Tissue-Engineered Fibrous Nerve Conduits Link Facial Nerve Repair with Central Network Reorganization

Peripheral nerve injury leads to persistent motor and sensory dysfunction and is increasingly recognized to induce alterations in central sensorimotor networks. However, most current repair strategies primarily focus on peripheral regeneration, with limited understanding of its relationship to central neural changes. Here, we performed clinical resting-state functional magnetic resonance (rs-fMRI) in patients with facial nerve injury and identified the sensorimotor network alterations associated with the nerve injury. Guided by the results, we developed a tissue-engineered fibrous nerve guidance conduit (NGC) integrating aligned nanofibers, sustained nerve growth factor delivery, and Schwann-like cells derived from bone marrow mesenchymal stem cells. In vitro, the combined biochemical and cellular cues enhanced neurite extension. In a rat facial nerve injury model, implantation of the Schwann-like cells-loaded tissue-engineered NGC promoted axonal regeneration and remyelination, achieving facial motor function recovery comparable to autografts. Moreover, rs-fMRI and voxel-based morphometric analyses revealed that peripheral nerve repair with the engineered conduit was accompanied by enhanced functional connectivity within the sensorimotor network and normalization of gray matter alterations. Taken together, these results suggest that biomaterial-assisted nerve repair may extend beyond local regeneration to influence central network dynamics, highlighting a strategy for integrating peripheral repair with central functional reorganization.