Enhanced Peripheral Nerve Regeneration by Mechano-electrical Stimulation

Abstract

AbstractTo address limitations in current approaches for treating large peripheral nerve defects, this study evaluated the efficacy of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were utilized to deliver mechanical actuation-activated electrical stimulation to nerve cells/tissues in a non-invasive manner. Using morphologically and piezoelectrically optimized nanofibers for neurite extension and Schwann cell maturation based on in vitro experiments, piezoelectric nerve conduits were implanted in a rat sciatic nerve transection model to bridge a critical-sized sciatic nerve defect (15 mm). A therapeutic shockwave system was utilized to activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation induced enhanced peripheral nerve regeneration, resulting in full axon reconnection with myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. Furthermore, superior functional recovery was observed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the excellent efficacy of the mechano-electrical stimulation strategy for treating peripheral nerve injuries.