Nanozyme Hydrogels Promote Nerve Regeneration in Spinal Cord Injury by Reducing Oxidative Stress

Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.