Polydopamine-coupled NT3-derived oriented conductive scaffolds with immunomodulatory properties accelerate peripheral nerve regeneration

Abstract Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves. Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options (e.g., nerve graft). However, nerve regeneration occurs within a complex environment, and elaborate modulation is needed to meet repair requirements. The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing, immune modulation to reshape the regenerative environment, and topographic cues and electrical signals to guide nerve growth. We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3. The resulting nerve scaffold exhibited favorable orientation, electrical conductivity, and mechanical properties. Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process. In vitro assessments confirmed the cytocompatibility, reactive oxygen species scavenging, and immune regulation capabilities of the nerve scaffolds. In a rat sciatic nerve defect model, the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period. These findings suggest that polydopamine-modified, electroactive, oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.