Piezoelectric conduit combined with multi-channel conductive scaffold for peripheral nerve regeneration

Due to the complex structural hierarchy and regenerative microenvironment of peripheral nerves, developing a nerve guidance conduit (NGC) that can replace autografts for repairing long-distance nerve defects remains a challenge. To overcome this limitation, a multi-channel NGC with dual electrical activity of piezoelectricity and conductivity was constructed to enhance peripheral nerve regeneration. Silk fibroin (SF) was adopted to prepare a multi-channel cryogel scaffold by gradient freezing method, and then poly(3,4-ethylenedioxythiophene) (PEDOT) in situ polymerization based on the porous structure of the cryogel was carried out to achieve good conductivity. Meanwhile, a polyvinylidene fluoride (PVDF)/poly (l-lactic acid-co-caprolactone) (PLCL) film with spontaneous electrical properties and high mechanical strength was constructed and wrapped in the outer layer of SF/PEDOT cryogel to construct an NGC with spontaneous electrical stimulation properties and surgical suture resistance, providing a biomimetic electrophysiological microenvironment for peripheral nerve regeneration. In vitro cell experiments indicated that the multi-channel electroactive NGC not only promoted the proliferation, maturation and myelination of Schwann cells (SCs), but also effectively promoted neuronal differentiation and axonal regeneration of Pheochromocytoma 12 (PC12) cells. Furthermore, a rat sciatic nerve defect model was constructed to evaluate the effect of multi-channel electroactive NGC on peripheral nerve repair and the results showed that electroactive NGC could significantly promote peripheral nerve regeneration and functional recovery after 12 weeks, achieving the repair effect of autografts through the positive synergistic effect of piezoelectric and conductive properties of NGC. These results demonstrated the great potential of multi-channel electroactive NGCs in repairing peripheral nerve injury (PNI).