Platelet concentrates for surgical topical applications are nowadays often used, but quantification of the long-term growth factor release from these preparations in most cases is impossible. Indeed, in most protocols, platelets are massively activated and there is no significant fibrin matrix to support growth factor release and cell migration. Choukroun's platelet-rich fibrin (PRF), a second generation platelet concentrate, is a leucocyte- and platelet-rich fibrin biomaterial. Here, we show that this dense fibrin membrane releases high quantities of three main growth factors (Transforming Growth Factor b-1 (TGFbeta-1), platelet derived growth factor AB, PDGF-AB; vascular endothelial growth factor, VEGF) and an important coagulation matricellular glycoprotein (thrombospondin-1, TSP-1) during 7 days. Moreover, the comparison between the final released amounts and the initial content of the membrane (after forcible extraction) allows us to consider that the leucocytes trapped in the fibrin matrix continue to produce high quantities of TGFbeta-1 and VEGF during the whole experimental time.

PRF was shown to improve soft tissue generation and limit dimensional changes post-extraction, with little available data to date supporting its use in GBR.

Platelet concentrates for surgical use are tools of regenerative medicine designed for the local release of platelet growth factors into a surgical or wounded site, in order to stimulate tissue healing or regeneration. Leukocyte content and fibrin architecture are 2 key characteristics of all platelet concentrates and allow to classify these technologies in 4 families, but very little is known about the impact of these 2 parameters on the intrinsic biology of these products. In this demonstration, we highlight some outstanding differences in the growth factor and matrix protein release between 2 families of platelet concentrate: Pure Platelet-Rich Plasma (P-PRP, here the Anitua's PRGF - Preparation Rich in Growth Factors - technique) and Leukocyte- and Platelet-Rich Fibrin (L-PRF, here the Choukroun's method). These 2 families are the extreme opposites in terms of fibrin architecture and leukocyte content. The slow release of 3 key growth factors (Transforming Growth Factor β1 (TGFβ1), Platelet-Derived Growth Factor AB (PDGF-AB) and Vascular Endothelial Growth Factor (VEGF)) and matrix proteins (fibronectin, vitronectin and thrombospondin-1) from the L-PRF and P-PRP gel membranes in culture medium is described and discussed. During 7 days, the L-PRF membranes slowly release significantly larger amounts of all these molecules than the P-PRP gel membranes, and the 2 products display different release patterns. In both platelet concentrates, vitronectin is the sole molecule to be released almost completely after only 4 hours, suggesting that this molecule is not trapped in the fibrin matrix and not produced by the leukocytes. Moreover the P-PRP gel membranes completely dissolve in the culture medium after less than 5 days only, while the L-PRF membranes are still intact after 7 days. This simple demonstration shows that the polymerization and final architecture of the fibrin matrix considerably influence the strength and the growth factor trapping/release potential of the membrane. It also suggests that the leukocyte populations have a strong influence on the release of some growth factors, particularly TGFβ1. Finally, the various platelet concentrates present very different biological characteristics, and an accurate definition and characterization of the different families of product is a key issue for a better understanding and comparison of the reported clinical effects of these surgical adjuvants.

Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In periodontology and dentoalveolar surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this first article, we describe and discuss the current published knowledge about the use of PRP and PRF during tooth avulsion or extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal intrabony defects, and regeneration of alveolar ridges using Guided Bone Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a confusing literature and to highlight the underlying universal mechanisms of these products. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the systematic use of L-PRF (Leukocyte- and Platelet- Rich Fibrin) clots and membranes during tooth avulsion, cyst exeresis or the treatment of gingival recessions by root coverage. The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges. In periodontology, this field of research will soon find his golden age by the development of user-friendly platelet concentrate procedures, and the definition of new efficient concepts and clinical protocols.

Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In bone graft, implant and reconstructive surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this second article, we describe and discuss the current published knowledge about the use of PRP and PRF during implant placement (particularly as surface treatment for the stimulation of osseointegration), the treatment of peri-implant bone defects (after peri-implantitis, during implantation in an insufficient bone volume or during immediate post-extraction or post-avulsion implantation), the sinuslift procedures and various complex implant-supported treatments. Other potential applications of the platelet concentrates are also highlighted in maxillofacial reconstructive surgery, for the treatment of patients using bisphosphonates, anticoagulants or with post-tumoral irradiated maxilla. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the use of L-PRF (Leukocyte- and Platelet-Rich Fibrin) clots and membranes during the regeneration of peri-implant bone defects, during the sinus-lift procedure and during complex implant-supported rehabilitations. The use of L-PRF allowed to define a new therapeutic concept called the Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges at the gingival and bone levels. As it is illustrated in this article, the NBR principles allow to push away some technical limits of global implant-supported rehabilitations, particularly when combined with other powerful biotechnological tools: metronidazole solution, adequate bone substitutes and improved implant designs and surfaces (for example here AstraTech Osseospeed or Intra-Lock Ossean implants). As a general conclusion, we are currently living a transition period in the use of PRP and PRF in oral and maxillofacial surgery. PRPs failed to prove strong strategic advantages that could justify their use in daily practice, and the use of most PRP techniques will probably be limited to some very specific applications where satisfactory results have been reached. Only a few simple, inexpensive and efficient techniques such as the L-PRF will continue to develop in oral and maxillofacial surgery in the next years. This natural evolution illustrates that clinical sciences need concrete and practical solutions, and not hypothetical benefits. The history of platelet concentrates in oral and maxillofacial surgery finally demonstrates also how the techniques evolve and sometimes promote the definition of new therapeutical concepts and clinical protocols in the today's era of regenerative medicine.