Functional Electrical Stimulation of Peripheral Nerve Tissue Via Regenerative Sieve Microelectrodes

摘要

Functional electrical stimulation (FES) of peripheral nervous tissue offers a promising method for restoring motor function in patients suffering from complex neurological injuries. However, existing microelectrodes designed to stimulate peripheral nerve are unable to provide the type of stable, selective interface required to achieve near-physiologic control of peripheral motor axons and distal musculature. Regenerative sieve electrodes offer a unique alternative to such devices, achieving a highly stable, selective electrical interface with independent groups of regenerated nerve fibers integrated into the electrode. Yet, the capability of sieve electrodes to functionally recruit regenerated motor axons for the purpose of muscle activation remains largely unexplored. The present dissertation aims to examine the potential role of regenerative electrodes in FES applications by testing the unifying hypothesis that sieve electrodes of various design and geometry are capable of selectively stimulating regenerated motor axons for the purpose of controlling muscle activation. This hypothesis was systematically tested through a series of experiments examining the ability of both micro-sieve electrodes and macro-sieve electrodes to achieve a stable interface with peripheral nerve tissue, electrically activate small groups of regenerated motor axons, and selectively recruit motor units present in multiple distal muscles. Custom sieve electrodes were fabricated via sacrificial photolithography. In vivo testing in rat sciatic nerve validated the ability of chronically-implanted regenerative sieve electrodes to support motor axon regeneration and integrate into peripheral nerve tissue. Sieve electrode geometry was shown to strongly modulate axonal regeneration, muscle reinnervation, and device functionality, as high-transparency macro-sieve electrodes facilitated superior neural integration and functional recovery compared to low-transparency micro-sieve electrodes. Inclusion of neurotrophic factors into sieve electrode assemblies increased axonal regeneration through implanted electrodes and improved the quality of the sieve/nerve interface in low-transparency devices. In vivo testing in rat sciatic nerve further validated the ability of chronically-implanted regenerative sieve electrodes to facilitate FES of regenerated motor axons and selective recruitment of distal musculature. Selective stimulation of regenerated motor axons using implanted micro- and macro-sieve electrodes enabled effective, external control of muscle activation within anterior and posterior compartments of the lower leg (e.g. ankle plantarflexion / dorsiflexion). Selective activation of distal musculature was achieved through modulation of stimulus amplitude, channel activation, and field steering. In summary, the present body of work provides initial evidence of the utility of regenerative electrodes as a means of selectively interfacing peripheral nerve tissue for the purpose of restoring muscle activation and motor control. These findings further highlight the clinical potential of implantable microelectrodes capable of intimately integrating into host neural tissue.