Evaluation of Cytotoxicity of Calcium Silicate-based Mineral Trioxide Aggregate Sealers: A Systematic Review of In Vitro Studies
Nezar Mohammed Boreak, Mazen Ahmed Qadi, Faisal Hadi Khormi, Luay Mutaen Faqiri, Sadeem Omar Zaylai, Yaser Ali Jad, Bassam Ali Hamdi, Asayil Juraybi
Keywords :
Cytotoxicity, Human periodontal stem cells, Mineral trioxide aggregate, MTT assay, Root canal sealers, XTT assay
Citation Information :
Boreak NM, Qadi MA, Khormi FH, Faqiri LM, Zaylai SO, Jad YA, Hamdi BA, Juraybi A. Evaluation of Cytotoxicity of Calcium Silicate-based Mineral Trioxide Aggregate Sealers: A Systematic Review of In Vitro Studies. J Contemp Dent Pract 2023; 24 (8):610-619.
Aim: This review aimed to evaluate the in vitro studies done with regard to the cytotoxicity associated with mineral trioxide aggregate (MTA)-based root canal sealers.
Background: Root canal sealers are used during endodontic treatment as fillers to seal the gaps between the canal gutta-percha cone and canal walls. It is necessary to understand the cytotoxicity of these materials on human-derived cells as these materials interact with human cells periapically.
Review results: Six in vitro studies were chosen for review. In these selected studies, along with MTA-based root canal sealers, other sealers were tested for cytotoxicity on human periodontal ligament (PDL) stem cells, human PDL fibroblasts, and human osteoblast cells. Regarding cytotoxicity, the studies were diverse, and most were based on 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide) (MTT) assay. In general, the studies suggested that root canal sealers cause mild to severe cytotoxic effects and that several factors influence this effect, such as material setting time, concentration, and duration of exposure.
Conclusion: All studies in the review indicated that MTA. Fillapex must be used cautiously as it exhibited the highest cytotoxic effect compared to other MTA-based and non-MTA-based sealers.
Clinical significance: Endodontic sealers do serve the purpose of bridging the gaps between the gutta-percha cone and the canal wall but knowing its biocompatibility becomes important as the material is extruded beyond the apical foramen where it comes in contact with the surrounding tissues. The effect of sealers on the surrounding tissues affects the healing and prognosis of the treatment.
Johnson W, Kulild JC, Tay F. Obturation of the cleaned and shaped root canal system In: Hargreaves KH, Berman LH, editors. Cohen's Pathway of the Pulp, 11th edition. St. Louis: Elsevier; 2016, pp. 280–323.
Vishwanath V, Rao HM. Gutta-percha in endodontics: A comprehensive review of material science. J Conserv Dent 2019;22(3):216–222. DOI: 10.4103/JCD.JCD_420_18.
Kaur A, Shah N, Logani A, et al. Biotoxicity of commonly used root canal sealers: A meta-analysis. J Conserv Dent 2015;18(2):83–88. DOI: 10.4103/0972-0707.153054.
Komabayashi T, Colmenar D, Cvach N, et al. Comprehensive review of current endodontic sealers. Dent Mater J 2020;39(5):703–720. DOI: 10.4012/dmj.2019-288.
Rosen E, Goldberger T, Taschieri S, et al. The prognosis of altered sensation after extrusion of root canal filling materials: A systematic review of the literature. J Endod 2016;42(6):873–879. DOI: 10.1016/j.joen.2016.03.018.
Al-Haddad A, Ab Aziz ZAC. Bioceramic-based root canal sealers: A Review. Int J Biomater 2016; 2016:9753210. DOI: 10.1155/2016/9753210.
Pelliccioni GA, Vellani CP, Gatto MR, et al. Proroot mineral trioxide aggregate cement used as a retrograde filling without addition of water: An in vitro evaluation of its microleakage. J Endod 2007;33(9):1082–1085. DOI: 10.1016/j.joen.2007.04.009.
Benetti F, de Azevedo Queiroz ÍO, Oliveira PHC, et al. Cytotoxicity and biocompatibility of a new bioceramic endodontic sealer containing calcium hydroxide. Braz Oral Res 2019;33:e042. DOI: 10.1590/1807-3107bor-2019.vol33.0042.
Parirokh M, Torabinejad M. Mineral trioxide aggregate: A comprehensive literature review. Part I: Chemical, physical, and antibacterial properties. J Endod 2010;36(1):16–27. DOI: 10.1016/j.joen.2009.09.006. PMID: 20003930.
Parirokh M, Torabinejad M. Mineral trioxide aggregate: A comprehensive literature review. Part III: Clinical applications, drawbacks, and mechanism of action. J Endod 2010;36(3):400–413. DOI: 10.1016/j.joen.2009.09.009.
Weller RN, Tay KC, Garrett LV, et al. Microscopic appearance and apical seal of root canals filled with gutta-percha and ProRoot Endo Sealer after immersion in a phosphate-containing fluid. Int Endod J 2008;41(11):977–986. DOI: 10.1111/j.1365-2591.2008.01462.x.
Tawil PZ, Trope M, Curran AE, et al. Periapical microsurgery: An in vivo evaluation of endodontic root-end filling materials. J Endod 2009;35(3):357–362. DOI: 10.1016/j.joen.2008.12.001.
Faraco IM Jr, Holland R. Response of the pulp of dogs to capping with mineral trioxide aggregate or a calcium hydroxide cement. Dent Traumatol 2001;17(4):163–166. DOI: 10.1034/j.1600-9657.2001.170405.x.
Namazikhah MS, Nekoofar MH, Sheykhrezae MS, et al. The effect of pH on surface hardness and microstructure of mineral trioxide aggregate. Int Endod J 2008;41(2):108–116. DOI: 10.1111/j.1365-2591.2007.01325.x.
Nagmode PS, Satpute AB, Patel AV, et al. The effect of mineral trioxide aggregate on the periapical tissues after unintentional extrusion beyond the apical foramen. Case Rep Dent 2016;2016:3590680. DOI: 10.1155/2016/3590680.
Kim EC, Lee BC, Chang HS, et al. Evaluation of the radiopacity and cytotoxicity of Portland cements containing bismuth oxide. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105(1):e54–e57. DOI: 10.1016/j.tripleo.2007.08.001.
Yoshino P, Nishiyama CK, Modena KC, et al. In vitro cytotoxicity of white MTA, MTA Fillapex® and Portland cement on human periodontal ligament fibroblasts. Braz Dent J 2013;24(2):111–116. DOI: 10.1590/0103-6440201302115.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol 2009;62(10):e1–e34. DOI: 10.1016/j.jclinepi.2009.06.006.
Riva JJ, Malik KM, Burnie SJ, et al. What is your research question? An introduction to the PICOT format for clinicians. J Can Chiropr Assoc 2012;56(3):167–171. PMID: 22997465.
Bob BCP, Dave S, Doug B. Oxford Centre for Evidence-Based Medicine: Levels of evidence (March 2009). Available at: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009. Accessed on: 20 February 2023.
Faggion CM Jr. Guidelines for reporting pre-clinical in vitro studies on dental materials. J Evid Based Dent Pract 2012;12(4):182–189. DOI: 10.1016/j.jebdp.2012.10.001.
Jagtap P, Shetty R, Agarwalla A, et al. Comparative evaluation of cytotoxicity of root canal sealers on cultured human periodontal fibroblasts: In vitro study. J Contemp Dent Pract 2018;19(7):847–852. PMID: 30066690.
Jung S, Sielker S, Hanisch MR, et al. Cytotoxic effects of four different root canal sealers on human osteoblasts. PLoS One 2018;13(3):e0194467. DOI: 10.1371/journal.pone.0194467.
Lee JK, Kim S, Lee S, et al. In vitro comparison of biocompatibility of calcium silicate-based root canal sealers. Materials (Basel) 2019;12(15):2411. DOI: 10.3390/ma12152411.
Gaudin A, Tolar M, Peters OA. Cytokine production and cytotoxicity of calcium silicate-based sealers in 2- and 3-dimensional cell culture models. J Endod 2020;46(6):818–826. DOI: 10.1016/j.joen.2020.03.011.
Erdogan H, Yildirim S, Cobankara FK. Cytotoxicity and genotoxicity of salicylate- and calcium silicate-based root canal sealers on primer human periodontal ligament fibroblasts. Aust Endod J 2021;47(3):645–653. DOI: 10.1111/aej.12537.
Só BB, Martins MD, So MV, et al. Genotoxicity and cytotoxicity comparison of calcium silicate-based and resin-based sealers on human periodontal ligament stem cells. Eur Endod J 2022;7(2):129–134. DOI: 10.14744/eej.2022.09326.
Seo DG, Lee D, Kim YM, et al. Biocompatibility and mineralization activity of three calcium silicate-based root canal sealers compared to conventional resin-based sealer in human dental pulp stem cells. Materials (Basel) 2019;12(15):2482. DOI: 10.3390/ma12152482.
Reszka P, Nowicka A, Lipski M, et al. A comparative chemical study of calcium silicate-containing and epoxy resin-based root canal sealers. Biomed Res Int 2016;2016:9808432. DOI: 10.1155/2016/9808432.
Huang TH, Yang JJ, Li H, et al. The biocompatibility evaluation of epoxy resin-based root canal sealers in vitro. Biomaterials 2002;23(1):77–83. DOI: 10.1016/s0142-9612(01)00081-3.
Bonson S, Jeansonne BG, Lallier TE. Root-end filling materials alter fibroblast differentiation. J Dent Res 2004;83(5):408–413. DOI: 10.1177/154405910408300511.
Roggendorf MJ, Ebert J, Petschelt A, et al. Influence of moisture on the apical seal of root canal fillings with five different types of sealer. J Endod 2007;33(1):31–33. DOI: 10.1016/j.joen.2006.07.006.
Holland R, Filho JA, de Souza V, et al. Mineral trioxide aggregate repair of lateral root perforations. J Endod 2001;27(4):281–284. DOI: 10.1097/00004770-200104000-00011.
Tay FR, Pashley DH, Rueggeberg FA, et al. Calcium phosphate phase transformation produced by the interaction of the portland cement component of white mineral trioxide aggregate with a phosphate-containing fluid. J Endod 2007;33(11):1347–1351. DOI: 10.1016/j.joen.2007.07.008.
Girao AV, Richardson IG, Porteneuve CB, et al. Composition, morphology and nanostructure of C-SH in white Portland cement pastes hydrated at 55°C. Cements Concrete Res 2007;37:1571–1582. DOI: 10.1016/j.cemconres.2007.09.001.
Bryan TE, Khechen K, Brackett MG, et al. In vitro osteogenic potential of an experimental calcium silicate-based root canal sealer. J Endod 2010;36(7):1163–1169. DOI: 10.1016/j.joen.2010.03.034.
Torabinejad M, Parirokh M. Mineral trioxide aggregate: A comprehensive literature review–part II: leakage and biocompatibility investigations. J Endod 2010;36(2):190–202. DOI: 10.1016/j.joen.2009.09.010.
Kuga CM, Edson Campos EA. Hydrogen ion and calcium releasing of M.T.A.Fillapex® and MTA-based formulations. RSBO 2011;8(3):271–276. DOI: 10.21726/rsbo.v8i3.1070.
Gomes-Filho JE, Watanabe S, Lodi CS, et al. Rat tissue reaction to M.T.A. Fillapex®. Dent traumatol 2012;28(6):452–455. DOI: 10.1111/j.1600-9657.2011.01096.x.
Tanomaru-Filho M, Tanomaru JM, Barros DB, et al. In vitro antimicrobial activity of endodontic sealers, MTA-based cements and Portland cement. J Oral Sci 2007;49(1):41–45. DOI: 10.2334/josnusd.49.41.
Pawińska M, Łuczaj-Cepowicz E, Kierklo A, et al. Assessment of cytotoxic potential of root canal sealers after hardening - an ex vivo study. Postepy Hig Med Dosw (Online). 2015;69:503–509. DOI: 10.5604/17322693.1150134.
Browne RM. The in vitro assessment of the cytotoxicity of dental materials–does it have a role? Int Endod J 1988;21(2):50–58. DOI: 10.1111/j.1365-2591.1988.tb00955.x.
Silva EJ, Rosa TP, Herrera DR, et al. Evaluation of cytotoxicity and physicochemical properties of calcium silicate-based endodontic sealer M.T.A. Fillapex. J Endod 2013;39(2):274–277. DOI: 10.1016/j.joen.2012.06.030.
Wang S, Yu H, Wickliffe JK. Limitation of the M.T.T. and X.T.T. assays for measuring cell viability due to superoxide formation induced by nanoscale TiO2. Toxicol In Vitro 2011;25(8):2147–2151. DOI:10.1016/j.tiv.2011.07.007.
Economides N, Kotsaki-Kovatsi VP, Poulopoulos A, et al. Experimental study of the biocompatibility of four root canal sealers and their influence on the zinc and calcium content of several tissues. J Endod 1995;21(3):122–127. DOI: 10.1016/s0099-2399(06)80436-x.
Huang TH, Ding SJ, Hsu TZ, et al. Root canal sealers induce cytotoxicity and necrosis. J Mater Sci Mater Med 2004;15(7):767–771. DOI: 10.1023/b:jmsm.0000032816.45489.54.
Zoufan K, Jiang J, Komabayashi T, et al. Cytotoxicity evaluation of gutta flow and endo sequence BC sealers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112(5):657–661. DOI: 10.1016/j.tripleo.2011.03.050.
Song YS, Choi Y, Lim MJ, et al. In vitro evaluation of a newly produced resin-based endodontic sealer. Restor Dent Endod 2016;41(3):189–195. DOI: 10.5395/rde.2016.41.3.189.
Lim ES, Park YB, Kwon YS, et al. Physical properties and biocompatibility of an injectable calcium-silicate-based root canal sealer: In vitro and in vivo study. BMC Oral Health 2015;15(1):129. DOI: 10.1186/s12903-015-0112-9.
Diomede F, Caputi S, Merciaro I, et al. Proinflammatory cytokine release and cell growth inhibition in primary human oral cells after exposure to endodontic sealer. Int Endod J 2014;47(9):864–872. DOI: 10.1111/iej.12230.
Liu J, Chen B, Bao J, et al. Macrophage polarization in periodontal ligament stem cells enhanced periodontal regeneration. Stem Cell Res Ther 2019;10(1):320. DOI: 10.1186/s13287-019-1409-4.
Couto RSD, Miyagi SPH, Moreira MS, et al. Cytotoxicity of substances leached from a rootncanal sealer based on mineral trioxide aggregate. Clin Lab Res Dent 2014;20:145–151. Available from: https://doi.org/10.11606/issn.m2357-8041.clrd.2014.63160.
Zhou HM, Du TF, Shen Y, et al. In vitro cytotoxicity of calcium silicate-containing endodontic sealers. J Endod 2015;41(1):56–61. DOI: 10.1016/j.joen.2014.09.012.
Vitti RP, Prati C, Sinhoreti MA, et al. Chemical-physical properties of experimental root canal sealers based on butyl ethylene glycol disalicylate and MTA. Dent Mater 2013;29(12):1287–1294. DOI: 10.1016/j.dental.2013.10.002.
Silva EJ, Perez R, Valentim RM, et al. Dissolution, dislocation and dimensional changes of endodontic sealers after a solubility challenge: a micro-CT approach. Int Endod J 2017;50(4):407–414. DOI: 10.1111/iej.12636.
Benetti F, de Azevedo Queiroz ÍO, Oliveira PHC, et al. Cytotoxicity and biocompatibility of a new bioceramic endodontic sealer containing calcium hydroxide. Braz Oral Res 2019;33:e042. DOI: 10.1590/1807-3107bor-2019.vol33.0042.
Yoshino P, Nishiyama CK, Modena KC, et al. In vitro cytotoxicity of white MTA, MTA Fillapex® and Portland cement on human periodontal ligament fibroblasts. Braz Dent J 2013;24(2):111–116. DOI: 10.1590/0103-6440201302115.
Silva EJ, Rosa TP, Herrera DR, et al. Evaluation of cytotoxicity and physicochemical properties of calcium silicate-based endodontic sealer MTA Fillapex. J Endod 2013;39(2):274–277. DOI: 10.1016/j.joen.2012.06.030.