Qin Si, Zhang Haobin, Li Huarun, Feng Yuqin, Zhao Xiangyue, Zheng Xinyao, Xu Jieru, Cai Xuexin, Zhou Xiuxian, Wen Ju
Department of Dermatology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Institute for Healthcare Artificial Intelligence Application, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
Int J Pharm. 2025 Jun 10;678:125727. doi: 10.1016/j.ijpharm.2025.125727. Epub 2025 May 15.
A persistent imbalance in the inflammatory microenvironment is a crucial cause of delayed healing in diabetic wounds. Improving the wound inflammatory microenvironment by modulating macrophage polarization is an important strategy to promote diabetic wound healing. However, modulating macrophage polarization through low-cost, biosafe and effective methods remains a challenge. In this work, a borate bond-based ROS-responsive nanocomposite hydrogel dressing (GelMC/PVA-UIO-66-NH@Que) was developed for efficient diabetic wound repair by on-demand release of quercetin (Que) with immunomodulatory activity. 4-Carboxyphenylboronic acid modified methacryloylated gelatin (GelMC) and polyvinyl alcohol (PVA) formed a hydrogel network through dynamic borate bonding and further photocrosslinking. Que-loaded metal-organic framework nanoparticles (UIO-66-NH@Que) was crosslinked into the hydrogel network through hydrogen bonding. The resulting hydrogel exhibited outstanding mechanical properties, distinct ROS-responsive release properties, and remarkable biocompatibility. In vitro cellular assays demonstrated that GelMC/PVA-UIO-66-NH@Que could effectively scavenge intracellular ROS and modulate macrophage polarization. In addition, GelMC/PVA-UIO-66-NH@Que was able to promote the expression of vascular endothelial growth factor (VEGFA) and enhance the vasculogenic function of human umbilical vein endothelial cells (HUVECs) by regulating macrophage polarization. In a diabetic rat model of full-thickness skin defect, GelMC/PVA-UIO-66-NH@Que effectively reduced the level of wound inflammation and promoted wound repair. After 14 days of treatment, the wound healing ratio in the GelMC/PVA-UIO-66-NH@Que group reached 92.02 ± 2.72 %, while the control group was only 48.48 ± 2.14 %. In conclusion, this ROS-responsive nanocomposite hydrogel dressing presents a promising approach to the safe and efficient management of diabetic wounds.
炎症微环境的持续失衡是糖尿病伤口愈合延迟的关键原因。通过调节巨噬细胞极化来改善伤口炎症微环境是促进糖尿病伤口愈合的重要策略。然而,通过低成本、生物安全且有效的方法调节巨噬细胞极化仍然是一个挑战。在这项工作中,开发了一种基于硼酸键的活性氧(ROS)响应性纳米复合水凝胶敷料(GelMC/PVA-UIO-66-NH@Que),通过按需释放具有免疫调节活性的槲皮素(Que)来实现高效的糖尿病伤口修复。4-羧基苯硼酸修饰的甲基丙烯酰化明胶(GelMC)和聚乙烯醇(PVA)通过动态硼酸键合和进一步的光交联形成水凝胶网络。负载Que的金属有机框架纳米颗粒(UIO-66-NH@Que)通过氢键交联到水凝胶网络中。所得水凝胶具有出色的机械性能、独特的ROS响应释放特性以及显著的生物相容性。体外细胞实验表明,GelMC/PVA-UIO-66-NH@Que能够有效清除细胞内ROS并调节巨噬细胞极化。此外,GelMC/PVA-UIO-66-NH@Que能够通过调节巨噬细胞极化促进血管内皮生长因子(VEGFA)的表达并增强人脐静脉内皮细胞(HUVECs)的血管生成功能。在糖尿病全层皮肤缺损大鼠模型中,GelMC/PVA-UIO-66-NH@Que有效降低了伤口炎症水平并促进了伤口修复。治疗14天后,GelMC/PVA-UIO-66-NH@Que组的伤口愈合率达到92.02±2.72%,而对照组仅为48.48±2.14%。总之,这种ROS响应性纳米复合水凝胶敷料为糖尿病伤口的安全有效管理提供了一种有前景的方法。
Biomacromolecules. 2025-3-10