{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:26:48Z","timestamp":1776284808583,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T00:00:00Z","timestamp":1544918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Neuroscience and Cellular Biology of the University of Coimbra","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]},{"name":"Gabinete de Apoio \u00e0 Investiga\u00e7\u00e3o, Faculty of Medicine of University of Coimbra","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.<\/jats:p>","DOI":"10.3390\/jfb9040074","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T02:15:59Z","timestamp":1545099359000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Effects of a New Bioceramic Material on Human Apical Papilla Cells"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-7611","authenticated-orcid":false,"given":"Diana B.","family":"Sequeira","sequence":"first","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra 3030-789, Portugal"},{"name":"PhD Program in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, Coimbra 3004-504, Portugal"},{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, Coimbra 3000-075 Portugal"}]},{"given":"Catarina M.","family":"Seabra","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra 3030-789, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-8072","authenticated-orcid":false,"given":"Paulo J.","family":"Palma","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, Coimbra 3000-075 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-4561","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra 3030-789, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-2129","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pe\u00e7a","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal"},{"name":"Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra 3030-789, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2865-9689","authenticated-orcid":false,"given":"Jo\u00e3o Miguel","family":"Santos","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, Coimbra 3000-075 Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00784-015-1443-2","article-title":"Calcium silicate\/calcium phosphate biphasic cements for vital pulp therapy: Chemical-physical properties and human pulp cells response","volume":"19","author":"Gandolfi","year":"2015","journal-title":"Clin. Oral Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/iej.12596","article-title":"Evaluation of cytocompatibility of calcium silicate-based endodontic sealers and their effects on the biological responses of mesenchymal dental stem cells","volume":"50","author":"Forner","year":"2017","journal-title":"Int. Endod. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joen.2009.09.006","article-title":"Mineral trioxide aggregate: a comprehensive literature review\u2014Part I: Chemical, physical, and antibacterial properties","volume":"36","author":"Parirokh","year":"2010","journal-title":"J. Endod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.dental.2004.05.010","article-title":"The constitution of mineral trioxide aggregate","volume":"21","author":"Camilleri","year":"2005","journal-title":"Dent. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1365-2591.2007.01248.x","article-title":"Hydration mechanisms of mineral trioxide aggregate","volume":"40","author":"Camilleri","year":"2007","journal-title":"Int. Endod. J."},{"key":"ref_6","first-page":"9203932","article-title":"In Vitro Cytotoxicity of Calcium Silicate-Based Endodontic Cement as Root-End Filling Materials","volume":"2016","author":"Zeybek","year":"2016","journal-title":"Scientifica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1016\/j.joen.2017.06.031","article-title":"Direct Pulp Capping with Calcium Hydroxide, Mineral Trioxide Aggregate, and Biodentine in Permanent Young Teeth with Caries: A Randomized Clinical Trial","volume":"43","author":"Brizuela","year":"2017","journal-title":"J. Endod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/iej.12605","article-title":"Assessment of Mineral Trioxide Aggregate pulpotomy in mature permanent teeth with carious exposures","volume":"50","author":"Taha","year":"2017","journal-title":"Int. Endod. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.joen.2012.10.007","article-title":"Treatment outcome of mineral trioxide aggregate in open apex teeth","volume":"39","author":"Mente","year":"2013","journal-title":"J. Endod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jdent.2018.08.003","article-title":"Effects of calcium silicate cements on dental pulp cells: A systematic review","volume":"77","author":"Emara","year":"2018","journal-title":"J. Dent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.joen.2010.04.027","article-title":"Effect of calcium phosphate cements on growth and odontoblastic differentiation in human dental pulp cells","volume":"36","author":"Lee","year":"2010","journal-title":"J. Endod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.joen.2012.11.026","article-title":"In vitro cytotoxicity evaluation of a novel root repair material","volume":"39","author":"Zhou","year":"2013","journal-title":"J. Endod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jdent.2013.12.011","article-title":"Effect of Biodentine on the proliferation, migration and adhesion of human dental pulp stem cells","volume":"42","author":"Luo","year":"2014","journal-title":"J. Dent."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.joen.2013.01.005","article-title":"Response of human dental pulp capped with biodentine and mineral trioxide aggregate","volume":"39","author":"Nowicka","year":"2013","journal-title":"J. Endod."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Palma, P., Marques, J., Falacho, R., Vinagre, A., Santos, J., and Ramos, J. (2018). Does Delayed Restoration Improve Shear Bond Strength of Different Restorative Protocols to Calcium Silicate-Based Cements?. Materials, 11.","DOI":"10.3390\/ma11112216"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.joen.2016.06.012","article-title":"1-Year In Vitro Evaluation of Tooth Discoloration Induced by 2 Calcium Silicate-based Cements","volume":"42","author":"Ramos","year":"2016","journal-title":"J. Endod."},{"key":"ref_17","first-page":"10","article-title":"Revisiting the definition of biocompatibility","volume":"14","author":"Williams","year":"2003","journal-title":"Med. Device Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.joen.2017.07.017","article-title":"Biocompatibility of New Pulp-capping Materials NeoMTA Plus, MTA Repair HP, and Biodentine on Human Dental Pulp Stem Cells","volume":"44","author":"Forner","year":"2018","journal-title":"J. Endod."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Santos, J.M., Pereira, S., Sequeira, D., Messias, A., Martins, J., Cunha, H., Palma, P.J., and Santos, A.C. (2019). Biocompatibility of a bioceramic silicon-based sealer in subcutaneous tissue. J. Oral Sci., in press.","DOI":"10.2334\/josnusd.18-0145"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.joen.2018.03.014","article-title":"Effect of Bioceramic Materials on Proliferation and Odontoblast Differentiation of Human Stem Cells from the Apical Papilla","volume":"44","author":"Wongwatanasanti","year":"2018","journal-title":"J. Endod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.joen.2007.11.021","article-title":"Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study","volume":"34","author":"Sonoyama","year":"2008","journal-title":"J. Endod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.archoralbio.2010.12.008","article-title":"Comparative analysis of in vitro osteo\/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP)","volume":"56","author":"Bakopoulou","year":"2011","journal-title":"Arch. Oral Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sonoyama, W., Liu, Y., Fang, D., Yamaza, T., Seo, B.M., Zhang, C., Liu, H., and Wang, S. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One, 1.","DOI":"10.1371\/journal.pone.0000079"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/5584_2018_252","article-title":"Dental Stem Cells and Tooth Regeneration","volume":"1107","author":"Shuai","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ten.2005.11.1","article-title":"Mediation of biomaterial-cell interactions by adsorbed proteins: A review","volume":"11","author":"Wilson","year":"2005","journal-title":"Tissue Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.dental.2017.01.011","article-title":"Biocompatibility of biomaterials\u2014Lessons learned and considerations for the design of novel materials","volume":"33","author":"Schmalz","year":"2017","journal-title":"Dent. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.1016\/j.dental.2016.03.001","article-title":"Properties of a novel polysiloxane-guttapercha calcium silicate-bioglass-containing root canal sealer","volume":"32","author":"Gandolfi","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/01.don.0000145423.89539.d7","article-title":"Effect of ProRoot MTA on pulp cell apoptosis and proliferation in vitro","volume":"31","author":"Mantellini","year":"2005","journal-title":"J. Endod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.joen.2012.04.018","article-title":"Biodentine induces immortalized murine pulp cell differentiation into odontoblast-like cells and stimulates biomineralization","volume":"38","author":"Zanini","year":"2012","journal-title":"J. Endod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/jemt.22780","article-title":"Effects of novel root repair materials on attachment and morphological behaviour of periodontal ligament fibroblasts: Scanning electron microscopy observation","volume":"79","author":"Akbulut","year":"2016","journal-title":"Microsc. Res. Tech."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/j.1365-2591.2004.00859.x","article-title":"Biocompatibility of two commercial forms of mineral trioxide aggregate","volume":"37","author":"Camilleri","year":"2004","journal-title":"Int. Endod. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"692","DOI":"10.4103\/0970-9290.152163","article-title":"Comparison of physical and mechanical properties of mineral trioxide aggregate and Biodentine","volume":"25","author":"Butt","year":"2014","journal-title":"Indian J. Dent. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"055006","DOI":"10.1088\/1748-6041\/7\/5\/055006","article-title":"MTA-enriched nanocomposite TiO2-polymeric powder coatings support human mesenchymal cell attachment and growth","volume":"7","author":"Shi","year":"2012","journal-title":"Biomed. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4103\/0972-0707.48834","article-title":"The chemical composition of mineral trioxide aggregate","volume":"11","author":"Camilleri","year":"2008","journal-title":"J. Conserv. Dent."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"160951","DOI":"10.1155\/2014\/160951","article-title":"A review on biodentine, a contemporary dentine replacement and repair material","volume":"2014","author":"Malkondu","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jdent.2016.12.009","article-title":"Nanoscale chemical surface characterization of four different types of dental pulp-capping materials","volume":"58","author":"Gong","year":"2017","journal-title":"J. Dent."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1016\/j.dental.2016.01.003","article-title":"Cytotoxicity and anti-inflammatory effects of zinc ions and eugenol during setting of ZOE in immortalized human oral keratinocytes grown as three-dimensional spheroids","volume":"32","author":"Lee","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.msec.2014.06.030","article-title":"Using calcium silicate to regulate the physicochemical and biological properties when using beta-tricalcium phosphate as bone cement","volume":"43","author":"Kao","year":"2014","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_39","first-page":"316","article-title":"Weight loss of endodontic sealers, cements and pastes in water. Scand","volume":"91","author":"Orstavik","year":"1983","journal-title":"J. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/iej.12636","article-title":"Dissolution, dislocation and dimensional changes of endodontic sealers after a solubility challenge: A micro-CT approach","volume":"50","author":"Silva","year":"2017","journal-title":"Int. Endod. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/0030-4220(93)90050-E","article-title":"Dimensional changes of endodontic sealers","volume":"76","author":"Kazemi","year":"1993","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4103\/0972-0707.153053","article-title":"Solubility of a new calcium silicate-based root-end filling material","volume":"18","author":"Singh","year":"2015","journal-title":"J. Conserv. Dent."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13005-015-0074-9","article-title":"An in vitro study of different material properties of Biodentine compared to ProRoot MTA","volume":"11","author":"Kaup","year":"2015","journal-title":"Head Face Med."}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/9\/4\/74\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:34:20Z","timestamp":1760196860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/9\/4\/74"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,16]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["jfb9040074"],"URL":"https:\/\/doi.org\/10.3390\/jfb9040074","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,16]]}}}