Zheng Yanfen, Zhuang Ziqi, Zhou Renwu, Zheng Luo, Li Changhong, Zhou Rusen, Gao Yuting, Zhang Liang, Zheng Yating, Zhao Liqian, Rizvi Syed Faheem Askari, Yang Bocheng, Jiang Lili, Lin Jinyong, Wang Anqi, Zhou Wei, Cheng Hongwei, Li Dong, Chu Chengchao, Thompson Erik W, Wu Yunlong, Liu Gang, Zeng Yun, Wang Peiyu
Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Department of Pharmacy, Stomatological Hospital of Xiamen Medical College, Xiamen, 361008, China.
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Adv Healthc Mater. 2025 Mar;14(6):e2403223. doi: 10.1002/adhm.202403223. Epub 2025 Feb 3.
Oral ulcers, affecting 27.9% of adults, can lead to malnutrition and dehydration, especially in individuals with diabetes, cancer, viral infections, and autoimmune diseases. Existing treatments-including oral films, sprays, frosts, and powders-often fail to be effective due to rapid dilution and clearance in the moist oral environment. This study is the first to investigate the use of Cold Atmospheric Plasma (CAP) for treating oral ulcers and its underlying molecular mechanisms. A novel high-bioavailability, mucoadhesive therapy combining handheld three dimensions (3D) multi-microhole CAP is developed with a nanogel-based pharmaceutical system containing glucose oxidase (GOx) and catalase (CAT), termed GCN. These results showed that both CAP alone and CAP combined with GCN significantly accelerate oral ulcer healing, modulate immune responses, and activate the Epidermal Growth Factor Receptor (EGFR) in acetic acid-induced oral ulcers, outperforming untreated controls and the conventional medication, Watermelon Frost (WF). Furthermore, the CAP+GCN combination enhances therapeutic effects by promoting fibroblast generation. CAP pretreatment also enhances cell permeability and nanoparticle uptake, improving tissue adhesion. These findings are validated in primary Human Gingival Fibroblasts (HGF) and Human Periodontal Ligament Stem Cells (PDLSC) from healthy donors, as well as an oral ulcer model in rats, demonstrating superior biocompatibility and safety.
口腔溃疡影响着27.9%的成年人，可导致营养不良和脱水，尤其是糖尿病、癌症、病毒感染及自身免疫性疾病患者。现有的治疗方法，包括口腔贴膜、喷雾剂、霜剂和散剂，由于在湿润的口腔环境中会迅速稀释和清除，往往效果不佳。本研究首次探究了冷大气等离子体（CAP）治疗口腔溃疡的用途及其潜在分子机制。一种新型的高生物利用度、粘膜粘附疗法被开发出来，它结合了手持式三维（3D）多微孔CAP和一种含有葡萄糖氧化酶（GOx）和过氧化氢酶（CAT）的基于纳米凝胶的药物系统，称为GCN。这些结果表明，单独使用CAP以及CAP与GCN联合使用，均可显著加速醋酸诱导的口腔溃疡的愈合、调节免疫反应并激活表皮生长因子受体（EGFR），其效果优于未治疗的对照组和传统药物西瓜霜（WF）。此外，CAP+GCN组合通过促进成纤维细胞生成增强了治疗效果。CAP预处理还可增强细胞通透性和纳米颗粒摄取，改善组织粘附性。这些发现已在来自健康供体的原代人牙龈成纤维细胞（HGF）和人牙周膜干细胞（PDLSC）以及大鼠口腔溃疡模型中得到验证，证明了其卓越的生物相容性和安全性。
