Effect of Different Root Canal Irrigant Solutions on the Release of Dentin-Growth Factors: A Systematic Review and Meta-Analysis

From MDPI via Jisc Publications RouterHistory: accepted 2021-09-29, pub-electronic 2021-10-05Publication status: PublishedIrrigant solutions are used to promote dentin-growth factors (GF) release for regenerative endodontics. This review aimed to evaluate the reports comparing the release of GFs using different root canal irrigant solutions. Eligible studies compared the in vitro GF release in human teeth after the use of at least two distinct solutions. A search was conducted on Pubmed, Scopus, Web of Science, and Lilacs on 11 August 2021. Risk of bias was assessed using SciRAP. Study characteristics and quantitative data were extracted, and meta-analyses were performed for the mean difference (95% confidence interval) of the release of transforming growth factors Beta 1 (TGF-β1) by EDTA compared to other irrigants. Of sixteen eligible studies, eight were included in quantitative analysis. ELISA assays showed higher TGF-β1 release from 10% EDTA compared to 10% citric acid (p 0.00001). Immunogold assays showed higher levels of TGF-β1 for 17% EDTA (p 0.00001) compared to 10% citric acid. GRADE identified a low to very low certainty of evidence. These results point to an increased release of TGF-β1 in dentin treated with EDTA. The high heterogeneity and very low certainty of the evidence demand further studies before EDTA indication as a better irrigant for regenerative endodontics. Registration: CRD42020160871 (PROSPERO)

18 Years of Medication-Related Osteonecrosis of the Jaw (MRONJ) Research: Where Are We Now?—An Umbrella Review

From MDPI via Jisc Publications RouterHistory: accepted 2021-09-16, pub-electronic 2021-09-23Publication status: PublishedBackground: Osteonecrosis of the jaw (ONJ) is a condition affecting patients exposed to medications used to treat benign and malignant conditions of bone tissue. Many studies have highlighted that ONJ is a severe condition, which is very challenging to manage, especially in individuals with oncologic disease. The aim of this umbrella review is to analyze all available interventional and non-interventional systematic reviews published on medication-related osteonecrosis of the jaw (MRONJ) and summarize this evidence. Material and methods: A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until June 2021. An additional manual search was also performed in systematic review registries (PROSPERO, INPLASY, JBI and OFS) to identify possible missing reviews. Data were extracted from relevant papers and analyzed according to the outcomes selected in this review. Results: The search generated 25 systematic reviews eligible for the analysis. The total number of patients included in the analysis was 80,840. Of the reviews, 64% (n = 16) were non-interventional and 36% (n = 9) were interventional. Study designs included case series 20.50% (n = 140), retrospective cohort studies 12.30% (n = 84) and case reports 12.20% (n = 83). It was unclear what study design was used for 277 studies included in the 25 systematic reviews. Conclusions: The data reviewed confirmed that the knowledge underpinning MRONJ in the last 20 years is still based on weak evidence. This umbrella review highlighted a widespread low-level quality of studies and many poorly designed reviews

Effects of platelet-rich fibrin produced by three centrifugation protocols on bone neoformation in defects created in rat calvaria.

This study evaluated the potential of Leukocyte-platelet-rich fibrin (L-PRF; fixed angle centrifugation protocol), Advanced-platelet-rich fibrin (A-PRF; low-speed fixed angle centrifugation protocol), and Horizontal-platelet-rich fibrin (H-PRF; horizontal centrifugation protocol) in bone neoformation in critical size defects (CSDs) in rat calvaria. Thirty-two rats were divided into groups: Control (C), L-PRF, A-PRF, and H-PRF. 5 mm diameter CSDs were created in the animals' calvaria. Defects from group Control (C) were filled with blood clots, while defects from groups L-PRF, A-PRF, and H-PRF were filled with respective platelet-rich fibrin (PRF) membranes. L-PRF, A-PRF, and H-PRF were prepared from animal blood collection and specific centrifugation protocols. At 14 and 30 days, calcein (CA) and alizarin (AL) injections were performed, respectively. Animals were euthanized at 35 days. Microtomographic, laser confocal microscopy, and histomorphometric analyzes were performed. Data were statistically analyzed (ANOVA, Tukey, p < .05). L-PRF, A-PRF, and H-PRF groups showed higher values of bone volume (BV), newly formed bone area (NFBA), and precipitation of CA and AL than the C group (p < .05). The H-PRF group showed higher values of BV, number of trabeculae (Tb. N), NFBA, and higher precipitation of AL than the A-PRF and L-PRF groups (p < .05). Therefore, it can be concluded that: i) L-PRF, A-PRF, and H-PRF potentiate bone neoformation in CSDs in rat calvaria; ii) H-PRF demonstrated more biological potential for bone healing

Maxillary sinus floor elevation using carbonated hydroxyapatite microspheres associated with growth factors: a randomized clinical trial

O objetivo deste estudo clínico, randomizado, controlado, boca dividida, foi avaliar o ganho do tecido ósseo utilizando a hidroxiapatita carbonatada nanoestruturada em procedimentos de elevação da membrana sinusal, comparando sua eficácia quando este material é utilizado sozinho ou associado à fatores de crescimento do sangue periférico. De forma aleatória, o biomaterial foi implantado, com soro fisiológico 0,9% como veículo ou fatores de crescimento em fase líquida, nos seios maxilares (direito e esquerdo) de 10 participantes de pesquisa. Todos os participantes realizaram tomografia cone beam inicial e após o período de 180 dias do procedimento. Nenhum participante de pesquisa foi retirado ou abandonou o estudo e todos receberam assistência pré e pós operatória, até a fase de reabilitação oral. Com este trabalho, foi possível observar uma grande vantagem clínica na utilização dos fatores de crescimento na fase líquida, pois após a polimerização da fibrina presente, observou-se a otimização do procedimento operatório, diminuindo o tempo e melhorando a adaptação do biomaterial no seio maxilar. Porém, após a avaliação cega, por um especialista, calibrado, foi observado que não há efeito sinérgico no aumento do tecido ósseo quando a hidroxiapatita carbonatada nanoestruturada é associada aos fatores de crescimento na fase líquida (p>0,05). Foi observado uma formação óssea equivalente em ambos os lados operados após seis meses do procedimento de elevação sinusal.The aim of this randomized, controlled, split-mouth clinical trial, was to evaluate the the bone augmentation using nanostructured-carbonated hydroxyapatite in sinus membrane elevation procedures, and its efficacy was compared when used alone or associated with peripheral blood growth factors. The procedures were performed in 10 participants, and the right and left maxillary sinuses of each participant were used in performing the bone graft. The biomaterial was randomly implanted using a 0.9% saline solution as the carrier or liquid concentrate of growth factors. All participants performed initial cone beam tomography and after the 180-day procedure period. No patients were withdrawn from the study, and all received pre- and postoperative care until the oral rehabilitation phase. With this work, a significant clinical advantage was observed in the use of the liquid concentrate of growth factors after the polymerization of the present fibrin, since it allowed optimizing the surgical procedure, thereby reducing the time and improving the adaptation of the biomaterial in the maxillary sinus. After a blind evaluation by a calibrated specialist, no synergistic effect was observed on the increase of the bone tissue when the nanostructured-carbonated hydroxyapatite was associated with the liquid concentrate of growth factors (p>0.05). An equivalent new bone formation for the mixture of nanostructured-carbonated hydroxyapatite with the liquid concentrate of growth factors after six months was observed in bilateral sinus floor elevation.48f

Biological characterization of an injectable platelet-rich fibrin mixture consisting of autologous albumin gel and liquid platelet-rich fibrin (Alb-PRF).

Platelet-rich fibrin (PRF) has been proposed as an autologous membrane with the advantages of host accumulation of platelets and leukocytes with entrapment of growth factors. However, limitations include its faster resorption properties (~2 weeks). Interestingly, recent studies have demonstrated that by heating a liquid platelet-poor plasma (PPP) layer, the resorption properties of heated albumin (albumin gel) can be extended from 2 weeks to greater than 4 months (e-PRF). The aim of the present study was to characterize the biological properties of this novel regenerative modality. Whole blood collected from peripheral blood in 9-mL plastic tubes was centrifuged at 700 g for 8 minutes. Thereafter, the platelet-poor plasma layer was heated at 75°C for 10 minutes to create denatured albumin (albumin gel). The remaining cells and growth factor found within the buffy coat layer (liquid PRF) were thereafter mixed back together with the cooled albumin gel to form Alb-PRF. Histological analysis, including the distribution of cells within Alb-PRF, was then performed. Seven different growth factor release kinetics from Alb-PRF were characterized up to 10 days, including PDGF-AA, PDGF-AB, PDGF-BB, TGF-β1, VEGF, IGF and EGF. Thereafter, gingival fibroblast cell responses to Alb-PRF were investigated by means of a live/dead assay at 24 hours; migration assay at 24 hours; proliferation assay at 1, 3 and 5 days; real-time PCR for the expression of TGF-β and collagen 1a2 at 3 and 7 days; and collagen 1 immunostaining at 14 days. It was first observed histologically that viable cells were evenly distributed throughout the Alb-PRF formulation. Growth factor release demonstrated a slow and gradual release, particularly for TGF-β1 and PDGF-AA/AB, during the entire 10-day period. Alb-PRF also exhibited statistically significantly higher cell biocompatibility at 24 hours and statistically significantly induced greater fibroblast proliferation at 5 days when compared to those of control TCP. Alb-PRF further induced statistically significantly greater mRNA levels of TGF-β at 3 and 7 days, as well as collagen 1 at 7 days. The present results indicate that Alb-PRF possesses regenerative properties induced by the slow and gradual release of growth factors found in liquid PRF via albumin gel degradation. Future studies are thus warranted to fully characterize the degradation properties of Alb-PRF in vivo and explore future clinical applications in various fields of medicine