Platelet concentrates for topical and infiltrative use - commonly termed Platetet-Rich Plasma (PRP) or Platelet-Rich Fibrin (PRF) - are used or tested as surgical adjuvants or regenerative medicine preparations in most medical fields, particularly in sports medicine and orthopaedic surgery. Even if these products offer interesting therapeutic perspectives, their clinical relevance is largely debated, as the literature on the topic is often confused and contradictory. The long history of these products was always associated with confusions, mostly related to the lack of consensual terminology, characterization and classification of the many products that were tested in the last 40 years. The current consensus is based on a simple classification system dividing the many products in 4 main families, based on their fibrin architecture and cell content: Pure Platelet-Rich Plasma (P-PRP), such as the PRGF-Endoret technique; Leukocyte- and Platelet-Rich Plasma (LPRP), such as Biomet GPS system; Pure Platelet-Rich Fibrin (P-PRF), such as Fibrinet; Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Intra-Spin L-PRF. The 4 main families of products present different biological signatures and mechanisms, and obvious differences for clinical applications. This classification serves as a basis for further investigations of the effects of these products. Perspectives of evolutions of this classification and terminology are also discussed, particularly concerning the impact of the cell content, preservation and activation on these products in sports medicine and orthopaedics.

L-PRF (leukocyte- and platelet-rich fibrin) is one of the four families of platelet concentrates for surgical use and is widely used in oral and maxillofacial regenerative therapies. The first objective of this article was to evaluate the mechanical vibrations appearing during centrifugation in four models of commercially available table-top centrifuges used to produce L-PRF and the impact of the centrifuge characteristics on the cell and fibrin architecture of a L-PRF clot and membrane. The second objective of this article was to evaluate how changing some parameters of the L-PRF protocol may influence its biological signature, independently from the characteristics of the centrifuge. In the first part, four different commercially available centrifuges were used to produce L-PRF, following the original L-PRF production method (glass-coated plastic tubes, 400 g force, 12 minutes). The tested systems were the original L-PRF centrifuge (Intra-Spin, Intra-Lock, the only CE and FDA cleared system for the preparation of L-PRF) and three other laboratory centrifuges (not CE/FDA cleared for L-PRF): A-PRF 12 (Advanced PRF, Process), LW-UPD8 (LW Scientific) and Salvin 1310 (Salvin Dental). Each centrifuge was opened for inspection, two accelerometers were installed (one radial, one vertical), and data were collected with a spectrum analyzer in two configurations (full-load or half load). All clots and membranes were collected into a sterile surgical box (Xpression kit, Intra-Lock). The exact macroscopic (weights, sizes) and microscopic (photonic and scanning electron microscopy SEM) characteristics of the L-PRF produced with these four different machines were evaluated. In the second part, venous blood was taken in two groups, respectively, Intra-Spin 9 ml glass-coated plastic tubes (Intra-Lock) and A-PRF 10 ml glass tubes (Process). Tubes were immediately centrifuged at 2700 rpm (around 400 g) during 12 minutes to produce L-PRF or at 1500 rpm during 14 minutes to produce A-PRF. All centrifugations were done using the original L-PRF centrifuge (Intra-Spin), as recommended by the two manufacturers. Half of the membranes were placed individually in culture media and transferred in a new tube at seven experimental times (up to 7 days). The releases of transforming growth factor β-1 (TGFβ-1), platelet derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) were quantified using ELISA kits at these seven experimental times. The remaining membranes were used to evaluate the initial quantity of growth factors of the L-PRF and A-PRF membranes, through forcible extraction. Very significant differences in the level of vibrations at each rotational speed were observed between the four tested centrifuges. The original L-PRF centrifuge (Intra-Spin) was by far the most stable machine in all configurations and always remained under the threshold of resonance, unlike the three other tested machines. At the classical speed of production of L-PRF, the level of undesirable vibrations on the original centrifuge was between 4.5 and 6 times lower than with other centrifuges. Intra-Spin showed the lowest temperature of the tubes. A-PRF and Salvin were both associated with a significant increase in temperature in the tube. Intra-Spin produced the heaviest clot and quantity of exudate among the four techniques. A-PRF and LW produced much lighter, shorter and narrower clots and membranes than the two other centrifuges. Light microscopy analysis showed relatively similar features for all L-PRF types (concentration of cell bodies in the first half). However, SEM illustrated considerable differences between samples. The original Intra-Spin L-PRF showed a strongly polymerized thick fibrin matrix and all cells appeared alive with a normal shape, including the textured surface aspect of activated lymphocytes. The A-PRF, Salvin and LW PRF-like membranes presented a lightly polymerized slim fibrin gel and most of the visible cell bodies appeared destroyed (squashed or shrunk). In the second part of this study, the slow release of the three tested growth factors from original L-PRF membranes was significantly stronger (more than twice stronger, p<0.001) at all experimental times than the release from A-PRF membranes. No trace of BMP2 could be detected in the A-PRF. A slow release of BMP2 was detected during at least 7 days in the original L-PRF. Moreover, the original L-PRF clots and membranes (produced with 9 mL blood) were always significantly larger than the A-PRF (produced with 10 mL blood). The A-PRF membranes dissolved in vitro after less than 3 days, while the L-PRF membrane remained in good shape during at least 7 days. Each centrifuge has its clear own profile of vibrations depending on the rotational speed, and the centrifuge characteristics are directly impacting the architecture and cell content of a L-PRF clot. This result may reveal a considerable flaw in all the PRP/PRF literature, as this parameter was never considered. The original L-PRF clot (Intra-Spin) presented very specific characteristics, which appeared distorted when using centrifuges with a higher vibration level. A-PRF, LW and Salvin centrifuges produced PRF-like materials with a damaged and almost destroyed cell population through the standard protocol, and it is therefore impossible to classify these products in the L-PRF family. Moreover, when using the same centrifuge, the original L-PRF protocol allowed producing larger clots/membranes and a more intense release of growth factors (biological signature at least twice stronger) than the modified A-PRF protocol. Both protocols are therefore significantly different, and the clinical and experimental results from the original L-PRF shall not be extrapolated to the A-PRF. Finally, the comparison between the total released amounts and the initial content of the membrane (after forcible extraction) highlighted that the leukocytes...

Aim: To analyse the regenerative potential of leucocyte‐ and platelet‐rich fibrin (L‐PRF) during periodontal surgery.Materials and Methods: An electronic and hand search were conducted in three databases. Only randomized clinical trials were selected and no follow‐up limitation was applied. Pocket depth (PD), clinical attachment level (CAL), bone fill, keratinized tissue width (KTW), recession reduction and root coverage (%) were considered as outcome. When possible, meta‐analysis was performed.Results: Twenty‐four articles fulfilled the inclusion and exclusion criteria. Three subgroups were created: intra‐bony defects (IBDs), furcation defects and periodontal plastic surgery. Meta‐analysis was performed in all the subgroups. Significant PD reduction (1.1 ± 0.5 mm, p < 0.001), CAL gain (1.2 ± 0.6 mm, p < 0.001) and bone fill (1.7 ± 0.7 mm, p < 0.001) were found when comparing L‐PRF to open flap debridement (OFD) in IBDs. For furcation defects, significant PD reduction (1.9 ± 1.5 mm, p = 0.01), CAL gain (1.3 ± 0.4 mm, p < 0.001) and bone fill (1.5 ± 0.3 mm, p < 0.001) were reported when comparing L‐PRF to OFD. When L‐PRF was compared to a connective tissue graft, similar outcomes were recorded for PD reduction (0.2 ± 0.3 mm, p > 0.05), CAL gain (0.2 ± 0.5 mm, p > 0.05), KTW (0.3 ± 0.4 mm, p > 0.05) and recession reduction (0.2 ± 0.3 mm, p > 0.05).Conclusions: L‐PRF enhances periodontal wound healing.

Aim: To analyse the effect of leucocyte‐ and platelet‐rich fibrin (L‐PRF) on bone regeneration procedures and osseointegration.Materials and Methods: An electronic and hand search was conducted in three databases (MEDLINE, EMBASE and Cochrane). Only randomized clinical trials, written in English where L‐PRF was applied in bone regeneration and implant procedures, were selected. No follow‐up restrictions were applied.Results: A total of 14 articles were included and processed. Three subgroups were created depending on the application: sinus floor elevation (SFE), alveolar ridge preservation and implant therapy. In SFE, for a lateral window as well as for the trans‐alveolar technique, histologically faster bone healing was reported when L‐PRF was added to most common xenografts. L‐PRF alone improved the preservation of the alveolar width, resulting in less buccal bone resorption compared to natural healing. In implant therapy, better implant stability over time and less marginal bone loss were observed when L‐PRF was applied. Meta‐analyses could not be performed due to the heterogeneity of the data.Conclusions: Despite the lack of strong evidence found in this systematic review, L‐PRF might have a positive effect on bone regeneration and osseointegration.