Piezoelectric stimulation from electrospun composite nanofibers for rapid peripheral nerve regeneration

Peripheral nerve injuries vary among patients. Cell-based or acellular nerve conduits have a high peripheral nerve regeneration potential. However, they are not ideal for complicated nerve differentiations and are prone to unclear effects of cytokine interactions. Delayed nerve axon regeneration could be ascribed to a lack of regulation of the regenerative microenvironment. Electrical stimulation influences nerve regeneration by regulating sensitive targets. Here, a piezoelectric nerve conduit was developed using a composite of PCL/ZnO nanofiber (PZNF) via electrospinning. Endogenous piezoelectric stimulation from PZNF facilitated sciatic nerve regeneration. This material inherits polycaprolactone characteristics and is a biocompatible material. It generated stable and desired endogenous electrical stimulations. PZNF demonstrated faster and superior sciatic nerve repair in vivo than polycaprolactone nanofiber and nerve bridging in situ. Piezoelectric stimulation of PZNF could substantially increase nerve growth factor/vascular endothelial growth factor expression. Furthermore, the PZNF considerably promoted rapid nerve repair and shortened function recovery (within 4 weeks) in vivo. Moreover, an increase in growth factor receptor-bound protein-2 (GRB2) expression activated downstrem pathway: RAS/MAPK pathway after piezoelectricity stimulation, indicating that GRB2 may be an electrically sensitive protein and a hint protein of electrical stimulation-induced regeneration. This study offers a novel strategy of applying piezoelectric stimulation in rapid peripheral nerve regeneration.