Gilberto Sammartino

Implant success, survival, and failure: the International Congress of Oral Implantologists (ICOI) Pisa Consensus Conference.

The primary function of a dental implant is to act as an abutment for a prosthetic device, similar to a natural tooth root and crown. Any success criteria, therefore, must include first and foremost support of a functional prosthesis. In addition, although clinical criteria for prosthetic success are beyond the scope of this article, patient satisfaction with the esthetic appearance of the implant restoration is necessary in clinical practice. The restoring dentist designs and fabricates a prosthesis similar to one supported by a tooth, and as such often evaluates and treats the dental implant similarly to a natural tooth. Yet, fundamental differences in the support system between these entities should be recognized. The purpose of this article is to use a few indices developed for natural teeth as an index that is specific for endosteal root-form implants. This article is also intended to update and upgrade what is purported to be implant success, implant survival, and implant failure. The Health Scale presented in this article was developed and accepted by the International Congress of Oral Implantologists Consensus Conference for Implant Success in Pisa, Italy, October 2007.

Slow release of growth factors and thrombospondin-1 in Choukroun's platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies

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. Choukrouns 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 (TGFβ-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 TGFβ-1 and VEGF during the whole experimental time.

Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF).

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 Anituas PRGF - Preparation Rich in Growth Factors - technique) and Leukocyte- and Platelet-Rich Fibrin (L-PRF, here the Choukrouns 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.

In Search of a Consensus Terminology in the Field of Platelet Concentrates for Surgical Use: Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), Fibrin Gel Polymerization and Leukocytes

In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anituas PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukrouns PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

Current Knowledge and Perspectives for the Use of Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in Oral and Maxillofacial Surgery Part 2: Bone Graft, Implant and Reconstructive Surgery

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 todays era of regenerative medicine.

Current Knowledge and Perspectives for the Use of Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in Oral and Maxillofacial Surgery Part 1: Periodontal and Dentoalveolar Surgery

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.

Prevention of postoperative bleeding in anticoagulated patients undergoing oral surgery: use of platelet-rich plasma gel

PURPOSE This study evaluated the effectiveness of a protocol using platelet-rich plasma (PRP) to prevent bleeding after dental extraction in patients treated with anticoagulant oral therapy. MATERIALS AND METHODS Forty patients with mechanical heart-value replacement who were treated with anticoagulant oral therapy were selected for the study. Each patient was treated with PRP gel placed into residual alveolar bone after extraction without heparin administration after suspension of oral anticoagulant drugs (36 hours). RESULTS Only 2 patients reported hemorrhagic complications (5%). Sixteen patients (40%) had mild bleeding that was easy to control with hemostatic topical agents; this mild bleeding terminated completely 1 to 3 days after the surgical procedures. The remaining 22 patients (55%) presented with adequate hemostasis. CONCLUSIONS Oral surgery in heart surgical patients under oral anticoagulant therapy may be facilitated with PRP gel. Its use is an advanced and safe procedure. This biological and therapeutical improvement can simplify systemic management and help avoid hemorrhagic and/or thromboembolic complications.

The relevance of Choukroun's platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part I: a new grafting protocol.

Extensive bone grafting remains a delicate procedure, because of the slow and difficult integration of the grafted material into the physiological architecture. The recent use of platelet concentrates aims to improve this process of integration by accelerating bone and mucosal healing. Choukroun’s platelet-rich fibrin (PRF) is a healing biomaterial that concentrates in a single autologous fibrin membrane, most platelets, leukocytes, and cytokines from a 10 mL blood harvest, without artificial biochemical modification (no anticoagulant, no bovine thrombin). Whether used as a membrane or as fragments, PRF allows a significant postoperative protection of the surgical site and seems to accelerate the integration and remodeling of the grafted biomaterial. These properties are particularly helpful for vestibular bone grafting on the alveolar ridges. Moreover, it provides a very high quality of gingival maturation.A small quantity of a 0.5% metronidazole solution (10 mg) can also be used to provide an efficient protection of the bone graft against unavoidable anaerobic bacterial contamination. This article describes a new technique of total maxillary preimplant bone grafting using allograft, Choukroun’s PRF membranes and metronidazole. This first part focused on the preimplant reconstructive treatment using allogeneic bone granules. PRF membranes are particularly helpful to protect the surgical site and foster soft tissue healing. This fibrin biomaterial represents a new opportunity to improve both the maturation of bone grafts and the final esthetic result of the peri-implant soft tissue.

The Relevance of Choukrounʼs Platelet-Rich Fibrin and Metronidazole During Complex Maxillary Rehabilitations Using Bone Allograft. Part II: Implant Surgery, Prosthodontics, and Survival

Extensive bone grafting remains a delicate procedure, due to the slow and difficult integration of the grafted material into the physiological architecture. The recent use of platelet concentrates aims to improve this process of integration by accelerating bone and mucosal healing. Choukrouns platelet-rich fibrin (PRF) is a healing biomaterial that concentrates in a single autologous fibrin membrane, most platelets, leukocytes, and cytokines from a 10-mL blood harvest, without artificial biochemical modification (no anticoagulant, no bovine thrombin). In this second part, we describe the implant and prosthetic phases of a complex maxillary rehabilitation, after preimplant bone grafting using allograft, Choukrouns PRF membranes, and metronidazole. Twenty patients were treated using this new technique and followed up during 2.1 years (1–5 years). Finally, 184 dental implants were placed, including 54 classical screw implants (3I, Palm Beach Gardens, FL) and 130 implants with microthreaded collar (46 from AstraTech, Mölndal, Sweden; 84 from Intra-Lock, Boca Raton, FL). No implant or graft was lost in this case series, confirming the validity of this reconstructive protocol. However, the number of implants used per maxillary rehabilitation was always higher with simple screw implants than with microthreaded implants, the latter presenting a stronger initial implant stability. Finally, during complex implant rehabilitations, PRF membranes are particularly helpful for periosteum healing and maturation. The thick peri-implant gingiva is related to several healing phases on a PRF membrane layer and could explain the low marginal bone loss observed in this series. Microthreaded collar and platform-switching concept even improved this result. Multiple healing on PRF membranes seems a new opportunity to improve the final esthetic result.

Shedding light in the controversial terminology for platelet-rich products: Platelet-rich plasma (PRP), platelet-rich fibrin (PRF), platelet-leukocyte gel (PLG), preparation rich in growth factors (PRGF), classification and commercialism

A recent series of letters were published in JBMR-A about platelet concentrates for surgical use, where both terminology and content of these materials were hotly debated. The definition and classification of the platelet concentrate products are indeed very important issues, as many misunderstandings are widely spread in the large literature on this topic. These techniques were initially gathered under the name ‘‘platelet-rich plasma (PRP),’’ in reference to the generic term used in transfusion hematology, but this name is too general for the qualification of the many products developed now. In the first letter, Everts et al. insisted on the presence of leukocytes in most platelet preparations for surgical use. These authors explained a very important truth that many PRPs were in fact leukocyteand platelet-rich plasmas (LPRPs), and that the presence of leukocytes in these surgical adjuvants may be highly beneficial. They thus, introduced the term of ‘‘platelet-leukocyte–rich plasma (P-LRP).’’ Moreover, they pointed out that the two activation forms of the product (liquid platelet suspension or gelified fibrin-platelet clot) have different characteristics, and that the concentrates activated with a fibrinogen-cleaving agent (thrombin, batroxobin) should be named in fact as ‘‘platelet-leukocyte gels (PLG).’’ In this letter, these authors resumed the clarification process of the platelet concentrate definitions started in 2006. However, their proposals for terminology were not complete and have been improved and systematized in the recent publication of a wide classification system for these products. The first concern is that all PRPs do not contain leukocytes. Many PRPs obtained from cell separator units or from the Anitua’s preparation rich in growth factors (PRGF) subfamilies do not contain leukocytes and were classified as pure PRP (P-PRP). On the contrary, PRPs containing leukocytes were classified as L-PRP: this acronym seems obviously more logical and reader-friendly than P-LRP, but we agree that a consensus should be found to solve this issue once for good. The second issue is related to the gel form terminology. ‘‘Platelet gel’’ and ‘‘PLG’’ are too general terms. Indeed, products with a high-density fibrin network also exist and were classified as ‘‘platelet-rich fibrin (PRF),’’ some with leukocytes [leukocyteand platelet-rich fibrin (L-PRF)] and some without leukocytes [pure platelet-rich fibrin (P-PRF)]. All these PRFs are only available in the form of a very dense fibrin gel, while PRP gels are never so strong and dense. We thus believe that the activated form of P-PRP or L-PRP should simply be named ‘‘P-PRP gel’’ and ‘‘L-PRP gel’’ to differentiate them from the products of the PRF families. In the second letter, Anitua et al. agreed that the recent development of many different techniques with various platelet and leukocyte contents led to a confusing jungle of terms and products. This notion of ‘‘jungle of platelet concentrates’’ was already pointed out some years ago, when the main confusion between PRPs and the first PRF appeared. Anitua et al. were right in their call for the definition of a relevant terminology but their approach was unfortunately partisan. First, Anitua et al. claimed that leukocytes should be avoided in platelet concentrates for surgical use, to avoid the proinflammatory effects of the proteases and acid hydrolases contained in white blood cells, particularly when injected in tendons. However, these authors did not justify their statement with scientific evidence; to sustain their claim, Anitua et al. cited Ref. 9 describing very positive anabolic effects on tendon cells obtained with a PRP, . . . but the PRP described in this study was in fact a leukocyte-rich PRP. This question of the leukocyte content within platelet concentrates for surgical use is in fact an old debate. There is however actually no proof that the leukocytes within these surgical preparations might have undesirable side effects. On the contrary, several studies showed that L-PRPs have antimicrobial effects, but no undesirable inflammatory reactions have been observed with L-PRPs