THE BIO-STIMULATORY EFFECT OF ADVANCE PLATELET RICH FIBRIN COMBINED WITH LASER ON DENTAL IMPLANT STABILITY: AN EXPERIMENTAL STUDY ON SHEEP.

Implant stability is the major important requirement for the progress of a dental implant in the bone bed before loading the dental implant without clinical micro motion of the macula. Advance platelet rich fibrin (A-PRF) can be considered a "tissue engineering marvel" due to the typical properties of an osteo promoting matrix that improve the sustained release of growth factors that modulate and support osteoblast proliferation, migration, and adhesion, and at the same time regulates the production of collagen proteins. Low level laser therapy (LLLT) biostimulation increases blood circulation, promotes the revitalization process, reduces the risk of infection, improves metabolic activity, and accelerates the healing of damaged tissues. This study aimed to assess the effect of Advance platelet rich fibrin (A- prf) with low level laser therapy biostimulation (LLL Biostimulation) on implant stability. Four healthy male sheep were randomly divided into 2 groups (two in each group).Group 1 (control), at of which ten implants were placed on one side of the tibia and ten dental implants on the other side of the tibia with no additions for a total of 10 implants and Group 2 (study) where ten implants were placed on one side and ten dental implants on the other side of the tibia augmented with Advanced Platelet Rich Fibrin Membrane and LLLT Bio stimulation. Primary and secondary dental implant stability were recorded by radiofrequency evaluation using Osstell device immediately after placement, four and eight weeks postoperatively. The results of the current study showed no significant difference between control and study group in implant stability at baseline (day of surgery) but after four and eight weeks there was a significant difference between the control group and the study group. Advance platelet rich fibrin (A- prf) with low level laser therapy biostimulation (LLL Biostimulation) plays a role in new bone formation and enhance implant stability.

In Vitro and Ex Vivo Kinetic Release Profile of Growth Factors and Cytokines from Leucocyte- and Platelet-Rich Fibrin (L-PRF) Preparations.

L-PRF is an autologous blood-derived biomaterial (ABDB) capable of releasing biologically active agents to promote healing. Little is known about its release profile of growth factors (GFs), cytokines, and MMPs. This study reported the in vitro and ex vivo release kinetics of GFs, cytokines, and MMPs from L-PRF at 6, 24, 72, and 168 h. The in vitro release rates of PDGF, TGF-ß1, EGF, FGF-2, VEGF, and MMPs decreased over time with different rates, while those of IL-1ß, IL-6, TNF-α, IL-8, and IL-10 were low at 6 h and then increased rapidly for up to 24 h and subsequently decreased. Of note, the release rates of the GFs followed first-order kinetics both in vitro and ex vivo. Higher rates of release were found ex vivo, suggesting that significant amounts of GFs were produced by the local cells within the wound. In addition, the half-life times of GFs locally produced in the wound, including PDGF-AA, PDGF-AB/BB, and VEGF, were significantly extended (p < 0.05). This work demonstrates that L-PRF can sustain the release of GFs and cytokines for up to 7 days, and it shows that the former can activate cells to produce additional mediators and amplify the communication network for optimizing the wound environment, thereby enhancing healing.

Plasma Rich in Growth Factors in the Treatment of Endodontic Periapical Lesions in Adult Patients: Case Reports.

Platelet-rich fibrin (PRF) is an autologous blood concentrate obtained without anticoagulants by centrifugation of patients' peripheral venous blood. PRF is considered to enhance the formation of new bone. The aim of this manuscript was to present two case reports of permanent teeth with closed apexes with periapical lesions, treated endodontically with the use of PRF. The root canals were mechanically cleaned and shaped with NiTi files and irrigated with 5.25% sodium hypochlorite (NaOCl), 40% citric acid (CA), and triple distillated water. Before the canal systems were obturated, A-PRF was used as a scaffold and was placed below the cementodentinal junction with hand pluggers. Cone beam computerized tomography (CBCT) was used to assess the resolutions of periapical radiolucencies. After 6 months, the measurements of both periapical lesions were significantly reduced. Although the performed root canal treatments (RCTs) can definitely be recognized as successful, it must be emphasized that mechanical shaping and cleaning of the root canals with special disinfecting solutions significantly affect the clinical efficacy of RCT. It seems impossible to state that PRF played a leading role in the healing process of the presented periapical lesions. Further studies must be performed to assess whether RCT of mature teeth with an additional PRF application is superior to RCT performed alone.

The Role of Platelet-Rich Fibrin (PRF) in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ).

Dentoalveolar surgery is probably the major risk factor for MRONJ and for other complications following a tooth extraction, especially in patients affected by systemic diseases. The aim of this retrospective study is to evaluate whether a PRF plug inserted in the post extraction socket can prevent the onset of MRONJ. The patients were divided into two groups according to the surgical protocol that included the insertion or not of the PRF following the extraction and all the anamnestic, and clinical data were analyzed. In the control group, 5 patients developed MRONJ (19.23%) while in the study group, any case of MRONJ was reported. In the control group, patients who developed MRONJ had a CTX with less than 100 pg/mL (5 high-risk patients, Spearman's rank r = .547, p < .001). The use of platelet concentrates in patients with high risk of MRONJ is a user-friendly technique with an excellent cost-benefit ratio in oral surgery.

The effect of platelet-rich fibrin (PRF) on wound healing, adhesion, and hemostasis after endoscopic sinus surgery in patients with nasal polyposis.

PURPOSE: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases seen worldwide. Endoscopic sinus surgery (ESS) has become a widely accepted procedure for medically refractory chronic rhinosinusitis and nasal polyps. Prevention of revision surgery often depends on good wound healing and less adhesion formation. In recent years, the effects of platelet-rich fibrin (PRF) on tissue healing have been addressed in many surgical branches, especially for dental implant surgery and plastic surgery. METHODS: This prospective study was conducted with 50 patients who underwent endoscopic sinus surgery for the diagnosis of nasal polyposis. While the middle meatus in one nasal cavity was filled with PRF and supported with Nasopore, only Nasopore was used in the other nasal cavity middle meatus. The patients were followed up clinically at weeks 1, 2, 3, 4, 8, and 12 postoperatively. The assessor determined the presence of adhesion, crusting, bleeding, frontal ostium stenosis, granulation, and infection, and if present, the grades of these complications were scored according to a questionnaire. RESULTS: In our study, adhesion, infection, bleeding, granulation, and frontal ostium stenosis were less common in the PRF group, and a statistically significant difference was found between the groups. CONCLUSION: In our study, better results were obtained in terms of adhesion, infection, bleeding, granulation, and frontal ostium stenosis after ESS as a result of the effects of PRF on wound healing. The application of PRF is an inexpensive and easy procedure. PRF can be a good alternative to other types of tampons after ESS.

Plasma rico en fibrina e injerto conectivo en la instalación de un implante dental / Fibrin-rich plasma and connective tissue graft in dental implant installation

Introducción: Combinar tratamientos regenerativos con injertos de tejido blando impide que el tejido periimplantario se atrofie y altere la estética. Los resultados de esta combinación son discutidos en la literatura actual cuando se trata de implantes inmediatos. Objetivo: Describir el tratamiento regenerativo combinando plasma rico en fibrina e injerto conectivo en la instalación de un implante dental en el sector anterosuperior. Presentación del caso: El paciente fue un varón de 40 años de edad sin antecedentes de enfermedades sistémicas, con trauma facial. Al examen clínico se observó una corona de porcelana fracturada a nivel cervical vestibular, secreción purulenta en proceso de cicatrización y contorno gingival alterado. En el examen radiográfico se evidenció una lesión periapical con aparente reabsorción radicular. Se extrajo el diente, se colocó plasma rico en fibrina para mejorar la cicatrización, se esperaron 6 semanas y se colocó un implante. Al cabo de 4 meses se realizó la segunda fase con un injerto de tejido conectivo y colocación del cicatrizal, se esperaron dos semanas y se colocó una corona de porcelana. Conclusiones: En el presente caso, la combinación de plasma rico en fibrina e injerto conectivo favoreció el aspecto estético periimplantario sin evidenciarse complicaciones durante el posoperatorio(AU)

Introduction: Combining regenerative treatments with soft tissue grafts prevents atrophy of the peri-implant tissue and alterations in esthetics. The results of this combination are discussed in the current literature. Objective: To describe the regenerative treatment, combining Fibrin-rich plasma and connective tissue graft in the installation of a dental implant in the upper anterior sector. Case presentation: Forty-year-old male patient with facial trauma. He has no history of systemic diseases. On clinical examination, a fractured porcelain crown was found at the vestibular cervical level. There was purulent discharge in the healing process and altered gingival contour. Radiographic examination revealed a periapical lesion with apparent root resorption. The tooth was extracted; fibrin-rich plasma was placed to improve healing. Six weeks after, an implant was placed. After the first four months, the second phase was performed with a connective tissue graft and placement of the scar tissue; two weeks after, a porcelain crown was placed. Conclusions: In the present case, the combination of Fibrin-rich plasma and connective tissue graft favored the peri-implant esthetic appearance without evidence of complications during the postoperative period(AU)

Evaluation of the regenerative potential of dentin conditioning and naturally derived scaffold for necrotic immature permanent teeth in a dog model.

This study evaluated the outcome of partial exposure of dentin matrix to ethylenediaminetetraacetic acid (EDTA) and application of platelet-rich fibrin (PRF) scaffold on regeneration of necrotic immature permanent teeth in a dog model. The present study was carried out on 216 permanent immature roots in nine mongrel dogs aged 6-9 months. Pulp necrosis and periapical pathosis were induced in 180 roots. These roots were divided into five equal groups (36 roots each) according to the treatment protocol: group I: blood clot; group II: 17% EDTA solution and blood clot; group III: PRF; group IV: 17% EDTA solution and PRF; and group V: without treatment (positive control). The negative control group (group VI) represented 36 untouched normal roots for normal maturation. The groups were followed up for 1, 2 and 3 months (subgroups). Maturation of the roots was monitored by radiography and histopathology. All data were statistically analysed. Group IV exhibited the highest increase in root length and thickness, decrease in apical diameter, the highest score of vital tissue infiltration and least inflammatory scores. There was a significant difference regarding the increase in root length and thickness and decrease in apical diameter in all subgroups of the experimental and negative control groups (P ≤ .05). PRF has a better regenerative potential than the blood clot during treatment of immature permanent teeth with necrotic pulp. Inclusion of 17% EDTA solution as a final irrigation enhances the regenerative potential of both PRF and blood clot.

Evaluation of PRF Efficiency in the Treatment of Infrabony Defects.

AIM: The present study aimed to investigate the effectiveness of PRF in the treatment of infrabony defects in patients with chronic periodontitis by evaluating the clinical outcome through periodontal depth, clinical attachment level at the baseline, 6 and 9 months post operatively. MATERIAL AND METHODS: Sixty infrabony defects with probing depth ≥ 5 mm were treated. The inclusion criterion was the necessity for surgical bilateral maxillary treatment. By using split-mouth study design, each patient had one side treated with conventional flap surgery and the other side with conventional flap surgery and PRF. Clinical parameters, such as probing depth (PD) and clinical attachment lost (CAL), were recorded in both groups at baseline, 6 and 9 months post operatively. RESULTS: Positive effects for all clinical and radiographic parameters were evident in the group with PRF. Mean PD reduction demonstrated statistically significant greater results in the test group (4.00±1.07 mm) compared to the control one (4.83±0.99 mm), p = 0.003 after 9 months postoperatively. After 9 months, there were better results in the test group compared to the control group for CAL (5.60±1.61 mm, 6.20±1.58 mm), but statistically not significant. CONCLUSION: Additional use of PRF in the conventional surgical treatment of infrabony defects demonstrated better parameters than the open flap debridement alone.

Resultados de los concentrados plaquetarios en la regeneración ósea guiada / Results of platelet concentrates in guided bone regeneration

Los defectos óseos alrededor de los implantes dentales son considerados enfermedades que afectan el soporte y estabilidad del implante dental lo que limita la oseointegración. El tratamiento de estos defectos involucra procedimientos de regeneración ósea guiada que se define como la reproducción o reconstitución de una parte perdida o dañada del tejido óseo periimplantario con el fin de restaurar su arquitectura y función. El plasma rico en plaquetas y el plasma rico en fibrina son concentrados de plaquetas autólogos ampliamente usados en la regeneración periodontal y regeneración ósea guiada; sin embargo, sus resultados clínicos, histológicos y radiográficos son discutidos cuando se tratan defectos óseos alrededor de implantes dentales. En la presente revisión se realizó una búsqueda de la información mediante las bases de datos de diferentes buscadores (PubMed, SciELO, Redalyc y ScienceDirect) para encontrar artículos que traten sobre el uso de los concentrados plaquetarios (plasma rico en plaquetas y plasma rico en fibrina) en la terapia de la regeneración ósea guiada. Clínicamente, los concentrados plaquetarios otorgan resultados favorables en la reducción de la profundidad de sondaje y ganancia de nivel de inserción clínica en el tratamiento de defectos infraóseos periodontales. Histológicamente, los concentrados plaquetarios favorecen la neoformación ósea aumentando la velocidad de regeneración. Radiográficamente, los concentrados plaquetarios favorecen el aumento de densidad ósea, relleno óseo y tejido mineralizado. Con ello, se logra una reducción significativa del tamaño del defecto óseo(AU)

Bone defects around dental implants are considered to be diseases affecting the support and stability of the implant, thus limiting osseointegration. Treatment of these defects involves guided bone regeneration procedures, defined as the reproduction or reconstitution of a part lost or damaged of the peri-implant bone tissue with the purpose of restoring its architecture and function. Platelet-rich plasma and fibrin-rich plasma are autologous platelet concentrates widely used in guided bone regeneration and periodontal regeneration. However, their clinical, histological and radiographic results are debated when bone defects around dental implants are dealt with. The present review included a search for information in the databases of various search engines (PubMed, SciELO, Redalyc and ScienceDirect) to find papers about the use of platelet concentrates (platelet-rich plasma and fibrin-rich plasma) in guided bone regeneration therapy. Clinically, platelet concentrates yield favorable results in reducing probing depth and raising the level of clinical insertion in the treatment of periodontal intraosseous defects. Histologically, platelet concentrates enhance bone neoformation, speeding up regeneration. Radiographically, platelet concentrates lead to an increase in bone density, bone filler and mineralized tissue. A significant reduction is thus achieved in the size of the bone defect(AU)

Surgical and Immunohistochemical Outcomes of Scleral Reconstruction with Autogenic, Allogenic and Xenogenic Grafts: An Experimental Rabbit Model.

Purpose: Choukroun's platelet-rich fibrin (PRF), a second-generation platelet concentrate, has unique morphological and chemical features and may be considered as a scaffold for scleral reinforcement and regeneration. The purpose of this study was to compare the use of xenogenic human-derived amniotic membrane (HAM), allogenic sclera, and autogenic PRF in rabbit lamellar scleral defect model with respect to both anatomical and immunohistochemical improvement. Methods: A total of 45 adult New Zealand rabbits were randomized into five groups: normal control; without surgical procedure, negative control; scleral defect model (SDM), xenogenic HAM; SDM+HAM graft, allogenic sclera; SDM+allogenic sclera graft, autogenic PRF; SDM+autogenic PRF graft. Clinical findings, Hematoxylin&Eozin (HE), Masson Trichrome, Verhoeff Acid Fuchsin, Transforming Growth Factor ß Receptor 1, Fibroblast Growth Factor, Bone Morphogenetic Protein 2, collagen type 1, aggrecan, and Matrix Metalloproteinase 2 were evaluated. Results: Ocular surface inflammation was significantly lower in normal control and autogenic PRF groups (p < .001). Graft was avascular and not integrated to scleral wound area in 25% rabbits of allogenic sclera group (p = .02), was out of the scleral wound in 33.3% rabbits of xenogenic HAM group (p > .05), all the grafts were at the normal location and viable in autogenic PRF group. The inflammation and vascularization in autogenic PRF group was significantly lower than negative control and xenogenic HAM groups in HE (p < .001). The collagen score of negative control and xenogenic HAM groups were significantly lower than normal control (p < .001) and autogenic PRF (p < .001) groups. There were insignificant differences between allogenic sclera and autogenic PRF groups (p > .05). For immunohistochemistry, the closest values to normal control group were detected in autogenic PRF group for all immunomarkers. Conclusion: Autogenic PRF showed superior features via its excellent anatomical and chemical composition for scleral regeneration when compared to single-layered xenogenic HAM and allogenic sclera grafts.

Advanced platelet-rich fibrin plus gold nanoparticles enhanced the osteogenic capacity of human mesenchymal stem cells.

OBJECTIVES: There is still insufficient clinical evidence of platelet-rich fibrin beneficial effects on bone regeneration. Gold nanoparticles have been shown to enhance osteogenic differentiation and bone mineralization. The purpose of this study was to investigate the effect of advanced-platelet-rich fibrin modified by gold nanoparticles on the osteoblastic differentiation of human mesenchymal stem cells. RESULTS: MTT assay revealed 0.0125 mM gold nanoparticles had no cytotoxic effects on stem cells after 7 days. The addition of 0.0125 mM gold nanoparticle to advanced-platelet-rich fibrin clot increased cell viability compared to the non-treated control group (p < 0.05). 7-day incubation of stem cells with advanced-platelet-rich fibrin modified by gold nanoparticles conditioned media was shown to promote alkaline phosphatase activity compared to the control cells and group treated with advanced-platelet-rich fibrin condition media (p < 0.05). By using Alizarin Red S staining, red-colored calcium deposits were observed in the group treated with advanced-platelet-rich fibrin and gold nanoparticles conditioned media in comparison with non-treated cells (p < 0.05). Advanced-platelet-rich fibrin conditioned medium was unable to promote calcium deposition compared to the combination of advanced-platelet-rich fibrin and gold nanoparticles (p < 0.05). Adding gold nanoparticles to advanced-platelet-rich fibrin and fibrin and platelet byproducts could be an alternative strategy to improve osteogenic capacity of stem cells.

Resultados del uso de la fibrina rica en plaquetas y rellenos óseos en la regeneración ósea guiada. Revisión sistemática / Results of platelet rich fibrin and bone grafts in guided bone regeneration. A systematic review

OBJETIVO: El propósito de esta revisión fue evaluar sistemáticamente la literatura científica sobre los resultados que se obtienen al combinar la fibrina rica en plaquetas (PRF) y rellenos óseos en la regeneración ósea guiada. MATERIALES Y MÉTODOS: Búsqueda detallada en las bases de datos PubMed, Scopus, Web of Science, ScienceDirect, Cochrane y SciELO para obtener la información más actualizada de los resultados (grado de relleno óseo, éxito de la cirugía, movilidad del implante, complicaciones posquirúrgicas, supervivencia del implante) entre los casos tratados con PRF y los casos donde se combinó PRF con algún tipo de relleno óseo. RESULTADOS: De las 965 publicaciones identificadas inicialmente, se excluyeron reportes clínicos, revisiones, estudios observacionales, etc. Se incluyeron 12 ensayos clínicos que contrastaron las variables entre la técnica con PRF solo y la combinación con un relleno óseo. CONCLUSIÓN: La combinación entre PRF más rellenos óseos promueve la neoformación ósea, aumenta el trabeculado y mejora los tiempos de cicatrización; sin embargo, al cabo de 6 meses de control los resultados no son diferentes significativamente de los de los grupos que no utilizaron PRF en el procedimiento de levantamiento de piso de seno maxilar con técnica de ventana lateral. Respecto a la preservación de reborde alveolar, los distintos estudios no son concluyentes: algunos indican que la mezcla de PRF con un relleno óseo parece mejorar las proporciones volumétricas; sin embargo, otros refirieron pérdidas óseas en anchura e incluso mayor grado de inflamación

OBJECTIVE: To evaluate systematically the results obtained by combining platelet rich fibrin (PRF) and bone fill in guided bone regeneration, according to scientific literature. MATERIALS AND METHOD: Detailed search of database from PubMed, Scopus, Web of Science, ScienceDirect, Cochrane and SciELO to obtain the most updated information of clinical results (bone filling degree, surgical success, implant mobility, post-surgical complications, and implant survival) of the cases treated with PRF and the cases where the platelet rich fibrin was combined with a bone filler. Those results registered and compared. RESULTS: From the 965 files initially identified, were excluded clinical reports, reviews, observational studies, comments, studies with pediatric patients and so on. There were included 12 clinical essays where the variables of the technique with PRF and the technique where the PRF was combined with a bone filler were contrasted. CONCLUSION: The combination of PRF plus bone filler promotes bone neoformation, increased trabecular bones, and improved healing times; however, after 6 months of monitoring, the results were not significantly different with the groups that did not use the PRF in the procedure of maxillary sinus floor lift with lateral window technique. Regarding the preservation of alveolar ridge the different studies are not conclusive: some indicate that the mixture of a concentrate with a bone filling seems to improve the volumetric proportions; however, other studies report bone loss in width and even greater degree of inflammation

Platelet-Rich Plasma and Platelet-Rich Fibrin Enhance the Outcomes of Fat Grafting: A Comparative Study.

BACKGROUND: Autologous fat grafting is an efficient procedure in plastic surgery. However, its long-term tissue absorption is variable and technique-dependent. Platelet-rich plasma positively affects fat-grafting outcomes but still has shortcomings, and platelet-rich fibrin has been reported to have efficacy in fat transplantation. Here, we compared the effects of platelet-rich fibrin and platelet-rich plasma in fat grafting using histologic analysis. METHODS: Twenty rabbits were divided randomly into two groups. In each group, the groin region fat pads were cut into 1-mm granules. Platelet-rich fibrin-treated or platelet-rich plasma-treated fat granules were transplanted into one ear, whereas the contralateral ear was transplanted with normal saline-treated fat granules. Histologic characteristics and capillary density of grafted tissue were analyzed 12 weeks after fat grafting. RESULTS: The grafted fat in the platelet-rich fibrin-treated group showed higher tissue retention than that in the control group [weight retention, 19.57 percent (interquartile range, 13.87 to 29.93 percent) versus 9.04 percent (interquartile range, 6.16 to 16.80 percent), p < 0.05; and volume retention, 18.00 percent (interquartile range, 10.50 to 26.50 percent) versus 8.00 percent (interquartile range, 5.75 to 13.25 percent), p < 0.05] and higher neovascularized capillary density than that in the platelet-rich plasma-treated and control groups. The platelet-rich plasma-treated group showed higher vessel density without superior tissue retention compared with the control group. CONCLUSION: Platelet-rich fibrin increased tissue retention, quality, and vascularization of grafted fat compared with the control group and showed effects similar to those of platelet-rich plasma on tissue retention and histologic graft improvement.

Fluid platelet-rich fibrin stimulates greater dermal skin fibroblast cell migration, proliferation, and collagen synthesis when compared to platelet-rich plasma.

BACKGROUND: Regenerative therapies in the field of facial aesthetics have become a growing field of interest with many recent advancements made over the past decade to meet the growing worldwide demand. While first versions of platelet-derived concentrates were formulated with anticoagulants (PRP), recent modifications to centrifugation speeds and times have permitted the development of a liquid platelet-rich fibrin (fluid-PRF) without use of anticoagulants. OBJECTIVE: To compare this entirely natural platelet concentrate (fluid-PRF) to formally utilized PRP on skin cell behavior and regeneration. METHODS: Dermal skin fibroblast was cultivated with either fluid-PRF or PRP and investigated for their ability to promote/influence cell viability, migration, spreading, proliferation, and mRNA levels of known mediators of dermal biology including PDGF, TGF-beta, and fibronectin. RESULTS: All platelet concentrates were nontoxic to cells demonstrating high cell survival. Skin fibroblasts migrated over 350% more in fluid-PRF when compared to control and PRP (200% increase). Fluid-PRF also significantly induced greater cell proliferation at 5 days. While both PRP and fluid-PRF induced significantly elevated cell mRNA levels of PDGF, it was observed that TGF-beta, collagen 1, and fibronectin mRNA levels were all significantly highest in the fluid-PRF group. Lastly, fluid-PRF demonstrated a significantly greater ability to induce collagen matrix synthesis when compared to PRP. CONCLUSION: The findings from the present study demonstrate greater regenerative potential of fluid-PRF on human skin fibroblasts. Future clinical use of fluid-PRF in the field of facial aesthetics is necessary to further evaluate the potential advantages of anticoagulant removal from platelet concentrates.

Histological Evaluation of the Effects of Growth Factors in a Fibrin Network on Bone Regeneration.

OBJECTIVE: The aim of this study was to evaluate the effect of mineralized plasmatic matrix (MPM), comprising a combination of synthetic graft and platelet concentrates, on bone regeneration. METHODS: Critical size defects of 6-mm diameter were created on the tibias of 6 male sheep, with the animals subsequently assigned into 2 groups. Of the 5 bone defects generated per animal, 4 were randomly filled with MPM, beta-tricalcium phosphate graft (ß-TCP), platelet-rich fibrin (PRF) + ß-TCP, and autogenous graft. One defect was left empty as a control group. Animals were killed at 3 weeks (early healing group) and 6 weeks (late healing group). The specimens underwent histologic and histomorphometric analysis to evaluate new bone formation. RESULTS: In both healing periods, new bone formation from autogenous bone was observed significantly more often than from biomaterials or the empty defect. The degree of new bone formation for MPM was significantly higher than that of the control group at all healing periods. In addition, it was significantly higher in both healing periods than that of ß-TCP albeit only in the late healing period than that of the PRF + ß-TCP combination. In all biomaterial groups, residual graft ratios decreased from early to late healing periods. CONCLUSION: The results indicated that MPM, representing growth factors in a fibrin network, increases new bone formation in surgically created defects in sheep tibia as confirmed by histologic assessment.

Effect of advanced platelet-rich fibrin on accelerating alveolar bone formation in dogs: a histological and immunofluorescence evaluation.

Several methods have been developed to regenerate lost alveolar bone. Platelet-rich fibrin (PRF) is a useful adjunct for new bone formation in dentistry. To elucidate the effect of advanced PRF (A-PRF) on bone formation, we inserted A-PRF clots in sockets after tooth extraction. Premolars were extracted from beagle dogs, and A-PRF was applied to the socket. New bone formation was assessed using histological and immunofluorescence examinations, and the bone formation ratio was evaluated 14 and 30 days postoperatively. Histological examination revealed newly formed bone filling the sockets up to the center in the A-PRF group at 14 days postoperatively, while thick and regular bone trabeculae were arranged in porous bone after 30 days. Higher expressions of osteocalcin and osteopontin were observed in newly formed bone in the A-PRF group, compared to the control group. The bone formation ratio was also higher in the A-PRF group than in the control group. Thus, A-PRF application may result in enhanced new bone formation and may aid in accelerating bone formation. A-PRF was more rapid than a self-limiting process during induction of bone formation by enhancing osteoblast activity and may be useful for bone formation in clinical medicine.

Local Application of Autologous Platelet-Rich Fibrin Patch (PRF-P) Suppresses Regulatory T Cell Recruitment in a Murine Glioma Model.

The immunosuppressive microenvironment is one of the major factors promoting the growth of glioblastoma multiforme (GBM). Infiltration of CD4+CD25+Foxp3+ regulatory T cells (Tregs) into the tumor microenvironment plays a significant role in the suppression of the anti-tumor immunity and portends a dismal prognosis for patients. Glioma-mediated secretion of chemo-attractant C-C motif ligand 2 and 22 (CCL2/22) has previously been shown by our group to promote Treg migration in vitro. In this study, we show that a local implantation of platelet-rich fibrin patch (PRF-P) into the brain of GL261 glioma-bearing mice prolonged the survival of affected animals by 42.85% (p = 0.0011). Analysis performed on brain tumor tissue harvested from PRF-P-treated mice revealed a specific decrease in intra-tumoral lymphocytes with a preferential depletion of immunosuppressive Tregs. Importantly, co-culture of GL261 or chemo-attractants (CCL2/22) with PRF-P abrogated Treg migration. Pharmacological blockade of the CCL2/22 interaction with their receptors potentiated the inhibitory effect of PRF-P on Tregs recruitment in culture. Moreover, our findings revealed the soluble CD40 ligand (sCD40L) as a major Treg inhibitory player produced by activated platelets entrapped within the fibrin matrix of the PRF-P. Blockade of sCD40L restored the migratory capacity of Tregs, emphasizing the role of PRF-P in preventing the Treg migration to glioma tissue. Our findings highlight autologous PRF-P as a personalized, Treg-selective suppression platform that can potentially supplement and enhance the efficacy of glioma therapies.

Histologic Evaluation of Leucocyte- and Platelet-Rich Fibrin in the Inflammatory Process and Repair of Noncritical Bone Defects in the Calvaria of Rats.

PURPOSE: This study aimed to evaluate the effects of leucocyte- and platelet-rich fibrin (L-PRF) on the inflammatory process, tissue repair, and expression of vascular endothelial growth factor (VEGF) on bone defects in the calvaria of rats. MATERIALS AND METHODS: L-PRF was obtained from three animals submitted to cardiac puncture to prepare the membranes. Two noncritical defects with a diameter of 2 mm were created in the calvaria of 15 Wistar rats. The defects on the right side were filled with a blood clot (CTRL) and the left side with L-PRF. After 5, 15, and 30 days, the animals were euthanized and the specimens processed for histologic, histomorphometric, and immunohistochemical analyses. In order to measure the intensity of the inflammatory infiltrate and VEGF expression, scores were assigned from 0 to 3, with 0 being no expression, 1 discrete (up to 25%), 2 moderate (between 25% and 50%), and 3 intense (> 50%) expression. The area of bone neoformation at the edges of the defects was also quantified. RESULTS: A less intense inflammatory infiltrate was observed in the defects filled with L-PRF compared with CTRL at all times analyzed (P < .05). At 5 days, no bone neoformation was observed in any of the groups evaluated. After 15 and 30 days, greater bone neoformation was observed in the group treated with L-PRF compared with the CTRL group (P < .05). At 15 days, 3,871.8 (1,070.15) µm2 were recorded for the CTRL and 49,978.5 (14,360.7) µm2 in the L-PRF. At 30 days, 62,284.5 (3,579.5) µm2 were observed in the CTRL and 154,076.6 (31,464.9) µm2 in the L-PRF. At all evaluated times, a lower inflammatory infiltrate was observed in the group treated with L-PRF compared with the CTRL. VEGF expression was observed in the initial phase and throughout the tissue repair process in both groups. At 5 days, there was no difference in VEGF expression between the groups. VEGF was present at the initial phase and throughout the tissue repair process in both groups. In the L-PRF group, a decrease in VEGF expression was observed at 15 and 30 days compared with the CTRL group. CONCLUSION: L-PRF had a positive effect on the regenerative process of bony defects, with a reduced inflammatory response and greater bone neoformation.

[Evaluation of the MRI Findings on a Tendon Graft after the Anatomic Anterior Cruciate Ligament Reconstruction in Patients with Versus without the Application of Platelet-Rich Fibrin - Results of the Prospective Randomised Study]. / Zhodnocení MRI nálezu na slachovém stepu po anatomické rekonstrukci predního zkrízeného vazu u pacientu s aplikací versus bez aplikace fibrinu bohatého na krevní desticky ­ výsledky prospektivní randomizované studie.

PURPOSE OF THE STUDY The purpose of the prospective randomised study was to assess the benefits of the platelet-rich fibrin (PRF) application during the anatomic anterior cruciate ligament reconstruction (ACLR) for tendon graft healing. MATERIAL AND METHODS The study included 40 patients with an isolated rupture of the anterior cruciate ligament in the knee. The MRI findings on the tendon graft were evaluated at 6 months and 12 months after the surgery in a total of 33 patients, namely in 10 women/23 men (21 right knee/12 left knee), with the mean age of 29.1 years and at the mean follow-up of 15.9 weeks after the injury. The randomisation using envelopes was carried out at the beginning of arthroscopy either in the group with the PRF application (Group 1) (17 patients) or in the group without the PRF application (Group 2) (16 patients). The followed-up patients underwent the ACLR with targeting the femoral tunnel through anteromedial portal using the autografts of m. semitendinosusand m. graciliswith Tightrope femoral fixation and Inion implant in tibia. In Group 1, during the surgery PRF was applied both in the drilled tunnels (intraosseously) and directly to the surface of the tendon graft itself (intraarticular part). The Group 2 was a control group in which the same intervention was performed, however without the PRF application. In the 6 th and 12 th month after the surgery, the signal intensity of the knee and occurrence of the ACL graft failure, bone (marrow) oedema rate near the tunnels were assessed by an independent radiologist using a 3 Tesla MRI. RESULTS In the 6 th and also in the 12 th postoperative month, neither a complete, nor a partial graft failure was found in the group with PRF, whereas in Group 2 a complete or a partial graft failure was observed in 12.5% (p = 0.23). In the 6th month, a bone marrow oedema near the intraosseous parts of the graft was reported in 94.1% of patients in Group 1 and in 81.3% of patients in Group 2, while in the 12 th month it was 23.5% of evaluated patients in Group 1 and 37.5% patients in Group 2. The differences between the two groups were not statistically significant in the 6 th (p = 0.096) or in the 12 th month (p = 0.43). In the 6 th month, a fully ligamentised graft was found in 52.9% of patients in Group 1 and in 37.5% of patients in Group 2 (p = 0.061), a partially ligamentised graft was present in 47.1% of patients in Group 1 and in 50% of patients in Group 2. In the 12 th month, a fully ligamentised graft was seen in 94.1% of patients in Group 1 and in 75% of patients in Group 2 (p = 0.26) and a partially ligamentised graft was present in 5.9% of patients in Group 1 and in 12.5% of patients in Group 2. In the remaining 12.5% of patients in Group 2, the finding was assessed as a graft with no signs of ligamentisation. DISCUSSION We have not encountered a paper in the Czech or world literature which would present results of a similar study, i.e. which would evaluate the potential benefits of the platelet-rich fibrin application in the course of the anatomic anterior cruciate ligament reconstruction. Majority of studies evaluate the benefits of the application of platelet-rich plasma aimed to achieve a positive effect on the LCA graft healing. CONCLUSIONS Our study proved a higher percentage of ligamentisation and healed grafts into the bone as well as a lower occurrence of graft failure in the group with PRF compared to the group without the PRF application, namely both in the 6 th and in the 12 th month. Nonetheless, the differences between the two groups assessed at the same time were not statistically significant. Key words: anterior cruciate ligament, arthroscopy, anatomic ACL reconstruction, magnetic resonance imaging of the graft, platelet-rich fibrin, graft healing, MRI signal intensity of the graft.

The use of platelet-rich fibrin to enhance the outcomes of implant therapy: A systematic review.

OBJECTIVE: To assess the impact of platelet-rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRF administration for bone regeneration and implant therapy? METHOD: A systematic literature search comprised three databases: MEDLINE, EMBASE, and Cochrane followed by a hand search of relevant scientific journals. Human studies using PRF for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria. Randomized controlled trials (RCT) and controlled clinical trials (CCT) were included. RESULTS: In total, 5,963 titles were identified with the search terms and by hand search. A total of 12 randomized controlled trials (RCT) met the inclusion criteria and were chosen for data extraction. Included studies focused on alveolar ridge preservation after tooth extraction, osseointegration process, soft tissue management, bone augmentation, bone regeneration after sinus floor elevation and surgical peri-implantitis treatment. Overall, the risk of bias was moderate or unclear. Nine studies showed superior outcomes for PRF for any of the evaluated variables, such as ridge dimension, bone regeneration, osseointegration process, soft tissue healing. Three studies failed to show any beneficial effects of PRF. No meta-analysis could be performed due to the heterogeneity of study designs. CONCLUSIONS: There is moderate evidence supporting the clinical benefit of PRF on ridge preservation and in the early phase of osseointegration. It remains unclear whether PRF can reduce pain and improve soft tissue healing. More research support is necessary to comment on the role of PRF to improve other implant therapy outcomes.