Distinct Molecular Mechanisms in Oral Mucosal Wound Healing: Translational Insights and Future Directions

Oral mucosal wound healing is a rapid, precisely regulated process distinct from cutaneous repair due to the specialized anatomical, microbial, and physiological features of the oral cavity. This review outlines the sequential healing phases-hemostasis, inflammation, proliferation, and remodeling-and examines the coordinated roles of keratinocytes, fibroblasts, endothelial cells, and immune cell subsets in tissue restoration. Central molecular pathways, including PI3K/Akt, JAK/STAT, Ras/MAPK, TGF-β/SMAD, and Wnt/β-catenin, along with growth factors such as TGF-β, FGF, EGF, and VEGF, are discussed in relation to their regulatory influence on cell behavior and extracellular matrix dynamics. Unique intraoral factors-namely saliva-derived histatins and a distinct resident microbiota-promote accelerated re-epithelialization and attenuated fibrosis. Systemic conditions such as diabetes, aging, and tobacco exposure are identified as key modulators that compromise repair efficiency. Emerging therapeutic strategies, including stem-cell-based interventions, microbiota modulation, bioengineered scaffolds, and photobiomodulation, offer translational potential to enhance clinical outcomes in oral tissue regeneration.