Dual biomimetic nanofiber conduits enable synergistic NGF delivery and endogenous piezoelectric stimulation for peripheral nerve regeneration, Advanced Fiber Materials, 2025.

Zhenwei Yi, Yaofa Lin, Rui Jing, Xiangru Feng, Xiaoxuan Lu, Diqi Tian, Haodong Lin* and Liming Zhao*

After peripheral nerve injury, decreased nerve growth factor (NGF) levels and interrupted bioelectrical signal transmission are key factors leading to delayed nerve regeneration. However, the nerve conduits currently applied in clinical practice fail to simultaneously achieve sustained nutritional support and electrical activity maintenance for the injured microenvironment, limiting their repair effects. Herein, a dual-functional-layer nerve conduit loaded with NGF and exhibiting a high piezoelectric response was fabricated using electrospinning technology. The inner layer was composed of heparin-functionalized chitosan nanofibers loaded with NGF (CPHN), whereas the outer layer was formed from polyvinylidene fluoride (PVDF) nanofibers incorporated with ZnO nanoparticles (PZ). The results showed that the heparin-functionalized chitosan nanofibers significantly enhanced the loading density and stability of NGF. Additionally, PZ nanofibers with 1 wt% ZnO generated stable and appropriate endogenous electrical stimulation under controlled external stimulation. In vitro experiments demonstrated that the combination of PZ and CPHN (PZ@CPHN) could compensate for TrkA receptor desensitization, improve NGF pharmacodynamics, and activate the NGF/TrkA signaling pathway to regulate PC12 cells proliferation, differentiation, and motility. In the rat sciatic nerve defect model, transplantation of the PZ@CPHN conduit significantly ed the reconstruction of regenerated nerve tissue and the recovery of muscle motor function after 12 weeks, achieving a repair outcome comparable to that of autologous nerve transplantation. In summary, a novel therapeutic strategy combining NGF administration with endogenous electrical stimulation is proposed to accelerate peripheral nerve regeneration.