Enhanced peripheral nerve regeneration by mechano-electrical stimulation

To address limitations in current approaches for treating large peripheral nerve defects, the presented study evaluated the feasibility 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 synthesized and 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 periodically activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation (MES) 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. In comparison, a control group, in which the implanted piezoelectric conduits were not activated in vivo, failed to exhibit such nerve regeneration. In addition, at both proximal and distal ends of the implanted conduits, a decreased number of damaged myelination (ovoids), an increased number of myelinated nerves, and a larger axonal diameter were observed under the MES condition as compared to the control condition. Furthermore, unlike the control group, the MES condition exhibited a superior functional nerve recovery, assessed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.

Automated summary

This study evaluated the feasibility of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were used to deliver electrical stimulation to nerve cells/tissues. Piezoelectric nerve conduits were synthesized and implanted in a rat sciatic nerve transection model, and the piezoelectric effect of the implanted nerve conduit was periodically activated. The results showed that MES-induced enhanced peripheral nerve regeneration, with full axon reconnection and myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. In addition, the number of damaged myelinations decreased, the number of myelinated nerves increased, and the axonal diameter increased under the MES condition. Functional nerve recovery was also superior under the MES condition. This study demonstrates the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.