Background and Objectives: This study aimed to evaluate the role of A-PRF (advanced platelet-rich fibrin) in the enhancement of wound healing and protecting the periodontal health of mandibular second molars after the extraction of mandibular third molars. Additionally, the study assessed the levels of pro-inflammatory cytokines in the gingival crevicular fluid (GCF) of mandibular second molars as markers of inflammation. Materials and Methods: Twenty-five systemically healthy adult patients with bilateral removal of impacted mandibular third molars were included. Each patient received A-PRF in one extraction site, while the contralateral site served as a control. Periodontal parameters of the adjacent second molar, including probing depth (PD) and clinical attachment level (CAL), were measured in distal–vestibular (DV) and distal–lingual (DL) sites. Pain, swelling, and overall healing were subjectively evaluated. Levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in the GCF were analyzed. Evaluations occurred at baseline and three months post-surgery. Results: A-PRF significantly improved PD (from 4.69 ± 0.61 mm to 3.85 ± 0.34 mm in DV, and from 4.71 ± 0.65 mm to 3.79 ± 0.27 mm in DL, respectively) and CAL (from 2.41 ± 0.25 mm to 1.82 ± 0.21 mm in DV, and from 2.40 ± 0.36 mm to 1.75 ± 0.19 mm in DL, respectively) of the adjacent second molar, compared to control sites, three months post-surgery. Pain and swelling scores were notably lower on the 7th postoperative day in the A-PRF group. A-PRF also reduced pro-inflammatory cytokines in GCF, significantly more than in control sites, at three months post-surgery. Conclusions: A-PRF enhances the periodontal and inflammatory status of adjacent teeth and wound healing after the extraction of mandibular third molars.
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