Bioactive nerve conduit enhance peripheral nerve regeneration through dual functions of ion-regulated dedifferentiation and particle-anchored migration

In this study, we designed a bioactive glass microspheres-embedded nerve conduit. Released ions activate c-Jun, inducing Schwann cell dedifferentiation and Büngner bands formation. Surface microspheres provide anchoring sites, accelerating integrin-β1-mediated Schwann cell migration to assemble Büngner bands, serving as a “cornerstone” and “high-speed track” for rapid axon regeneration like trains on a railway. • A novel dual-function bioactive nerve conduit enhances nerve regeneration through ion release and physical anchoring. • Ion-activated c-Jun signaling drives Schwann cell dedifferentiation into a repair phenotype. • Microsphere-coated conduit surfaces accelerate integrin-β1-mediated Schwann cell adhesion and migration. • Orderly Büngner bands assembly is facilitated, improving axonal guidance in long-segment defects. The regeneration of long-segment peripheral nerve defects remains a critical and challenging clinical problem. The key step in nerve regeneration involves the dedifferentiation of Schwann cells into a repair phenotype, followed by their orderly migration to form Büngner bands that guide axonal elongation. However, due to the lack of bioactive factors for stimulation, the repair of current nerve conduits is generally slow. In this study, we designed a bioactive glass microspheres-embedded nerve conduit. The ions released from these microspheres activate c-Jun to induce Schwann cell dedifferentiation. Meanwhile, the microspheres coated onto the conduit surface provide physical anchoring sites, which accelerate integrin- β 1-mediated Schwann cell adhesion and orderly migration to facilitate Büngner bands assembly. This study confirms that dual-function bioactive glass microspheres promote nerve regeneration through ion-regulated dedifferentiation and particle-anchored migration, offering a novel approach for the design of nerve conduits.