Alginate Hydrogel Scaffolds Carrying Methylprednisolone Modulate Neuroinflammation after Spinal Cord Injury through NF-κB/JAK-STAT pathways

Abstract Spinal cord injury (SCI) produces profound sensorimotor and autonomic impairment and often results in lasting disability. Secondary inflammatory processes develop after the initial mechanical insult and can influence subsequent tissue damage and recovery. The inflammatory response is a prominent change after SCI, which affects the recovery process in subsequent stage. Herein, we developed alginate hydrogel scaffolds (AHS) loaded with methylprednisolone (AHS@MP) for sustained MP release aiming to repair the injured spinal cords. This scaffold structure exerted long-lasting effects of inhibiting neuroinflammation in both cell-based experiments and the rat SCI model. Additionally, AHS@MP upregulated neuronal and oligodendrocytic differentiation of neural stem cells, and downregulated astrocytic differentiation in vitro. Axonal regeneration was significantly enhanced, followed by recovery of neurological functions. Mechanistically, AHS@MP treatment was associated with reduced activation of NF-κB/JAK-STAT pathways. Taken together, these findings suggest that AHS@MP are a promising approach for SCI treatment.