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Thin-film Wireless Implants Facilitate Therapeutic and Diagnostic Electrical Stimulation of Peripheral Nerve Tissue Following Injury
Matthew MacEwan, PhD; Paul Gamble, MD; Manu Stephen Wilson Ray, MD
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO
Introduction: Brief electrical stimulation has previously been shown to improve axonal regeneration and functional recovery following peripheral nerve injury. Unfortunately, intraoperative methods of applying electrical stimulation to injured peripheral nerves are time consuming, cumbersome, and incompatible with existing clinical work flow. The present study highlights the design and evaluation of a novel system of implantable, thin-film wireless receiver capable of non-invasively and serially stimulating peripheral nerve tissue for therapeutic and diagnostic applications. In vivo implementation in a rodent model demonstrated the ability of wireless implants to deliver therapeutic stimulation to injured sciatic nerve and track differing time-courses of recovery following nerve crush and nerve transaction/repair. The present study provides preliminary evidence of the translational potential of the present system of wireless implantable devices.
Materials and Methods: Flexible thin-film wireless receivers were manufactured via sacrificial photolithography by Red Rock Laboratories (St. Louis, MO). Fabricated receivers were subcutaneously implanted into thirty three male Lewis rats and proximally attached to the sciatic nerve prior to injury. In Phase I, animals underwent either nerve crush injury (n=5), nerve crush injury with electrical stimulation (n=5), or sham surgery (n=5). Electrical stimulation consistent with prior studies was delivered intraoperatively per the wireless implant at the time of surgery (freq. = 20 Hz, duration = 1 hr.). In Phase II, animals underwent either nerve crush injury (n=6), transection / repair (n=6), or sham surgery (n=6). Post-operatively, all animals underwent weekly non-invasive functional assessment utilizing thin-film implants. Three months post-operatively all animals underwent terminal functional assessment and histomorphometric evaluation of explanted nerve tissue.
Results and Discussion: Thin-film receivers were successfully implanted in male Lewis rats, facilitating wireless serial stimulation of interfaced sciatic nerves. Animals receiving therapeutic electrical stimulation in Phase I demonstrated improved functional recovery compared to control animals 1-4 weeks post-operatively. Animals receiving wireless receivers in Phase II demonstrated varying time courses of functional recovery following nerve crush and nerve transaction / repair. Implanted devices successfully facilitated serial assessment of nerve and muscle function post-operatively, as measured via EMG, evoked muscle force measurement, and evoked joint torque. Resulting data demonstrated the unique diagnostic function of the wireless implants and the varied time-courses of functional recovery following peripheral nerve injury.
Conclusions: The present study suggests that thin-film wireless implants may serve as a unique clinical tool in the future treatment and characterization of peripheral nerve injuries.
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