Joseph Choukroun

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.

Advanced Platelet-Rich Fibrin: A New Concept for Cell-Based Tissue Engineering by Means of Inflammatory Cells

Choukrouns platelet-rich fibrin (PRF) is obtained from blood without adding anticoagulants. In this study, protocols for standard platelet-rich fibrin (S-PRF) (2700 rpm, 12 minutes) and advanced platelet-rich fibrin (A-PRF) (1500 rpm, 14 minutes) were compared to establish by histological cell detection and histomorphometrical measurement of cell distribution the effects of the centrifugal force (speed and time) on the distribution of cells relevant for wound healing and tissue regeneration. Immunohistochemistry for monocytes, T and B -lymphocytes, neutrophilic granulocytes, CD34-positive stem cells, and platelets was performed on clots produced from four different human donors. Platelets were detected throughout the clot in both groups, although in the A-PRF group, more platelets were found in the distal part, away from the buffy coat (BC). T- and B-lymphocytes, stem cells, and monocytes were detected in the surroundings of the BC in both groups. Decreasing the rpm while increasing the centrifugation time in the A-PRF group gave an enhanced presence of neutrophilic granulocytes in the distal part of the clot. In the S-PRF group, neutrophils were found mostly at the red blood cell (RBC)-BC interface. Neutrophilic granulocytes contribute to monocyte differentiation into macrophages. Accordingly, a higher presence of these cells might be able to influence the differentiation of host macrophages and macrophages within the clot after implantation. Thus, A-PRF might influence bone and soft tissue regeneration, especially through the presence of monocytes/macrophages and their growth factors. The relevance and feasibility of this tissue-engineering concept have to be proven through in vivo studies.

L-PRP/L-PRF in Esthetic Plastic Surgery, Regenerative Medicine of the Skin and Chronic Wounds

The use of platelet concentrates for topical use is of particular interest for the promotion of skin wound healing. Fibrin-based surgical adjuvants are indeed widely used in plastic surgery since many years in order to improve scar healing and wound closure. However, the addition of platelets and their associated growth factors opened a new range of possibilities, particularly for the treatment of chronic skin ulcers and other applications of regenerative medicine on the covering tissues. In the 4 families of platelet concentrates available, 2 families were particularly used and tested in this clinical field: L-PRP (Leukocyte- and Platelet-rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). These 2 families have in common the presence of significant concentrations of leukocytes, and these cells are important in the local cleaning and immune regulation of the wound healing process. The main difference between them is the fibrin architecture, and this parameter considerably influences the healing potential and the therapeutical protocol associated to each platelet concentrate technology. In this article, we describe the historical evolutions of these techniques from the fibrin glues to the current L-PRP and L-PRF, and discuss the important functions of the platelet growth factors, the leukocyte content and the fibrin architecture in order to optimize the numerous potential applications of these products in regenerative medicine of the skin. Many outstanding perspectives are appearing in this field and require further research.

Optimized Platelet Rich Fibrin With the Low Speed Concept: Growth Factor Release, Biocompatibility and Cellular Response.

BACKGROUND Over the past decade, use of leukocyte platelet-rich fibrin (L-PRF) has gained tremendous momentum in regenerative dentistry as a low-cost fibrin matrix used for tissue regeneration. This study characterizes how centrifugation speed (G-force) along with centrifugation time influence growth factor release from fibrin clots, as well as the cellular activity of gingival fibroblasts exposed to each PRF matrix. METHODS Standard L-PRF served as a control (2,700 revolutions per minute [rpm]-12 minutes). Two test groups using low-speed (1,300 rpm-14 minutes, termed advanced PRF [A-PRF]) and low-speed + time (1,300 rpm-8 minutes; A-PRF+) were investigated. Each PRF matrix was tested for growth factor release up to 10 days (eight donor samples) as well as biocompatibility and cellular activity. RESULTS The low-speed concept (A-PRF, A-PRF+) demonstrated a significant increase in growth factor release of platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β1, epidermal growth factor, and insulin-like growth factor, with A-PRF+ being highest of all groups. Although all PRF formulations were extremely biocompatible due to their autogenous sources, both A-PRF and A-PRF+ demonstrated significantly higher levels of human fibroblast migration and proliferation compared with L-PRF. Furthermore, gingival fibroblasts cultured with A-PRF+ demonstrated significantly higher messenger RNA (mRNA) levels of PDGF, TGF-β, and collagen1 at either 3 or 7 days. CONCLUSIONS The findings from the present study demonstrate modifications to centrifugation speed and time with the low-speed concept favor an increase in growth factor release from PRF clots. This, in turn, may directly influence tissue regeneration by increasing fibroblast migration, proliferation, and collagen mRNA levels. Future animal and clinical studies are now necessary.

Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review

The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and dentistry.

High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Results

The present preclinical and clinical study assessed the inflammatory response to a high-temperature-treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the material was well integrated into both species without any adverse reactions. Material-induced multinucleated giant cells were observed in both species and were associated with enhanced vascularization. These results revealed the high heat treatment led to an increase in the inflammatory tissue response to the biomaterial, and a combined increase in multinucleated giant cell formation. Further clarification of the differentiation of the multinucleated giant cells toward so-called osteoclast-like cells or foreign-body giant cells is needed to relate these cells to the physicochemical composition of the material.

Controlling systematic perioperative anaerobic contamination during sinus-lift procedures by using metronidazole: an innovative approach.

Background and Objectives:Analysis of tomodensitometric controls following sinus grafts clearly demonstrates a quite systematic lack of homogeneity. Sinus contamination by anaerobic bacteria seems almost unavoidable during bone graft surgery, and this problem may jeopardize the healing process. The aim of this study was to characterize in a systematic way the nonhomogeneities observed at 1, 2, or 3 months postsurgery within allogenous sinus grafts, and to assess the possible influence of a 0.5% sterile solution of metronidazole incorporated in the sinus bone graft. Materials:This clinical study was conducted on 72 patients treated with single or bilateral sinus-lifts: 94 sinus elevations performed with freeze-dried bone allograft (Phœnix, TBF, Mions, France), with (test group) or without (control group) metronidazole. In the test group, each bone graft was hydrated with 2 mL of a 0.5% metronidazole solution, i.e., only 10 mg of metronidazole. All the patients went through a first presurgical computerized tomography (CT)-scan followed by a second scan performed at 1, 2, or 3 months postsurgery (which was used as the preimplant reference scan). For 11 patients, 2 postsurgical CT-scans were performed respectively at 10 days and 2 months. Using an arbitrary gray scale (Arbitrary Densitometric Unit) which functions according to the Hounsfield unit principle, the degree of radiographic homogeneity of the grafts was established. Density scattering provides some information on the homogeneity or nonhomogeneity of the bone graft. Results:The 12 grafts performed without metronidazole show significant nonhomogeneities at 1, 2, or 3 months. Moreover, when a CT-scan is performed during the first postoperative days (at 10 days), the presence of air bubbles in the graft is confirmed. The tomodensitometric aspects of all grafts treated with metronidazole in this series are absolutely identical: they show a high degree of homogeneity. Sixty-three cases (76.8%) are homogeneous, and 19 cases (23.2%) are significantly homogeneous. The time at which the control scan is performed (10 days, 1, 2, or 3 months) does not seem to influence significantly the degree of homogeneity assessed. In the control group, some inflammatory events associated with facial oedema were observed in 25% of the cases. In the test group, no such event was recorded for the 82 sinus-lifts treated with metronidazole. Conclusion:A possible correlation may exist between the occurrence of non homogeneities within the bone grafts and the anaerobic bacterial contamination. The local use of a very small quantity of metronidazole (equivalent to only 1/20 of a common 200 mg oral tablet) could provide more security when performing sinus-lift procedures and an improved quality of the graft. This protocol should not be considered as an antibiotherapy, but only as way to limit the initial contamination of bone graft.

Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization

The present study aimed to analyze the effects of the addition of blood to the phycogenic bone substitute Algipore(®) on the severity of in vivo tissue reaction. Initially, Fourier-transform infrared spectroscopy (FTIR) of the bone substitute was conducted to analyze its chemical composition. The subcutaneous implantation model in Balb/c mice was then applied for up to 30 d to analyze the tissue reactions on the basis of specialized histochemical, immunohistochemical, and histomorphometrical methods. The data of the FTIR analysis showed that the phycogenic bone substitute material is mainly composed of hydroxyapatite with some carbonate content. The in vivo analyses revealed that the addition of blood to Algipore(®) had a major impact on both angiogenesis and vessel maturation. The higher vascularization seemed to be based on significantly higher numbers of multinucleated TRAP-positive cells. However, mostly macrophages and a relatively low number of multinucleated giant cells were involved in the tissue reaction to Algipore(®). The presented data show that the addition of blood to a bone substitute impacts the tissue reaction to it. In particular, the immune response and the vascularization were influenced, and these are believed to have a major impact on the regenerative potential of the process of bone tissue regeneration.

Effects of an injectable platelet-rich fibrin on osteoblast behavior and bone tissue formation in comparison to platelet-rich plasma

Abstract Platelet-rich plasma (PRP) has been utilized for many years as a regenerative agent capable of inducing vascularization of various tissues using blood-derived growth factors. Despite this, drawbacks mostly related to the additional use of anti-coagulants found in PRP have been shown to inhibit the wound healing process. For these reasons, a novel platelet concentrate has recently been developed with no additives by utilizing lower centrifugation speeds. The purpose of this study was therefore to investigate osteoblast behavior of this novel therapy (injectable-platelet-rich fibrin; i-PRF, 100% natural with no additives) when compared to traditional PRP. Human primary osteoblasts were cultured with either i-PRF or PRP and compared to control tissue culture plastic. A live/dead assay, migration assay as well as a cell adhesion/proliferation assay were investigated. Furthermore, osteoblast differentiation was assessed by alkaline phosphatase (ALP), alizarin red and osteocalcin staining, as well as real-time PCR for genes encoding Runx2, ALP, collagen1 and osteocalcin. The results showed that all cells had high survival rates throughout the entire study period irrespective of culture-conditions. While PRP induced a significant 2-fold increase in osteoblast migration, i-PRF demonstrated a 3-fold increase in migration when compared to control tissue-culture plastic and PRP. While no differences were observed for cell attachment, i-PRF induced a significantly higher proliferation rate at three and five days when compared to PRP. Furthermore, i-PRF induced significantly greater ALP staining at 7 days and alizarin red staining at 14 days. A significant increase in mRNA levels of ALP, Runx2 and osteocalcin, as well as immunofluorescent staining of osteocalcin was also observed in the i-PRF group when compared to PRP. In conclusion, the results from the present study favored the use of the naturally-formulated i-PRF when compared to traditional PRP with anti-coagulants. Further investigation into the direct role of fibrin and leukocytes contained within i-PRF are therefore warranted to better elucidate their positive role in i-PRF on tissue wound healing.

Porcine Dermis-Derived Collagen Membranes Induce Implantation Bed Vascularization Via Multinucleated Giant Cells: A Physiological Reaction?

In this study, the tissue reactions to 2 new porcine dermis-derived collagen membranes of different thickness were analyzed. The thicker material (Mucoderm) contained sporadically preexisting vessel skeletons and fatty islands. The thinner membrane (Collprotect) had a bilayered structure (porous and occlusive side) without any preexisting structures. These materials were implanted subcutaneously in mice to analyze the tissue reactions and potential transmembranous vascularization. Histological and histomorphometrical methodologies were performed at 4 time points (3, 10, 15, and 30 days). Both materials permitted stepwise connective tissue ingrowth into their central regions. In the Mucoderm matrix, newly built microvessels were found within the preexisting vessel and fatty island skeletons after 30 days. This vascularization was independent of the inflammation-related vascularization on both material surfaces. The Collprotect membrane underwent material disintegration by connective tissue strands in combination with vessels and multinucleated giant cells. The histomorphometric analyses revealed that the thickness of Mucoderm did not decrease significantly, while an initial significant decrease of membrane thickness in the case of Collprotect was found at day 15. The present results demonstrate that the 2 analyzed collagen membranes underwent a multinucleated giant cell-associated vascularization. Neither of the materials underwent transmembraneous vascularization. The microvessels were found within the preexisting vessel and fatty island skeletons. Additional long-term studies and clinical studies are necessary to determine how the observed foreign body giant cells affect tissue regeneration.