Transient Implantable Nerve Stimulator for Enhancing Regeneration Across Long Segmental Peripheral Nerve Defects
Abstract
Recovery from peripheral nerve injuries requiring the use of nerve grafts is often incomplete. Despite ongoing investigation into new interventions (e.g., exogenous growth factors, transient immunosuppression), no effective clinical therapy has been developed to improve the rate of post-operative nerve regeneration and functional recovery. Therapeutic electrical stimulation of injured nerve tissue represents a unique and attractive intervention to enhance peripheral nerve regeneration. Numerous studies have demonstrated that brief intraoperative electrical stimulation (1 hour, 20 Hz) enhances nerve regeneration in both human and animal models of peripheral nerve injury. Our laboratory has further demonstrated that repeat electrical stimulation continued up to 6 days post-operatively further enhances functional recovery beyond that of existing stimulation paradigms. Yet, optimal methods and devices for applying repeat electrical stimulation to injured nerve tissue in a post-operative setting have yet to be identified. Recent work conducted in our laboratories has resulted in the fabrication of a fully transient (i.e., dissolvable) implantable nerve stimulator capable of delivering therapeutic electrical stimulation to injured nerve tissue over multiple weeks prior to complete dissolution into the body. Preliminary studies conducted in our laboratories have validated the ability of transient nerve stimulators to effectively deliver brief electrical stimulation to rat sciatic nerves over 14 days following nerve transection and repair injuries without the need for a permanent medical implant or power supply. These results confirm that transient nerve stimulators enable delivery of therapeutic electrical stimulation well outside the constraints of prior studies and existing nerve stimulation/interfacing technologies. The goal of the present project is to utilize transient nerve stimulators to identify optimal dosages and protocols for therapeutic electrical stimulation of injured peripheral nerve tissue and to evaluate the potential of brief electrical stimulation to accelerate nerve regeneration through long nerve graft in order to enhance functional recovery following severe nerve injury. Our central hypothesis is that prolonged/repeat electrical stimulation enabled by transient implantable nerve stimulators will enhance nerve regeneration across long nerve grafts and significantly improve functional recovery compared to existing clinical therapies. The design of the proposed study involves the implantation of transient nerve stimulators in adult male and female rats and therapeutic electrical stimulation of the sciatic nerve following nerve injury and either direct repair, short graft repair, or long graft repair. Electrophysiological, behavioral, and histological methods will be utilized to measure the effect of electrical stimulation paradigms on the rate, quality, and success of axonal regeneration and functional sensorimotor recovery. The present study has the potential to identify the first post-operative therapeutic intervention for Veterans and civilians affected by peripheral nerve injury. Modern wars have resulted in significant numbers of peripheral nerve injuries due to the prevalence of body armor and the nature of the threat. Development of a novel bioelectric therapy to encourage peripheral nerve regeneration could improve and accelerate functional recovery and bring new rehabilitative strategies to the many Veterans already served, as well as those yet unserved. Improved restoration of sensory and motor function in our wounded Soldiers represents a significant advance in the current treatment paradigm.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810170
Entities
People
- Matthew Macewan
Organizations
- United States Army
- Washington University in St. Louis