The Effect of Topical Application of a Hyaluronic Acid–Melatonin Mixture Following Surgical Extraction of Impacted Mandibular Third Molars: A Randomized Clinical Trial

Abstract

Aim: To evaluate the effect of topical application of a hyaluronic acid–melatonin mixture following surgical removal of impacted mandibular third molars, with postoperative pain as the primary outcome and maximum mouth opening, facial oedema, and CBCT-derived relative bone density as secondary outcomes. Materials and Methods: This randomized clinical trial was conducted at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Kafrelsheikh University, Egypt. Forty patients requiring surgical removal of impacted mandibular third molars were randomly assigned to two groups (n = 20). The test group received a mixture of 0.2% hyaluronic acid gel and 3 mg melatonin in the extraction socket using gel foam, while the control group received gel foam only. Pain, facial oedema, and maximum mouth opening (MMO) were evaluated preoperatively and on postoperative days 1, 3, and 7. CBCT-derived relative bone density was assessed at baseline and six months postoperatively. Data were analysed using the independent Student’s t-test, Mann–Whitney U test, Friedman test, and repeated-measures ANOVA. Results: Baseline characteristics were comparable between the groups. The test group demonstrated significantly lower postoperative pain scores, greater MMO, and lower facial oedema than the control group throughout the postoperative follow-up period (p ≤ 0.020). At six months, CBCT-derived relative bone density was significantly greater in the test group than in the control group (391.25 ± 38.89 vs. 179.05 ± 41.73 HU; p < 0.001). Conclusion: Topical application of a hyaluronic acid–melatonin mixture was associated with reduced postoperative pain, facial oedema, and trismus, and greater CBCT-derived relative bone density following impacted mandibular third molar surgery. The combination may represent a promising adjunctive approach for improving postoperative recovery. Further well-designed multicentre randomized clinical trials with larger sample sizes and longer follow-up periods are warranted to confirm these findings and establish their long-term clinical relevance.