A clinical & laboratory investigation of the use of leukocyte and platelet-rich fibrin (L-PRF) in alveolar ridge preservation and management of peri-implant defects

Abstract

Overall Aim of PhD: To evaluate the efficacy of leukocyte- and platelet-rich fibrin (L-PRF) in the management of both alveolar ridge preservation (ARP) and peri-implantitis defects. STUDY 1. Methods: A systematic review of the English-language literature (8 databases) compared use of L-PRF alone versus L-PRF in combination with any bone substitute material for alveolar ridge preservation (ARP). Included studies were randomised (RCT) and controlled clinical trials (CCT) and prospective cohort studies of ≥3 month’s duration, and pre-clinical animal studies conducted up to 30 June 2023. Results: From 7554 identified articles, 2835 were included for screening. Four RCTs were included for final analysis, of which 3 presented some concerns/high risk of bias. Studies were heterogeneous in terms of the biomaterial combined with PRF, tooth location and evaluation methods and outcomes used, rendering meta-analysis impractical. Conclusions: The combination of PRF with another graft material does not appear to consistently offer statistically significant advantages in terms of ridge preservation or mean radiographic bone density values versus PRF alone. Limited data is available to evaluate impact on post-operative pain, other patient-reported outcomes or histologic findings. Additional clinical studies are indicated on this research topic. STUDY 2. Methods: A randomised controlled clinical trial compared the use of L-PRF and L-PRF Block for ARP at non-molar extraction sockets in 35 healthy adults. Clinical and radiographic follow-up was at 4 months with additional clinical measures recorded at 5-6 months in the 21 subjects who had dental implant placement. Results: Although L-PRF Block trended towards improving maintenance of horizontal and vertical ridge dimensions, clinical and radiographic differences between grafting protocols were not statistically significant. No adverse events were noted. Soft tissue healing after both protocols was favourable. Patient-reported outcomes including average pain and maximum pain intensity were not statistically significant between protocols. Conclusions: Results support our systematic review questioning the adjunctive benefit of hybrid grafts for ARP versus L-PRF alone. STUDY 3. Methods: An in vitro study compared enzymatic degradation of L-PRF and A-PRF membranes. Blood from 8 healthy adults was used to prepare 8 PRF membranes per donor; half were prepared using the L-PRF centrifugation protocol (2700 rpm for 12 minutes; RCF-clot 408g) and the remainder using the Advanced-Platelet Rich Fibrin (A-PRF) protocol (1500 rpm for 14 minutes; RCF-clot 126g) in an IntraSpin centrifuge. Membranes were placed in 2 μg/mL plasmin in Dulbecco’s modified Eagle’s medium (DMEM) and incubated at 37C. DMEM-alone served as control medium. Membrane degradation was assessed at fixed time points (1 d, 3 d, 6 d, 7 d , 10 d, 14 d). Results: L-PRF clots were larger and heavier at baseline. However, the mean percentage weight change (decrease) overall and at each time point was significantly greater for L-PRF membranes versus A-PRF. Mean percentage weight loss was greater for test membranes than controls. Changes in membrane length and width were uncommon and generally minor in nature but more likely for L-PRF. Visual signs of degradation were infrequent (17/64 membranes) and not significant between protocols. Conclusion: PRF preparation protocol appears to influence both baseline characteristics and degradation profile. Plasmin in DMEM appears a suitable medium to compare degradation of PRF membrane types. STUDY 4. Methods: A longitudinal analysis on treatment of peri-implantitis (26 patients, 86 implants) prospectively evaluated medium-to-long term impact of treatment on clinical parameters and implant stability quotient (ISQ) values. Four different treatment modalities were used: 1) Non-surgical (NS) therapy (as monotherapy); 2) NS followed by open-flap debridement (OFD); 3) NS followed by OFD and application of L-PRF only (plugs and/or membranes); and 4) NS therapy followed by OFD and application of a hard tissue regenerative material - with or without L-PRF. Clinical parameters (including probing depth, mucosal recession, bleeding, suppuration, plaque and width of keratinised tissue),and ISQ measurements were recorded at each implant site at baseline and repeated at 6, 12 and 24–36-months following treatment. Results: All 4 treatment modalities improved clinical and radiographic peri-implant parameters, while ISQ scores remained stable. Conclusions: L-PRF treated peri-implantitis sites demonstrated improvement in clinical parameters up to 2-3 years. ISQ cannot be recommended as an adjunctive diagnostic tool to periodontal and radiographic measurements to demonstrate post-operative implant stability following the treatment of peri-implant disease.