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A Multifunctional Nanocomposite Hydrogel Delivery System Based on Dual-Loaded Liposomes for Scarless Wound Healing
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2024-07-16 , DOI: 10.1002/adhm.202401619
Danlei Xing 1 , Guoqing Xia 2 , Xudong Tang 1 , Zhiwei Zhuang 1 , Jie Shan 1 , Xiao Fang 1 , Le Qiu 1 , Xiaojun Zha 3 , Xu-Lin Chen 1
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Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-β)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy.

中文翻译:


一种基于双负载脂质体的多功能纳米复合水凝胶递送系统,用于无疤痕伤口愈合



皮肤创伤后伤口部位的炎症反应和氧化应激增加会损害愈合。此外,皮肤瘢痕形成使成纤维细胞处于严重的机械应力下,并加重病理纤维化。一种新型脂质体复合水凝胶专为伤口微环境重塑而设计,将双负载脂质体掺入甲基丙烯酸明胶中,以产生纳米复合水凝胶。值得注意的是,四氢姜黄素 (THC) 和肝细胞生长因子 (HGF) 分别封装在脂质体的疏水层和亲水层中。复合水凝胶保持多孔纳米结构,表现出可持续的 THC 和 HGF 释放,并增强了机械性能和生物相容性。该系统有效促进细胞增殖和血管生成,并减轻细胞凋亡。它通过抑制晚期糖基化终末产物/NF-κB (HMGB1/RAGE/NF-κB) 通路的高迁移率组箱/受体来降低炎症因子的表达,并在体外增加巨噬细胞从 M1 到 M2 的极化,有效控制炎症反应。它通过清除过量的活性氧和自由基表现出显着的抗氧化特性。最重要的是,它通过抑制下调相关纤维化因子的转化生长因子 β (TGF-β)/Smads 通路来有效防止疤痕形成。它在具有生物安全性的大鼠皮肤伤口模型中显示出对炎症和纤维化的强大治疗作用,推动了用于临床无疤痕伤口治疗的创新基于水凝胶的治疗递送策略的开发。
更新日期:2024-07-16
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