Bioactive Silk Sericin/Bioceramic Nerve Guidance Conduit for Effective Repair of Long‐Gap Transected Peripheral Nerve Injury through Regulating Schwann Cells

Abstract Schwann cells are pivotal in generating a pro‐regenerative microenvironment for long‐gap peripheral nerve injury (PNI) repair via their orchestrated behaviors, including cell migration, proliferation, and secretion. Bioceramics can release bioactive ions to regulate “repair” cells for regenerating damaged tissues. Herein, bioceramic akermanite (AT) is screened and found to significantly enhance Schwann cell proliferation, migration, and secretion by activating the PI3K/AKT and MAPK/ERK signaling pathways. Integration with silk sericin (SS), a natural biomaterial possessing excellent bioactivity, promotes the release of Ca and Mg from AT, synergistically enhancing Schwann cell pro‐regenerative behaviors and accelerating axon elongation. The AT‐SS composite conduit effectively restores nerve structure and function in a 13 mm transected PNI. Compared with commercial eton conduit, AT‐SS conduit promotes axons and myelin sheaths regeneration, improves nerve conduction, and effectively alleviates gastrocnemius muscle atrophy. The AT‐SS conduit achieves autograft‐comparable behavioral recovery as evidenced by the paw withdrawal latency, hind limb grip force, and sciatic function index. The excellent degradation and biosafety of AT‐SS conduit indicate its potential for clinical translation. This study introduces an ion‐based therapeutic approach for enhancing the pro‐regenerative functions of Schwann cells, and provides novel insights and strategies for clinically managing long‐gap PNI and other nerve tissue injuries.