Maresin 1 delivered via a poly(lactic-co-glycolic acid) conduit enhances sciatic nerve regeneration in rats and is associated with glycogen synthase kinase-3β/β-catenin signaling

OBJECTIVE: To fabricate Maresin 1 (MaR1)-loaded poly(lactic-co-glycolic acid) (PLGA) nerve conduits, evaluate their therapeutic effects on sciatic nerve defect repair in rats, and explore the association with glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. METHODS: A 10-mm sciatic nerve defect model was established in Sprague-Dawley rats and randomly assigned to four groups: Sham, Injury, PLGA conduit, and MaR1-loaded PLGA conduit (PLGA/MaR1). Sciatic functional index (SFI) was assessed longitudinally after surgery. At 10 weeks postoperation, the wet weight ratio of the gastrocnemius muscle was measured, and regenerated nerve tissue was examined by hematoxylin-eosin (H&E) staining. Western blotting was performed to determine the expression of GSK-3β, β-catenin, and regeneration/myelination-related proteins (GAP-43, MBP, and S100). In vitro, oxidative stress injury was induced in PC12 cells using H2O2. Cells were treated with MaR1 with or without differentiation-inducing factor-3 (DIF-3), and changes in cell viability and regeneration-related phenotypes were evaluated. RESULTS: Compared with the PLGA group, the PLGA/MaR1 group showed significantly improved SFI and an increased gastrocnemius wet weight ratio (P < 0.05). H&E staining indicated more compact regenerated nerve tissue and better-organized nerve fiber arrangement in the PLGA/MaR1 group. Western blot analysis showed upregulated β-catenin levels accompanied by increased expression of GAP-43, MBP, and S100. In PC12 cells, MaR1 alleviated oxidative stress-induced impairment and promoted regeneration-related phenotypes, whereas DIF-3 partially attenuated these effects. CONCLUSION: MaR1-loaded PLGA nerve conduits facilitate structural and functional recovery after sciatic nerve defects in rats. The beneficial effects may be associated with modulation of GSK-3β/β-catenin signaling and enhanced expression of axonal regeneration- and myelination-related proteins.