Nonthermal Atmospheric Plasma Modulates Palatal Wound Healing in Rats: A Morphometric, Histopathologic and Immunohistochemical Analysis.

Background/Objectives: Non-thermal atmospheric plasma (NTAP) has recently gained attention as a promising tool for tissue regeneration due to its ability to modulate cellular signaling and enhance wound repair. However, its effects on oral mucosal healing and associated molecular pathways remain insufficiently characterized. This study aimed to investigate the histological and immunohistochemical effects of NTAP on palatal wound healing in rats and to evaluate key biomarkers involved in angiogenesis, proliferation, and extracellular matrix remodeling. Methods: Sixty rats were randomly assigned to three groups: Saline Control Group (SCG), Chlorhexidine Gluconate Group (CHG), and NTAP-Treated Group (NTAPG). Standardized full-thickness excisional wounds were created in the central palatal mucosa. Animals were sacrificed on postoperative days 7, 14, and 21. Histological assessments included vascularization, inflammatory cell infiltration, collagen fiber organization, and epithelial gap measurements. Immunohistochemical analyses were performed using antibodies targeting VEGF-A, TGF-β, FGF-2, CD34, α-SMA, and Ki67 to evaluate angiogenesis, fibroblast activity, and cellular proliferation. Results: NTAP treatment significantly elevated TGF-β levels at all time points and increased α-SMA-positive cell counts on days 7 and 14. FGF-2 expression was the highest in NTAPG, while VEGF-A and CD34 levels were significantly elevated, indicating robust angiogenic activity. NTAP also reduced inflammatory cell infiltration relative to the other groups. NTAPG exhibited enhanced fibroblast proliferation, increased collagen deposition, improved vascularization, and accelerated re-epithelialization compared with SCG and CHG. Conclusions: NTAP significantly promoted palatal wound healing by enhancing proliferative activity, stimulating growth factor expression, and accelerating tissue repair. These findings suggest that NTAP may serve as an effective therapeutic approach for improving oral mucosal wound healing.