Peripheral　nerve　defects　present　complex　orthopedic　challenges　with　limited　efficacy　of　clinical　interventions.　The　inadequate　proliferation　and　dysfunction　of　Schwann　cells　within　the　nerve　scaffold　impede　the　effectiveness　of　nerve　repair.　Our　previous　studies　suggested　the　effectiveness　of　a　magnesium-encapsulated　bioactive　hydrogel　in　repairing　nerve　defects.　However,　its　rapid　release　of　magnesium　ions　limited　its　efficacy　to　long-term　nerve　regeneration,　and　its　molecular　mechanism　remains　unclear.　This　study　utilized　electrospinning　technology　to　fabricate　a　MgO/MgCO3/polycaprolactone　(PCL)　multi-gradient　nanofiber　membrane　for　peripheral　nerve　regeneration.　Our　findings　indicated　that　by　carefully　adjusting　the　concentration　or　proportion　of　rapidly　degradable　MgO　and　slowly　degradable　MgCO3,　as　well　as　the　number　of　electrospun　layers,　the　multi-gradient　scaffold　effectively　sustained　the　release　of　Mg2+　over　a　period　of　6 weeks.　Additionally,　this　study　provided　insight　into　the　mechanism　of　Mg2+-induced　nerve　regeneration　and　confirmed　that　Mg2+　effectively　promoted　Schwann　cell　proliferation,　migration,　and　transition　to　a　repair　phenotype.　By　employing　transcriptome　sequencing　technology,　the　study　identified　the　Wingless/integrase-1　(Wnt)　signaling　pathway　as　a　crucial　mechanism　influencing　Schwann　cell　function　during　nerve　regeneration.　After　implantation　in　10 mm　critically　sized　nerve　defects　in　rats,　the　MgO/MgCO3/PCL　multi-gradient　nanofiber　combined　with　a　3D-engineered　PCL　nerve　conduit　showed　enhanced　axonal　regeneration,　remyelination,　and　reinnervation　of　muscle　tissue　12 weeks　post-surgery.　In　conclusion,　this　study　successfully　developed　an　innovative　multi-gradient　long-acting　MgO/MgCO3/PCL　nanofiber　with　a　tunable　Mg2+　release　property,　which　underscored　the　molecular　mechanism　of　magnesium-encapsulated　biomaterials　in　treating　nervous　system　diseases　and　established　a　robust　theoretical　foundation　for　future　clinical　translation.　©　The　Author(s)　2024.