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亚铁离子诱导的甘草次酸水凝胶的形成用于金黄色葡萄球菌感染的伤口愈合。

Ferrous iron-induced formation of glycyrrhizic acid hydrogels for Staphylococcus aureus-infected wound healing.

机构信息

School of Medicine, Institute of Translational Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, PR China.

Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, PR China.

出版信息

Colloids Surf B Biointerfaces. 2023 Jan;221:112977. doi: 10.1016/j.colsurfb.2022.112977. Epub 2022 Oct 29.

DOI:10.1016/j.colsurfb.2022.112977
PMID:36343479
Abstract

Severe skin wound healing is mainly hindered by bacterial infection and uncontrolled inflammatory reaction. As a wound dressing, multifunctional hydrogel is expected to offer the potential possibility for overcoming current barriers in wound therapeutics. Herein, a natural drug molecule (glycyrrhizic acid, GA) and metal ion (Fe) were used to achieve the metal coordination-induced gelation. This as-prepared Fe-induced GA hydrogel showed excellent injectability, self-healing property, and sustained release behavior at a relatively lower concentration of GA, thereby reducing the high dose-caused cytotoxicity. In addition to acting as an inducer of gelation, Fe promoted the antibacterial performance of hydrogel against Escherichia coli and Staphylococcus aureus through causing lipid peroxidation, membrane damage, and DNA degradation. Moreover, the released GA from hydrogel significantly accelerated cell migration and inhibited the inflammatory reaction by mediation of NF-κB signaling pathway to downregulate levels of important inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells. Using a mouse skin infected model, we revealed that the Fe/GA hydrogel applied to the wound resulted in the rapid wound healing. It is believed that the construction of natural drug molecule-derived hydrogel with antibacterial and anti-inflammatory capabilities may shed a new light to serve as a promising dressing for managing the severe skin wounds.

摘要

严重的皮肤伤口愈合主要受到细菌感染和失控的炎症反应的阻碍。作为一种伤口敷料,多功能水凝胶有望为克服当前伤口治疗的障碍提供潜在的可能性。在此,使用天然药物分子(甘草酸,GA)和金属离子(Fe)实现了金属配位诱导的凝胶化。所制备的 Fe 诱导的 GA 水凝胶表现出优异的可注射性、自修复性和在相对较低 GA 浓度下的持续释放行为,从而降低了高剂量引起的细胞毒性。除了作为凝胶化诱导剂外,Fe 通过引起脂质过氧化、膜损伤和 DNA 降解,促进水凝胶对大肠杆菌和金黄色葡萄球菌的抗菌性能。此外,水凝胶中释放的 GA 通过 NF-κB 信号通路介导显著促进细胞迁移并抑制脂多糖刺激的 RAW264.7 细胞中的炎症反应,下调重要炎症细胞因子的水平。使用小鼠皮肤感染模型,我们揭示了应用于伤口的 Fe/GA 水凝胶可实现快速伤口愈合。相信具有抗菌和抗炎能力的天然药物分子衍生水凝胶的构建可能为严重皮肤伤口的管理提供一种有前途的敷料。

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