基于黄芩素的纳米递送系统通过PPAR信号通路恢复线粒体稳态以促进糖尿病伤口愈合。
Baicalein based nano-delivery system restores mitochondrial homeostasis through PPAR signaling pathway to promote wound healing in diabetes.
作者信息
Qin Danlei, Hu Weiting, Guo Yanqin, Cheng Rui, Hao Fengxiang, Zhao Bin
机构信息
Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi, 030001, China.
Department of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
出版信息
J Nanobiotechnology. 2025 May 19;23(1):360. doi: 10.1186/s12951-025-03427-6.
Wound healing in diabetes is a substantial clinical challenge due to the hyperglycemic microenvironment, high pH, bacterial infection, persistent inflammation, and impaired cellular functions, attributed to mitochondrial dysfunction. Here, we have developed an injectable photo-crosslinking nanocomposite hydrogel (BA/GOx@ZIF-8@GelMA, BGZ@GelMA) with baicalein (BA) and glucose oxidase (GOx) loaded Zinc metal-organic framework (ZIF-8) based on methacrylated gelatin (GelMA) to accelerate diabetic infected wound healing by regulating subcellular and cellular functions. The combination of ZIF-8 and BA gives the hydrogel excellent antibacterial properties. A high blood sugar environment triggers the release of GOx in BGZ@GelMA, reducing local glucose and pH, producing hydrogen peroxide (HO), and releasing BA and Zinc ions (Zn). This process provides a suitable microenvironment for wound healing. Zn can significantly inhibit the proliferation of Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli). The released BA can clear ROS in cells and mitochondria, restore mitochondrial function and stability, and make the hydrogel fundamentally improve the cell function damage induced by hyperglycemia, and ultimately promote cell proliferation, migration and angiogenesis. In general, our multifunctional nanocomposite hydrogel provides a new strategy for diabetes wound healing at the subcellular and cellular functional levels.
由于高血糖微环境、高pH值、细菌感染、持续炎症以及归因于线粒体功能障碍的细胞功能受损,糖尿病患者的伤口愈合是一项重大的临床挑战。在此,我们基于甲基丙烯酸化明胶(GelMA)开发了一种可注射的光交联纳米复合水凝胶(BA/GOx@ZIF-8@GelMA,BGZ@GelMA),其负载了黄芩苷(BA)和葡萄糖氧化酶(GOx)的锌金属有机框架(ZIF-8),以通过调节亚细胞和细胞功能来加速糖尿病感染伤口的愈合。ZIF-8和BA的组合赋予水凝胶优异的抗菌性能。高血糖环境触发BGZ@GelMA中GOx的释放,降低局部葡萄糖和pH值,产生过氧化氢(HO),并释放BA和锌离子(Zn)。这一过程为伤口愈合提供了适宜的微环境。Zn可显著抑制金黄色葡萄球菌(S.aureus)和大肠杆菌(E.coli)的增殖。释放的BA可清除细胞和线粒体中的活性氧,恢复线粒体功能和稳定性,使水凝胶从根本上改善高血糖诱导的细胞功能损伤,并最终促进细胞增殖、迁移和血管生成。总体而言,我们的多功能纳米复合水凝胶在亚细胞和细胞功能水平上为糖尿病伤口愈合提供了一种新策略。