Next-Generation Oral Ulcer Management: Integrating Cold Atmospheric Plasma (CAP) with Nanogel-Based Pharmaceuticals...

Area of Science:

• Biomedical Engineering
• Plasma Medicine
• Regenerative Medicine

Background:

• Oral ulcers affect a significant portion of the adult population, leading to complications like malnutrition, especially in vulnerable groups.
• Current treatments for oral ulcers are often ineffective due to rapid clearance in the oral environment.
• Understanding the molecular mechanisms of oral ulcer healing is crucial for developing advanced therapies.

Purpose of the Study:

• To investigate the efficacy of Cold Atmospheric Plasma (CAP) in treating oral ulcers and elucidate its molecular mechanisms.
• To develop and evaluate a novel mucoadhesive nanogel system (GCN) combined with CAP for enhanced oral ulcer therapy.
• To compare the therapeutic effects of CAP-based treatments with conventional methods and untreated controls.

Main Methods:

• Development of a novel three-dimensional (3D) multi-microhole CAP device combined with a nanogel containing glucose oxidase (GOx) and catalase (CAT) (GCN).
• Induction of oral ulcers using acetic acid in a rat model.
• Evaluation of healing rates, immune response modulation, and Epidermal Growth Factor Receptor (EGFR) activation.
• In vitro validation using Human Gingival Fibroblasts (HGF) and Human Periodontal Ligament Stem Cells (PDLSC).

Main Results:

• Both CAP alone and the CAP+GCN combination significantly accelerated oral ulcer healing compared to controls and Watermelon Frost (WF).
• CAP+GCN therapy modulated immune responses and activated EGFR signaling pathways.
• The CAP+GCN combination enhanced fibroblast generation and improved tissue adhesion through enhanced cell permeability and nanoparticle uptake.
• CAP pretreatment improved nanoparticle uptake and tissue adhesion.

Conclusions:

• The novel CAP-based therapy (CAP+GCN) demonstrates significant potential for accelerating oral ulcer healing and improving therapeutic outcomes.
• CAP+GCN therapy offers a superior, safe, and biocompatible approach for managing oral ulcers, outperforming conventional treatments.
• This study validates the efficacy and safety of CAP and GCN in preclinical models, paving the way for clinical translation.