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 in-vivo 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.