Platelet-rich fibrin after mandibular third molar extraction: a split-mouth and parallel-group stratified meta-analysis of randomized controlled trials (RCTs).

Abstract

Background: Platelet-rich fibrin (PRF) has been increasingly used as an autologous biomaterial to enhance healing after tooth extraction because of its potential to modulate inflammation, promote angiogenesis, and stimulate tissue regeneration. However, evidence regarding its effectiveness across postoperative outcomes remains heterogeneous, and the comparative performance of PRF subtypes, particularly leukocyte-platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF), is not fully established. This systematic review and meta-analysis evaluated the effects of PRF on postoperative outcomes following mandibular third molar extraction, with emphasis on postoperative pain and comparison of PRF subtypes.

Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted from inception to March 2026. Randomized controlled trials comparing PRF with natural clot healing after mandibular third molar extraction were included. The primary outcome was postoperative pain. Secondary outcomes included alveolar osteitis (AO), edema, trismus, analgesic consumption, and bone-related outcomes. Risk of bias was assessed using RoB 2. Meta-analyses were performed using random-effects models, and heterogeneity was evaluated with the I² statistic.

Results: Twenty-eight studies were included. PRF significantly reduced the incidence of AO (RR = 0.17, 95% CI: 0.06-0.49), postoperative pain from day 1 to day 7, and analgesic consumption at postoperative days 2-3. Significant improvements were also observed in trismus at all assessed timepoints. Bone density, assessed descriptively across six studies due to substantial methodological heterogeneity in imaging methods, showed a consistent trend favoring PRF, although this could not be quantitatively pooled. Edema reduction was inconsistent, with only modest short-term benefits. L-PRF demonstrated more consistent effects across outcomes than A-PRF, although evidence for A-PRF was limited to a single trial. Heterogeneity was substantial in some analyses, likely due to differences in PRF protocols and outcome assessment methods.

Conclusion: PRF, particularly L-PRF, reduces postoperative morbidity after mandibular third molar extraction, although further standardized trials, particularly head-to-head comparisons of L-PRF and A-PRF, are needed to clarify subtype-specific effects.