Regenerative Peripheral Neurointerfacing Of Upper Extremity Prostheses
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Abstract
Current robotic prosthetic devices provide limited functionality to the user as they rely on gross myogenic control and lack critical sensory feedback needed for fine movement control. Interfacing the nervous system with the robotic prosthesis would facilitate amputees to control them naturally, in resemblance to the human hand. Functional neuro-electrode connections have been demonstrated in the brain and peripheral nervous system; however, gliosis, micro hemorrhages, axonopathy and excessive inflammation limit their long-term use. We evaluated the possibility of enticing peripheral nerve regeneration through a multi-electrode array with an open architecture as an alternative to enhance longevity of nerve-electrode interface. Regenerative conduits deploying 18-electrode arrays were implanted into the transected sciatic nerve of acute and chronic (n=6) injured adult rats, and electrophysiological recordings, behavioral and histological analysis were performed at 19-223 days post implantation. In both acute and chronic implanted animals, axons regenerated in close proximity (10-150 µm) to the electrodes. Myelinated and ummyelinated axons were visualized by double-immunostaining of myelin basic protein and calcitonin gene related peptide; respectively. The accumulation of activated macrophages (ED1+) was limited to 2-3 cell layers coating the electrodes. Behavioral studies showed partial motor function recovery in acute injury group, demonstrating the ability of the interfaced peripheral nerves to reconnect with their original target organs. Action potentials in a form of single/multi-unit activity from regenerating axons were recorded as early as one week, and up to two months post implantation, with high signal to noise ratio (SNR). We also sought to segregate different sub-types of regenerating axons via specific growth factors induction. Successful enrichment of pain and proprioceptive sensory fibers was achieved by nerve growth factor and NT-3 stimulation respectively. Finally we worked in improving the electrode array itself, as those used are made of conductive metal. In order to enhance the electrochemical stability of these implantable electrodes, we used conductive nanomaterials to augment the sensitivity of the implant. Together, our findings support the notion that regenerative multi-electrodes would provide an enhanced neurointerface for the control of robotic prosthesis.