Bioresorbable nerve stimulators enhance regeneration across segmental peripheral nerve defects
Matthew MacEwan, PhD, Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, Nathan Birenbaum, MS, Washington University School of Medicine, Saint Louis, MO and Wilson Z Ray, MD, Washington University School of Medicine, St. Louis, MO
Introduction: Electrical stimulation of injured peripheral nerve tissue has been demonstrated to restore sensorimotor function and accelerate axonal regeneration in vivo. Yet, existing methods of applying electrical stimulation to peripheral nerve tissue have presented significant barriers to clinical translation. The present study describes the implementation of a bioresorbable wireless nerve stimulator capable of delivering therapeutic electrical stimulation to injured peripheral nerve tissue. Both brief and prolonged courses of electrical stimulation were delivered by the bioresorbable wireless nerve stimulator to peripheral nerve tissue following nerve crush, transection / direct repair, transection / short graft repair, and transection / long graft repair in order to evaluate the role of varied doses of electrical stimulation on nerve regeneration and functional recovery.
Methods: Bioresorbable implantable wireless stimulators were manufactured from transient polymer substrates and metallics. Fabricated bioresorbable stimulators were engineered to function electronically for 2 weeks following implantation prior to complete dissolution. Bioresorbable stimulators were subcutaneously implanted into Lewis rats. Implanted devices were utilized to deliver both brief (1 hr, 20 Hz) and prolonged (1, 3, 6, 9, 12 days x 1 hr, 20 Hz) electrical stimulation to sciatic nerves following nerve crush, transection / direct repair, transection / short isograft repair (20mm), and transection / long isograft repair (40mm). Nerve conduction / CNAP studies, EMG measurements, and evoked muscle force production was utilized to quantify functional motor recovery in additional to histological analysis of axonal regeneration.
Results: Bioresorbable wireless nerve stimulators were shown to successfully facilitate therapeutic stimulation of peripheral nerve tissue for 2 weeks after nerve injury. Brief therapeutic electrical stimulation delivered by the implants was observed to increase both the rate of functional recovery and maximal capacity for functional recovery following nerve transection and repair, as observed in prior studies. Prolonged electrical stimulation was observed to increase the rate and capacity for functional motor recovery beyond that of brief electrical stimulation alone. Both 6 day and 12 day regimens of therapeutic electrical stimulation resulted in significant improvements in functional recovery over brief electrical stimulation alone in both direct repair and short isograft models. Prolonged therapeutic electrical stimulation in long isograft models was also shown to increase axonal regeneration across long segmental defects.
Discussion: The present study highlights the potential role of a bioresorbable implantable nerve stimulator and prolonged therapeutic electrical stimulation as unique adjuncts in the treatment of peripheral nerve injury, and particularly segmental nerve injuries repaired with nerve isografts.
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