{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:18:26Z","timestamp":1788369506943,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"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>Blood clot formation in the apical third of the root canal system has been shown to promote further root development and reinforcement of dentinal walls by the deposition of mineralized tissue, resulting in an advancement from traditional apexification procedures to a regenerative endodontic treatment (RET) for non-vital immature permanent teeth. Silicate-based hydraulic biomaterials, categorized as bioactive endodontic cements, emerged as bright candidates for their use in RET as coronal barriers, sealing the previously induced blood clot scaffold. Human stem cells from the apical papilla (hSCAPs) surviving the infection may induce or at least be partially responsible for the regeneration or repair shown in RET. The aim of this study is to present a qualitative synthesis of available literature consisting of in vitro assays which analyzed the viability and stimulation of hSCAPs induced by silicate-based hydraulic biomaterials. A systematic electronic search was carried out in Medline, Scopus, Embase, Web of Science, Cochrane and SciELO databases, followed by a study selection, data extraction, and quality assessment following the PRISMA protocol. In vitro studies assessing the viability, proliferation, and\/or differentiation of hSCAPs as well as their mineralization potential and\/or osteogenic, odontogenic, cementogenic and\/or angiogenic marker expression in contact with commercially available silicate-based materials were included in the present review. The search identified 73 preliminary references, of which 10 resulted to be eligible for qualitative synthesis. The modal materials studied were ProRoot MTA and Biodentine. Both bioceramic materials showed significant positive results when compared to a control for hSCAP cell viability, migration, and proliferation assays; a significant up-regulation of hSCAP odontogenic\/osteogenic marker (ALP, DSPP, BSP, Runx2, OCN, OSX), angiogenic growth factor (VEGFA, FIGF) and pro-inflammatory cytokine (IL-1\u03b1, IL-1\u03b2, IL-6, TNF-\u03b1) expression; and a significant increase in hSCAP mineralized nodule formation assessed by Alizarin Red staining. Commercially available silicate-based materials considered in the present review can potentially induce mineralization and odontogenic\/osteogenic differentiation of hSCAPs, thus prompting their use in regenerative endodontic procedures.<\/jats:p>","DOI":"10.3390\/ma13040974","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T08:59:47Z","timestamp":1582275587000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Viability and Stimulation of Human Stem Cells from the Apical Papilla (hSCAPs) Induced by Silicate-Based Materials for Their Potential Use in Regenerative Endodontics: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-8085","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Sanz","sequence":"first","affiliation":[{"name":"Dental Pathology and Therapeutics Unit, Department of Stomatology, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-9883","authenticated-orcid":false,"given":"Leopoldo","family":"Forner","sequence":"additional","affiliation":[{"name":"Dental Pathology and Therapeutics Unit, Department of Stomatology, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Almud\u00e9ver","sequence":"additional","affiliation":[{"name":"Dental Pathology and Therapeutics Unit, Department of Stomatology, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Guerrero-Giron\u00e9s","sequence":"additional","affiliation":[{"name":"Special Care and Gerodontology Unit, Department of Stomatology, University of Murcia, 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3942-2820","authenticated-orcid":false,"given":"Carmen","family":"Llena","sequence":"additional","affiliation":[{"name":"Dental Pathology and Therapeutics Unit, Department of Stomatology, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1111\/iej.12954","article-title":"Regenerative endodontics: A comprehensive review","volume":"51","author":"Kim","year":"2018","journal-title":"Int. Endod. J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saoud, T., Ricucci, D., Lin, L., and Gaengler, P. (2016). Regeneration and Repair in Endodontics\u2014A Special Issue of the Regenerative Endodontics\u2014A New Era in Clinical Endodontics. Dent. J., 4.","DOI":"10.3390\/dj4010003"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.joen.2017.04.018","article-title":"Regenerative Endodontic Therapy in the Management of Nonvital Immature Permanent Teeth: A Systematic Review\u2014Outcome Evaluation and Meta-analysis","volume":"43","author":"Tong","year":"2017","journal-title":"J. Endod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.joen.2012.10.027","article-title":"Characterization of a stem cell of apical papilla cell line: Effect of passage on cellular phenotype","volume":"39","author":"Ruparel","year":"2013","journal-title":"J. Endod."},{"key":"ref_5","first-page":"39","article-title":"The Origin and Identification of Mesenchymal Stem Cells in Teeth: From Odontogenic to Non-odontogenic","volume":"13","author":"Cui","year":"2018","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Spagnuolo, G., Codispoti, B., Marrelli, M., Rengo, C., Rengo, S., and Tatullo, M. (2018). Commitment of Oral-Derived Stem Cells in Dental and Maxillofacial Applications. Dent J., 6.","DOI":"10.3390\/dj6040072"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1002\/stem.1681","article-title":"Concise review: The surface markers and identity of human mesenchymal stem cells","volume":"32","author":"Lv","year":"2014","journal-title":"Stem Cells"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3389\/fbioe.2018.00103","article-title":"Stem Cells From the Apical Papilla (SCAP) as a Tool for Endogenous Tissue Regeneration","volume":"6","author":"Nada","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.archoralbio.2013.06.018","article-title":"Comparative characterization of STRO-1neg\/CD146pos and STRO-1pos\/CD146pos apical papilla stem cells enriched with flow cytometry","volume":"58","author":"Bakopoulou","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.joen.2006.07.010","article-title":"Immature Teeth with Periradicular Periodontitis or Abscess Undergoing Apexogenesis: A Paradigm Shift","volume":"32","author":"Chueh","year":"2006","journal-title":"J. Endod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jds.2013.02.029","article-title":"Conservative treatment of immature teeth with apical periodontitis using triple antibiotic paste disinfection","volume":"11","author":"Wang","year":"2016","journal-title":"J. Dent. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.joen.2008.03.023","article-title":"Biologically Based Treatment of Immature Permanent Teeth with Pulpal Necrosis: A Case Series","volume":"34","author":"Jung","year":"2008","journal-title":"J. Endod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jdent.2008.03.002","article-title":"A paradigm shift in endodontic management of immature teeth: Conservation of stem cells for regeneration","volume":"36","author":"Huang","year":"2008","journal-title":"J. Dent."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.joen.2016.09.024","article-title":"Survival of the Apical Papilla and Its Resident Stem Cells in a Case of Advanced Pulpal Necrosis and Apical Periodontitis","volume":"43","author":"Chrepa","year":"2017","journal-title":"J. Endod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cden.2016.08.004","article-title":"Regenerative Endodontic Procedures: Clinical Outcomes","volume":"61","author":"Diogenes","year":"2017","journal-title":"Dent. Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5395\/rde.2015.40.3.179","article-title":"A review of the regenerative endodontic treatment procedure","volume":"40","author":"Lee","year":"2015","journal-title":"Restor. Dent. Endod."},{"key":"ref_19","first-page":"S128","article-title":"Bioceramics in endodontics\u2014A review","volume":"51","author":"Raghavendra","year":"2017","journal-title":"J. Istanb. Univ. Fac. Dent."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.joen.2012.11.014","article-title":"Revascularization: A treatment for permanent teeth with necrotic pulp and incomplete root development","volume":"39","author":"Wigler","year":"2013","journal-title":"J. Endod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.dental.2018.03.001","article-title":"Bioactive dental materials\u2014Do they exist and what does bioactivity mean?","volume":"34","author":"Vallittu","year":"2018","journal-title":"Dent. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Staffoli, S., Plotino, G., Torrijos, B.G.N., Grande, N.M., Boss\u00f9, M., Gambarini, G., and Polimeni, A. (2019). Regenerative endodontic procedures using contemporary endodontic materials. Materials (Basel), 16.","DOI":"10.3390\/ma12060908"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sanz, J.L., Rodr\u00edguez-Lozano, F.J., Llena, C., Sauro, S., and Forner, L. (2019). Bioactivity of bioceramic materials used in the dentin-pulp complex therapy: A systematic review. Materials (Basel), 12.","DOI":"10.3390\/ma12071015"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.dental.2015.09.020","article-title":"Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularization","volume":"31","author":"Bortoluzzi","year":"2015","journal-title":"Dent. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.dental.2016.07.007","article-title":"Mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells following their exposure to a discoloration-free calcium aluminosilicate cement","volume":"32","author":"Niu","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jebdp.2018.05.002","article-title":"Efficacy of Biodentine and Mineral Trioxide Aggregate in Primary Molar Pulpotomies\u2014A Systematic Review and Meta-Analysis With Trial Sequential Analysis of Randomized Clinical Trials","volume":"19","author":"Nagendrababu","year":"2019","journal-title":"J. Evid. Based Dent. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"466","DOI":"10.4103\/JCD.JCD_198_18","article-title":"Biodentine versus mineral trioxide aggregate as a direct pulp capping material for human mature permanent teeth\u2014A systematic review","volume":"21","author":"Mahmoud","year":"2018","journal-title":"J. Conserv. Dent."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.adaj.2018.06.003","article-title":"The effect of dental pulp-capping materials on hard-tissue barrier formation: A systematic review and meta-analysis","volume":"149","author":"Didilescu","year":"2018","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_29","first-page":"148","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"20","author":"Moher","year":"2016","journal-title":"Revista Espa\u00f1ola de Nutrici\u00f3n Humana y Diet\u00e9tica"},{"key":"ref_30","first-page":"359","article-title":"Evaluation of PICO as a knowledge representation for clinical questions","volume":"2006","author":"Huang","year":"2006","journal-title":"AMIA Annu. Symp. Proc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jebdp.2012.10.001","article-title":"Guidelines for reporting pre-clinical in vitro studies on dental materials","volume":"12","author":"Faggion","year":"2012","journal-title":"J. Evid. Based Dent. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, Y., Liu, X.M., Bi, J., Yu, S., Yang, N., Song, B., and Chen, X. (2019). Cell migration and osteo\/odontogenesis stimulation of iRoot FS as a potential apical barrier material in apexification. Int. Endod. J.","DOI":"10.1111\/iej.13237"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2147\/CCIDE.S211893","article-title":"Proliferation, odontogenic\/osteogenic differentiation, and cytokine production by human stem cells of the apical papilla induced by biomaterials: A comparative study","volume":"11","author":"Saberi","year":"2019","journal-title":"Clin. Cosmet. Investig. Dent."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.joen.2017.12.018","article-title":"Effect of 3 Bioceramic Materials on Stem Cells of the Apical Papilla Proliferation and Differentiation Using a Dentin Disk Model","volume":"44","author":"Miller","year":"2018","journal-title":"J. Endod."},{"key":"ref_35","first-page":"94","article-title":"Effect of MTA and CEM on Mineralization-Associated Gene Expression in Stem Cells Derived from Apical Papilla","volume":"13","author":"Hajizadeh","year":"2018","journal-title":"Iran. Endod. J."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","unstructured":"Sequeira, D.B., Seabra, C.M., Palma, P.J., Cardoso, A.L., Pe\u00e7a, J., and Santos, J.M. (2018). Effects of a New Bioceramic Material on Human Apical Papilla Cells. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9040074"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/iej.12923","article-title":"iRoot FM exerts an antibacterial effect on Porphyromonas endodontalis and improves the properties of stem cells from the apical papilla","volume":"51","author":"Bi","year":"2018","journal-title":"Int. Endod. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/iej.12571","article-title":"Effects of two calcium silicate cements on cell viability, angiogenic growth factor release and related gene expression in stem cells from the apical papilla","volume":"49","author":"Peters","year":"2016","journal-title":"Int. Endod. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.joen.2013.11.021","article-title":"White mineral trioxide aggregate induces migration and proliferation of stem cells from the apical papilla","volume":"40","author":"Schneider","year":"2014","journal-title":"J. Endod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.joen.2014.01.042","article-title":"Mineral Trioxide Aggregate Promotes the Odonto\/Osteogenic Differentiation and Dentinogenesis of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway","volume":"40","author":"Yan","year":"2014","journal-title":"J. Endod."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/13\/4\/974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:59:46Z","timestamp":1760173186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/13\/4\/974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ma13040974"],"URL":"https:\/\/doi.org\/10.3390\/ma13040974","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,21]]}}}