Photobiomodulation Modulates Temporal VEGF Dynamics and Tissue Repair During Diabetic Oral Mucosal Wound Healing in Rats

Photobiomodulation (PBM) may improve diabetic wound repair, but the temporal relationship between local angiogenic signaling and tissue-level healing remains incompletely defined. We examined previously unreported tissue vascular endothelial growth factor (VEGF) and histopathological outcomes from 72 ulcer-bearing male Wistar rats from a previously reported experimental cohort, using a balanced 2 × 2 × 3 design comprising metabolic status, PBM treatment, and healing day (3, 7, or 10; n = 6 per cell). Tissue VEGF was quantified by ELISA and normalized to total protein; histopathological outcomes included exploratory inflammation/injury and tissue repair composite scores. In the factorial log-VEGF model, diabetes × day (p = 0.0017) and LLLT × day (p = 0.0010) interactions demonstrated phase-dependent responses. On day 3, PBM-treated animals had an adjusted VEGF ratio of 2.13 versus untreated animals (95% CI 1.63–2.78; Holm-adjusted p < 0.001), whereas diabetic animals had lower VEGF than healthy animals (ratio 0.50, 95% CI 0.39–0.66; adjusted p < 0.001). VEGF concentrations converged by day 10. PBM remained associated with a higher exploratory tissue repair score after adjustment for healing day, diabetes status, and contemporaneous VEGF, whereas VEGF itself was not independently associated with repair. These findings demonstrate phase-dependent differences in tissue VEGF and suggest that contemporaneous VEGF concentrations do not fully explain treatment-associated variation in exploratory histopathological repair scores.