负载ROS激活的硫化氢供体的双网络水凝胶可加速伤口愈合并抑制瘢痕形成。

Dual-Network Hydrogel Loaded With ROS-activated Hydrogen Sulfide Donor to Accelerate Wound Healing and Inhibit Scar Production.

作者信息

Zhou Ziqiang, Ning Xuyang, Wei Wenlong, Lu Huangjie, Wen Haoyang, Zeng Huiying, Chen Yuan, Liu Jie, Xie Youfu, Hu Ping

机构信息

Department of Burns & Plastic Surgery, Guangzhou Red Cross Hospital, Faculty of Medical Science, Jinan University, Guangzhou, 510006, China.

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510006, China.

出版信息

Adv Healthc Mater. 2025 Jun;14(15):e2500264. doi: 10.1002/adhm.202500264. Epub 2025 May 2.

Abstract

The wound healing process consists of four continuous and overlapping stages-hemostasis, inflammation, proliferation, and remodeling-involving a variety of cells, growth factors, and the extracellular matrix. In recent years, growing evidence has shown that enhancing endogenous hydrogen sulfide (HS) synthesis or providing exogenous HS can promote angiogenesis, inhibit inflammation, reduce excessive oxidative stress, and support collagen deposition. However, the administration of exogenous HS often presents challenges related to controlling its release duration and achieving targeted delivery. To achieve controlled and site-specific delivery of HS to the wound area, a dual-network cross-linked injectable hydrogel formed by grafted ε-poly-L-lysine (designed as EG) and oxidized dextran (OD) (EGODF) loaded with a hydrogen sulfide donor (HSDF-NH) to study its potential in wound healing is developed. The hydrogel exhibits excellent injectability, self-healing capability, and mechanical strength. Upon reactive oxygen species (ROS) stimulation, HSDF-NH releases both self-reporter fluorescence (HSDG-NH) and HS. Changes in the self-reporter fluorescence signal reflect HS production and its entry into the body to exert therapeutic effects. Finally, using a wound model and a hypertrophic scar repair model, it is demonstrated that EGODF hydrogel is effective in promoting wound healing and inhibiting scar production.

摘要

伤口愈合过程包括四个连续且重叠的阶段——止血、炎症、增殖和重塑,涉及多种细胞、生长因子和细胞外基质。近年来,越来越多的证据表明,增强内源性硫化氢(HS)的合成或提供外源性HS可促进血管生成、抑制炎症、减少过度的氧化应激并支持胶原蛋白沉积。然而,外源性HS的给药通常面临着控制其释放持续时间和实现靶向递送方面的挑战。为了实现HS向伤口区域的可控和位点特异性递送,开发了一种由接枝ε-聚-L-赖氨酸(设计为EG)和氧化葡聚糖(OD)形成的双网络交联可注射水凝胶(EGODF),其负载硫化氢供体(HSDF-NH)以研究其在伤口愈合中的潜力。该水凝胶具有优异的可注射性、自愈能力和机械强度。在活性氧(ROS)刺激下,HSDF-NH释放自报告荧光(HSDG-NH)和HS。自报告荧光信号的变化反映了HS的产生及其进入体内发挥治疗作用。最后,使用伤口模型和肥厚性瘢痕修复模型,证明了EGODF水凝胶在促进伤口愈合和抑制瘢痕产生方面具有有效性。

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