Biohybrid Peripheral Neural Interfaces: Combining Cell Transplantation and Flexible Electronics for Functional Neurological Restoration

Abstract

Peripheral nerve injuries result in a disconnection in the nervous system communication and a consequent loss in neurological function. Currently, there is very limited treatment for these conditions. Neuroprosthetics and cell transplantation are promising approaches to restore lost neurological function: the former aims to bypass the site of injury, connecting directly one part of the nervous system to another (or a prosthetic limb); while the latter aims to repair the injury site. To date, both strategies have shown limited efficacy and lifetime due to several challenges. However, a combinational approach of implantable electronics and stem cell-derived cells for functional neurological restoration could address these issues. The integration between implantable electronics and existing tissue is of paramount importance, this biohybrid strategy with the incorporation of cells may allow for a ‘controllable’ synaptic integration between implanted cells and existing circuitry. Attributes to such a biohybrid implant are: an ability to host and interact with stem-cell derived cells; promotion of organised functional cellular integration with living tissue; and restoration of lost function. Here I report the new design of a biohybrid peripheral nerve multielectrode neural interface device. My devices are fabricated using photolithography and chemical etching techniques to establish a functional electronic device. This multielectrode neural device contains 32 electrodes. Each electrode consisting of planar gold, coated with a conducting polymer (PEDOT:PSS) to decrease the electrode impedance and improve the signal to noise ratio. The layers of Parylene C give a desirable stiffness compatible with that of native nerve. The device hosts iPSC derived myocytes on the electrically active surface, allowing their efficient electrical recording. I have shown survival of human iPSC derived muscle in a rat for up to seven days post implantation in a rat model. I have developed a strong bonded hydrogel that allows for biofabrication on top of flexible electronics. Finally, I showed long term recordings from my biohybrid neural interfaces in a chronic rat peripheral nerve injury model for 30 days duration. These findings strongly suggest that biohybrid peripheral neural interfaces could be an efficient way to record the peripheral nervous system in a rat peripheral nerve injury model.