Effects of Leukocyte–Platelet-Rich Fibrin (L-PRF) in Different Intraoral Bone Grafting Procedures: A Systematic Review
A systematic review of 17 controlled clinical trials found that leukocyte-platelet-rich fibrin (L-PRF) offered modest benefits in reducing bone loss and post-operative pain following tooth extraction, but showed no significant advantage in sinus augmentation procedures, with the authors emphasizing the need for standardized protocols and further high-quality research to better define its clinical applications.
Dr. Theo Katsaros
Periodontist
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Background & clinical context
Leukocyte–platelet-rich fibrin (L-PRF) is a second-generation autologous platelet concentrate introduced by Dr. Joseph Choukroun in the early 2000s.
Unlike first-generation concentrates, it requires no anticoagulants or biochemical activator. Venous blood is centrifuged directly, producing three layers, with the intermediate L-PRF layer forming a dense fibrin scaffold that entraps platelets and leukocytes. This leukocyte-inclusive composition distinguishes L-PRF from PRGF and differentiates its biological profile: neutrophils and macrophages contribute to wound debridement and infection prevention, while growth factors including TGF-β1, PDGF, VEGF, and IGF are released over an extended period of up to 10 days.
L-PRF has been applied across a wide range of oral surgery indications, with promising early reports in third molar surgery, periodontal regeneration, and root coverage. Its application in implant-site development procedures has attracted increasing clinical interest, but published results have been variable.
This systematic review critically evaluated the available controlled trial evidence across all three domains.
Evidence quality — a critical note
Not a single included study was rated low risk of bias. Twelve of 17 studies (70%) were rated high risk, primarily due to unclear blinding of participants, personnel, and outcome assessors. This is the weakest evidence quality profile across the platelet concentrate systematic reviews in this series and should frame how all findings below are interpreted.
Key findings by procedure
Ridge preservation
Eight controlled studies assessed L-PRF in post-extraction ridge management, with most comparing L-PRF against natural blood clot healing. Results were broadly favorable for L-PRF over unassisted healing, though one study found no difference.
Study | Comparison | Key outcome | L-PRF effect |
|---|---|---|---|
Temmerman et al. (2016) — split-mouth RCT | L-PRF vs. blood clot | Horizontal/vertical bone loss, socket fill at 3 months (CBCT); pain days 1–7 | Significant benefit — less buccal bone loss, greater socket fill; less pain days 3–5 |
Hauser et al. (2013) | L-PRF ± flap vs. blood clot | Ridge width, bone microarchitecture at 8 weeks (micro-CT) | Significant benefit — 0.06 mm width reduction vs. 0.43 mm control; improved trabecular number and separation |
Alzahrani et al. (2017) | L-PRF vs. blood clot | Horizontal width reduction, radiographic bone fill at 1, 4, 8 weeks | Significant benefit at weeks 4 and 8 for both width and bone fill |
Suttapreyasri & Leepong (2013) — split-mouth RCT | L-PRF vs. blood clot | Ridge contour, vertical bone loss, socket orifice at 8 weeks | No significant difference across all parameters |
Thakkar et al. (2016) | DFDBA + L-PRF vs. DFDBA alone | Horizontal and vertical bone loss at 180 days | Horizontal loss SS reduced (0.75 vs. 1.36 mm); vertical loss not SS different |
Marenzi et al. (2015) — split-mouth RCT | L-PRF vs. blood clot | Post-op pain at 24–72h; soft tissue healing index at 3–21 days | Less pain (SS); improved healing index at days 7, 14, and 21 |
Yerke et al. (2017) | L-PRF vs. collagen dressing, calcium sulfate + PRP, blood clot | Soft tissue closure at 10 and 21 days | No significant difference between any groups at 21 days |
Ridge augmentation
Only one controlled study (Moussa et al., 2016) assessed L-PRF in ridge augmentation. L-PRF membranes were placed over autogenous palatal block grafts in the anterior maxilla. Bone width gain at 4 months was comparable between groups (2.8 vs. 2.4 mm by CBCT), but graft resorption was significantly less in the L-PRF group (0.8 ± 0.6 mm vs. 1.6 ± 0.9 mm). No soft tissue healing or post-operative outcomes were reported. The single study with a CCT design prevents any meaningful conclusions for this indication.
Maxillary sinus augmentation
Eight controlled studies assessed L-PRF in direct sinus augmentation, using xenograft, FDBA, alloplast, or β-TCP as grafting materials. Findings were uniformly negative for histomorphometric bone outcomes, with no statistically significant benefit demonstrated in any study.
Outcome domain | No. of studies | Finding |
|---|---|---|
New bone formation (%) | 5 studies | No benefit — no SS difference in vital bone % between L-PRF + graft vs. graft alone across all five studies, regardless of graft material |
Residual graft material | 5 studies | No benefit — residual graft percentages comparable in all studies |
Bone maturation / healing time | 2 studies | Inconclusive — authors claimed reduced healing time but histomorphometry and ISQ values showed no SS difference; study designs did not allow direct temporal comparison |
L-PRF vs. collagen membrane (lateral window coverage) | 2 studies | Comparable outcomes — L-PRF membrane performed equivalently to collagen membrane for lateral window coverage |
Post-operative pain and swelling | 1 study | No significant difference — Gurler & Delilbasi found no SS improvement in any self-assessed parameter over the first 7 days |
Methodological note on sinus augmentation studies
Histomorphometric comparability across sinus studies was limited by significant heterogeneity in biopsy timing (3.5 to 6 months), biopsy location (crestal bone vs. lateral window site), and lateral window dimensions — all factors known to independently affect bone formation outcomes. This variability may explain the wide range in reported new bone percentages across studies and should be considered when evaluating the consistency of the null findings.
Summary of evidence
Ridge preservation
Modest benefit over unassisted healing for dimensional preservation and early post-op pain
Ridge augmentation
Reduced graft resorption in one study — insufficient evidence for broader conclusions
Sinus augmentation
No histomorphometric benefit across eight studies; comparable to collagen membrane for lateral window coverage
Clinical bottom line
For the practitioner
L-PRF offers a modest but reasonably consistent benefit over unassisted socket healing in ridge preservation, reducing post-extraction dimensional changes and early post-operative pain in the majority of studies that assessed these outcomes.
Its application in maxillary sinus augmentation does not appear to improve bone regeneration outcomes regardless of graft material, though it may serve as an acceptable alternative to collagen membrane for lateral window coverage.
The single ridge augmentation study suggests a possible role in limiting graft resorption, but this cannot be considered actionable evidence.
Given the complete absence of low-risk-of-bias studies in this review, all findings should be interpreted with substantial caution. L-PRF's autologous nature, low cost, and chairside preparation make it a low-risk adjunct, but the current evidence does not establish it as a material that reliably enhances bone regeneration in implant site development procedures.
Research gaps & limitations
The 70% high-risk-of-bias rate across included studies substantially limits the reliability of all reported findings. No studies were identified addressing L-PRF as a standalone grafting material in sinus augmentation compared to established bone substitutes, leaving the graft-substitute question unanswered.
Variability in L-PRF preparation protocols across studies undermines comparability and makes meta-analysis impossible.
Future research should prioritize standardized centrifugation protocols, blinded outcome assessment, larger sample sizes, and longer follow-up periods before clinical guidelines for L-PRF in implant-site development can be established.
