Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators

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OBJECTIVE

Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery.

METHODS

Flexible wireless stimulators were fabricated and implanted into Lewis rats. Thin-film implants were used to deliver brief electrical stimulation (1 hour, 20 Hz) to sciatic nerves after nerve crush or nerve transection-and-repair injuries.

RESULTS

Electrical stimulation of injured nerves via implanted wireless stimulators significantly improved functional recovery. Brief electrical stimulation was observed to increase the rate of functional recovery after both nerve crush and nerve transection-and-repair injuries. Wireless stimulators successfully facilitated therapeutic stimulation of peripheral nerve tissue and serial assessment of nerve recovery.

CONCLUSIONS

Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings.

ABBREVIATIONS EDL = extensor digitorum longus; EMG = electromyographic; GM = gluteus maximus; GS = gastrocnemius; PL = plantaris; TA = tibialis anterior.

Article Information

Correspondence Wilson Z. Ray: Washington University School of Medicine, St. Louis, MO. rayz@wudosis.wustl.edu.

INCLUDE WHEN CITING Published online February 9, 2018; DOI: 10.3171/2017.8.JNS163020.

Disclosures W.Z.R. has served as a consultant for Globus and has ownership in Acera Surgical, Inc.

© AANS, except where prohibited by US copyright law.

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Figures

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    Fabricated thin-film wireless receivers containing integrated spiral antennae, surface mount pads for fixation of tuning circuitry, and bonding sites for Pt/Ir leads. These thin-film receivers are a flexible, low-profile implant suitable for use in small rodent models. Figure is available in color online only.

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    Left: Assembly of thin-film wireless receivers for in vivo implantation. Flexible thin-film receivers are bonded to Pt/Ir leads that are integrated into silicone nerve cuff electrodes sized for the rat sciatic nerve. Right: Implantable wireless nerve stimulators are implanted subcutaneously in laboratory rats and interfaced with the sciatic nerve. Shown is an intraoperative view of the implanted wireless nerve stimulator. Silicone nerve cuff electrodes wired to flexible thin-film receivers were applied to the rat sciatic nerve and secured using 8-0 nylon suture to facilitate an intimate noncompressive interface between active Pt/Ir leads and peripheral nerve tissue. PDMS = polydimethylsiloxane. Figure is available in color online only.

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    Output voltage of potted wireless receivers after prolonged immersion in an aqueous bath of sterile saline. Submersion of potted receivers was performed to test the hermetic seal of implantable devices and confirm reliable repeatable activation of the constructed devices. Stable output of immersed receivers revealed reliable operation over prolonged periods of time in near-physiological conditions.

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    Maximum amplitude of electromyograms evoked in the GM after electrical activation of uninjured, crushed, and cut-and-repaired sciatic nerves in both the presence and the absence of brief electrical stimulation via the implanted wireless nerve stimulator. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation. Figure is available in color online only.

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    Maximum amplitude of electromyograms evoked in the TA after electrical activation of uninjured, crushed, and cut-and-repaired sciatic nerves in both the presence and the absence of brief electrical stimulation via the implanted wireless nerve stimulator. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation. Figure is available in color online only.

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    Maximum amplitude of electromyograms evoked in the GS after electrical activation of uninjured, crushed, and cut-and-repaired sciatic nerves in both the presence and the absence of brief electrical stimulation via the implanted wireless nerve stimulator. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation. Figure is available in color online only.

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    Maximum amplitude of electromyograms evoked in the PL after electrical activation of uninjured, crushed, and cut-and-repaired sciatic nerves in both the presence and the absence of brief electrical stimulation via the implanted wireless nerve stimulator. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation. From Ray et al: An update on addressing important peripheral nerve problems: challenges and potential solutions. Acta Neurochir (Wien) 159:1765–1773, 2017. Published with permission. Figure is available in color online only.

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    Maximum isometric twitch forces (upper) and maximum isometric tetanic forces (lower) evoked by TA and EDL muscles after stimulation of uninjured, crushed, and cut-and-repaired sciatic nerves in both the presence and the absence of brief electrical stimulation via the implanted wireless nerve stimulator. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation.

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    Wet mass of TA and EDL muscles after sham surgery (no nerve injury), crush injury of the sciatic nerve, and cut-and-repair injury of the sciatic nerve in both the presence and the absence of brief electrical stimulation. Mean values and SDs are shown. *p < 0.05 versus time-matched injury model with no electrical stimulation.

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