journal article·2026-06-21Open access

Cytomorphometric and Clinical Analysis of the Effects of Azithromycin and Platelet-Rich Fibrin on Wound Healing After Surgical Removal of an Impacted Mandibular Third Molar

Milan Spasić, Kosta Todorović, Nikola Živković, Milica Petrović, Simona Stojanović, Ana Todorović, Branislava Stojković, Sanja Jocić, Vladan Krunić, Milan Stoiljković

Abstract

Impacted mandibular third molars present a common challenge in oral surgery, often associated with postoperative complications such as delayed healing and periodontal defects; therefore, optimizing adjunctive therapies is clinically important. In this study, we aimed to evaluate the efficacy of platelet-rich fibrin (PRF) and preoperative azithromycin in modulating inflammation and enhancing wound healing following surgical extraction of impacted mandibular third molars. In this prospective clinical study, healthy subjects aged 18–50 years were randomly assigned to three groups: a control group receiving standard postoperative amoxicillin therapy, a PRF group receiving PRF with standard therapy, and a PRF-plus-azithromycin group receiving PRF, standard therapy, and a single preoperative dose of azithromycin. Clinical parameters were assessed and cytomorphometric analysis was performed preoperatively and postoperatively. Clinical parameters generally improved over time in all groups (p < 0.001). Differences between groups were observed for interincisal distance, Landry Index, and pain scores, with a trend toward more favorable outcomes in the combined-therapy group. Cytomorphometric analysis revealed cellular alterations in the control group, relative stability in the PRF group, and intermediate changes in the combined-therapy group. Within the limitations of this study, the combination of PRF and preoperative azithromycin showed potential benefits in several postoperative outcomes. However, given the study design and sample characteristics, these findings should be considered preliminary and require confirmation in larger prospective studies before definitive clinical recommendations can be made.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Periodontal Regeneration and Treatments · Oral microbiology and periodontitis research · Dental Radiography and Imaging

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oral Surgery, Dental Clinic, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Pathology, Institute of Pathological Anatomy, Clinical Center, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Oral Medicine and Periodontology, Dental Clinic, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Orthodontics, Dental Clinic, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Preventive and Pediatric Dentistry, Dental Clinic, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Pharmacology, Faculty of Medicine, University of Niš, 18108 Niš, Serbia

Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510, USA

Funding

“Multidisciplinary research of the orofacial region and the dentoalveolar complex: biological, clinical, and technological aspects” · Ministry of Science and Technological Development and Innovation

References (43)

Show source-provided references
1. Peterson, L.J., Ellis, E., Hupp, J.R., and Tucker, M.R. (2003). Contemporary Oral and Maxillofacial Surgery, Mosby. [4th ed.].
2. Prevalence of impacted teeth among young adults: A retrospective radiographic study
3. Pinto, A.C., Francisco, H., Marques, D., Martins, J.N.R., and Caramês, J. (2024). Worldwide prevalence and demographic predictors of impacted third molars—Systematic review with meta-analysis. J. Clin. Med., 13.10.3390/jcm13247533 ↗
4. Postoperative complications of impacted mandibular third molar extraction related to patient’s age and surgical difficulty level: A cross-sectional retrospective study10.1155/2022/7239339 ↗
5. Miloro, M., Ghali, G.E., Larsen, E., and Waite, P. (2004). Management of impacted teeth other than third molar. Peterson’s Principles of Oral and Maxillofacial Surgery, BC Decker Inc.. [2nd ed.].
6. Recovery after third molar surgery: Clinical and health-related quality of life outcomes10.1053/joms.2003.50106 ↗
7. Complications of third molar surgery10.1016/j.coms.2006.11.013 ↗
8. Piezoelectric versus conventional rotary techniques for impacted third molar extraction: A meta-analysis of randomized controlled trials10.1097/MD.0000000000001685 ↗
9. Effect of submucosal dexamethasone injection on postoperative pain, edema, and trismus following mandibular third molar surgery: A prospective randomized clinical trial10.1016/j.ijom.2016.11.006 ↗
10. Efficacy of a single dose of low-level laser therapy in reducing pain, swelling, and trismus following third molar extraction surgery10.1016/j.ijom.2015.10.023 ↗
11. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery10.2174/138920112800624391 ↗
12. Effects of leukocyte- and platelet-rich fibrin alone and combined with hyaluronic acid on pain, edema, and trismus after surgical extraction of impacted mandibular third molars10.1016/j.joms.2017.12.005 ↗
13. Randomized double-blind clinical trial evaluation of bone healing after third molar surgery with leukocyte- and platelet-rich fibrin10.1016/j.ijom.2019.01.020 ↗
14. Application of PRF in surgical management of periapical lesions10.4103/0975-5950.117825 ↗
15. The opportunity in perio-implantology: The PRF
16. Platelet-rich fibrin (PRF): A second-generation platelet concentrate10.1016/j.tripleo.2005.07.010 ↗
17. Advanced platelet-rich fibrin: A new concept for tissue engineering10.1563/aaid-joi-D-14-00138 ↗
18. Platelet-rich fibrin as a bioscaffold and reservoir of growth factors10.1089/ten.tea.2010.0327 ↗
19. Azithromycin as prophylaxis for prevention of postoperative infection in impacted mandibular third-molar surgery10.1007/s10156-005-0419-6 ↗
20. Nagano, T., Yamaguchi, T., Kajiyama, S., Suzuki, T., Matsushima, Y., Yashima, A., Shirakawa, S., and Gomi, K. (2021). Effect of azithromycin on proinflammatory cytokine production in gingival fibroblasts. J. Clin. Med., 10.10.3390/jcm10010099 ↗
21. European Medicines Agency (2026, April 11). Changes to the Use of Antibiotic Azithromycin. Available online: https://www.ema.europa.eu.
22. Periodontal tissue disposition of azithromycin10.1902/jop.1997.68.12.1206 ↗
23. Winter, G.B. (1926). Principles of Exodontia, American Medical Book Company.
24. Impacted mandibular third molars: Classification and technique
25. Optimized platelet-rich fibrin with the low-speed concept10.1902/jop.2016.160443 ↗
26. Oxidative stress and osteoimmunology: The two missing pieces of the oral osseointegration puzzle
27. Comparative histological evaluation of two PRF formulations10.1016/j.jcms.2023.02.004 ↗
28. Use of leukocyte- and platelet-rich fibrin in soft tissue healing10.1016/j.jcms.2020.02.020 ↗
29. Effect of sutureless surgery on postoperative pain and swelling
30. Alrayyes, Y., Aloraini, S., Alkhalaf, A., and Aljasser, R. (2022). Soft-tissue healing using PRF in smokers. Diagnostics, 12.10.3390/diagnostics12102403 ↗
31. Jovanovic, M., Zivkovic, N., Gligorijevic, N., Igic, M., Petrovic, M., Bojovic, M., Jovanovic, R., and Kostic, M. (2023). Cytomorphometric and Clinical Changes in Gingival Tissue after Subgingival Tooth Preparation—A Pilot Study. Healthcare, 11.10.3390/healthcare11030414 ↗
32. Exfoliative Cytology of Buccal Squames: A Quantitative Cytomorphometric Analysis of Patients with Diabetes10.4103/2231-0762.142024 ↗
33. The R Development Core Team (2013). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http://www.R-project.org/.
34. Unusual complications associated with third molar surgery
35. Accidents and complications in third molar surgery10.1007/s10006-013-0439-9 ↗
36. Miguel, D.C.N., dos Santos Oliveira, R., and Panzarella, F.K. (2025). Postoperative pain after extraction of impacted mandibular third molars. BMC Oral Health, 25.
37. Efficacy of single dose azithromycin as prophylactic antibiotic in surgical removal of mandibular third molars: A clinical study10.1007/s12663-012-0464-5 ↗
38. PRF vs. collagen plugs in socket preservation
39. Platelet-rich fibrin and wound healing: A systematic review10.1089/ten.teb.2016.0233 ↗
40. Platelet concentrates in socket preservation10.1159/000488061 ↗
41. Benefit of azithromycin with platelet-rich fibrin in clinical osteoimmunology regarding autogenous bone grafting: A retrospective cohort study
42. Cytomorphometric and clinical investigation of the gingiva before and after low-level laser therapy of gingivitis in children10.1007/s10103-011-0993-z ↗
43. Clinical, microbiological and cytomorphometric evaluation of low-level laser therapy as an adjunct to periodontal therapy in patients with chronic periodontitis