Effect of chitosan/graphene quantum dot/stem cell-derived exosome nanocomposite hydrogel on inflammation and neuronal preservation in spinal cord injury

Spinal cord injury (SCI) is associated with persistent inflammation, neuronal damage, and impaired functional recovery. This study aimed to develop and evaluate a thermosensitive chitosan/graphene quantum dot/stem cell-derived exosome (CS-GQD-Exo) nanocomposite hydrogel with potential for injectable application in SCI treatment. CS, CS-GQD, CS-Exo, and CS-GQD-Exo hydrogels were prepared and characterized for their physicochemical properties, cytocompatibility, swelling, degradation, mechanical properties, and exosome release. Their therapeutic effects were subsequently evaluated in a mouse model of SCI using behavioral, histological, immunofluorescence, and inflammatory assessments. All hydrogel formulations exhibited a porous structure and supported PC12 cell viability. The wet CS hydrogel exhibited compressive properties suitable for the spinal cord tissue environment. The CS-GQD-Exo hydrogel showed sustained exosome release over 21 days, with a cumulative release of 274.13 ± 1.06 µg/mL. In vivo, CS-GQD-Exo produced the greatest improvement in locomotor recovery, with significantly higher BBB scores than the other treatment groups. It also markedly reduced serum IL-6 and TNF-α levels to 82.09 and 1.17 pg/mL, respectively. Histological analysis demonstrated reduced lesion formation, while NeuN immunoreactivity was highest in the CS-GQD-Exo group, indicating enhanced neuronal preservation. The CS-GQD-Exo nanocomposite hydrogel demonstrated the most favorable overall therapeutic performance among the tested formulations by combining sustained exosome delivery with improved functional recovery, reduced inflammation, and enhanced tissue and neuronal preservation. These findings support its potential as an injectable platform for SCI repair.