Multifunctional Diselenide-Based Antioxidative Nanozymes Promote Spinal Cord Repair via Oxidative Stress Alleviation...

Area of Science:

• Biomaterials Science
• Neuroscience
• Immunology

Background:

• Spinal cord injury (SCI) causes oxidative stress and inflammation, hindering neural repair.
• Current therapies lack the ability to simultaneously address both ROS and immune dysregulation.
• A multifunctional therapeutic agent is needed to reconstruct the damaged microenvironment post-SCI.

Purpose of the Study:

• To develop and evaluate a hyaluronic acid-based diselenide cross-linked nanogel (Se-Se@HA) for SCI treatment.
• To investigate the ROS scavenging and immunomodulatory capabilities of Se-Se@HA.
• To assess the therapeutic efficacy of Se-Se@HA in promoting neural regeneration and functional recovery after SCI.

Main Methods:

• Synthesis and characterization of Se-Se@HA nanogel.
• In vitro assessment of ROS scavenging, anti-inflammatory effects, and neuronal protection.
• In vivo evaluation of Se-Se@HA in an SCI model, including behavioral tests, histological analysis, and transcriptome sequencing.

Main Results:

• Se-Se@HA demonstrated excellent structural stability and potent ROS scavenging activity.
• The nanogel effectively inhibited M1 macrophage polarization, reduced pro-inflammatory cytokines, and promoted M2 phenotype.
• In vitro studies showed protection of neurons and enhanced neurite growth; in vivo studies revealed improved motor function, reduced inflammation, enhanced axonal continuity, and decreased scar formation.
• Transcriptome analysis indicated downregulation of NF-κB, TNF, and MAPK pathways, with enrichment of synaptic transmission and regeneration pathways.

Conclusions:

• Se-Se@HA acts as a multifunctional nanozyme platform for SCI.
• It effectively coordinates oxidative stress relief, immune homeostasis, and neuroregeneration.
• This nanogel presents a promising therapeutic strategy for spinal cord injury recovery.