Objectives: This systematic review aimed to compare the cytotoxicity of root canal filling materials (RCFMs) assessed using tetrazolium salt‐based tests (TSBT), including the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay, with those obtained using other cell viability assays.Methods: A search was performed on PubMed, Scopus, Web of Science and OpenGrey up to March 2019, followed by a manual search. According to the Participants, Exposure, Comparator and Outcomes (PECO) criteria, in vitro studies that evaluated the cytotoxic effect of RCFMss on animal and/or human cells through TSBT and at least one other viability assay were compared. The methodological quality of selected papers was assessed using ToxRTool^® and SciRAP^®. Data were analysed using Wilcoxon’s signed‐rank test for paired samples and linear weighting kappa.Results: A total of 230 non‐duplicated records were identified. After applying the eligibility criteria, 55 studies were selected for methodological evaluation, seven were selected by manual searching, 22 were excluded for methodological reasons, and 40 were included. A total of 410 comparisons were performed between TSBT and distinct cell viability tests (DCVT). MTT had moderate concordance with DCVT using human cells (n = 138 samples) (P = 0.507; k = 0.4225) and animal cells (n = 122 samples) (P = 0.124; k = 0.5775). XTT had good concordance using human (n = 110 samples) (P = 0.507; k = 0.6336) and animal cells (n = 12 samples) (P = 0.564; k = 0.6604). MTT, XTT, WST and MTS assays showed moderate concordance with DCVT (n = 410 samples) (P = 0.375; k = 0.5138) and complete agreement in 226 samples.Discussion: The included studies had methodological heterogeneity that was minimized by the systematic review methodology.Conclusions: MTT and XTT do not cause over‐ or underestimation of cell viability during cytotoxicity screening of root canal filling materials, implying that these assays can be considered reliable for this purpose. Nonetheless, the development of protocols for the cytotoxic screening of these materials on 3D tissue‐like cultures aiming to improve their predictability in the clinical scenario is suggested.

This work aimed to investigate the use of Regenerative Endodontic Procedures (REP) on the treatment of pulp necrosis in mature teeth through systematic review and meta-analysis of evidence on clinical and radiographic parameters before and after REP. A search was performed in different databases on 9 September 2020, including seven clinical studies and randomized controlled trials (RCT). The methodological quality was assessed using Revised Cochrane risk-of-bias (RoB 2) and Before-and-After tools. Meta-analyses were performed to evaluate the success incidences regarding the reduction of periapical lesion and recovery of sensitivity. The certainty of the evidence was assessed using GRADE. Meta-analysis showed a high overall success of 0.95 (0.92, 0.98) I² = 6%, with high periapical lesion reduction at 12 months (0.93 (0.86, 0.96) I² = 37%) and by the end of follow-up (0.91 (0.83, 0.96) I² = 13%). Lower incidences of positive sensitivity response were identified for the electrical (0.58 (0.46, 0.70) I² = 51%) and cold tests (0.70 (0.54, 0.84) I² = 68%). The calculated levels of REP success were similar to those reported for immature teeth. With a very low certainty of evidence, the meta-analysis showed a high incidence of REP’s success for mature teeth with necrotic pulp evidenced by periapical lesion reduction and moderate positive responses to sensitivity tests.

Irrigant 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).

Optisol-GS is the most widely used pharmaceutical composition to preserve corneas for transplantation. This systematic review investigated the effects of different cold corneal storage media (CCSM) compared with Optisol-GS on the quality of stored corneas. The literature was searched throughout May 2022 on six databases and grey literature. Studies including corneas (population) exposed to distinct cold storage media (exposure) and Optisol-GS (comparison) that reported qualitative and/or quantitative parameters of cornea quality (outcome) were included. Methodological quality was assessed using ToxRTool. From 4520 identified studies, fourteen were included according to the eligibility criteria, comprising 769 evaluated cornea samples comparing Optisol-GS with commercial and noncommercial media. All studies showed good methodological quality. Experimental times ranged from 1–28 days, mainly using 4 °C as the preservation temperature. Viable endothelial cell density (ECD) and endothelial cell morphology (EC) were the most assessed parameters. ECD results for Cornisol were higher than Optisol-GS in 10 days (p = 0.049) and favored Cornea Cold^TM up to 4 weeks (p < 0.05), which also showed better qualitative results. While the standardization of test protocols could improve comparisons, evidence indicates that most CCSM present similar performances on cornea preservation for transplantation at seven days, while some formulations may increase preservation at extended times.