Anisotropic topological scaffolds synergizing non-invasive wireless magnetic stimulation for accelerating long-distance peripheral nerve regeneration

Abstract

Long-distance peripheral nerve regeneration is the challenging clinical problem that needs to be resolved urgently. In this study, an anisotropic topological Chitosan@Artemisia sphaerocephala (CS@AS) scaffold containing Fe3O4 nanoparticles for achieving non-invasive wireless magnetic stimulation on nerve regeneration process under external static magnetic field (SMF) was developed using surface modification and micro-molding method, aiming to provide a synergistic stimulus for the repair of long-distance peripheral nerve injury. The results showed that the anisotropic topological scaffolds and non-invasive wireless magnetic stimulation under exogenous SMF could synergistically regulate the morphological change, proliferation and oriented growth of Schwann cells. In vivo experiments confirmed that magnetic CS@AS nerve conduit could better promote the functional recovery and reconstruction of the long-distance injured sciatic nerve under SMF, close to that of the autograft transplantation. Further on, the scaffolds were found to activate the magnetic induction receptors, promote the gene expression related to proliferation, migration and myelin formation, regulate the homeostasis of intracellular Ca2+ and enhance the signal transduction via cGMP-PKG, VEGF, MAPK, and TNF signaling pathways. Therefore, the combination of anisotropic topological nerve grafts and non-invasive wireless magnetic stimulation under external SMF can promote the repair and functional recovery of long-distance nerve injury, providing a new strategy for the treatment of peripheral nerve injury.