Abstract
Understanding the cues that guide axons and how we can optimize these cues to achieve directed neuronal growth is imperative for neural tissue engineering. Cells in the local environment influence neurons with a rich combination of cues. This study deconstructs the complex mixture of guidance cues by working at the biomimetic interface--isolating the topographical information presented by cells and determining its capacity to guide neurons. We generated replica materials presenting topographies of oriented astrocytes (ACs), endothelial cells (ECs), and Schwann cells (SCs) as well as computer-aided design materials inspired by the contours of these cells (bioinspired-CAD). These materials presented distinct topographies and anisotropies and in all cases were sufficient to guide neurons. Dorsal root ganglia (DRG) cells and neurites demonstrated the most directed response on bioinspired-CAD materials which presented anisotropic features with 90 degrees edges. DRG alignment was strongest on SC bioinspired-CAD materials followed by AC bioinspired-CAD materials, with more uniform orientation to EC bioinspired-CAD materials. Alignment on replicas was strongest on SC replica materials followed by AC and EC replicas. These results suggest that the topographies of anisotropic tissue structures are sufficient for neuronal guidance. This work is discussed in the context of feature dimensions, morphology, and guidepost hypotheses.