Next‐Generation Oral Ulcer Management: Integrating Cold Atmospheric Plasma (CAP) with Nanogel‐Based Pharmaceuticals for Inflammation Regulation
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.
Authors
- Syed Faheem Askari Rizvi (ORCID: https://orcid.org/0000-0002-8671-9168)
- Yanfen Zheng (ORCID: https://orcid.org/0000-0003-3076-9614)
- Ziqi Zhuang (ORCID: https://orcid.org/0009-0007-2144-6182)
- Liqian Zhao (ORCID: https://orcid.org/0000-0001-5068-3688)
- Zheng Luo (ORCID: https://orcid.org/0000-0001-9666-8184)
- Renwu Zhou (ORCID: https://orcid.org/0000-0003-1773-7095)
- Erik W. Thompson (ORCID: https://orcid.org/0000-0002-9723-4924)
- Chengchao Chu (ORCID: https://orcid.org/0000-0002-1694-9363)
- Rusen Zhou (ORCID: https://orcid.org/0000-0002-0762-7792)
- Bocheng Yang (ORCID: https://orcid.org/0009-0008-6433-7661)
- Hongwei Cheng (ORCID: https://orcid.org/0000-0002-4251-0645)
- Yun Zeng (ORCID: https://orcid.org/0000-0002-5747-3349)
- Lili Jiang
- Jinyong Lin (ORCID: https://orcid.org/0009-0007-9540-2414)
- Yating Zheng
- Anqi Wang (ORCID: https://orcid.org/0000-0002-3369-1499)
- Gang Liu (ORCID: https://orcid.org/0000-0003-2613-7286)
- Yun‐Long Wu (ORCID: https://orcid.org/0000-0001-6426-6340)
- Wei Zhou (ORCID: https://orcid.org/0009-0000-3005-2010)
- Peiyu Wang (ORCID: https://orcid.org/0000-0002-6455-5043)
- Changhong Li (ORCID: https://orcid.org/0009-0006-2213-0481)
- Liang Zhang (ORCID: https://orcid.org/0000-0003-0782-0688)
- Yuting Gao (ORCID: https://orcid.org/0000-0001-5912-193X)
- Li Dong (ORCID: https://orcid.org/0000-0003-0811-2640)
Institutions
- Translational Research Institute (AU)
- Harbin Medical University (CN)
- Queensland University of Technology (AU)
- Jimei University (CN)
- Xiamen University (CN)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- University of Macau (MO)
- Inner Mongolia University of Science and Technology (CN)
- Fourth Affiliated Hospital of Harbin Medical University (CN)
- Zhongshan Hospital of Xiamen University (CN)
- Peking University Third Hospital (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Xiamen Medical College
- Zhejiang University (CN)
- Xi'an Jiaotong University (CN)
Publication Details
- Journal
- Advanced Healthcare Materials
- Published
- 2025-02-03
- DOI
- https://doi.org/10.1002/adhm.202403223
- Citations
- 12
- Primary Topic
- Heme Oxygenase-1 and Carbon Monoxide
- Type
- article
- Field-Weighted Citation Impact
- 9.67
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- National Key Research and Development Program of China