Leukocyte- And Platelet-rich Fibrin Research Articles

A randomised Trial of Autologous Blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in LEprosy: The TABLE trial.

Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. ISRCTN14933421. Date of trial registration: 16 June 2020.

L-PRF Secretome from Both Smokers/Nonsmokers Stimulates Angiogenesis and Osteoblast Differentiation In Vitro.

Leukocyte and Platelet-Rich Fibrin (L-PRF) is part of the second generation of platelet-concentrates. L-PRF derived from nonsmokers has been used in surgical procedures, with its beneficial effects in wound healing being proven to stimulate biological activities such as cell proliferation, angiogenesis, and differentiation. Cigarette smoking exerts detrimental effects on tissue healing and is associated with post-surgical complications; however, evidence about the biological effects of L-PRF derived from smokers is limited. This study evaluated the impact of L-PRF secretome (LPRFS) derived from smokers and nonsmokers on angiogenesis and osteoblast differentiation. LPRFS was obtained by submerging L-PRF membranes derived from smokers or nonsmokers in culture media and was used to treat endothelial cells (HUVEC) or SaOs-2 cells. Angiogenesis was evaluated by tubule formation assay, while osteoblast differentiation was observed by alkaline phosphatase and osterix protein levels, as well as in vitro mineralization. LPRFS treatments increased angiogenesis, alkaline phosphatase, and osterix levels. Treatment with 50% of LPRFS derived from smokers and nonsmokers in the presence of osteogenic factors stimulates in vitro mineralization significantly. Nevertheless, differences between LPRFS derived from smokers and nonsmokers were not found. Both LPRFS stimulated angiogenesis and osteoblast differentiation in vitro; however, clinical studies are required to determine the beneficial effect of LPRFS in smokers.

Treatment of Multiple RT1 Gingival Recessions Using a Coronally Advanced Flap Associated with L-PRF or Subgingival Connective Tissue Graft from Maxillary Tuberosity: A Randomized, Controlled Clinical Trial.

The goal of plastic periodontal surgery is to obtain complete root coverage, increasing gingival thickness (GT), a positive prognostic factor for gingival margin stability over time. The aim of this study was to compare the effectiveness of the Coronally Advanced Flap (CAF) in RT1 (GR; gingival recession with no loss of interproximal attachment) when associated with a connective tissue graft from the maxillary tuberosity (tCTG) or with leukocyte and platelet-rich fibrin (L-PRF) membranes in obtaining root coverage and increasing the thickness and width of the keratinized tissue, along with aesthetic improvement, taking into account a number of patient-related outcomes. Thirty patients with two adjacent RT1 GRs (GRs with no loss of interproximal attachment) were each treated using CAF associated with tCTG (15 patients) or L-PRF. The main outcome was a GT increase; secondary outcomes were keratinized tissue width (KT), gingival recession (GR), probing depth (PD), clinical attachment level (CAL), root coverage percentage (RC%), complete root coverage (CRC), and root coverage esthetic score (RES). Patient-reported outcomes were discomfort (D), dentine hypersensitivity (DH), patient-related esthetic score (PRES), and overall treatment satisfaction (OTS). After 12 months, clinical and patient-reported parameters did not show significant differences between groups, with the only exception being a GT gain, which was significantly greater in the CAF + tCTG group. Our results showed that both techniques were effective in treating RT1 GRs, with comparable patient-related outcomes. However, the use of tCTG produces significantly thicker tissue, covering the exposed root surface.

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.

Effect of local application of leukocyte and platelet-rich fibrin (L-PRF) on postoperative swelling and salivary IL-6 levels after surgical removal of impacted mandibular third molars.

Effect of local application of leukocyte and platelet-rich fibrin (L-PRF) on postoperative swelling and salivary IL-6 levels after surgical removal of impacted mandibular third molars.

Leukocyte- and platelet-rich fibrin in cranial surgery: a single-blinded, prospective, randomized controlled noninferiority trial.

CSF leakage is a major complication after cranial surgery, and although fibrin sealants are widely used for reinforcing dural closure, concerns exist regarding their safety, efficacy, and cost. Leukocyte- and platelet-rich fibrin (L-PRF), an autologous platelet concentrate, is readily available and inexpensive, making it a cost-effective alternative for commercially available fibrin sealants. This study aimed to demonstrate the noninferiority of L-PRF compared with commercially available fibrin sealants in preventing postoperative CSF leakage in supra- and infratentorial cranial surgery, with secondary outcomes focused on CSF leakage risk factors and adverse events. In a single-blinded, prospective, randomized controlled interventional trial conducted at a neurosurgery department of a tertiary care center (UZ Leuven, Belgium), patients undergoing elective cranial neurosurgery were randomly assigned to receive either L-PRF (active treatment) or commercially available fibrin sealants (control) for dural closure in a 1:1 ratio. Among 350 included patients, 328 were analyzed for the primary endpoint (44.5% male, mean age 52.3 ± 15.1 years). Six patients (5 in the control group, 1 in the L-PRF group) presented with CSF leakage requiring any intervention (relative risk [RR] 0.20, one-sided 95% CI -∞ to 1.02, p = 0.11), confirming noninferiority. Of these 6 patients, 1 (in the control group) presented with CSF leakage requiring revision surgery. No risk factors for reconstruction failure in combination with L-PRF were identified. RRs for adverse events such as infection (0.72, 95% CI -∞ to 1.96) and meningitis (0.36, 95% CI -∞ to 1.25) favored L-PRF treatment, although L-PRF treatment showed slightly more bleeding events (1.44, 95% CI -∞ to 4.66). Dural reinforcement with L-PRF proved noninferior to commercially available fibrin sealants, with no safety issues. Introducing L-PRF to standard clinical practice could result in important cost savings due to accessibility and lower cost. Clinical trial registration no.: NCT03812120 (ClinicalTrials.gov).

CHARACTERIZATION OF PHYSICAL AND CELLULAR PROPERTIES OF MEMBRANES OF L-PRF PRODUCED BY DIFFERENT CENTRIFUGES/ CENTRIFUGATION PROTOCOLS.

Leukocyte and platelet-rich fibrin (L-PRF), an essential source of cytokines and growth factors, has been widely used to regulate the healing process. The quality of the L-PRF obtained is dependent on technical factors and the centrifugation protocol used. Thus, the present study aimed to macro and microscopically evaluate the formation of the L-PRF membrane/clot in two centrifuge models and protocols recommended by manufacturers. Four blood samples from 8 healthy volunteers undergoing rehabilitation surgery with dental implants were used. In group 1 of the Montserrat centrifuge (model 80-2B 15mL) 400g of centrifugal force were used for 10 minutes, 27ºC, and 2700 rpm, while in group 2 of the Intra Spin-Intra-Lock centrifuge (IntraSpin™, Intra-Lock Iberia) 400g of centrifugal force were used for 12 minutes, 27ºC and 2700 rpm. After obtaining 32 L-PRF clots/membranes, the pieces were recorded, measured, and weighed, separating the L-PRF from the supernatant/clot of red blood cells, remaining in the tubes. The specimens were then histologically processed for Hematoxylin/Eosin (H/E) staining and each slide was divided into three called areas: proximal, center, and distal. The presence of leukocytes was analyzed semi-quantitatively in each area. The results revealed no significant macroscopic differences in L-PRF between the two groups. However, the central areas of the L-PRF membranes produced in group 2 showed higher intensity of leukocytes (p=0.012), as well as the presence of concomitant leukocytes in at least 2 of the evaluated areas (p=0.003). In the proximal area, no significant differences were observed between the two groups. The results allow us to postulate that technical protocol factors influence the presence and distribution of leukocytes between the L-PRF membranes, obtained in different centrifuges.

Evaluation of Post-Operative Morbidity and Palatal Wound Healing after Implant Uncovering Surgical Procedure Performed with Apically Positioned Flap (APF) and Leukocyte and Platelet-Rich-Fibrin (L-PRF): An Original Technique.

Background and Objectives: Dental implants are recognized as an effective treatment in the management of edentulous patients; controversies surround the connection between the sufficiency of keratinized gingiva (KG) and peri-implant health. Maintaining an ample amount of peri-implant KG is crucial for minimizing gingival inflammation, highlighting the need for regular consideration of soft-tissue augmentation. Among the diverse periodontal plastic surgical procedures, the apically positioned flap (APF) is notable for its ability to enhance the width of keratinized tissue while minimizing patient morbidity. The aim of this study was to evaluate the effects of L-PRF on palatal wound healing and patient discomfort after surgery. Materials and Methods: Twenty patients with two adjacent submerged fixtures in the maxilla and buccal keratinized gingiva widths < 2 mm were treated with APF and L-PRF. Clinical evaluations were performed at 1, 2, 3, and 4 weeks post-surgery, focusing on parameters such as complete wound epithelialization (CWE), postoperative discomfort (D), changes in feeding habits (CFH), alteration of sensitivity (AS) around the wound area, and the consumption of analgesics. Results: Our data revealed CWE in 5 patients by the end of the second week, with the remaining 15 achieving CWE by the end of the third week. For D and CHF, a statistically significant improvement was recorded for all cases between the first and second weeks, as well as AS, although less substantial, by the third week. No significant changes were noted for AS over the initial two weeks. Conclusions: These findings suggest that L-PRF may enhance wound healing and decrease patient discomfort following APF for fixture uncovering.

Leukocyte- and Platelet-Rich Fibrin (L-PRF) Obtained from Smokers and Nonsmokers Shows a Similar Uniaxial Tensile Response In Vitro.

We evaluated and compared the biomechanical properties of Leukocyte-and Platelet Rich Fibrin L-PRF clots and membranes derived from smoker and nonsmoker donors. Twenty venous-blood donors (aged 18 to 50 years) were included after signing informed consent forms. L-PRF clots were analyzed and then compressed to obtain L-PRF membranes. L-PRF clot and membrane samples were tested in quasi-static uniaxial tension and the stress-stretch response was registered and characterized. Furthermore, scanning electron microscope representative images were taken to see the fibrin structure from both groups. The analysis of stress-stretch curves allowed us to evaluate the statistical significance in differences between smoker and nonsmoker groups. L-PRF membranes showed a stiffer response and higher tensile strength when compared to L-PRF clots. However, no statistically significant differences were found between samples from smokers and nonsmokers. With the limitations of our in vitro study, we can suggest that the tensile properties of L-PRF clots and membranes from the blood of smokers and nonsmokers are similar. More studies are necessary to fully characterize the effect of smoking on the biomechanical behavior of this platelet concentrate, to further encourage its use as an alternative to promote wound healing in smokers.

Comparison of histologic and radiographic changes of sockets grafted with LPRF and sockets without intervention after tooth extraction.

After tooth extraction, marked resorption occurs in extraction socket walls, leading to functional and esthetic problems in that area. One of the methods introduced to reduce this resorption is the use of platelet derivatives. This study aimed to evaluate the effects of leukocyte and platelet-rich fibrin (L-PRF) on the changes following tooth extraction. The participants were 24 patients who needed to replace at least one single-rooted tooth with an implant. They were randomly divided into test and control groups. After the tooth extraction, the sockets in the test group received LPRF clots, while in the control group, the sockets were left free of any interventions. CBCT scans were obtained from the extraction site both immediately after the tooth extraction and 8 weeks later. The histologic biopsy was also obtained while the implant site was being prepared 8 weeks after the extraction. The average vertical bone loss in the buccal crest was not significantly different between the two groups (1.67 ± 1.67 in the test group and 2.3 ± 1.36 in the control group; mean difference =  - 0.36, 95% CI: - 1.65-0.93, p-value = 0.57). Nor was the difference in resorption of the palatal wall (mean difference =  - 0.19, 95% CI: - 1.51.12, p-value = 0.76). The mean ridge width resorption in 25% of the coronal aspect of sockets was also measured in the test (1.30 ± 0.66) and control group (0.58 ± 0.95) (mean difference = 0.73, 95% CI: 0.03-1.42, p-value = 0.04). The new bone formation in histologic view was not statistically different between groups (p-value = 0.15). The LPRF neither reduces the rate of ridge resorption in vertical or horizontal dimensions of extraction sockets nor induces more new bone formation. This study helps dentists choose the appropriate material for ridge preservation.

Do blood concentrates influence inflammatory signs and symptoms after mandibular third molar surgery? A systematic review and network meta-analysis of randomized clinical trials.

To investigate, through a network meta-analysis, the effectiveness of blood concentrates in reducing pain perception, trismus, and edema after mandibular third molar extraction. An electronic search was performed in nine databases to locate randomized clinical trials comparing blood concentrate use after mandibular third molar extraction. Two authors selected and extracted the data independently. The individual risk of bias in the studies was assessed with the RoB v2.0 tool. A network meta-analysis compared postoperative pain and trismus scores after applying different blood concentrates, using the mean difference (MD) as an effect estimate. The GRADE approach assessed the certainty of evidence. Thirty-one randomized clinical trials were included in the review and 18 in the meta-analysis. Leukocyte- and platelet-rich fibrin (L-PRF) was the most used blood concentrate, followed by platelet-rich plasma (PRP). The network meta-analysis, depending on the analyzed period, evaluated up to 1240 surgeries. Among the analyzed blood concentrates, advanced platelet-rich fibrin (A-PRF) performed better among the analyzed blood concentrates, decreasing postoperative pain in 1, 2, 3, and 7 days and reducing trismus up to the inflammatory peak compared to blood clots. Only two studies had a low risk of bias. Based on very low certainty of evidence, using concentrates seemed efficient compared to blood clots in reducing pain and trismus after mandibular third molar surgeries. A-PRF decreased postoperative pain throughout the evaluated time and trismus during the acute inflammatory peak. A-PRF after mandibular third molar extractions performed better among the analyzed blood concentrates and seemed efficient in improving postoperative quality by decreasing inflammatory signs and symptoms.

The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons-Implications for Biomaterial Applicability.

Leukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient's own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications.

Proteomic Analysis of Mesenchymal Stromal Cells Secretome in Comparison to Leukocyte- and Platelet-Rich Fibrin.

Secretomes of mesenchymal stromal cells (MSCs) are emerging as a novel growth factor (GF)-based strategy for periodontal and bone regeneration. The objective of this study was to compare the secretome of human bone marrow MSC (BMSC) to that of leukocyte- and platelet-rich fibrin (L-PRF), an established GF-based therapy, in the context of wound healing and regeneration. Conditioned media from human BMSCs (BMSC-CM) and L-PRF (LPRF-CM) were subjected to quantitative proteomic analysis using liquid chromatography with tandem mass spectrometry. Global profiles, gene ontology (GO) categories, differentially expressed proteins (DEPs), and gene set enrichment (GSEA) were identified using bioinformatic methods. Concentrations of selected proteins were determined using a multiplex immunoassay. Among the proteins identified in BMSC-CM (2157 proteins) and LPRF-CM (1420 proteins), 1283 proteins were common. GO analysis revealed similarities between the groups in terms of biological processes (cellular organization, protein metabolism) and molecular functions (cellular/protein-binding). Notably, more DEPs were identified in BMSC-CM (n = 550) compared to LPRF-CM (n = 118); these included several key GF, cytokines, and extracellular matrix (ECM) proteins involved in wound healing. GSEA revealed enrichment of ECM (especially bone ECM)-related processes in BMSC-CM and immune-related processes in LPRF-CM. Similar trends for intergroup differences in protein detection were observed in the multiplex analysis. Thus, the secretome of BMSC is enriched for proteins/processes relevant for periodontal and bone regeneration. The in vivo efficacy of this therapy should be evaluated in future studies.

The effect of leukocyte- and platelet-rich fibrin on the bone loss and primary stability of implants placed in posterior maxilla: a randomized clinical trial

PurposeIn this study, we investigated the effects of leukocyte- and platelet-rich fibrin (L-PRF) on implant stability and alterations in the marginal bone surrounding posterior maxillary implants.MethodsThis randomized clinical trial was conducted to compare the variable of L-PRF placement around maxillary implants. Resonance frequency analysis (RFA) was used to evaluate the implant stability immediately after surgery and at 1, 2, 4, 6, 8, and 12 weeks after surgery (t0 to t6, respectively). In addition, the amount of marginal bone changes around the implant at t6 was compared with the baseline using periapical radiography.ResultsThe RFA outcomes were statistically significant within each group (P < 0.001, Eta2 = 0.322); however, in none of the follow-ups and immediately after the surgery, there was a significant difference between the two groups in terms of the implant stability quotient (ISQ) scores (P > 0.05). At t0, the test and control groups' respective mean levels of marginal bone loss around the implants were 0.4836 mm and 0.7343 mm, significantly different from the corresponding values at t6. On the other hand, marginal bone loss around the implant was not significantly different between the two groups in t0 and t6 (P = 0.532).ConclusionsL-PRF did not improve the RFA outcomes of implants three months after implant placement, and changes in the ISQ values over time were the same in both groups. In addition, L-PRF had no superior effect on the marginal bone loss around the implants.Trial registration number: The research was registered in the Iranian Registry of Clinical Trials on 22 December 2020 (No: IRCT20200624047906N1), available at http://www.irct.ir

Review of Dohan Eherenfest et al. (2009) on “Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)”

This classic discusses the original publication of Dohan Eherenfest et al. on "Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)", in which the authors propose four categories of platelet concentrates depending on their leukocyte and fibrin content (P-PRP, leucocyte- and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), and L-PRF) to group a "jungle" of products in which the term platelet-rich plasma (PRP) was used indistinctly. They were able to identify common factors such as: (1) the use of anticoagulant and immediate centrifugation of the blood after its collection, (2) most preparation techniques allowed platelet concentrate preparation within an hour, (3) the centrifugation aimed to separate the blood in layers that would allow the extraction of specific fractions, and (4) the product was activated with thrombin or calcium chloride. The reviewed manuscript has been listed among the most cited PRP articles in regenerative medicine, with more than 800 citations, driving the current scientific research and clinical practice by categorizing L-PRP and P-PRP (now, leukocyte-poor PRP). The classification has also opened the door to understanding intrinsic biological mechanisms between the platelets, leukocytes, fibrin, and growth factors, later considered for studying the proliferation and differentiation of cells in different tissues affected by PRP. Since the initial classification of platelet concentrates, several other classification systems have been proposed and published in the current literature, such as the PAW, Mishra, PLRA, DEPA, MARSPILL, etc. These classifications have identified important aspects of PRP that affect the biological composition and, ultimately, the indications and outcomes. To date, there is still a lack of standardization in sample preparation, cohort heterogeneity, and incomplete reporting of sample preparation utilized, leading to a lack of clarity and challenging researchers and clinicians.

Horizontal Alveolar Ridge Augmentation in the Mandibular Posterior Region Using Biphasic Calcium Phosphate and Leukocyte- and Platelet rich fibrin (L-PRF): A case report.

In bone defects caused by tooth loss, tissue reconstructions are necessary to enable prosthetic rehabilitation with dental implants. Diverse techniques and materials of different origins are used for this purpose.  Leukocyte- and Platelet-Rich Fibrin (L-PRF) has been used in association with osteoconductive biomaterials in procedures of bone regeneration and for covering grafted areas. The aim of this article was to demonstrate a clinical case of bone grafting in the posterior region of the mandible, performed with the use of synthetic biomaterial composed of biphasic calcium phosphate associated with Leukocyte- and Platelet-Rich Fibrin for performing bone augmentation in an alveolar ridge with a horizontal defect, thereby enabling later installation of dental implants and prosthetic rehabilitation in the region. Keywords: bone graft, biomaterials, leukocyte- and platelet-rich fibrin, bone substitutes, dental implants.

Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial

BackgroundRecent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement.Methods/designThis multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed.DiscussionWith this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants.Trial registrationClinicalTrials.gov NCT03910374. Registered on 10 April 2019.

Does leucocyte- and platelet-rich fibrin enhance neurosensory recovery after genioplasty? A double-blind, split-mouth, randomised clinical trial

Neurosensory disturbances (NSD) are common after genioplasty. In this study we aimed to assess the recovery of NSDs with or without leukocyte- and platelet-rich fibrin (L-PRF) following genioplasty. In this double-blind, split-mouth, randomised clinical trial, L-PRF was applied around the mental nerve at the osteotomy site in genioplasty (treatment side). The contralateral side was considered the control side. Two-point discrimination (TPD) test, brush test, and self-reported NSDs (SR-NSD) were used to determine NSD at one, four, and 12 months after genioplasty. Twenty patients were studied. At one and four months after osteotomy, the mean scores of TPD and SR-NSDs were significantly different between the treatment and control sides (p = 0.04, p = 0.01, respectively). The mean of TPD and SR-NSDs was not statistically different on both sides 12 months after operation (p = 0.05, p = 0.71, respectively). The application of L-PRF may enhance the speed of NSD recovery four months after genioplasty.

Effect of Leukocyte- and Platelet-Rich Fibrin in Postoperative Recovery Following Impacted Mandibular Third Molar Surgery: A Split Mouth Study

Objective: The surgeries for extraction of impacted lower third molars are more associated with complications such as pain and postoperative edema. The purpose of the present study was to evaluate the impact of the use of Leukocyte- and Platelet-Rich Fibrin (L-PRF) on pain and edema after extraction of impacted mandibular third molars.&#x0D; Material and Methods: A cross-sectional split-mouth study was conducted with 15 volunteer patients who had both impacted mandibular third molars with indication for extraction. The removal surgery was performed one side at a time, with an interval of 14 days. One side received L-PRF while the other did not. Patients were evaluated on the 2nd and 7th postoperative days for mouth opening, pain and edema.&#x0D; Results: In total, data from 14 patients (4 men and 10 women), with a mean age of 21.83 ± 2.8 years were evaluated. There was no statistically significant difference regarding mouth opening, pain and edema on the 7th postoperative day. On the second postoperative day, greater edema was observed in the control group with a statistically significant difference (p = 0.01).&#x0D; Conclusions: Under controlled conditions, the L-PRF does not appear to alter postoperative recovery after extraction of the lower third molars in terms of pain, edema and the ability to open the mouth. Despite the statistically significant difference in edema on the second day, the means were very close and were not clinically relevant.

Clinical Efficacy of Platelet Derivatives in Periodontal Tissue Regeneration: An Umbrella Review.

This umbrella review aimed to consolidate the best available evidence regarding the clinical efficacy of platelet derivatives in the treatment of periodontal defects associated with periodontitis and in the management of mucogingival deformities. The "umbrella review" strategy was used to identify systematic reviews and meta-analyses. The search was performed without language restrictions and updated at the end of February 2023. The PubMed and Scopus databases, together with gray literature, were included in the search. The search yielded 412 studies. Subsequently, 12 articles were selected for further examination based on relevance. Finally, eight systematic reviews and meta-analyses were assessed. Regarding intrabony defects, in terms of clinical attachment level (CAL) gain, platelet-rich fibrin (PRF) was observed to lead to a statistically significant attachment gain compared to surgical therapy alone. PRF was also found to show greater CAL gain compared to platelet-rich plasma (PRP) and other biomaterials. The parameter probing depth decreased significantly when PRF was used compared to surgical therapy alone (P < 0.05). Similar results were seen when leukocyte- and platelet-rich fibrin (L-PRF) was applied. In terms of radiographic bone fill, both PRF and PRP showed significantly greater bone fill compared to surgical therapy. Regarding the results of periodontal plastic surgery, PRF favored a slight root coverage compared to the coronally displaced flap. This result depended on the number of PRF and L-PRF membranes used, but Emdogain or connective tissue graft produced better results regardless. However, an improvement in the healing of periodontal tissues was reported. Therapies with platelet derivatives applied to intrabony defects provided superior regenerative results compared to monotherapies, except in the case of root coverage.