3D engineered neural networks coupled to Micro-Electrode Arrays: Development of an innovative in-vitro experimental model for neurophysiological studies

2D neuronal populations coupled to Micro-Electrode-Arrays (MEAs) constitute a well-established experimental in-vitro platform to study neurobiology, network electrophysiology, and basic injury-disease mechanisms. They are also widely used for neuropharmacological screening and neurotoxicity tests. Here we propose a new experimental in-vitro paradigm constituted by 3D engineered networks coupled to both planar and innovative 3D-MEAs. The advantage of such a model is clearly its improved representation of the actual in-vivo environment while maintaining some of the advantages (control, observation) of in-vitro systems. We constructed a physically connected 3D neural network and we demonstrate how the 3D network dynamic differs from the corresponding 2D model, resembling the one detected in the invivo situation. The obtained results suggest new avenues for the use of such 3D models for neurophysiological studies or for the development of biohybrid microsystems for in-vivo neural repair.