A novel method for patterning cellular co-cultures that uses the layer-by-layer deposition of ionic biopolymers is described. Nonbiofouling hyaluronic acid (HA) micropatterns were used to immobilize cells and proteins to glass substrates. Subsequent ionic adsorption of poly-l-lysine (PLL) to HApatterns was used to switch the HAsurfaces from cell repulsive to adherent thereby facilitating the adhesion of a second cell type. The utility of this approach to pattern co-cultures of hepatocytes or embryonic stem cells with fibroblasts was demonstrated. In addition, the versatility of this approach to generate patterned co-cultures irrespective of the primary cell seeding and relative adhesion of the seeded cells was demonstrated. Thus, the proposed method may be a useful tool for fabricating controlled cellular co-cultures for cell–cell interaction studies and tissue engineering applications.
Khademhosseini, Ali, Kahp Y. Suh, Jen M. Yang, George Eng, Judy Yeh, Shulamit Levenberg, Robert Langer