Shen Yuting, Li Shaoyue, Hou Xiaodong, Yu Jifeng, Zhu Yuli, Zhao Chongke, Niu Zhiyuan, Guan Xin, Xiong Bing, Wang Sirui, Yang Yifei, Li Xiao, Sun Liping, Wu Shengbo, Huang Bin, Xu Huixiong, Yin Haohao
Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, Ultrasound Education and Research Institute, School of Medicine, Tongji University, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Shanghai, 200072, China.
Adv Sci (Weinh). 2025 Jun;12(23):e2500720. doi: 10.1002/advs.202500720. Epub 2025 May 8.
Diabetic foot ulcers (DFUs) are a complex mixture of neuropathy, peripheral arterial disease, and infection, where excessive reactive oxygen species (ROS) exacerbates inflammation and impairs healing. Therefore, there is an urgent need to design a hydrogel dressing with a 'lever' function to balance ROS levels in the wound to achieve both antimicrobial and anti-inflammatory effects on DFUs. In this study, we synthesised ROS-responsive diselenide liposomes loaded with a pro-skin healing factor (ergothioneine (ET)), thrombin, and a sonosensitizer (HMME) and constructed nanocomposite 'lever' hydrogels modulated by ultrasound (US). During early infection, sonodynamic therapy (SDT) under US generates bactericidal ROS, cleaving diselenide bonds to release ET and thrombin. Upon US cessation, thrombin/fibrinogen forms an in situ gel, while ET scavenges residual ROS and promotes M2 macrophage polarization in later stages. In addition, the potential immunomodulatory mechanisms of the nanocomposite 'lever' hydrogels were investigated via RNA sequencing. In conclusion, the novel nanocomposite 'lever' hydrogels effectively achieved a balance between ROS production and annihilation during different stages of wound repair while providing antibacterial and anti-inflammatory properties to promote neovascularisation and improve diabetic peripheral neuropathy. In conclusion, by precisely controlling ROS levels across wound-healing phases, this strategy offers a promising solution for refractory DFUs.
糖尿病足溃疡（DFUs）是神经病变、外周动脉疾病和感染的复杂混合病症，其中过量的活性氧（ROS）会加剧炎症并阻碍愈合。因此，迫切需要设计一种具有“杠杆”功能的水凝胶敷料，以平衡伤口中的ROS水平，从而对糖尿病足溃疡实现抗菌和抗炎效果。在本研究中，我们合成了负载有促皮肤愈合因子（麦角硫因（ET））、凝血酶和一种声敏剂（HMME）的ROS响应性二硒化物脂质体，并构建了由超声（US）调制的纳米复合“杠杆”水凝胶。在早期感染期间，超声作用下的声动力疗法（SDT）产生杀菌性ROS，裂解二硒键以释放ET和凝血酶。超声停止作用后，凝血酶/纤维蛋白原形成原位凝胶，而ET则清除残留的ROS，并在后期促进M2巨噬细胞极化。此外，还通过RNA测序研究了纳米复合“杠杆”水凝胶潜在的免疫调节机制。总之，这种新型纳米复合“杠杆”水凝胶在伤口修复的不同阶段有效地实现了ROS产生与消除之间的平衡，同时提供抗菌和抗炎特性，以促进新血管形成并改善糖尿病周围神经病变。总之，通过精确控制伤口愈合各阶段的ROS水平，该策略为难治性糖尿病足溃疡提供了一种有前景的解决方案。
