Current neuromodulation strategies mainly rely on pharmaceutical interventions, with limited efficiency over time in chronic progressive neurodegenerative disorders. Alternate therapeutical approaches include electric neuromodulation like deep brain stimulation for Parkinson’s disease. Nowadays, a variety of neural prostheses has been successfully developed to restore damaged/lost neural functions such as the ability to communicate in a fully paralyzed patient, or to walk in cases of partial spinal lesions. However, despite proven therapeutic benefits, most available neural implants mainly rely on an open-loop configuration and are energy-intensive, which limits their application potential. This highlights the need for closed-loop interfaces enabling real-time communications with living neuronal networks, thus permanently adjusting stimulation parameters to each patient’s need. The present works aims at developing such bidirectional neurobiohybrid interfaces. In this view, we chose a material approach based on an original artificial neuron with optimized energy efficiency (Sourikopoulos et al. 2017) and conducted an interdisciplinary study involving the fabrication/characterization of neurobiohybrid devices enabling in vitro maintenance of various neurons directly onto planar gold electrodes. Calcium imaging and patch clamp techniques ensured the biological reality of recorded spikes. Our results show the actual stimulation of electrically active cells plated within neurobiohybrids. In addition, we were able to record electric activity within the devices. Taken together, our results set the bases for establishing a full bidirectional communication loop between artificial and biological neurons. In conclusion, the present work paves the way for developing next-generation closed-loop neuroprostheses.