Biodegradable multimodal biomaterials with microenvironmental adaptability and orderly delivery of H2S and bFGF for the treatment of spinal cord injury

Spinal cord injury (SCI) is a complex and interactive process involving multiple pathological stages. Single-type biomaterials often struggle to rapidly adapt to the imbalanced regenerative microenvironment and orderly resolve the symptoms of different stages, resulting in slow neural regeneration and limited functional recovery. Herein, we developed a microenvironment- adaptive and time-adaptive multimodal biomaterial (custom-designed with silk fibroin hydrogel-SF and endogenous stimulus responsive nanomedicine-G@Mn, SF-G@Mn) for the treatment of SCI. Based on pathological signals after SCI, the SF-G@Mn achieves the precise release of drugs that inhibit microenvironment regulation (H₂S and Mn^2 +) and nerve regeneration drugs (basic fibroblast growth factor (bFGF)) under different needs in the early and late stages of secondary SCI through asynchronous release kinetics. In the early stages of inflammation, oxidative stress and hypoxia, Mn²⁺ can continuously decompose H₂O₂ to generate oxygen, and synergistic effects with H₂S can jointly relieve oxidative stress, improve hypoxia and inhibit inflammation, thus comprehensively adjusting the microenvironment that is not conducive to tissue repair. As the injury progresses to a later stage dominated by nerve regeneration, bFGF is slowly released to support axon growth and myelin regeneration, helping to restore the function of the damaged nerve. After this multi-dimensional, orderly and multi-stage treatment, the motor function of the SCI mice was significantly restored. In general, this work provides a pathological signal response, on-demand, orderly release of multi-modal biomaterials of drugs at different pathological stages, to achieve spatio-temporal selectivity and adaptive treatment, and provides a valuable example for the development of personalized medicine in the future.