You Wenjie, Cai Zichao, Xiao Feng, Zhao Jiaxin, Wang Guanyi, Wang Wang, Chen Zesheng, Hu Weikang, Chen Yun, Wang Zijian
Department of Urology, Institute of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Department of Biomedical Engineering, Hubei Province Key Laboratory of Allergy and Immune Related Disease, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China.
Adv Sci (Weinh). 2025 Mar;12(11):e2417314. doi: 10.1002/advs.202417314. Epub 2025 Jan 23.
Reactive oxygen species (ROS) play a dual role in wound healing. They act as crucial signaling molecules and antimicrobial agents when present at moderate levels. However, excessive levels of ROS can hinder the healing process for individuals with diabetes. As a result, targeting ROS levels to maintain redox balance has become a promising strategy for improving wound recovery. Currently, no biomaterials have been reported to simultaneously up-regulate and down-regulate ROS to achieve broad-spectrum antibacterial and antioxidant properties. Inspired by the site-dependent effect of nanomaterials, a micron-sized ferroferric oxide (FeO)/MXene (FM) heterojunction is synthesized using a hydrothermal method. The FM heterojunction could scavenge extracellular ROS by activating catalase (CAT)-like and superoxide dismutase (SOD)-like nanozyme activities. Meanwhile, FM heterojunction could release ferric ions and ferrous ions by defect engineering to induce bacterial ferroptosis, up-regulating intercellular ROS, and lipid peroxidation. For applications in vivo, FM heterojunction is incorporated into the tips of gelatin methacryloyl (GelMA)-based microneedle (termed as GFM microneedle) using a two-step casting technique. The results showed that GFM microneedle combined with photothermal therapy could improve S. aureus-infected skin regeneration in diabetic rats. The effectiveness and safety of GFM microneedle are not less favorable than that of a commercial wound dressing. This study provides a proof-of-concept for heterojunction-mediated regenerative medicine via a site-dependent ROS-targeting strategy.
活性氧（ROS）在伤口愈合中发挥着双重作用。当处于适度水平时，它们作为关键的信号分子和抗菌剂发挥作用。然而，对于糖尿病患者而言，过量的ROS会阻碍愈合过程。因此，针对ROS水平以维持氧化还原平衡已成为改善伤口恢复的一种有前景的策略。目前，尚未有生物材料被报道能够同时上调和下调ROS以实现广谱抗菌和抗氧化性能。受纳米材料的位点依赖性效应启发，采用水热法合成了微米级的四氧化三铁（FeO）/MXene（FM）异质结。FM异质结可通过激活过氧化氢酶（CAT）样和超氧化物歧化酶（SOD）样纳米酶活性来清除细胞外ROS。同时，FM异质结可通过缺陷工程释放铁离子和亚铁离子，诱导细菌铁死亡，上调细胞内ROS和脂质过氧化。对于体内应用，使用两步浇铸技术将FM异质结合入基于甲基丙烯酰化明胶（GelMA）的微针尖端（称为GFM微针）。结果表明，GFM微针联合光热疗法可改善糖尿病大鼠金黄色葡萄球菌感染的皮肤再生。GFM微针的有效性和安全性不低于市售伤口敷料。本研究通过位点依赖性ROS靶向策略为异质结介导再生医学提供了概念验证。
