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Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft-Antenna.

ABSTRACT: An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft-antenna). The graft-antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft-antenna and stimulated by the TMS for 1 h per week. The graft-antenna is an innovative and minimally-invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair.

SUBMITTER: Sliow A

PROVIDER: S-EPMC6548953 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft-Antenna.

Sliow Ashour A Ma Zhi Z Gargiulo Gaetano G Mahns David D Mawad Damia D Breen Paul P Stoodley Marcus M Houang Jessica J Kuchel Rhiannon R Tettamanzi Giuseppe C GC Tilley Richard D RD Frost Samuel J SJ Morley John J Longo Leonardo L Lauto Antonio A

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190403 11

An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft-antenna). The graft-antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle ...[more]

PMID: 31179205

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Project description:Objective: Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates. Approach: Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses. Main Results: One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and followed stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes. Significance: These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a animal model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Together, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.

Project description:Background. Electrical neuromodulation remains an effective therapy for multiple neurological disorders. One strategy to electrically stimulate nerves utilizes the interference of multiple high frequency waveforms. This technique, known as temporal interference stimulation or interferential current stimulation, has recently gained significant attention as a method to improve the state-of-the-art in neurostimulation in both animal studies and human clinical trials.Objective.Here we report our investigation into the fundamental properties of the neuronal response to these types of waveforms-the effects of carrier and envelope frequencies, thresholds, firing behavior, and phase and asymmetric interference patterns.Methods.We utilized a cuff electrode on the rat sciatic nerve to apply a variety of interferential signals. We recorded muscle activity in the plantar muscles and biceps femoris, which are proxies for activity on two of the major branches of the sciatic, which are spatially distinct in the target volume. We tested both fundamental recruitment properties as well as spatial techniques to selectively activate either muscle group.Results.Our data suggest, contrary to the currently accepted explanation, that neurons do not extract envelopes at all, and that the response to these signals is well explained by a resistor-capacitor (i.e. integrator) membrane with a fixed firing threshold. Basic interference techniques do not change recruitment far from electrodes. Techniques can produce regions of both phasic activation and tonic activation/conduction block.Conclusions.An integrator model suggests that interference techniques are less capable of minimally invasive stimulation for a subcortical brain target than previously thought. Human clinical trials using these techniques should reevaluate their methods. Interference stimulation allows significant target selectivity in a peripheral cuff electrode with targets near electrodes. These techniques can allow spatially distinct regions of phasic firing, tonic firing, conduction block, and no effect.

Dataset Information

Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft-Antenna.

Publications

Stimulation and Repair of Peripheral Nerves Using Bioadhesive Graft-Antenna.

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