Journal
BIOMATERIALS ADVANCES
Volume 135, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bioadv.2022.212743
Keywords
Silk fibroin; Injectable hydrogel; Hydrogen sulfide; Intracerebral hemorrhage; Pyroptosis
Categories
Funding
- National Natural Science Foundation of China [82071382, 81971800, 81601306]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Maternal and Child Health Research Key Project [F202013]
- Jiangsu Talent Youth Medical Program [QNRC2016245]
- Shanghai Key Lab of Forensic Medicine [KF2102]
- Suzhou Science and Technology Development Project [SYS2020089]
- Fifth Batch of Gusu District Health Talent Training Project [GSWS2019060]
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The study demonstrates the effectiveness of a silk fibroin-based hydrogel with sustained hydrogen sulfide (H2S) delivery in treating brain injury. The results indicate that the injectable silk fibroin hydrogel holds promise as a biomaterial for clinical application in brain injury treatment.
Hydrogen sulfide (H2S), 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 H2S 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 H2S delivery (H2S@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 H2S@SF hydrogel sustained H2S release in vitro and in vivo. The physicochemical properties of H2S@SF hydrogel were studied using FE-SEM, Raman spectroscopy and Rheological analysis. Treatment with H2S@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 H2S@SF hydrogel may reduce cell pyroptosis in the striatum, cortex and hippocampus. However, when using endogenous H2S production inhibitor AOAA, H2S@SF hydrogel could not suppress ICH-induced cell pyroptosis. Hence, the therapeutic effect of the H2S@SF hydrogel may be partly the result of the slow-release of H2S and/or the effect of the SF hydrogel on the production of endogenous H2S. Altogether, the results exhibit promising attributes of injectable silk fibroin hydrogel and the utility of H2Sloaded injectable SF hydrogel as an alternative biomaterial toward brain injury treatment for clinical application.
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