Photobiomodulation Modulates Temporal VEGF Dynamics and Tissue Repair During Diabetic Oral Mucosal Wound Healing in Rats
8 affiliations
- 1Department of Dentistry, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 2Institute of Biochemistry, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 3Institute of Pathology, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 4Institute of Physiology, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 5Institute of Pharmacology, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 6Institute of Histology, Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 7Faculty of Medicine, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia
- 8Clinic for Dental Medicine, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
Abstract
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.
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BibTeX
@article{đorđevic2026photobiomodulation,
title = {{Photobiomodulation Modulates Temporal VEGF Dynamics and Tissue Repair During Diabetic Oral Mucosal Wound Healing in Rats}},
author = {Nadica S. Đorđević and Ilija M. Dragojević and Milica Mijović and Jelena T. Todić and Dragan Marjanović and Aleksandar M. Đorđević and Zvezdan Milanović and Julijana Rašić and Bojana Kisić and Zlatibor Anđelković and Miljana Z. Stašević and Milena M. Kostić},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219395},
url = {https://www.mdpi.com/1422-0067/27/21/9395},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Photobiomodulation Modulates Temporal VEGF Dynamics and Tissue Repair During Diabetic Oral Mucosal Wound Healing in Rats
AU - Nadica S. Đorđević
AU - Ilija M. Dragojević
AU - Milica Mijović
AU - Jelena T. Todić
AU - Dragan Marjanović
AU - Aleksandar M. Đorđević
AU - Zvezdan Milanović
AU - Julijana Rašić
AU - Bojana Kisić
AU - Zlatibor Anđelković
AU - Miljana Z. Stašević
AU - Milena M. Kostić
PY - 2026
DA - 2026/10/22
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219395
UR - https://www.mdpi.com/1422-0067/27/21/9395
AB - 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.
SN - 1422-0067
ER -