Li Hao, Wei Shuzhen, Ling Qiangjun, Wang Ruinan, Liu Tuozhou, Yu Hong, Zhao Pengchao, Zhang Kunyu, Bian Liming, Liao Weiming
Department of Joint Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Adv Mater. 2025 Aug;37(34):e2504829. doi: 10.1002/adma.202504829. Epub 2025 Jun 10.
The accumulation of reactive oxygen species (ROS) and poor oxygen supply are two prominent factors of the inflammatory microenvironment that delay diabetic wound healing. However, current clinical treatments cannot achieve effective ROS scavenging and sustained oxygenation. Herein, a ROS-driven oxygenation hydrogel (OxyGel) spray that integrates a multifunctional nanozyme with a dynamically crosslinked sprayable hydrogel matrix is presented. The nanozyme, which is fabricated based on the ceria-zoledronic acid nanoparticles modified with tannic acid (TCZ nanozymes), can mimic the cascade catalytic activities of superoxide dismutase (SOD) and catalase (CAT) to effectively scavenge ROS while generating oxygen. These synergistic actions rebalance the oxidative and hypoxic microenvironment of the diabetic wound, promote M1-to-M2 macrophage repolarization, and enhance the survival, migration, and angiogenesis of endothelial cells. A single administration of the nanozyme via the hydrogel spray stably deposits the nanozymes at the target sites to accelerate full-thickness back skin wound and refractory foot ulcer wound healing in diabetic rats. Furthermore, RNA-seq results revealed the upregulation of multiple signaling pathways related to wound healing by the OxyGel spray, highlighting the potential of this platform not only for the treatment of refractory diabetic wounds but also other diseases associated with oxidative stress and hypoxia.
活性氧（ROS）的积累和氧气供应不足是延迟糖尿病伤口愈合的炎症微环境的两个突出因素。然而，目前的临床治疗无法实现有效的ROS清除和持续的氧合作用。在此，我们提出了一种ROS驱动的氧合水凝胶（OxyGel）喷雾剂，它将多功能纳米酶与动态交联的可喷涂水凝胶基质相结合。这种纳米酶是基于用单宁酸修饰的二氧化铈-唑来膦酸纳米颗粒（TCZ纳米酶）制备的，它可以模拟超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的级联催化活性，在产生氧气的同时有效清除ROS。这些协同作用重新平衡了糖尿病伤口的氧化和缺氧微环境，促进M1型巨噬细胞向M2型巨噬细胞的极化，并增强内皮细胞的存活、迁移和血管生成。通过水凝胶喷雾剂单次给药纳米酶可将纳米酶稳定地沉积在靶位点，以加速糖尿病大鼠全层背部皮肤伤口和难治性足部溃疡伤口的愈合。此外，RNA测序结果显示OxyGel喷雾剂上调了多个与伤口愈合相关的信号通路，突出了该平台不仅在治疗难治性糖尿病伤口方面的潜力，而且在治疗其他与氧化应激和缺氧相关疾病方面的潜力。
