A Dynamic Silver-Sulfur/Schiff Base Hydrogel for Delivering Neural Stem Cells in Cerebral Palsy

To address the critical challenges of low cell retention and poor survival in neural stem cell (NSC) transplantation for cerebral palsy, we developed an injectable conductive hydrogel (TT-gel) through dynamic silver-sulfur/Schiff base cross-linking of thiolate oxidized sodium alginate and silk fibroin. The optimized TT-gel demonstrated ideal rheological properties (recovery yield in 40 s > 95%) and electrical conductivity (1.47 ± 0.01 S/m), enabling effective 3D NSC culture with high viability (93.8 ± 1.6% at 5 days) while supporting multilineage differentiation. In a rat cerebral palsy (CP) model, NSC delivery via TT-gel achieved significantly promoted substantial functional recovery, evidenced by 2.6-fold improvement in rotarod endurance and 81.3% reduction in water maze escape latency. Proteomics and histological analysis confirmed enhanced neuroregeneration, showing greater neuronal density and elevated synaptic plasticity markers in treated animals. The therapeutic efficacy of TT-gel stems from its unique dynamic scaffold properties and injectable capability, combined with its electroconductive nature that promotes neuronal differentiation. This multifunctional design collectively addresses the key limitations of conventional NSC transplantation approaches, highlighting its significant clinical potential for CP treatment.