Three-dimensional polymer scaffolds for high throughput cell-based assay systems

Many whole cell-based assays in use today rely on flat, two-dimensional (2D) glass or plastic substrates that may not produce results characteristic of in vivo conditions. In this study, a three-dimensional (3D) cell-based assay platform was established by integrating 3D synthetic polymer scaffolds with standard cell culture dishes and multi-well plates. This technology can be used to feasibly modify any traditional 2D cell-based assay vessels for 3D cell-based assay with currently used high throughput screening (HTS) systems. We examined neural stem (NS) cellsʹ growth profile, morphology, cell–matrix interaction, gene expression and voltage gated calcium channel (VGCC) functionality of this novel 3D assay platform. Our results showed that unlike the NS cells cultured on traditional 2D planar surfaces, cells in 3D scaffolds are more physiologically relevant with respect to in vivo characteristics exhibited by in-vivo surrogates such as neural spheres. This new biomimetic cell-based assay platform may provide a broadly applicable 3D cell-based system for use in drug discovery programs and other research fields.