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Neuroregenerative Electrodes Enable Functional Electrical Stimulation of Peripheral Motor Axons and Distal Musculature
Wilson Z. Ray, MD, Manu Stephen, Paul Gamble, Erik Zellmer and Matthew MacEwan, PhD
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO
INTRODUCTION Development of advanced neuroprosthetic systems depend on the creation of a microelectrode device capable of selectively interfacing peripheral nerve tissue. One device capable of achieving such an interface is the regenerative sieve electrode. Unfortunately, sieve electrodes are dependent upon robust, successful nerve regeneration through the device.1 Therefore, we hypothesized that the incorporation of fibrin-based delivery systems loaded with GDNF into sieve electrode assemblies will enhance nerve regeneration through the electrode and provide superior nerve/electrode interface capabilities in vivo.2 EXPERIMENTAL METHODS Custom-designed sieve electrodes were fabricated out of polyimide and gold using sacrificial photolithography. (Fig. 1) Prior to implantation in the sciatic nerve of male Lewis rats, silicone conduits attached to the electrodes were filled with either fibrin-based delivery system loaded with 100 ng/ml GDNF, or saline. Post-operatively, functional nerve regeneration through implanted devices and nerural interfacing capabilities were assessed in situvia nerve conduction studies and evoked muscle force mesaurement upon sciatic nerve stimulation. Regenerated nerve segments were terminally explanted and fixed, for histomorphometric evaluation. RESULTS & DISCUSSION Histological analysis demonstrated that sieve electrode assemblies containing GDNF-loaded matrices supported greater numbers of nerve fibers and improved functional recovery, CNAP conduction, and muscle force production compared to saline controls. Sieve electrode assemblies containing GDNF further supported stable interfaces with multiple groups of regenerated motor axons over >5 months, allowing for graded recruitment of multiple muscles within the lower leg. Implanted sieve electrodes assemblies containing GDNF demonstrated a threshold of motor activation of ~10uA, were capable of recruiting 99.8% of regenerated motor units, and demonstrated 99.5% selectivity of activation for all independent muscle tested. CONCLUSION The present study demonstrates that controlled delivery of trophic factors may modulate neural activity at the tissue/electrode interface, supporting future investigation into devices capable of simultaneously interacting with peripheral nerve tissue through bioelectric and biomolecular stimuli.
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