Background The effects of ethylenediaminetetraacetic acid (EDTA) on regenerative endodontic procedures (REPs) are controversial, because, despite releasing growth factors from dentine, some studies show negative effects on cell behaviour. Objectives The aim of the study was to investigate the influence of the use of EDTA in REP on the growth factors’ release, cell behaviour and tissue regeneration. Methods A systematic search was conducted (PubMed/Medline, Scopus, Cochrane Library, Web of Science, Embase, OpenGrey and reference lists) up to February 2021. Only in vivo and in vitro studies evaluating the effects of EDTA on the biological factors of dentine, pulp/periapical tissues and cell behaviour were eligible. Studies without a control group or available full text were excluded. The growth factors’ release was the primary outcome. Risk of bias in the in vitro and in vivo studies was performed according to Joanna Briggs Institute's Checklist and SYRCLE’s RoB tool, respectively. Results Of the 1848 articles retrieved, 36 were selected. Amongst these, 32 were in vitro, three animal studies and one with both models. The EDTA concentrations ranged from 3% to 15%, at different times. Regarding growth factors’ release (17 studies), 15 studies found significant transforming growth factor (TGF)‐β release after dentine conditioning with EDTA, and most found no influence on vascular endothelial growth factor release. Regarding cell behaviour (26 studies), eight studies showed no influence of EDTA‐treated dentine on cell viability, whereas, five, nine and six studies showed higher cell migration, adhesion and differentiation respectively. No influence of EDTA conditioning was observed in animal studies. In vitro studies had a low risk of bias, whereas animal studies had high risk of bias. Meta‐analysis was unfeasible. Discussion This review found that EDTA increased TGF‐β release and improved cell activity. However, well‐designed histological analyses using immature teeth models are needed. Conclusions High‐quality in vitro evidence suggests that EDTA‐treated dentine positively influences TGF‐β release, cell migration, attachment and differentiation; further research to evaluate its influence on tissue regeneration is necessary due to low methodological quality of the animal studies.

ObjectivesThis systematic review (PROSPERO CRD42021227711) evaluated the influence of diabetes mellitus (DM) on the response of the pulp tissue and in the pulp cells behaviour.Materials and MethodsSearches in PubMed/MEDLINE, Embase, Web of Science and OpenGrey were performed until March 2022. Studies evaluating the effects of DM in the pulp tissue inflammation and in the cell behaviour were included, followed by risk of bias assessment (Methodological Index for Non‐Randomized Studies and SYRCLE's RoB tools). The meta‐analysis was unfeasible, and a narrative synthesis for each outcome was provided.ResultsOf the 615 studies, 21 were eligible, mainly with in vivo analysis (16 studies). The pulp inflammation (10 studies) was analysed mainly by haematoxylin–eosin stain; DM increased pulp inflammation/degeneration in 9 studies, especially after dental procedures. The cell viability (5 studies) was analysed mostly using MTT assay; DM and glycating agents decreased cellular viability in 3 studies. DM reduced collagen in all of three studies. There were controversial results regarding mineralization; however, increased alkaline phosphatase was reported in three of four studies.ConclusionsDM seems to increase inflammation/degeneration and mineralization in the pulp tissue while reducing cell proliferation. Further analyses in human pulp are important to provide stronger evidence.

No abstract