Impact of autologous platelet concentrates on the osseointegration of dental implants.

Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant-bone interface via "biomimicry," a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L-PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L-PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.

Differences between first- and second-generation autologous platelet concentrates.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.

Essential principles for blood centrifugation.

Currently, autologous platelet concentrates (APCs) are frequently used for soft- and hard-tissue regeneration, not only within the oral cavity, but also extra-orally including chronic wounds, burns, joints, dermatological conditions, among others. The benefits of APCs are largely influenced by the treatment strategy but also their preparation. This paper therefore discusses in detail: the physical properties of blood cells, the basic principles of blood centrifugation, the impact of the centrifugation protocol (rotations/revolutions per minute, g-force, variation between centrifuges), the importance of timing during the preparation of APCs, the impact of the inner surface of the blood tubes, the use/nonuse of anticoagulants within APC tubes, the impact of the patient's hematocrit, age, and gender, as well as the important requirements for an optimal centrifugation protocol. All these variables indeed have a significant impact on the clinical outcome of APCs.

Periodontal regeneration using platelet-rich fibrin. Furcation defects: A systematic review with meta-analysis.

The objective of the study was to compare the treatment outcomes of periodontal furcation defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with those of other modalities for the treatment of furcation defects. Studies were classified into 11 categories in 3 different groups as follows: Group I (addition of PRF): (1) open flap debridement (OFD) alone versus OFD/PRF, (2) OFD/bone graft (OFD/BG) versus OFD/BG/PRF; Group II (comparative studies to PRF): (3) OFD/BG versus OFD/PRF, (4) OFD/collagen membrane versus OFD/PRF, (5) OFD/PRP versus OFD/PRF, (6) OFD/rhBMP2 versus OFD/PRF; and Group III (addition of biomaterial/biomolecule to PRF): OFD/PRF versus … (7) OFD/PRF/BG, (8) OFD/PRF/amniotic membrane (AM), (9) OFD/PRF/metformin, (10) OFD/PRF/bisphosphonates, (11) OFD/PRF/statins. Weighted means and forest plots were calculated for the reduction of probing pocket depth (PPD), gain of vertical and horizontal clinical attachment levels (VCAL and HCAL), gain in vertical and horizontal bone levels (VBL, HBL), and radiographic bone fill (RBF). From 45 articles identified, 21 RCTs reporting on class II furcations were included. The use of OFD/PRF and OFD/BG/PRF statistically significantly reduced PPD and improved VCAL and HCAL when compared to OFD or OFD/BG, respectively. The comparison between OFD/PRF alone versus OFD/BG, OFD/CM, OFD/PRP, or OFD/rhBMP2 led to similar outcomes for all investigated parameters, including a reduction in PPD, VCAL/HCAL gain, and RBF. The additional incorporation of a BG to OFD/PRF only mildly improved outcomes, whereas the addition of AM improved clinical outcomes. The addition of small biomolecules such as metformin, bisphosphonates, or statins all led to significant improvements in PPD, VCAL, and HCAL when compared to OFD/PRF alone. Noteworthy, a very high heterogeneity was found in the investigated studies. The use of PRF significantly improved clinical outcomes in class II furcation defects when compared to OFD alone, with similar levels being observed between OFD/PRF and/or OFD/BG, OFD/CM, OFD/PRP, or OFD/rhBMP2. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future histological research investigating PRF in human furcation defects is largely needed. The use of PRF in conjunction with OFD statistically significantly improved PPD, VCAL, and HCAL values, yielding comparable outcomes to commonly used biomaterials. The combination of PRF to bone grafts or the addition of small biomolecules may offer additional clinical benefits, thus warranting future investigation.

Comprehensive analysis of bone tissue in extraction sockets of third molars after leukocyte and platelet rich fibrin and photobiomodulation applications.

OBJECTIVES: The aim of this study was to compare leukocyte and platelet-rich fibrin (L-PRF) and photobiomodulation (PBM) applications, which have been repeatedly reported to be superior to control groups, in terms of pain, soft tissue and bone healing in tooth extraction sockets. MATERIALS AND METHODS: This double-blind, randomized clinical study was completed with 34 patients, who had an indication for extraction of their bilaterally impacted teeth. The right and left teeth of the patients were randomly divided into L-PRF and PBM groups. L-PRF group was treated with the blood product centrifuged for 12 min at 2700 rpm, and the PBM group was treated with a diode laser at different points for 60 s with a wavelength of 940 nm in repeated sessions. Postoperative pain was evaluated using Visual Analogue Scale (VAS), soft tissue healing with Landry Index (LI), tissue healing in the distal region of mandibular second molar by probing depth measurement, and bone healing via panoramic x-ray using the Image J program. RESULTS: No statistically significant difference was found for any variable compared between the groups. CONCLUSION: L-PRF and PBM applications provide similar support in the healing of extraction sockets. Nevertheless, the advantages and disadvantages of both methods determine their usage areas. CLINICAL RELEVANCE: While L-PRF is advantageous in the early healing of extraction sockets, PBM may be preferred in terms of bone trabeculation in the long term.

Comprehensive analysis of L-PRF exudate components and their impact on whole blood platelets.

OBJECTIVE: This study assessed the cellular composition and effects of leukocyte-platelet-rich fibrin (L-PRF) exudate on whole blood platelets from healthy volunteers. Key objectives included evaluating leukocyte subpopulations, platelet activation markers, platelet-leukocyte interactions and quantifying inflammatory cytokines within the L-PRF exudate. MATERIALS AND METHODS: L-PRF was obtained from 20 healthy donors. Flow cytometry methodologies were used to assess intracellular calcium kinetics and activated GPIIbIIIa, and P-selectin expression. Leukocyte subpopulations and platelet-leukocyte interactions were characterized using monoclonal antibodies. Inflammatory cytokines (IL-8, IL-1ß, IL-6, IL-10, TNF, IL-12p70) within L-PRF exudate were quantified using a cytometric bead array. RESULTS: The expression of activated GPIIbIIIa, and P-selectin exhibited a significant increase (p < 0.001) when L-PRF exudate was added to platelets of whole blood. Regarding intracellular Ca2+ mobilization, the L-PRF exudate elicited significant responses (p < 0.001). L-PRF exudate contained different leukocytes populations, being TCD4 + the most representative of T cells. It was possible to stablish a profile of cytokines produced by the L-PRF exudate, with human IL-8 cytokine exhibiting the highest average (16.90 pg/mL). CONCLUSIONS: Despite the study limitations, the research yielded important insights: 1- L-PRF exudate can stimulate platelet activation, essential in healing, tissue inflammation and remodeling. 2-The presence of leukocyte subpopulations within L-PRF exudate reflexes its complexity and potential to enhance immune responses. 3-The analysis of inflammatory cytokines within L-PRF exudate revealed its immunomodulatory potential. These findings are valuable evidences for understanding the potential role of L-PRF exudate in regenerative dentistry and medicine, offering innovative therapeutic strategies. CLINICAL RELEVANCE: This research highlights crucial aspects that could significantly influence the clinical use of L-PRF exudate in the oral cavity. The findings support the application of L-PRF exudate in both surgical and regenerative dentistry, facilitating the development of innovative therapeutic strategies to enhance patient outcomes.

Leukocytes within Autologous Blood Concentrates Have No Impact on the Growth and Proliferation of Human Primary Osteoblasts: An In Vitro Study.

Platelet-rich fibrin (PRF) is a widely used autologous blood concentrate in regenerative medicine. This study aimed to characterize the cellular composition and distribution of different PRF matrices generated by high (710 g) and low (44 g) relative centrifugal forces (RCFs) and to analyze their bioactivity on human primary osteoblasts (pOBs). PRF was separated into upper layer (UL) and buffy coat (BC) fractions, and their cellular contents were assessed using histological and immunohistochemical staining. The release of platelet-derived growth factor (PDGF) and transforming growth factor (TGF-ß) was quantified using an ELISA. Indirect PRF treatment on pOBs was performed to evaluate cell viability and morphology. A histological analysis revealed higher quantities of leukocytes and platelets in the low-RCF PRF. TGF-ß release was significantly higher in the low-RCF PRF compared to the high-RCF PRF. All PRF fractions promoted pOB proliferation regardless of the centrifugation protocol used. The low-RCF PRF showed higher TGF-ß levels than the high-RCF PRF. These findings contribute to understanding the cellular mechanisms of PRF and provide insights into optimizing PRF protocols for bone regeneration, advancing regenerative medicine, and improving patient outcomes.

Optimization of platelet-rich fibrin.

The use of platelet-rich fibrin (PRF) has gained tremendous popularity in recent years owing to its ability to speed wound healing postsurgery. However, to date, many clinicians are unaware of methods designed to optimize the technology. This overview article will discuss the advancements and improvements made over the years aimed at maximizing cell and growth factor concentrations. First, a general understanding explaining the differences between RPM and RCF (g-force) is introduced. Then, the low-speed centrifugation concept, fixed angle versus horizontal centrifugation, and methods to maximize platelet concentrations using optimized protocols will be discussed in detail. Thereafter, the importance of chemically modified PRF tubes without the addition of chemical additives, as well as regulation of temperature to induce/delay clotting, will be thoroughly described. This article is a first of its kind summarizing all recent literature on PRF designed to optimize PRF production for clinical treatment.

Ten years of injectable platelet-rich fibrin.

The use of platelet-rich fibrin (PRF) has seen widespread advantages over platelet-rich plasma (PRP) in many fields of medicine. However, until 2014, PRF remained clinically available only in its solid clotted form. Modifications to centrifugation protocols and tube technology have led to the development of a liquid injectable version of PRF (i-PRF). This narrative review takes a look back at the technological developments made throughout the past decade and further elaborates on their future clinical applications. Topics covered include improvements in isolation techniques and protocols, ways to further concentrate i-PRF, and the clinical impact and relevance of cooling i-PRF. Next, various uses of i-PRF are discussed, including its use in regenerative periodontology, implantology, endodontics, temporomandibular joint injections, and orthodontic tooth movement. Furthermore, various indications in medicine are also covered, including its use in sports injuries and osteoarthritis of various joints, treatment of diabetic ulcers/wound care, and facial esthetics and hair regrowth. Finally, future applications are discussed, mainly its use as a drug delivery vehicle for small biomolecules, such as growth factors, antibiotics, exosomes, and other medications that may benefit from the controlled and gradual release of biomolecules over time.

Do autologous platelet concentrates (APCs) have a role in intra-oral bone regeneration? A critical review of clinical guidelines on decision-making process.

In the past decades, personalized regenerative medicine has gained increased attention. Autologous platelet concentrates (APCs) such as PRP, PRGF, and L-PRF, all serving as a source of a large variety of cells and growth factors that participate in hard and soft tissue healing and regeneration, could play a significant role in regenerative periodontal procedures. This narrative review evaluated the relative impact of APCs in alveolar ridge preservation, sinus floor augmentation, and the regeneration of bony craters around teeth, both as a single substitute or in combination with a xenograft. L-PRF has a significant beneficial effect on alveolar ridge preservation (bone quality). The data for PRGF are less convincing, and PRP is controversial. L-PRF can successfully be used as a single substitute during transcrestal (≥3.5 mm bone gain) as well as 1-stage lateral window sinus floor elevation (>5 mm bone gain). For PRGF and especially PRP the data are very scarce. In the treatment of bony craters around teeth, during open flap debridement, L-PRF as a single substitute showed significant adjunctive benefits (e.g., >PPD reduction, >CAL gain, >crater depth reduction). The data for PRP and PRGF were non-conclusive. Adding PRP or L-PRF to a xenograft during OFD resulted in additional improvements (>PPD reduction, >CAL gain, >bone fill), for PRGF no data were found. Autologous platelet concentrates demonstrated to enhance bone and soft tissue healing in periodontal regenerative procedures. The data for L-PRF were most convincing. L-PRF also has the advantage of a greater simplicity of production, and its 100% autologous character.

Fat enhanced leukocyte-platelet-rich fibrin versus fascia lata in endoscopic reconstruction of CSF leaks.

PURPOSE: The aim of this study was to use a new biological active fat enhanced leukocyte-platelet-rich fibrin membrane (L-PRF) for skull base defect reconstruction and compare its validity and reliability with the time-honored fascia lata. METHODS: This prospective study was conducted on 48 patients with spontaneous CSF leaks who were divided into 2 matched groups by stratified randomization, 24 patients in each group. In group A we performed multilayer repair using fat enhanced L-PRF membrane. In group B we used fascia lata for the multilayer repair. In both groups we enforced the repair with mucosal grafts/flaps. RESULTS: The two groups were statistically matched for age, sex, intracranial pressure, and site and size of the skull base defect. There was no statistically significant difference between the two groups regarding the outcome of the repair or recurrence of CSF leak during the first postoperative year. Meningitis occurred in one patient in group B and was successfully treated. Another patient in group B developed thigh hematoma which resolved spontaneously. CONCLUSION: The fat enhanced L-PRF membrane is a valid reliable option in repair of CSF leaks. The membrane is autologous, readily available, easily prepared, and has the advange of including stromal fat, stromal vascular fraction (SVF), and leukocyte-platelet-rich fibrin (L-PRF). The present study showed that fat enhanced L-PRF membrane is stable, non-absorbable, not liable to shrink or become necrotic, and can establish good seal of the skull base defect and further enhance the healing process. The use of the membrane also has the advantage of avoiding thigh incision and possible hematoma formation.

Effect of leukocyte-platelet-rich fibrin (L-PRF) on the rate of orthodontic tooth movement and expression of various biomarkers in gingival crevicular fluid.

OBJECTIVES: To assess the outcome of leukocyte-platelet-rich fibrin (L-PRF) on the rate of maxillary canine retraction and its correlation with the levels of Receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and RANKL:OPG in the gingival crevicular fluid (GCF) during comprehensive orthodontic treatment. SUBJECTS AND METHODS: Eighteen females who required all 1st premolars extraction for the correction of their class I bimaxillary protrusion malocclusions were included. The L-PRF plugs were placed in the experimental side 1st premolar extraction sockets. Canine retraction was performed by sliding mechanics. Canine retraction was assessed from the maxillary study models prepared just before the extraction (T0) and then at 1 week (T1), 2 weeks (T2), 4 weeks (T3), and 8 weeks (T4) after the 1st premolar extraction and placement of L-PRF plugs. The concentrations of RANKL and OPG in the GCF were evaluated at T0, T1, T2, T3, and T4. RESULTS: In experimental sides, the amount of canine retraction was statistically more during the T0-T1, T1-T2, and T2-T3 periods. The mean concentration of RANKL at T1, T2, and T3 was significantly more in the experimental sides. The mean concentration of OPG was significantly less in the experimental sides at T2, T3, and T4. The RANKL:OPG was significantly more in the experimental sides at T1, T2, T3, and T4. No significant correlation was found between amount of canine retraction and concentration of RANKL and OPG and RANKL to OPG ratio in GCF. CONCLUSIONS: The L-PRF accelerated the rate of maxillary canine retraction by 0.28 mm over an 8-week period. The L-PRF favored the local osteoclastogenesis by enhancing the RANKL and suppressing the OPG concentrations. There was no significant correlation between the rate of maxillary canine retraction and expression of RANKL, OPG, and RANKL:OPG in GCF. TRIAL REGISTRATION: The Clinical Trials Registry of India (Reg. No. CTRI/2020/10/028390, Date-13.10.2020).

Histomorphometric evaluation of different graft associations for maxillary sinus elevation in wide antral cavities: a randomized controlled clinical trial.

OBJECTIVES: Pneumatization of the maxillary sinus can make it difficult, if not impossible, to install osseointegrated implants, and undertake their eventual functional rehabilitation, which may ultimately require regenerative techniques to achieve. This randomized controlled study proposed conducting a histological evaluation of the behavior of different graft materials in wide maxillary sinuses, at a height of 8 to 10 mm from the alveolar ridge, combined with bone remnants less than 3mm. MATERIALS AND METHODS: Thirty-six patients underwent a sinus elevation procedure through the lateral window. The sinuses were randomly filled with the following materials (n=12/group): group 1, xenogenic bone + autogenous bone (ratio 70:30, respectively); group 2, xenogenic bone + L-PRF; and group 3, xenogenic bone. At 8 months, bone biopsies of engrafted sites were harvested and analyzed histomorphometrically in order to quantify newly formed bone tissue. RESULTS: The results showed a greater area of newly formed bone for G1, averaging 2678.37 (1116.40) µm2, compared with G2 at 984.87 (784.27) µm2, and G3 at 480.66 (384.76) µm2 (p < 0.05). Additionally, fewer xenogenic bone particles and a large amount of connective tissue were observed in G2. CONCLUSIONS: In maxillary sinuses with large antral cavities, autogenous bone combined with xenogenic bone seems to demonstrate better graft remodeling and improve bone formation, compared with the addition of L-PRF. CLINICAL RELEVANCE: L-PRF produces few advantages regarding new bone formation in the wide maxillary sinuses. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC) number RBR-2pbbrvg.

Platelet activation and antimicrobial activity of L-PRF: a preliminary study.

Leukocyte and platelet rich fibrin (L-PRF) is one of the platelet concentrates used to support regeneration and healing process. Many studies showed possible immunological and antibacterial properties of L-PRF. We perform an in vitro study to analyze the effect of L-PRF on platelet activation, platelet-leukocytes interactions and antimicrobial activity, important components in the healing process. Molecular biomarkers related with platelet activation and platelet-leukocyte interactions were analyzed by means of flow cytometry when L-PRF exudate was added to whole blood platelets. L-PRF membrane was used to evaluate antimicrobial activity using Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC 90028). Our experimental design allows to evaluate platelet activation and analyze molecular biomarkers of other immune cells and platelet-leukocyte interactions. From the results obtained we can conclude that L-PRF can be a valuable tool in healing process, efficient in activating platelets of whole blood and inhibiting microbial growth. In our opinion, the use of L-PRF exudate, in addition to L-PRF membrane, presents some advantages that have to be considered in clinical trials. Additional research on the characterization and quantification of cells and its products present in the L-PRF exudate, as well as on the temporal factor released. Also, further studies using strains isolated from clinical cases are needed.

Histological comparison of Platelet rich fibrin clots prepared by fixed-angle versus horizontal centrifugation.

Platelet-rich fibrin (PRF) is prepared from whole blood without any exogenous coagulation factors. Several preparation methods have now been introduced, particularly with differences in centrifugation parameters including g-force and time to improve their regenerative potential. Nevertheless, the centrifugation systems have not yet been clearly investigated for their influences on the PRF clot properties. The aim of the present study was to visually and histologically characterize the cell separation manner and blood cell localization on the whole PRF clots prepared by two different centrifugation system, fixed-angle and horizontal centrifugation. Leukocyte- and platelet-rich fibrin (L-PRF) was prepared on a fixed-angle centrifuge machine (IntraSpin, Intra-Lock, FL, USA) at 2700 rpm (~400 g at the RCF-clot; ~700 g at the RCF-max) for 12 min. The PRF prepared by horizontal centrifugation was prepared on a horizontal centrifugation (H-PRF) (Eppendorf 5702, Eppendorf, Germany) at 700 g at the RCF-max for 8 min. The cell morphology and localization were observed on the surface of PRF clots by scanning electron microscopy (SEM) and histologically by transaxial frozen sections by means of a film method. L-PRF clots demonstrated a sloped separation between the upper plasma and the bottom red blood cell (RBC) layers according to the angle of the rotor. Red dots were often observed on the distal walls of the tubes in the upper layers, consisting of aggregations of RBCs, leukocytes and platelets by SEM and histology. Clots produced on the horizontal centrifuge showed much smoother cell layer distribution/separation along the tube surfaces when compared to L-PRF. Horizontal centrifugation also demonstrated more evenly distributed platelets throughout the PRF clots when compared to L-PRF that gathered the majority of cells along the distal tube surface or within the buffy-coat region. In summary, it was found that horizontal centrifugation resulted in a more uniform blood cell separation of PRF clots when compared to the accumulation of cells gathered along the distal tube surfaces produced prepared by fixed-angle centrifugation. Future research is needed to evaluate the benefit of horizontal centrifugation in clinical practice.

Evaluation of local hemostatic efficacy after dental extractions in patients taking antiplatelet drugs: a randomized clinical trial.

OBJECTIVES: The purpose of this study was to evaluate clinical efficacy of four different local hemostatics in patients taking oral antiplatelet therapy, after multiple dental extractions without discontinuing drugs. MATERIALS AND METHODS: Study sample included 102 patients (mean age 64.1 ± 17.4 years) in treatment with oral antiplatelet agents needing multiple dental extractions. After surgery, the sockets were randomly sealing with suture alone (control group), hemostatic plug (HEM), advanced platelet-rich fibrin (A-PRF+), and leukocyte-platelet-rich fibrin (L-PRF). Primary outcomes were post-operative bleeding, wound healing index, and possible complications. Secondary outcomes were correlation between primary outcomes and patient's comorbidities and voluptuous habits. Descriptive statistics, bivariate comparisons, and logistic regression analysis were performed (p < 0.05). RESULTS: Both A-PRF+ and L-PRF showed a reduced bleeding risk when compared with suture alone (OR = 0.09, p = 0.001 for A-PRF+; OR = 0.09, p = 0.005 for L-PRF). Only L-PRF showed a reduced risk for incomplete wound healing when compared with the control site (OR = 0.43, p = 0.019). Patients affected by hypertension (OR 3.91, p = 0.015) and diabetes (OR 3.24, p = 0.026) had the highest bleeding risk. Smoking (OR 4.30, p = 0.016) and diabetes (OR 3.79, p = 0.007) interfered with healing process. CONCLUSION: L-PRF and A-PRF represent a valid alternative to the traditional hemostatics, reducing post-surgical bleeding and promoting wound healing. CLINICAL RELEVANCE: In patients taking antiplatelet drugs, different local hemostatics are useful to control potential post-operative bleeding and to favor wound healing. However, comorbidities and voluptuous habits may increase bleeding risk, interfering with healing process.

Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis.

OBJECTIVES: This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF). RESULTS: From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF. CONCLUSIONS: The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed. CLINICAL RELEVANCE: The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.

A technical note on contamination from PRF tubes containing silica and silicone.

BACKGROUND: Platelet-rich fibrin (PRF) has been widely utilized in modern medicine and dentistry owing to its ability to rapidly stimulate neoangiogenesis, leading to faster tissue regeneration. While improvements over traditional platelet rich plasma therapies (which use chemical additives such as bovine thrombin and calcium chloride) have been observed, most clinicians are unaware that many tubes utilized for the production of 'natural' and '100% autologous' PRF may in fact contain chemical additives without appropriate or transparent knowledge provided to the treating clinician. The aim of this overview article is therefore to provide a technical note on recent discoveries related to PRF tubes and describe recent trends related to research on the topic from the authors laboratories. METHODS: Recommendations are provided to clinicians with the aim of further optimizing PRF clots/membranes by appropriate understanding of PRF tubes. The most common additives to PRF tubes reported in the literature are silica and/or silicone. A variety of studies have been performed on their topic described in this narrative review article. RESULTS: Typically, PRF production is best achieved with plain, chemical-free glass tubes. Unfortunately, a variety of other centrifugation tubes commonly used for lab testing/diagnostics and not necessarily manufactured for human use have been utilized in clinical practice for the production of PRF with unpredictable clinical outcomes. Many clinicians have noted an increased variability in PRF clot sizes, a decreased rate of clot formation (PRF remains liquid even after an adequate protocol is followed), or even an increased rate in the clinical signs of inflammation following the use of PRF. CONCLUSION: This technical note addresses these issues in detail and provides scientific background of recent research articles on the topic. Furthermore, the need to adequately select appropriate centrifugation tubes for the production of PRF is highlighted with quantitative data provided from in vitro and animal investigations emphasizing the negative impact of the addition of silica/silicone on clot formation, cell behavior and in vivo inflammation.

Improvement of bone repair with l-PRF and bovine bone in calvaria of rats. histometric and immunohistochemical study.

OBJECTIVES: The effect of leucocyte- and platelet-rich fibrin (L-PRF), associated with DBBM (deproteinized bovine bone mineral; Bio-Oss®) was investigated and compared with autogenous bone graft as a standard material for filling bone defects. MATERIAL AND METHODS: A defect of 5 mm in diameter was performed in 40 calvaria of rats. The animals were divided into 5 groups and received blood clot (CO), autogenous bone (AUT), DBBM (BIO), L-PRF, or DBBM associated with L-PRF (BIO-LPRF). After 4 and 8 weeks, bone regeneration was assessed by histometric and immunohistochemical analyses. RESULTS: The highest mean percentage of bone formation found at 4 and 8 weeks was observed for the BIO-L-PRF group (54.0% ± 2.8 and 63.6% ± 2.2). The lowest mean percentage at 4 and 8 weeks was observed for the CO group (16.7% ± 2.5 and 20.5% ± 1.0). There was statistical similarity among the AUT, BIO, and L-PRF groups. The expressions OC, RUNX 2, and VEGF showed a favorable aspect in the formation of new bone for BIO-L-PRF. VEGF was the marker with the highest expression because it was related to the initial healing process, promoting the migration and proliferation of endothelial cells in the region of the defect. Even after weeks, VEGF maintained a moderate expression. CONCLUSIONS: The association of L-PRF with DBBM improved bone repair when these biomaterials were inserted into the defects of the calvaria of rats. CLINICAL RELEVANCE: This reinforces the good performance of bovine bone and L-PRF as filler materials, especially when associated.

Use of platelet-rich fibrin for the treatment of gingival recessions: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to compare the use of platelet-rich fibrin (PRF) with other commonly utilized treatment modalities for root coverage procedures. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the performance of PRF with that of other modalities in the treatment of Miller class I or II (Cairo RT I) gingival recessions. Studies were classified into 5 categories as follows: (1) coronally advanced flap (CAF) alone vs CAF/PRF, (2) CAF/connective tissue graft (CAF/CTG) vs CAF/PRF, (3) CAF/enamel matrix derivative (CAF/EMD) vs CAF/PRF, (4) CAF/amnion membrane (CAF/AM) vs CAF/PRF, and (5) CAF/CTG vs CAF/CTG/PRF. Studies were evaluated for percentage of relative root coverage (rRC; primary outcome), clinical attachment level (CAL), keratinized mucosa width (KMW), and probing depth (PD) (secondary outcomes). RESULTS: From 976 articles identified, 17 RCTs were included. The use of PRF statistically significantly increased rRC and CAL compared with CAF alone. No change in KMW or reduction in PD was reported. Compared with PRF, CTG resulted in statistically significantly better KMW and RC. No statistically significant differences were reported between the CAF/PRF and CAF/EMD groups or between the CAF/PRF and CAF/AM groups for any of the investigated parameters. CONCLUSIONS: The use of CAF/PRF improved rRC and CAL compared with the use of CAF alone. While similar outcomes were observed between CAF/PRF and CAF/CTG for CAL and PD change, the latter group led to statistically significantly better outcomes in terms of rRC and KTW. In summary, the use of PRF in conjunction with CAF may represent a valid treatment modality for gingival recessions exhibiting adequate baseline KMW. CLINICAL RELEVANCE: The data indicate that the use of PRF in conjunction with CAF statistically significantly improves rRC when compared with CAF alone but did not improve KMW. Therefore, in cases with limited baseline KMW, the use of CTG may be preferred over PRF.