Gao Suyue, He Xuefeng, Liu Hengdeng, Liu Yiling, Wang Hanwen, Zhou Ziheng, Chen Lei, Ji Xiaoyuan, Yang Ronghua, Xie Julin
Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
Adv Healthc Mater. 2025 Mar;14(8):e2401580. doi: 10.1002/adhm.202401580. Epub 2024 Jul 30.
The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO₂-Au-mSiO₂@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO₂ head and MnO₂ extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO₂-Au-mSiO₂@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS-scavenging and growth factor-releasing system, is developed. The HAMA-mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti-inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.
糖尿病伤口愈合过程中从炎症到增殖的漫长转变带来了重大挑战，持续的炎症反应和血管化不足使这些挑战更加严峻。为了解决这些问题，设计了一种利用不对称结构的MnO₂-Au-mSiO₂@aFGF Janus纳米颗粒的新型纳米酶治疗方法。合成了以mSiO₂头部和MnO₂延伸部分为特征的纳米酶，其中包裹了酸性成纤维细胞生长因子（aFGF），从而形成MnO₂-Au-mSiO₂@aFGF Janus纳米颗粒（mSAM@aFGF）。这种纳米酶系统有效地模拟了过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的酶活性，催化活性氧（ROS）的降解并产生氧气。此外，aFGF的可控释放促进了组织再生和血管化。体外研究表明，mSAM@aFGF显著减轻细胞中的氧化应激，并增强细胞增殖、迁移和血管生成。开发了一种基于光交联透明质酸（HAMA）的可注射水凝胶，其包含纳米酶ROS清除和生长因子释放系统。HAMA-mSAM@aFGF水凝胶在糖尿病伤口模型中展现出多方面的益处，包括可注射性、伤口粘附性、止血、抗炎作用、巨噬细胞从M1表型向M2表型的极化以及血管生成的促进。这些特性突出了该系统促进从慢性炎症向伤口修复增殖期转变的潜力，为糖尿病伤口管理提供了一种有前景的治疗策略。
