Remote shockwaves to externally activate piezoelectric PVDF-TrFE nanofibers for peripheral nerve system regeneration.

Abstract

Electric stimulation (ES) has the potential to enhance cellular function in major cell types involved in peripheral nervous system (PNS) repair through augmenting regeneration of axons, extending dorsal root ganglion neurites, and mediating the plasticity of Schwann cells. Furthermore, ES has been shown to induce calcium dependent nerve growth factor release in Schwann cells. Together, these phenomena may be harnessed to promote nerve regeneration by enhancing survival and outgrowth of damaged nerves. Electrospun polyvinylidene flouride-triflouroethylene (PVDF-TrFE) nanofibers are biocompatible piezoelectric materials capable of producing electrical currents in response to mechanical deformations. Here we introduce PVDF-TrFE as a cell stimulation platform able to deliver controlled ES in response to external mechanical stimulation from shock waves. We first characterize current generated from shock waves stimulated PVDF-TrFE scaffolds with treatments at pressure and frequency values of 0.5 bar at 1 Hz, 1 bar at 1 Hz, and 3 bar at 2 Hz. PVDF-TrFE nanofibers were seeded with NIH-3T3 fibroblasts and RT4-D6P2T Schwann cells and subjected to 1000 counts of 0.5 bar 1 Hz every 24 hours. Results indicated significant cell proliferation for treatment groups on days 2 and 4 of culture compared to controls for both cell types. This platform can be further engineered to optimize ES on cells to elucidate mechanisms associated with generating a “pro-repair” phenotype in Schwann cells and the PNS.