MnO2-loaded hydrogel nerve guidance conduit for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve defect model

Peripheral nerve defect repair remains a clinical challenge. Nerve guidance conduits (NGCs) are potential alternatives to autografts, but their performance can be compromised by the oxidative and inflammatory microenvironment after injury. Here, we fabricated MnO₂-loaded hydrogel NGCs at concentrations of 10, 50, and 100 μg/mL and evaluated them in a rat model of a 10-mm sciatic nerve defect. Among the three concentrations, the MnO₂@NMgel-10 (10 μg/mL) group yielded a higher sciatic functional index, denser and more orderly regenerated nerve tissue, and less gastrocnemius muscle atrophy than the hydrogel-only and higher-dose conduit groups. Early tissue analysis showed that the MnO₂@NMgel-10 group exhibited increased infiltration of CD68⁺CD206⁺ cells, upregulated expression of IL-10, and significantly downregulated expression of IL-1β, TNF-α, and 4-HNE. Furthermore, the MnO₂@NMgel-10 group showed satisfactory biosafety and biocompatibility. These findings reveal a non-monotonic concentration response and preliminarily confirm the feasibility of low-dose MnO₂-functionalized hydrogel NGCs for repairing peripheral nerve defects, providing new insights into the application of MnO₂ as a supplementary material for NGC fabrication.