Abstract

Spinal cord injury (SCI) involves oxidative stress, inflammation, and mitochondrial dysfunction that impair neural cell survival, while conventional therapies fail to sustainably improve the lesion microenvironment. Here, we developed a composite hydrogel patch (Mg-CDs/Exo@EW) by leveraging the enzyme-mimicking activity and coordination crosslinking ability of magnesium-doped carbon dots (Mg-CDs) to induce egg white gelation, with uniform incorporation of orange juice–derived exosomes (Exo). Orange peel-derived CDs displayed strong antioxidative nanozyme activity, which was further enhanced by magnesium ion doping to promote M2 macrophage polarization, axonal regeneration, and neural repair. Transcriptomic and Western blot analyses revealed that Mg-CDs activate the GPX4/ACSL4 pathway to suppress neuronal ferroptosis. Untargeted metabolomics showed that Exo are enriched in flavonoids and vitamin C with potent antioxidative and anti-inflammatory effects, while their negatively charged surface and adhesion molecules provide targeted delivery and enhanced repair efficacy. In vivo, Mg-CDs/Exo@EW effectively alleviated oxidative stress, regulated inflammation, reduced glial scar formation, and supported axonal regeneration, ultimately improving motor functional recovery. This multifunctional platform offers a promising therapeutic strategy for SCI.