Implantation of injectable SF hydrogel with sustained hydrogen sulfide delivery reduces neuronal pyroptosis and enhances functional recovery after severe intracerebral hemorrhage.

Hydrogen sulfide (HS), an important endogenous signaling molecule, plays an important neuroprotective role in the central nervous system. However, there is no ideal delivery material or method involving the sustained and controlled release of HS for clinical application in brain diseases. Silk fibroin (SF)-based hydrogels have become a potentially promising strategy for local, controlled, sustained drug release in the treatment of various disorders. Here, we show a silk fibroin (SF)-based hydrogel with sustained HS delivery (HS@SF hydrogel) is effective in treating brain injury through stereotactic orthotopic injection in a severe intracerebral hemorrhage (ICH) mouse model. In this study, we observed HS@SF hydrogel sustained HS release in vitro and in vivo. The physicochemical properties of HS@SF hydrogel were studied using FE-SEM, Raman spectroscopy and Rheological analysis. Treatment with HS@SF hydrogel attenuated brain edema, reduced hemorrhage volume and improved the recovery of neurological deficits after severe ICH following stereotactic orthotopic injection. Double immunofluorescent staining also revealed that HS@SF hydrogel may reduce cell pyroptosis in the striatum, cortex and hippocampus. However, when using endogenous HS production inhibitor AOAA, HS@SF hydrogel could not suppress ICH-induced cell pyroptosis. Hence, the therapeutic effect of the HS@SF hydrogel may be partly the result of the slow-release of HS and/or the effect of the SF hydrogel on the production of endogenous HS. Altogether, the results exhibit promising attributes of injectable silk fibroin hydrogel and the utility of HS-loaded injectable SF hydrogel as an alternative biomaterial toward brain injury treatment for clinical application.