Neural implants have been the focus of recent technological developments in the field of neuroengineering. The most commonly addressed challenges dealt with electrode materials to ensure their biocompatibility, with packaging and substrate materials for enabling long-term implantations, and with energy consumption and autonomy issues. Most neuroprostheses currently available were designed either for recording nervous system/brain activity or for stimulating neurons in order to restore or replace lost physiological functions. Nowadays, such bioelectronic devices are widely used in various clinical conditions such as blindness (retinal implants), deafness (cochlear implants), epilepsy (flexible IcEEG arrays), tetra/paraplegia (paddle electrodes) or Parkinson’s disease (deep brain stimulation). Despite the progressesachieved, current neuroprostheses still require analogous to digital conversions thus leading to overt energy expenditure, and imply remote data processing with cable-wire and cluttering connections to PCs. In addition, very few neural implants enable a bidirectional communication between the neural tissue and the bioelectronics device. To address these critical issues, our team developed a neurobiohybrid system based on our formerly published original highly energy efficient artificial neuron, designed in 65 nm CMOS technology. The present work will discuss the following technological challenges: a) development of the neurobiohybrid device enabling proper interfacing of biological neurons with gold electrodes, b) development of a in-house electronic bench enabling both the stimulation and recording of various living neuronal cells, and coupled with calcium imaging to ensure the biology reality of recorded electric events. Taken together, our current data pave the way for next-generation implantable medicaldevices/neuroprostheses.