Grants Funded

Abstract

Project Summary: Despite development of advanced prostheses, an ideal user-prosthetic interface that facilitates complete functional recovery has yet to be achieved. The lack of an ideal interface allowing for sophisticated motor control leads to abandonment of artificial limbs. Prosthetic control relies on surgically acquired electromyography (EMG) signal sites from reinnervated muscle targets. However, there remains barriers to get intuitive control of the prosthetic limb and widespread implementation of these surgical techniques. Sub-optimal results are especially noticeable when transected peripheral nerves remain without a distal target for a longer amount of time after amputation. In these circumstances, chronic axotomy severely reduces the regenerative capacity of nerves, which results in reinnervation failure of Neuromuscular junctions (NMJs). Our lab has previously developed the Regenerative Peripheral Nerve Interface (RPNI) that offers real-time control of myoelectric prosthetic devices to restore extremity function in individuals with amputation. Prior studies confirmed the biologic stability of the interface and demonstrated successful axonal regeneration, reinnervation, and signal amplification. However, a fundamental gap in knowledge exists in the regenerative capacity and meaningful functional recovery of chronically axotomized axons following delayed RPNI creation. The overall objective of the current study is to determine whether delayed RPNI implantation promotes robust neuronal regeneration following chronic axotomy by altering the microenvironment favorably, and to identify the impact of this delay on signal amplification. The central hypothesis is that the longer the RPNI is delayed, the less favorable the microenvironment is for nerve regeneration, reinnervation, and signal amplification necessary for intuitive control of a prosthetic device. This hypothesis will be tested by pursuing the following two specific aims: (1) determine electrophysiological signal transduction capabilities and functional recovery of delayed RPNI at 3 and 6 months following chronic axotomy; and (2) characterize the tissue microenvironment following delayed RPNI implantation at 3 and 6 months following chronic axotomy. Demonstration of these aims would encourage applications of peripheral nerve interfaces to provide intuitive prosthetic control in the setting of chronic axotomy and improve functional outcomes when treatment with RPNI is delayed.

Impact Statement: More than 185,000 people undergo amputations in the US each year. Limb loss severely limits participation in physical and occupational activities, often results in poor quality of life. RPNI has the potential to offer intuitive control of modern prostheses to restore independence. When peripheral nerves remain without a distal target, regenerative capacity progressively declines due to chronic axotomy, significantly limiting the functional recovery. The major impact of this study is that the utilization of the RPNI will provide prosthetic control in the setting of chronic axotomy and delayed treatment, the functional outcomes of which are currently poor. These results are expected to vertically advance applications of peripheral nerve interfaces and improve outcomes when RPNI is delayed.

Biography
Stephen Kemp, PhD completed his Honours Bachelor of Science at the University of Toronto, where he conducted his undergraduate thesis under the supervision of Dr. Gerald Cupchik. During this time, Dr. Kemp’s research focused on the psychology of creativity, and the development of a "matching and modulation" psychological model of aesthetic response. Dr. Kemp’s undergraduate thesis led to the publication of two peer-reviewed publications, and one book chapter. Following graduation, Dr. Kemp completed his Master’s degree at Wilfrid Laurier University in Waterloo, under the supervision of Linda Parker, PhD. His research focused on the effect of delta-9-tetrahydrocannabinol (THC) on lithium induced sickness behaviours in both rats and house musk shrews. Stephen completed his PhD at the University of Calgary, under the mentorship of Rajiv Midha, MD, focusing on the anatomical, sensorimotor, and functional evaluation of peripheral nerve regeneration through bio-engineered conduits in rodents. During this tenure, Dr. Kemp became a member of numerous scientific societies, including the Society for Neuroscience, the Canadian Society for Neuroscience, and the American Society for Peripheral Nerve. Dr. Kemp also published nine peer-reviewed publications. One of his papers was highlighted in Experimental Neurology as an outstanding paper. Following his tenure in Calgary, Dr. Kemp accepted a postdoctoral fellowship at the University of Toronto and The Hospital for Sick Children with Gregory Borschel, MD and Tessa Gordon, PhD. Dr. Kemp continues to investigate treatment of nerve injuries, and has expanded his research to focus on treatment of neonatal nerve injuries. Dr. Kemp has won numerous awards during his scientific career, including prestigious postdoctoral awards. Overall, Dr. Kemp has 14 published peer reviewed publications, two book chapters, two News and Views commentaries, 18 abstracts, and 21 international conference presentations.