Surface-fill H2S-releasing Silk Fibroin Hydrogel for Brain Repair through the Repression of Neuronal Pyroptosis

Elsevier

Available online 17 November 2022

Acta BiomaterialiaAuthor links open overlay panelAbstract

Traumatic brain injury (TBI) remains the major cause of disability and mortality worldwide due to the persistent neuroinflammation and neuronal death induced by TBI. Among them, pyroptosis, a specific type of programmed cell death (PCD) triggered by inflammatory signals, plays a significant part in the pathological process after TBI. Inhibition of neuroinflammation and pyroptosis is considered a possible strategy for the treatment of TBI. In our previous study, exogenous hydrogen sulfide(H2S) exerted a neuroprotective effect after TBI. Here, we developed a surface-fill H2S-releasing silk fibroin (SF) hydrogel (H2[email protected] hydrogel) to achieve small-dose local administration and avoid volatile and toxic side effects. We used a controlled cortical impact (CCI) to establish a mild TBI model in mice to examine the effect of H2[email protected] hydrogel on TBI-induced pyroptosis. We found that H2[email protected] hydrogel inhibited the expression of H2S synthase in neurons after TBI and significantly inhibited TBI-induced neuronal pyroptosis. In addition, immunofluorescence staining results showed that the necroptosis protein receptor-interacting serine/threonine-protein kinase 1 (RIPK1) partially colocalized with the pyroptosis protein Gasdermin D (GSDMD) in the same cells. H2[email protected] hydrogel can also inhibit the expression of the necroptosis protein. Moreover, H2[email protected] hydrogel also alleviates brain edema and the degree of neurodegeneration in the acute phase of TBI. The neuroprotective effect of H2[email protected] hydrogel was further confirmed by wire-grip test, open field test, Morris water maze, beam balance test, radial arm maze, tail suspension, and forced swimming test. Lastly, we also measured spared tissue volume, reactive astrocytes and activated microglia to demonstrate H2[email protected] hydrogel impacts on long-term prognosis in TBI. Our study provides a new theoretical basis for the treatment of H2S after TBI and the clinical application of H2[email protected] hydrogel.

Statement of Significance

: Silk fibroin (SF) hydrogel controls the release of hydrogen sulfide (H2S) to inhibit neuronal pyroptosis and neuroinflammation in injured brain tissue. In this study, we synthesized a surface-fill H2S-releasing silk fibroin hydrogel, which could slowly release H2S to reshape the homeostasis of endogenous H2S in injured neurons and inhibit neuronal pyroptosis in a mouse model of traumatic brain injury. Meanwhile, H2[email protected] hydrogel could alleviate brain edema and the degree of neurodegeneration, improve motor dysfunction, anxious behavior and memory impairment caused by TBI, reduce tissue loss and ameliorate neuroinflammation. Our study provides a new theoretical basis for the treatment of H2S after TBI and the clinical application of H2[email protected] hydrogels.

Keywords

traumatic brain injury

silk fibroin hydrogel

hydrogen sulfide

pyroptosis

necroptosis

© 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc.

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