Publications by authors named "Joseph Choukroun"

36 Publications

Injectable platelet-rich fibrin and microneedling for gingival augmentation in thin periodontal phenotype: A randomized controlled clinical trial.

J Clin Periodontol 2020 04 11;47(4):489-499. Epub 2020 Feb 11.

Department of Periodontology, Faculty of Dentistry, Bezmialem Vakif University, Istanbul, Turkey.

Aim: The aim of this present study was to evaluate the effect of gingival thickness (GT) and keratinized tissue width (KTW) using injectable platelet-rich fibrin (i-PRF) alone and with microneedling (MN) in individuals with thin periodontal phenotypes.

Materials And Methods: In this split-mouth study, 33 systemically healthy patients with thin periodontal phenotypes were randomly treated with MN + i-PRF and i-PRF. I-PRF was injected on one side, and MN + i-PRF was performed on the other side of the same patient at 4 sessions with 10-day intervals. Clinical periodontal measurements, GT and KTW were assessed before the treatment and every month for six months after the final injection.

Results: After the evaluation of GT between the groups, a statistically significant difference was found in MN + i-PRF group at the sixth month. In the intra-group comparisons, a statistically significant increase in GT was observed within both i-PRF [from 0.43 mm ± 0.14 to 0.62 mm ± 0.11 (p < .001)] and MN + i-PRF [from 0.4 mm ± 0.14 to 0.66 mm ± 0.12 (p < .001)] groups at the sixth month.

Conclusions: In individuals with thin periodontal phenotypes, standalone i-PRF and i-PRF with MN may have an influence in increasing GT. The results suggest that application of i-PRF and MN may be a first step of non-surgical method for increasing gingival thickness.
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http://dx.doi.org/10.1111/jcpe.13247DOI Listing
April 2020

Biologization of Collagen-Based Biomaterials Using Liquid-Platelet-Rich Fibrin: New Insights into Clinically Applicable Tissue Engineering.

Materials (Basel) 2019 Dec 2;12(23). Epub 2019 Dec 2.

Department for Oral, Cranio-Maxillofacial, and Facial Plastic Surgery, Frankfurt Orofacial Regenerative Medicine (FORM) Lab, University Hospital Frankfurt Goethe University, 60590 Frankfurt am Main, Germany.

Platelet-rich fibrin (PRF) is a blood concentrate derived from venous blood that is processed without anticoagulants by a one-step centrifugation process. This three-dimensional scaffold contains inflammatory cells and plasma proteins entrapped in a fibrin matrix. Liquid-PRF was developed based on the previously described low-speed centrifuge concept (LSCC), which allowed the introduction of a liquid-PRF formulation of fibrinogen and thrombin prior to its conversion to fibrin. Liquid-PRF was introduced to meet the clinical demand for combination with biomaterials in a clinically applicable and easy-to-use way. The aim of the present study was to evaluate, ex vivo, the interaction of the liquid-PRF constituents with five different collagen biomaterials by histological analyses. The results first demonstrated that large variability existed between the biomaterials investigated. Liquid-PRF was able to completely invade Mucograft (MG; Geistlich Biomaterials, Wolhusen, Switzerland) and to partly invade Bio-Gide (BG; Geistlich Biomaterials, Wolhusen, Switzerland) and Mucoderm (MD; Botiss Biomaterials, Berlin, Germany), and Collprotect (CP; Botiss Biomaterials, Berlin, Germany) showed only a superficial interaction. The BEGO collagen membrane (BCM; BEGO Implant Systems) appeared to be completely free of liquid-PRF. These results were confirmed by the different cellular penetration and liquid-PRF absorption coefficient (PAC) values of the evaluated membranes. The present study demonstrates a system for loading biomaterials with a complex autologous cell system (liquid-PRF) in a relatively short period of time and in a clinically relevant manner. The combination of biomaterials with liquid-PRF may be clinically utilized to enhance the bioactivity of collagen-based biomaterials and may act as a biomaterial-based growth factor delivery system.
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http://dx.doi.org/10.3390/ma12233993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926831PMC
December 2019

Reply from authors: RE: Optimized platelet-rich fibrin with the low-speed concept: Growth factor release, biocompatibility, and cellular response: Necessity for standardization of relative centrifugal force values in studies on platelet-rich fibrin.

J Periodontol 2019 02 28;90(2):122-125. Epub 2018 Dec 28.

FORM, Frankfurt Oral Regenerative Medicine, Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

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http://dx.doi.org/10.1002/JPER.18-0329DOI Listing
February 2019

A Proof of the Low Speed Centrifugation Concept in Rodents: New Perspectives for In Vivo Research.

Tissue Eng Part C Methods 2018 11;24(11):659-670

2 Department of Molecular and Cell Biology, Institute of Biology, Fluminense Federal University , Niterói, Brazil .

Impact Statement: This study evaluated for the first time the composition and bioactivity of platelet-rich fibrin (PRF) produced from small animal blood by reducing the initial blood volume needed for the preparation of PRF from 10 to 3 mL. The results showed that different preparation protocols of PRF produced using 3 mL of animal blood exhibit the same composition, properties, and bioactivity as PRF prepared using 10 mL human blood.
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http://dx.doi.org/10.1089/ten.TEC.2018.0236DOI Listing
November 2018

Liquid platelet-rich fibrin injections as a treatment adjunct for painful temporomandibular joints: preliminary results.

Cranio 2020 Sep 20;38(5):292-304. Epub 2018 Sep 20.

Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery. FORM (Frankfurt Orofacial Regenerative Medicine) Lab, University Hospital Frankfurt Goethe University , Frankfurt am Main, Germany.

Objective: To evaluate the clinical benefits of liquid platelet-rich fibrin (PRF) in patients with temporomandibular joint (TMJ) pain and dysfunction.

Methods: Forty-eight TMJs in 37 patients with painful internal derangement (ID) (Wilkes' I-V) were included. Patients were injected with 1.5-2cc of PRF within the superior joint space at 2-week intervals. Pain and subjective dysfunction were recorded using a visual analog scale. Statistical analyses were done using the ANOVA test.

Results: Thirty-three of 48 TMJs (69%) showed significant reduction in pain at 8 weeks, and at 3, 6, and 12 months (Responders). Fifteen of 48 TMJs (31%) did not improve (Non-responders). The best Responders to liquid PRF injections were ID stages Wilkes' IV (78.5%) and V (100%), compared to Wilkes' I (0%), II (47%), and III (33%). A non-significant, but notable decrease in dysfunction was found.

Conclusion: Preliminary findings support that liquid PRF exhibits long-term analgesic effects in most patients with painful TMJ ID.
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http://dx.doi.org/10.1080/08869634.2018.1516183DOI Listing
September 2020

Fifteen Years of Platelet Rich Fibrin in Dentistry and Oromaxillofacial Surgery: How High is the Level of Scientific Evidence?

J Oral Implantol 2018 Dec 5;44(6):471-492. Epub 2018 Jun 5.

1   Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Frankfurt Orofacial Regenerative Medicine (FORM) Lab, University Hospital Frankfurt Goethe University, Frankfurt, Germany.

Platelet-rich fibrin is a blood concentrate system used for soft tissue and bone tissue regeneration. In the last decade, platelet rich fibrin (PRF) has been widely used in different indication fields, particularly in oral and maxillofacial surgery. This review investigates the level of scientific evidence of published articles related to the use of PRF for bone and soft tissue regeneration in dentistry and maxillofacial surgery. An electronic literature research using the biomedical search engine "National Library of Medicine" (PubMed-MEDLINE) was performed in May 2017. A total of 392 articles were found, 72 of which were classified for each indication field. When comparing PRF with biomaterials vs biomaterial alone in sinus lift (5 studies; IIa), no statistically significant differences were detected. Socket preservation and ridge augmentation using PRF significantly enhanced new bone formation compared to healing without PRF (7 studies Ib, IIa, IIb). Reepithelialization and bone regeneration was achieved in 96 of 101 patients diagnosed with medication-related osteonecrosis of the jaw (5 studies, III). In periodontology, PRF alone (6 studies; Ib, IIa, IIb) or its combination with biomaterials (6 studies; Ib, IIa, IIb) significantly improved the pocket depth and attachment loss compared to a treatment without PRF. Over 70% of the patients were part of studies with a high level of scientific evidence (randomized and controlled prospective studies). This published evidence (38 articles), with a high scientific level, showed that PRF is a beneficial tool that significantly improves bone and soft tissue regeneration. However, the clinical community requires a standardization of PRF protocols to further examine the benefit of PRF in bone and soft tissue regeneration in reproducible studies, with a higher scientific level of evidence.
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http://dx.doi.org/10.1563/aaid-joi-D-17-00179DOI Listing
December 2018

Telomere length and genetic variations affecting telomere length as biomarkers for facial regeneration with platelet-rich fibrin based on the low-speed centrifugation concept.

J Cosmet Dermatol 2019 Feb 15;18(1):408-413. Epub 2018 May 15.

Medical School, University of Crete, Heraklion, Greece.

Background: Platelet-Rich Fibrin (PRF), a fibrin matrix produced by single blood centrifugation that contains leukocytes, platelets, and growth factors, is increasingly being utilized for facial regeneration purposes. However, our understanding of the involved pathophysiological mechanisms affecting regeneration is limited and current protocols require better optimization. Biomarkers that are related to skin aging such as telomere length (TL) have been proposed as a mean to analyze patients' stratification.

Objective: Our aim is to study whether the outcomes of a facial regeneration protocol performed with PRF are related to TL and genetic variations affecting TL. This can aid in the standardization of a surgical aesthetic protocol.

Patients And Methods: In all, 41 patients treated with PRF produced with the low-speed centrifugation concept were included in this observational study. The correlation between TL and genetic variations were assessed versus treatment outcomes, namely the number of sessions and aesthetic results utilizing the FACE-Q skin satisfaction questionnaire.

Results: In all, 39 of the 41 patients completed the treatment. TL correlated with the initial responses to FACE-Q (ρ = .33, P = .05). Genetic variations affecting TL was related to the change of FACE-Q (ρ = .35, P = .034) as well as to the number of treatment sessions (ρ = .38, P = .019).

Conclusions: Telomere length (TL) was related to patient perceived facial skin appearance. In addition, genetic variations affecting TL were related to the final outcomes (number of sessions and improvements of FACE-Q results) and may be a useful biomarker for future regenerative procedures performed with PRF for facial regeneration.
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http://dx.doi.org/10.1111/jocd.12666DOI Listing
February 2019

A low-speed centrifugation concept leads to cell accumulation and vascularization of solid platelet-rich fibrin: an experimental study in vivo.

Platelets 2019 6;30(3):329-340. Epub 2018 Mar 6.

a Frankfurt Orofacial Regenerative Medicine (FORM) -Lab, Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery , University Hospital Frankfurt Goethe University , Frankfurt am Main , Germany.

Platelet-rich fibrin (PRF) is generated from the patients' own venous blood by a single centrifugation step without the additional use of anticoagulants. Based on the previously described LSCC (low-speed centrifugation concept), our group showed that modification of the centrifugation setting, that is, reducing the relative centrifugal force (RCF) and mildly increasing the centrifugation time, resulted in modified solid and liquid PRF-matrices with increased number of platelets, leukocytes, and growth factors' concentrations. The aim of this study was to determine whether RCF reduction might also result in different tissue reactions toward the two PRF-based matrices, especially vascularization and cell distribution in vivo. Two centrifugation protocols (PRF-high [719 g] and PRF-medium [222 g]) were compared in a subcutaneous implantation model of SCID mice at 5 and 10 days. Histological and histomorphometrical analyses were performed to quantify lymphocyte, neutrophil, human macrophage, and monocyte populations. CD31 was used to detect newly formed vessels, while all human cells were detected by using human vimentin as a pan-cellular marker. The results demonstrated that PRF-high elicited a dense and stable fibrin structure and prevented cellular penetration of the host tissue. By contrast, PRF-medium was more porous, had a significantly higher in vivo vascularization rate, and included significantly more human cells, especially at day 10, compared to PRF-high. These findings highlight the possibility of modifying the structure and composition of PRF matrices and thus selectively altering their regenerative potential in vivo. Clinical studies now must evaluate the different PRF matrices for bone and soft-tissue regeneration to validate possible benefits using personalized preparation protocols.
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http://dx.doi.org/10.1080/09537104.2018.1445835DOI Listing
April 2019

Soft-Tissue Grafting Techniques Associated With Immediate Implant Placement.

Compend Contin Educ Dent 2018 Feb;39(2):e1-e4

Adjunct Faculty, Department of Periodontics, Nova Southeastern University, Fort Lauderdale, Florida.

Immediate implant placement often presents challenges in terms of predictably obtaining soft-tissue coverage over the implant site. While delayed implant placement offers the ability for soft tissues to grow and invade the extraction socket making their attachment around implants more predictable, immediate implant placement poses a significant risk of bacterial invasion towards the implant surface as a result of insignificant soft-tissue volume. Soft-tissue grafting techniques have often been proposed for use during immediate implant placement to augment soft-tissue deficiencies, including the use of either palatal connective tissue grafts (CTGs) or collagen-derived scaffolds. However, both of these approaches have significant drawbacks in that CTGs are harvested with high patient morbidity and collagen scaffolds remain avascular and acelluar posing a risk of infection/implant contamination. More recently, platelet-rich fibrin (PRF) has been proposed as an economical and biological means to speed soft-tissue wound healing. In combination with immediate implant placement, PRF offers an easily procurable low-cost regenerative modality that offers an efficient way to improve soft-tissue attachment around implants. Furthermore, the supra-physiological concentration of defense-fighting leukocytes in PRF, combined with a dense fibrin meshwork, is known to prevent early bacterial contamination of implant surfaces, and the biological concentrations of autologous growth factors in PRF is known to increase tissue regeneration. This article discusses soft-tissue grafting techniques associated with immediate implant placement, presents several cases demonstrating the use of PRF in routine immediate implant placement, and further discusses the biological and economic advantages of PRF for the management of soft-tissue grafting during immediate implant placement.
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February 2018

Injectable-platelet rich fibrin using the low speed centrifugation concept improves cartilage regeneration when compared to platelet-rich plasma.

Platelets 2019 14;30(2):213-221. Epub 2017 Dec 14.

e Department of Periodontology, School of Dental Medicine , University of Bern , Bern, Switzerland.

The aim of the present study was to evaluate the effect of injectable platelet-rich fibrin (i-PRF) on cultivated chondrocytes and osteochondral regeneration in critical-sized osteochondral defect of the rabbit's knee in comparison to autologous platelet-rich plasma (PRP). Chondrocytes were first investigated for their ability to proliferate and differentiate in response to PRP and i-PRF. Thereafter, full-thickness critical-sized osteochondral defects 5 mm in diameter and 5 mm in depth were created in the knee joint of 12 adult female New Zealand White rabbits. Defects were regenerated with either PRP or i-PRF and compared to control. Animals were sacrificed at 4 and 12 weeks postoperatively and evaluated histologically by macroscopic and microscopic examination for cartilage regeneration. i-PRF significantly promoted chondrocyte proliferation and mRNA levels of Sox9, collagen type II, and aggrecan when compared to PRP and control. Histological analysis revealed that at 4 weeks, macroscopic ICRS scores from the i-PRF group were significantly enhanced when compared to the PRP and control groups. At 12 weeks post surgery, the microscopic ICRS scores demonstrated that the i-PRF group significantly improved cartilage regeneration when compared to PRP. In conclusion, the use of i-PRF using the low speed centrifugation concept significantly promoted chondrocyte activity and further improved cartilage regeneration when compared to PRP. The histological results revealed early and better cartilage regeneration within 4 weeks postoperatively when i-PRF was utilized and the results were maintained at 12 weeks. Future clinical studies are now needed investigating the regenerative potential of i-PRF in comparison to PRP for knee regeneration.
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http://dx.doi.org/10.1080/09537104.2017.1401058DOI Listing
April 2019

Basics of Platelet-Rich Fibrin Therapy.

Dent Today 2017 Apr;36(4):74-6

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April 2017

Reduction of the relative centrifugal force influences cell number and growth factor release within injectable PRF-based matrices.

J Mater Sci Mater Med 2017 Oct 25;28(12):188. Epub 2017 Oct 25.

Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, FORM (Frankfurt Orofacial Regenerative Medicine) Lab, University Hospital Frankfurt Goethe University, Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.

Platelet rich fibrin (PRF) is a blood concentrate system obtained by centrifugation of peripheral blood. First PRF matrices exhibited solid fibrin scaffold, more recently liquid PRF-based matrix was developed by reducing the relative centrifugation force and time. The aim of this study was to systematically evaluate the influence of RCF (relative centrifugal force) on cell types and growth factor release within injectable PRF- in the range of 60-966 g using consistent centrifugation time. Numbers of cells was analyzed using automated cell counting (platelets, leukocytes, neutrophils, lymphocytes and monocytes) and histomorphometrically (CD 61, CD- 45, CD-15+, CD-68+, CD-3+ and CD-20). ELISA was utilized to quantify the concentration of growth factors and cytokines including PDGF-BB, TGF-β1, EGF, VEGF and MMP-9. Leukocytes, neutrophils, monocytes and lymphocytes had significantly higher total cell numbers using lower RCF. Whereas, platelets in the low and medium RCF ranges both demonstrated significantly higher values when compared to the high RCF group. Histomorphometrical analysis showed a significantly high number of CD61+, CD-45+ and CD-15+ cells in the low RCF group whereas CD-68+, CD-3+ and CD-20+ demonstrated no statistically significant differences between all groups. Total growth factor release of PDGF-BB, TGF-β1 and EGF had similar values using low and medium RCF, which were both significantly higher than those in the high RCF group. VEGF and MMP-9 were significantly higher in the low RCF group compared to high RCF. These findings support the LSCC (low speed centrifugation concept), which confirms that improved PRF-based matrices may be generated through RCF reduction. The enhanced regenerative potential of PRF-based matrices makes them a potential source to serve as a natural drug delivery system. However, further pre-clinical and clinical studies are required to evaluate the regeneration capacity of this system.
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http://dx.doi.org/10.1007/s10856-017-5992-6DOI Listing
October 2017

Use of platelet-rich fibrin in regenerative dentistry: a systematic review.

Clin Oral Investig 2017 Jul 27;21(6):1913-1927. Epub 2017 May 27.

Pain Clinic, Nice, France.

Objectives: Research across many fields of medicine now points towards the clinical advantages of combining regenerative procedures with platelet-rich fibrin (PRF). This systematic review aimed to gather the extensive number of articles published to date on PRF in the dental field to better understand the clinical procedures where PRF may be utilized to enhance tissue/bone formation.

Materials And Methods: Manuscripts were searched systematically until May 2016 and separated into the following categories: intrabony and furcation defect regeneration, extraction socket management, sinus lifting procedures, gingival recession treatment, and guided bone regeneration (GBR) including horizontal/vertical bone augmentation procedures. Only human randomized clinical trials were included for assessment.

Results: In total, 35 articles were selected and divided accordingly (kappa = 0.94). Overall, the use of PRF has been most investigated in periodontology for the treatment of periodontal intrabony defects and gingival recessions where the majority of studies have demonstrated favorable results in soft tissue management and repair. Little to no randomized clinical trials were found for extraction socket management although PRF has been shown to significantly decrease by tenfold dry sockets of third molars. Very little to no data was available directly investigating the effects of PRF on new bone formation in GBR, horizontal/vertical bone augmentation procedures, treatment of peri-implantitis, and sinus lifting procedures.

Conclusions: Much investigation now supports the use of PRF for periodontal and soft tissue repair. Despite this, there remains a lack of well-conducted studies demonstrating convincingly the role of PRF during hard tissue bone regeneration. Future human randomized clinical studies evaluating the use of PRF on bone formation thus remain necessary.

Clinical Relevance: 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.
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http://dx.doi.org/10.1007/s00784-017-2133-zDOI Listing
July 2017

Platelet-rich fibrin-based matrices to improve angiogenesis in an in vitro co-culture model for bone tissue engineering.

J Tissue Eng Regen Med 2018 03 30;12(3):598-610. Epub 2017 Aug 30.

FORM, Frankfurt Oral Regenerative Medicine, Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

In the context of prevascularization strategies for tissue-engineering purposes, co-culture systems consisting of outgrowth endothelial cells (OECs) and primary osteoblasts (pOBs) have been established as a promising in vitro tool to study regeneration mechanisms and to identify factors that might positively influence repair processes such as wound healing or angiogenesis. The development of autologous injectable platelet-rich fibrin (PRF), which can be generated from peripheral blood in a minimal invasive procedure, fulfils several requirements for clinically applicable cell-based tissue-engineering strategies. During this study, the established co-culture system of OECs and pOBs was mixed with injectable PRF and was cultivated in vitro for 24 h or 7 days. The aim of this study was to analyse whether PRF might have a positive effect on wound healing processes and angiogenic activation of OECs in the co-culture with regard to proinflammatory factors, adhesion molecules and proangiogenic growth factor expression. Histological cell detection revealed the formation of lumina and microvessel-like structures in the PRF/co-culture complexes after 7 days of complex cultivation. Interestingly, the angiogenic activation of OECs was accompanied by an upregulation of wound healing-associated factors, as well as by a higher expression of the proangiogenic factor vascular endothelial growth factor, which was evaluated both on the mRNA level as well as on the protein level. Thus, PRF might positively influence wound healing processes, in particular angiogenesis, in the in vitro co-culture, making autologous PRF-based matrices a beneficial therapeutic tool for tissue-engineering purposes by simply profiting from the PRF, which contains blood plasma, platelets and leukocytes.
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http://dx.doi.org/10.1002/term.2475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888144PMC
March 2018

A Novel Technique in Root-Coverage Procedures: The Fibrin-Assisted Soft-Tissue Promotion Concept.

Compend Contin Educ Dent 2017 Apr;38(4):220-225; quiz 226

Private Practice, Nice, France.

The goal of periodontal plastic surgery is to correct the soft-tissue deformities associated with the loss of attached and keratinized tissue. A variety of flap manipulations related to the use of subepithelial connective tissue grafts are described with great success in the literature but are linked with morbidity and harvesting-quality issues, inclining clinicians and researchers to find alternatives to such techniques. Advanced platelet-rich fibrin, which is widely used in medicine and oral therapy, represents a newer generation of blood-derived growth factors. This article discusses a simple and reproducible root-coverage procedure utilizing the fibrin-assisted soft-tissue promotion concept.
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April 2017

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

Platelets 2018 Jan 29;29(1):48-55. Epub 2017 Mar 29.

d Department of Periodontology, College of Dental Medicine , Nova Southeastern University , Fort Lauderdale , Florida , USA.

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.
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http://dx.doi.org/10.1080/09537104.2017.1293807DOI Listing
January 2018

Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP.

Int J Mol Sci 2017 Feb 4;18(2). Epub 2017 Feb 4.

Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient's own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF) was compared to standard platelet-rich plasma (PRP) with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× ) for 3 min) were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), collagen1 (COL1) and fibronectin (FN). The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA) levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.
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http://dx.doi.org/10.3390/ijms18020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343867PMC
February 2017

Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry?

Clin Oral Investig 2017 Nov 2;21(8):2619-2627. Epub 2017 Feb 2.

Pain Clinic, Nice, France.

Objectives: Platelet rich plasma (PRP) has been utilized in regenerative dentistry as a supra-physiological concentrate of autologous growth factors capable of stimulating tissue regeneration. Despite this, concerns have been expressed regarding the use of anti-coagulants, agents known to inhibit wound healing. In this study, a liquid formulation of platelet rich fibrin (PRF) termed injectable-PRF (i-PRF) without the use of anti-coagulants was investigated.

Materials And Methods: Standard PRP and i-PRF (centrifuged at 700 rpm (60G) for 3 min) were compared for growth factor release up to 10 days (8 donor samples). Furthermore, fibroblast biocompatibility at 24 h (live/dead assay); migration at 24 h; proliferation at 1, 3, and 5 days, and expression of PDGF, TGF-β, and collagen1 at 3 and 7 days were investigated.

Results: Growth factor release demonstrated that in general PRP had higher early release of growth factors whereas i-PRF showed significantly higher levels of total long-term release of PDGF-AA, PDGF-AB, EGF, and IGF-1 after 10 days. PRP showed higher levels of TGF-β1 and VEGF at 10 days. While both formulations exhibited high biocompatibility and higher fibroblast migration and proliferation when compared to control tissue-culture plastic, i-PRF induced significantly highest migration whereas PRP demonstrated significantly highest cellular proliferation. Furthermore, i-PRF showed significantly highest mRNA levels of TGF-β at 7 days, PDGF at 3 days, and collagen1 expression at both 3 and 7 days when compared to PRP.

Conclusions: i-PRF demonstrated the ability to release higher concentrations of various growth factors and induced higher fibroblast migration and expression of PDGF, TGF-β, and collagen1. Future animal research is now necessary to further validate the use of i-PRF as a bioactive agent capable of stimulating tissue regeneration.

Clinical Relevance: The findings from the present study demonstrate that a potent formulation of liquid platelet concentrates could be obtained without use of anti-coagulants.
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http://dx.doi.org/10.1007/s00784-017-2063-9DOI Listing
November 2017

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

Tissue Eng Part B Rev 2017 02 10;23(1):83-99. Epub 2016 Oct 10.

6 Pain Clinic , Nice, France .

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.
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http://dx.doi.org/10.1089/ten.TEB.2016.0233DOI Listing
February 2017

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

J Periodontol 2017 01 2;88(1):112-121. Epub 2016 Sep 2.

Pain Clinic, Nice, France.

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.
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http://dx.doi.org/10.1902/jop.2016.160443DOI Listing
January 2017

Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation.

J Oral Implantol 2016 Jun 29;42(3):273-7. Epub 2016 Jan 29.

1   Frankfurt Oral Regenerative Medicine, Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt Am Main, Germany.

Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (48.25%) surrounding the remaining bone substitute granules (42.13%) was observed. Accordingly, the amount of bone tissue (9.62%) built the smallest fraction within the biopsy. Further, tartrate-resistant acid phosphatase-positive and -negative multinucleated giant cells (4.35 and 3.93 cells/mm(2), respectively) were detected on the material-tissue interfaces. The implantation bed showed a mild vascularization of 10.03 vessels/mm(2) and 0.78%. The present case report shows that after 3 years, a comparable small amount of bone tissue was observable. Thus, the foreign body response to the bone substitute seems to be folded without further degradation or regeneration.
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http://dx.doi.org/10.1563/aaid-joi-D-15-00133DOI Listing
June 2016

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

Biomed Mater 2015 Sep 11;10(5):055007. Epub 2015 Sep 11.

Frankfurt Orofacial Regenerative Medicine (FORM) Lab, Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University, Theodor-Stern-Kai 7, D-60590, Frankfurt, Germany. Repair-Lab, Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

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.
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http://dx.doi.org/10.1088/1748-6041/10/5/055007DOI Listing
September 2015

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

J Oral Implantol 2015 Dec 29;41(6):e238-51. Epub 2014 Dec 29.

1  Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany.

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.
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http://dx.doi.org/10.1563/aaid-joi-D-14-00274DOI Listing
December 2015

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

J Oral Implantol 2015 Oct 8;41(5):e212-22. Epub 2014 Aug 8.

1  FORM-Lab, Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany.

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.
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http://dx.doi.org/10.1563/aaid-joi-D-14-00168DOI Listing
October 2015

Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells.

J Oral Implantol 2014 Dec;40(6):679-89

1  FORM - Frankfurt Orofacial Regenerative Medicine, Clinic of Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany.

Choukroun's 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.
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http://dx.doi.org/10.1563/aaid-joi-D-14-00138DOI Listing
December 2014

Two neglected biologic risk factors in bone grafting and implantology: high low-density lipoprotein cholesterol and low serum vitamin D.

J Oral Implantol 2014 Feb 9;40(1):110-4. Epub 2013 Oct 9.

1  Pain Clinic, Nice, France.

Following a failure of a bone graft or an implant placement, the hypothesis of a biological abnormality is rarely considered as a possible cause. A systematic search of peer-reviewed literature for dyslipidemia or vitamin D deficiency may explain this lack of consideration. Excess low-density lipoprotein cholesterol (dyslipidemia) is responsible for a slower bone metabolism or lower dental implant osseointegration. In addition, vitamin D is a key factor for linking innate and adaptive immunity. Both of these factors are compromised under the conditions of vitamin D deficiency. Therefore, vitamin D deficiency slows implant osseointegration and increases the risk of graft infection. Vitamin D is also involved in immune function and therefore allergic reactions.
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http://dx.doi.org/10.1563/AAID-JOI-D-13-00062DOI Listing
February 2014

Nanocrystalline hydroxyapatite-based material already contributes to implant stability after 3 months: a clinical and radiologic 3-year follow-up investigation.

J Oral Implantol 2014 Feb 17;40(1):103-9. Epub 2013 Sep 17.

1  Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany.

The present study reports on a 3-year clinical and radiologic follow-up investigation of dental implants placed 3 and 6 months after sinus augmentation in 14 patients. Augmentation was performed with a synthetic bone substitute material composed of nanocrystalline hydroxyapatite. The aim of the study was to determine how the integration period of the bone substitute material, that is, 3 months or 6 months, influences implant integration within the patient's upper jaw. Therefore, the following clinical and radiologic parameters were investigated: implant being in situ; Periotest value; and presence of peri-implant osteolysis, bleeding on probing, plaque, and soft tissue recession around the implants. At the follow-up investigation 3 years after placement, 23 of 24 implants were in situ and suitable for prosthetic rehabilitation. No implants in either study group were mobile or showed peri-implant osteolysis. Only a few implants showed plaque or soft tissue variations. Within its limits, the present study showed comparable clinical performance of dental implants placed 3 months after sinus floor augmentation to implants placed 6 months after augmentation. The results of all investigated parameters were in accordance with results found in the literature. It can be concluded that augmentation with the applied synthetic bone substitute material already forms a sufficient implantation bed 3 months after augmentation, which enables long-term, stable, implant-retained restoration. These findings might contribute to a reduced healing time after augmentation, which would be favorable for patients and clinicians.
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http://dx.doi.org/10.1563/AAID-JOI-D-13-00232DOI Listing
February 2014

L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and chronic wounds.

Curr Pharm Biotechnol 2012 Jun;13(7):1266-77

Department and Clinic of Cranio and Maxillofacial Surgery, Medical University of Silesia, ul. Francuska 22-24, 040-096 Katowice, Poland.

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.
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http://dx.doi.org/10.2174/138920112800624463DOI Listing
June 2012

Simultaneous sinus-lift and implantation using microthreaded implants and leukocyte- and platelet-rich fibrin as sole grafting material: a six-year experience.

Implant Dent 2011 Feb;20(1):2-12

Department of Odontostomatological and Maxillofacial Sciences, University Federico II of Naples, Italy.

Purpose: To assess the relevance of simultaneous sinus-lift and implantation with leukocyte- and platelet-rich fibrin (L-PRF, Choukroun's technique) as sole subsinus filling material.

Materials: Twenty-three lateral sinus elevations (SA4 sinus) were performed on 20 patients with simultaneous implant placement. Seven patients were treated with 19 Astra implants (AstraTech, Mölndal, Sweden) and 13 patients with 33 Intra-Lock implants (Intra-Lock Ossean, Boca Raton, FL). L-PRF membranes were used to cover the Schneiderian membrane, the implant tips served as "tent pegs" for the L-PRF-patched sinus membranes, and the subsinus cavity was finally filled with L-PRF clots. Clinical and radiographic follow-up was performed just after implant placement, after 6 months, 1 year and each following year.

Results: Six months after surgery, all implants were clinically stable during abutment tightening. The maximum follow-up was 6 years, and all patients were followed up for a minimum of 2 years. No implant was lost during this 6-year experience, and the vertical bone gain was always substantial, between 8.5 and 12 mm bone gain (10.4 ± 1.2). The final level of the new sinus floor was always in continuation with the implant apical end, and the periimplant crestal bone height was stable.

Conclusion: The use of L-PRF as sole filling material during simultaneous sinus-lift and implantation seems to be a reliable surgical option promoting natural bone regeneration.
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http://dx.doi.org/10.1097/ID.0b013e3181faa8afDOI Listing
February 2011

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

Implant Dent 2008 Sep;17(3):257-70

Pain Clinic Center, Nice, France.

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 (Phoenix, 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.
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http://dx.doi.org/10.1097/ID.0b013e318181349aDOI Listing
September 2008
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