Technology platform for facile handling of 3D hydrogel cell culture scaffolds

Hydrogels are used extensively as cell-culture scaffolds for both 2D and 3D cell cultures due to their biocompatibility and the ease in which their mechanical and biological properties can be tailored to mimic natural tissue. The challenge when working with hydrogel-based scaffolds is in their handling, as hydrogels that mimic e.g. brain tissue, are both fragile and brittle when prepared as thin (sub-mm) membranes. Here, we describe a method for facile handling of thin hydrogel cell culture scaffolds by molding them onto a polycaprolactone (PCL) mesh support attached to a commonly used Transwell set-up in which the original membrane has been removed. In addition to demonstrating the assembly of this set-up, we also show some applications for this type of biological membrane. A polyethylene glycol (PEG)-gelatin hydrogel supports cell adhesion, and the structures can be used for biological barrier models comprising either one or multiple hydrogel layers. Here, we demonstrate the formation of a tight layer of an epithelial cell model comprising MDCK cells cultured over 9 days by following the build-up of the transepithelial electrical resistances. Second, by integrating a pure PEG hydrogel into the PCL mesh, significant swelling is induced, which leads to the formation of a non-adherent biological scaffold with a large curvature that is useful for spheroid formation. In conclusion, we demonstrate the development of a handling platform for hydrogel cell culture scaffolds for easy integration with conventional measurement techniques and miniaturized organs-on-chip systems.