Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática

Abstract

This thesis presented three objectives to characterize the biocompatibility of endodontic sealers: (1) to evaluate, through the Artemia salina lethality test, the toxicity of a novel calcium silicatebased root canal sealer (Bio-C Sealer) in comparison to Endosequence BC Sealer and AH Plus; (2) to determine in silico toxicity predictions of test compounds from Endosequence BC Sealer and AH Plus and perform a computational simulation via molecular docking of the interaction between these substances and mediators of periapical inflammation; (3) to compare histocompatibility, cytotoxicity and genotoxicity of premixed calcium silicate-based root canal sealers, with the AH Plus, systematically reviewing in vivo animal and in vitro laboratory studies. In the first study, the lethality test determined the larval survival rate and acute toxicity (LC50). Data were analyzed using ANOVA, Newman-Keuls and Dunett tests, with a significance level of 5%. Bio-C Sealer and Endosequence BC Sealer showed lower toxicity than AH Plus and the latter had the lowest LC50. In the second study, chemical information of the test compounds was obtained from the PubChem site and predictions were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the program Autodock4 AMDock v.1.5.2 to analyze interactions between different proteins present in the periapical inflammatory process (IL-1β, IL-6, IL-8, IL-10 and TNF-α) and ligands present in the sealers (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate). Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favorable docking, however bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. The third study followed the PRISMA guidelines and electronic searches were performed in PubMed/MEDLINE and EMBASE. Inclusion criteria encompassed in vivo animal and in vitro laboratory studies that evaluated histocompatibility, cytotoxicity and/or genotoxicity of premixed calcium silicatebased root canal sealers compared to AH Plus. Meta-analysis was performed using Stata program and random effect model. Fifty-two studies were included for data extraction and 14 in the meta-analysis. The premixed calcium silicate-based sealers showed better histocompatibility at 30 days and greater cell viability of undiluted extracts at 72 hours and extracts with 1:2 and 1:4 dilutions at 24 and 72 hours. However, there was no difference between materials for genotoxicity. According to the results, it can be concluded that premixed calcium silicate-based root canal sealers have a biological behavior superior to the “gold standard” AH Plus.