Bio-Compatibility Analysis of Newly Developed Plug and Cuff Electrodes for Future Neuronal Interface Applications.

The NerveRepack project is a European initiative that aims to develop biomimetic exoskeletons/exoprostheses for amputated or paralyzed leg patients that will receive and transmit signals to enable movements and sensations for the patient. To implement the project, it is fundamental to develop implantable neuronal electrodes that will allow bidirectional signaling between the sensors placed on the exoskeletons/exoprostheses and the nervous system. In this direction, two electrodes, plug and cuff, have been designed as integral parts of the final implantable device. The electrodes should comply with strict regulations to ensure their safe implantation in patients. The purpose of this study was to support the compliance of the implant platforms of certain key components with the ISO and ASTM standards that would be required for clinical applications. We have used an indirect method to assess the biocompatibility of the developed electrodes against neuronal cells, fibroblasts, and keratinocytes. Also, we assessed hemocompatibility, i.e., the potential of implantable electrodes to induce hemolysis or complement activation. Finally, the mutagenic/genotoxic potential was tested against the internationally recommended CHO cells. Both representative plug and cuff electrode components were found non-cytotoxic, non-mutagenic, and unable to induce hemolysis. Therefore, from the point of early evaluation of in vitro material and process biocompatibility, the selected implant platforms for the electrodes could be implanted in preclinical models to delineate their potential in vivo applications as neuronal interface with the biomimetic exoskeleton/exoprostheses.