Institute of Forensic Sciences, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China.
Department of Textile Engineering, College of Textile and Clothing Engineering, Soochow University, Suzhou 215001, China.
Biomater Adv. 2022 Apr;135:212743. doi: 10.1016/j.bioadv.2022.212743. Epub 2022 Mar 17.
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.
硫化氢（HS）作为一种重要的内源性信号分子，在中枢神经系统中发挥着重要的神经保护作用。然而，目前还没有理想的输送材料或方法可以实现 HS 在脑部疾病中的持续和控制释放用于临床应用。丝素蛋白（SF）基水凝胶已成为局部、控制、持续释放药物治疗各种疾病的一种有前途的策略。在这里，我们通过立体定向原位注射在严重脑出血（ICH）小鼠模型中展示了一种具有持续 HS 释放功能的丝素蛋白（SF）基水凝胶（HS@SF 水凝胶）在治疗脑损伤方面的有效性。在这项研究中，我们观察到 HS@SF 水凝胶在体外和体内持续释放 HS。通过 FE-SEM、拉曼光谱和流变学分析研究了 HS@SF 水凝胶的物理化学性质。通过立体定向原位注射，HS@SF 水凝胶治疗减轻脑水肿、减少出血体积并改善严重 ICH 后的神经功能缺损恢复。双重免疫荧光染色还表明，HS@SF 水凝胶可能减少纹状体、皮质和海马中的细胞焦亡。然而，当使用内源性 HS 产生抑制剂 AOAA 时，HS@SF 水凝胶不能抑制 ICH 诱导的细胞焦亡。因此，HS@SF 水凝胶的治疗效果可能部分是由于 HS 的缓慢释放和/或 SF 水凝胶对内源性 HS 产生的影响。总之，这些结果展示了可注射丝素蛋白水凝胶的有前途的特性，以及载 HS 的可注射 SF 水凝胶作为治疗脑损伤的替代生物材料的应用潜力。
