Bilayer Bio-instructive Conduits Drive Neuropathic Pain Relief via Multi-level Molecular Reprogramming

In this study, an autonomous, bio-instructive bilayer nerve guidance conduit (NGC) is engineered, integrating a piezoelectric PLLA inner layer (output 1151.35 mV) with a ropivacaine (RVC)-loaded PCL outer layer (83.63% release over 14 days).

This dual-functional platform aims to achieve synchronized structural restoration and long-term analgesia. In vitro, the piezo-induced surface potentials triggers Ca2+ mobilization and activates the NGF, GDNF Mmp-9, Jun, Olig1, and Shh genes, promoting Schwann cells (SCs) proliferation, migration, and phenotypic reprogramming, which effectively blocked the peripheral sensitization. In vivo, using a rat chronic constriction injury (CCI) model, PLLA-PCL-RVC@NGC significantly alleviates mechanical, thermal, and cold hypersensitivity while accelerating functional recovery (SFI), thereby preventing the central sensitization.