{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:57:42Z","timestamp":1775170662218,"version":"3.50.1"},"reference-count":114,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>(1) Aim: To perform a systematic review of the literature on the biocompatibility of root canal sealers that encompasses the various types of sealers that are commercially available as well as both in vitro and in vivo evidence. (2) Methods: This systematic review has been registered in PROSPERO (ID 140445) and was carried out according to PRISMA guidelines using the following databases: PubMed, Cochrane Library, ClinicalTrials.gov, Science Direct, and Web of Science Core Collection. Studies published between 2000 and 11 June 2019 that evaluated cytotoxicity (cell viability\/proliferation) and biocompatibility (tissue response) of root canal sealers were included. (3) Results: From a total of 1249 studies, 73 in vitro and 21 in vivo studies were included. In general, studies suggest that root canal sealers elicit mild to severe toxic effects and that several factors may influence biocompatibility, e.g., material setting condition and time, material concentration, and type of exposure. Bioactive endodontic sealers seem to exhibit a lower toxic potential in vitro. (4) Conclusions: The available evidence shows that root canal sealers exhibit variable toxic potential at the cellular and tissue level. However, the methodological heterogeneity among studies included in this systematic review and the somewhat conflicting results do not allow a conclusion on which type of sealer presents higher biocompatibility. Further research is crucial to achieve a better understanding of the biological effects of root canal sealers.<\/jats:p>","DOI":"10.3390\/ma12244113","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"4113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Biocompatibility of Root Canal Sealers: A Systematic Review of In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-139X","authenticated-orcid":false,"given":"Diogo Afonso","family":"Fonseca","sequence":"first","affiliation":[{"name":"Institute of Endodontics, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-4173","authenticated-orcid":false,"given":"Anabela Baptista","family":"Paula","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-5417","authenticated-orcid":false,"given":"Carlos Miguel","family":"Marto","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Institute of Experimental Pathology, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-7926","authenticated-orcid":false,"given":"Ana","family":"Coelho","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-2423","authenticated-orcid":false,"given":"Siri","family":"Paulo","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO \u2013 Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Jos\u00e9 Pedro","family":"Martinho","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO \u2013 Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-5557","authenticated-orcid":false,"given":"Eunice","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-6161","authenticated-orcid":false,"given":"Manuel Marques","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Coimbra Institute for Clinical and Biomedical Research (iCBR), CIBB Center for Innovative Biomedicine and Biotechnology, CIMAGO \u2013 Center of Investigation on Environment, Genetics and Oncobiology, CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"ref_1","unstructured":"Hargreaves, K.M., and Berman, L.H. 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