Fabrication of patterned cell co-cultures on albumin-based substrate: Applications for microfluidic devices

Abstract

A surface coated with cross-linked albumin film resists the adhesion of cells, and subsequent exposure to UV irradiation or electrostatic adsorption of a cationic polymer switches the surface from non-adherent to adherent. Taking advantage of this unique property of cross-linked albumin, the authors fabricated patterned cell co-cultures with desired patterns and cell types. In this scheme, the cell-adherent region was initially created in the cell-non-adhesive albumin substrate, on which a first cell type was attached. Subsequently, the remaining region was also changed to adherent for the attachment of secondary cells in the same manner, thereby allowing distinctly localized co-cultures. As a proof of concept demonstration of the feasibility of this approach, a patterned co-culture of Neuro-2a cells with L929 cells was successfully prepared on the substrate. Furthermore, combining this technique with a microfluidic technique, a micropatterned co-culture of PA6 cells with 3T3 fibroblasts was created inside microfluidic devices. This approach could potentially be a useful tool for fundamental investigations of cell–cell interactions and for tissue engineering applications.