{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:16:04Z","timestamp":1782926164161,"version":"3.54.5"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Aim<\/jats:title>\n<jats:p>This study aimed to develop a modified gutta-percha (GP) multifunctional endodontic material by incorporating mesoporous calcium silicate nanoparticles (MCSNs) or silver-incorporated mesoporous calcium silicate nanoparticles (Ag-MCSNs) as bioactive nanoparticle fillers to enhance bioactivity, biomineralization, and radiopacity while achieving low cytotoxicity and improved antibacterial activity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology<\/jats:title>\n<jats:p>MCSNs and Ag-MCSNs were synthesized and incorporated into GP at concentrations of 1%, 5%, and 10% by weight. The chemical and structural characterization of the new GP materials was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive spectrometry (EDS), and field emission-scanning electron microscopy (FE-SEM) to assess filler distribution. Biomineralization was evaluated using XRD, EDS, and scanning electron microscopy (SEM). Ion release, pH changes, MTT assays, and culture-based techniques were employed to assess bioactivity, biocompatibility, and antibacterial properties. Finally, radiopacity testing was conducted.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>All samples of the newly developed GP exhibited uniform particle distribution within the GP matrix. Bioactivity and biomineralization tests revealed hydroxyapatite (HA) layer precipitation at 3, 7, 14, and 28 days, with maximum HA formation observed with prolonged immersion. Samples containing MCSNs or Ag-MCSNs created a weakly alkaline microenvironment initially, maintaining a suitable pH over time. All groups demonstrated non-cytotoxicity, with cell viability exceeding 70%. Antibacterial tests showed larger inhibition zones in all experimental groups compared to the control, with GP containing 10% MCSNs or Ag-MCSNs exhibiting the highest antibacterial activity, particularly Ag-MCSNs. Radiopacity tests indicated no significant difference between the experimental and control groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Gutta-percha materials incorporated with 10% MCSNs or Ag-MCSNs demonstrated enhanced bioactivity, biomineralization, and antibacterial properties compared to the control GP, while maintaining suitable levels of biocompatibility in accordance with ISO 10993\/2009 standards. The incorporation of Ag-MCSNs significantly improved antibacterial effects, particularly against <jats:italic><jats:italic>Enterococcus faecalis<\/jats:italic><\/jats:italic>, and increased radiopacity, making it a promising material for root canal therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0329435","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:40:09Z","timestamp":1755020409000},"page":"e0329435","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhancing gutta-percha with silver mesoporous calcium silicate nanoparticles for advanced endodontic applications"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-6732","authenticated-orcid":true,"given":"Amer 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for endodontic use","volume":"47","author":"R Alhashimi","year":"2014","journal-title":"Int Endod J"},{"key":"pone.0329435.ref030","author":"R Al-Hashimi","year":"2014"},{"issue":"2","key":"pone.0329435.ref031","doi-asserted-by":"crossref","first-page":"025003","DOI":"10.1088\/2631-6331\/ab20c1","article-title":"In situ FTIR analysis in determining possible chemical reactions for peroxide crosslinked LDPE in the presence of triallylcyanurate","volume":"1","author":"CS Sipaut","year":"2019","journal-title":"Functional Composites and Structures"},{"issue":"1","key":"pone.0329435.ref032","first-page":"55","article-title":"Incorporation of bioactive glass nanoparticles in electrospun PCL\/chitosan fibers by using benign solvents","volume":"3","author":"L Liverani","year":"2018","journal-title":"Bioact Mater"},{"issue":"5","key":"pone.0329435.ref033","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1134\/S0040579523050214","article-title":"Studying the Effect of Successive Irradiation by Electrons and Solar Spectrum Quanta on the Optical Properties of a Nanoparticle-Modified Barium Sulfate Powder","volume":"57","author":"MM Mikhailov","year":"2023","journal-title":"Theor Found Chem Eng"},{"issue":"15","key":"pone.0329435.ref034","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1016\/j.biomaterials.2006.01.017","article-title":"How useful is SBF in predicting in vivo bone bioactivity?","volume":"27","author":"T Kokubo","year":"2006","journal-title":"Biomaterials"},{"issue":"2","key":"pone.0329435.ref035","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1834-7819.2011.01321.x","article-title":"Tricalcium silicate induced mineralization for occlusion of dentinal tubules","volume":"56","author":"Z Dong","year":"2011","journal-title":"Aust Dent J"},{"issue":"2","key":"pone.0329435.ref036","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/jbm.b.30813","article-title":"A template route to the preparation of mesoporous amorphous calcium silicate with high in vitro bone-forming bioactivity","volume":"83","author":"X Li","year":"2007","journal-title":"J Biomed Mater Res B Appl Biomater"},{"issue":"10","key":"pone.0329435.ref037","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.joen.2016.05.021","article-title":"Antibacterial nanoparticles in endodontics: a review","volume":"42","author":"A Shrestha","year":"2016","journal-title":"J Endodont"},{"issue":"4","key":"pone.0329435.ref038","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0142-9612(96)00059-2","article-title":"Formation of surface reaction products on bioactive glass and their effects on the expression of the osteoblastic phenotype and the deposition of mineralized extracellular matrix","volume":"18","author":"A el-Ghannam","year":"1997","journal-title":"Biomaterials"},{"issue":"2","key":"pone.0329435.ref039","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/jbm.a.31623","article-title":"Incorporation of titanium into calcium silicate improved their chemical stability and biological properties","volume":"86","author":"C Wu","year":"2008","journal-title":"J Biomed Mater Res A"},{"key":"pone.0329435.ref040","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.colsurfb.2014.11.044","article-title":"Fabrication of nano-structured calcium silicate coatings with enhanced stability, bioactivity and osteogenic and angiogenic activity","volume":"126","author":"X Wang","year":"2015","journal-title":"Colloids Surf B Biointerfaces"},{"issue":"10","key":"pone.0329435.ref041","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1016\/j.gca.2006.02.023","article-title":"Influence of glass composition and alteration solution on leached silicate glass structure: a solid-state NMR investigation","volume":"70","author":"F Angeli","year":"2006","journal-title":"Geochimica et Cosmochimica Acta"},{"issue":"4","key":"pone.0329435.ref042","doi-asserted-by":"crossref","first-page":"59","DOI":"10.26477\/jbcd.v34i4.3287","article-title":"Continuous Chelation Concept in Endodontics","volume":"34","author":"AH Adham","year":"2022","journal-title":"J Baghdad College Dentistry"},{"issue":"8","key":"pone.0329435.ref043","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3390\/nano10081566","article-title":"The Potential of Silver Nanoparticles for Antiviral and Antibacterial Applications: A Mechanism of Action","volume":"10","author":"A Salleh","year":"2020","journal-title":"Nanomaterials (Basel)"},{"issue":"1","key":"pone.0329435.ref044","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1016\/j.actbio.2012.09.024","article-title":"Mesoporous bioactive scaffolds prepared with cerium-, gallium- and zinc-containing glasses","volume":"9","author":"S Shruti","year":"2013","journal-title":"Acta Biomater"},{"issue":"2","key":"pone.0329435.ref045","doi-asserted-by":"crossref","first-page":"32","DOI":"10.26477\/jbcd.v35i2.3397","article-title":"Antibacterial and cytotoxic effect of a novel biological Nano-silver fluoride synthesized from moringa oleifera leaf extract","volume":"35","author":"DJ Kadhem","year":"2023","journal-title":"J Bagh Coll Dent"},{"issue":"1","key":"pone.0329435.ref046","article-title":"Nanoparticle elasticity regulates the formation of cell membrane-coated nanoparticles and their nano-bio interactions","volume":"120","author":"D Zou","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0329435.ref047","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.joen.2017.09.017","article-title":"Evaluation of Physicochemical Properties of a New Root Canal Sealer","volume":"44","author":"GC Vertuan","year":"2018","journal-title":"J 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