocytes and their supportive stromal cells, and their effective contact distance is within 30 μm. This technical platform would potentially enable investigations of dynamic cell-cell interaction in a multitude of applications including organogenesis, development or even neoplastic transformation.