{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:14:28Z","timestamp":1789154068466,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nano- and microparticles are currently being discussed as potential risk factors for peri-implant disease. In the present study, we compared the responses of human gingival mesenchymal stromal cells (hG-MSCs) on titanium and zirconia nanoparticles (&lt;100 nm) in the absence and presence of Porphyromonas gingivalis lipopolysaccharide (LPS). The primary hG-MSCs were treated with titanium and zirconia nanoparticles in concentrations up to 2.000 \u00b5g\/mL for 24 h, 72 h, and 168 h. Additionally, the cells were treated with different nanoparticles (25\u2013100 \u00b5g\/mL) in the presence of P. gingivalis LPS for 24 h. The cell proliferation and viability assay and live\u2013dead and focal adhesion stainings were performed, and the expression levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were measured. The cell proliferation and viability were inhibited by the titanium (&gt;1000 \u00b5g\/mL) but not the zirconia nanoparticles, which was accompanied by enhanced apoptosis. Both types of nanoparticles (&gt;25 \u00b5g\/mL) induced the significant expression of IL-8 in gingival MSCs, and a slightly higher effect was observed for titanium nanoparticles. Both nanoparticles substantially enhanced the P. gingivalis LPS-induced IL-8 production; a higher effect was observed for zirconia nanoparticles. The production of inflammatory mediators by hG-MSCs is affected by the nanoparticles. This effect depends on the nanoparticle material and the presence of inflammatory stimuli.<\/jats:p>","DOI":"10.3390\/ijms231710022","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of Titanium and Zirconia Nanoparticles on Human Gingival Mesenchymal Stromal Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-0261","authenticated-orcid":false,"given":"Michael","family":"Nemec","sequence":"first","affiliation":[{"name":"Clinical Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-3200","authenticated-orcid":false,"given":"Christian","family":"Behm","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Maierhofer","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Gau","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya","family":"Kolba","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Jonke","sequence":"additional","affiliation":[{"name":"Clinical Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Rausch-Fan","sequence":"additional","affiliation":[{"name":"Clinical Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Center for Clinical Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0485-2142","authenticated-orcid":false,"given":"Oleh","family":"Andrukhov","sequence":"additional","affiliation":[{"name":"Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jdent.2019.03.008","article-title":"Long-term (10-year) dental implant survival: A systematic review and sensitivity meta-analysis","volume":"84","author":"Howe","year":"2019","journal-title":"J. Dent."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12185","article-title":"Modern implant dentistry based on osseointegration: 50 years of progress, current trends and open questions","volume":"73","author":"Buser","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1600-0757.1998.tb00119.x","article-title":"Titanium\u2014The material of choice?","volume":"17","author":"Steinemann","year":"2000","journal-title":"Periodontology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/prd.12180","article-title":"Zirconia dental implants: Where are we now, and where are we heading?","volume":"73","author":"Cionca","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1563\/AAID-JOI-D-09-00079","article-title":"Zirconia Dental Implants: A Literature Review","volume":"37","year":"2011","journal-title":"J. Oral Implantol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1600-0501.2008.01543.x-i2","article-title":"The mucosal barrier at implant abutments of different materials","volume":"19","author":"Welander","year":"2008","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/clr.13425","article-title":"Zirconia compared to titanium dental implants in preclinical studies\u2014A systematic review and meta-analysis","volume":"30","author":"Roehling","year":"2019","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"671","DOI":"10.11607\/jomi.3831","article-title":"Immediate occlusal loading of one-piece zirconia implants: Five-year radiographic and clinical evaluation","volume":"30","author":"Grassi","year":"2015","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/cid.12742","article-title":"On osseointegration in relation to implant surfaces","volume":"21","author":"Albrektsson","year":"2019","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6285620","DOI":"10.1155\/2016\/6285620","article-title":"Impact of Dental Implant Surface Modifications on Osseointegration","volume":"2016","author":"Smeets","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/prd.12179","article-title":"Osseointegration of titanium, titanium alloy and zirconia dental implants: Current knowledge and open questions","volume":"73","author":"Bosshardt","year":"2017","journal-title":"Periodontology 2000"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.dental.2021.02.005","article-title":"Race to invade: Understanding soft tissue integration at the transmucosal region of titanium dental implants","volume":"37","author":"Guo","year":"2021","journal-title":"Dent. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/prd.12150","article-title":"Comparison of peri-implant and periodontal marginal soft tissues in health and disease","volume":"76","author":"Ivanovski","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.actbio.2021.01.001","article-title":"Orchestrating soft tissue integration at the transmucosal region of titanium implants","volume":"124","author":"Guo","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_15","first-page":"e8","article-title":"Periodontitis, implant loss and peri-implantitis. A meta-analysis","volume":"26","author":"Sgolastra","year":"2015","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S158","DOI":"10.1111\/jcpe.12334","article-title":"Peri-implant health and disease. A systematic review of current epidemiology","volume":"42","author":"Derks","year":"2015","journal-title":"J. Clin. Periodontol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/prd.12372","article-title":"Peri-implantitis is not periodontitis: Scientific discoveries shed light on microbiome-biomaterial interactions that may determine disease phenotype","volume":"86","author":"Kotsakis","year":"2021","journal-title":"Periodontology 2000"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0022034520949851","article-title":"Microbial Community-Driven Etiopathogenesis of Peri-Implantitis","volume":"100","author":"Belibasakis","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/clr.13305","article-title":"What is the impact of titanium particles and biocorrosion on implant survival and complications? A critical review","volume":"29","author":"Mombelli","year":"2018","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jre.12479","article-title":"Can degradation products released from dental implants affect peri-implant tissues?","volume":"53","author":"Schunemann","year":"2018","journal-title":"J. Periodontal Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/j.biomaterials.2003.09.017","article-title":"Early detachment of titanium particles from various different surfaces of endosseous dental implants","volume":"25","author":"Franchi","year":"2004","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.msec.2014.11.055","article-title":"How do titanium and Ti6Al4V corrode in fluoridated medium as found in the oral cavity? An in vitro study","volume":"47","author":"Souza","year":"2015","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40729-020-00247-1","article-title":"Particle release from implantoplasty of dental implants and impact on cells","volume":"6","author":"Barrak","year":"2020","journal-title":"Int. J. Implant Dent."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bressan, E., Ferroni, L., Gardin, C., Bellin, G., Sbricoli, L., Sivolella, S., Brunello, G., Schwartz-Arad, D., Mijiritsky, E., and Penarrocha, M. (2019). Metal Nanoparticles Released from Dental Implant Surfaces: Potential Contribution to Chronic Inflammation and Peri-Implant Bone Loss. Materials, 12.","DOI":"10.3390\/ma12122036"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/clr.13372","article-title":"Dental implants-associated release of titanium particles: A systematic review","volume":"29","author":"Fretwurst","year":"2018","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.dental.2020.01.013","article-title":"Titanium and zirconium release from titanium- and zirconia implants in mini pig maxillae and their toxicity in vitro","volume":"36","author":"He","year":"2020","journal-title":"Dent. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.3390\/ijms11062383","article-title":"Effects of Titanium Dioxide Nanoparticle Aggregate Size on Gene Expression","volume":"11","author":"Takaku","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/prd.12076","article-title":"Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair","volume":"68","author":"Chiquet","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"604","DOI":"10.4252\/wjsc.v11.i9.604","article-title":"Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration","volume":"11","author":"Andrukhov","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1016\/j.dental.2020.04.003","article-title":"Effect of implant surface material and roughness to the susceptibility of primary gingival fibroblasts to inflammatory stimuli","volume":"36","author":"Andrukhov","year":"2020","journal-title":"Dent. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/jre.12121","article-title":"Differential response of human gingival fibroblasts to titanium- and titanium-zirconium-modified surfaces","volume":"49","author":"Ramis","year":"2014","journal-title":"J. Periodontal Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rausch, M., Shokoohi-Tabrizi, H., Wehner, C., Pippenger, B.E., Wagner, R.S., Ulm, C., Moritz, A., Chen, J., and Andrukhov, O. (2021). Impact of Implant Surface Material and Microscale Roughness on the Initial Attachment and Proliferation of Primary Human Gingival Fibroblasts. Biology, 10.","DOI":"10.3390\/biology10050356"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.11607\/jomi.6929","article-title":"The Biologic Effect of Particulate Titanium Contaminants of Dental Implants on Human Osteoblasts and Gingival Fibroblasts","volume":"34","author":"Happe","year":"2019","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1111\/jcpe.12136","article-title":"Influence of titanium on in vitro fibroblast-Porphyromonas gingivalis interaction in peri-implantitis","volume":"40","author":"Irshad","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40729-019-0178-2","article-title":"Cytotoxicity and proinflammatory effects of titanium and zirconia particles","volume":"5","author":"Schwarz","year":"2019","journal-title":"Int. J. Implant Dent."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1902\/jop.2017.170123","article-title":"Microbiome and Microbial Biofilm Profiles of Peri-Implantitis: A Systematic Review","volume":"88","author":"Lafaurie","year":"2017","journal-title":"J. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.bbrc.2017.08.054","article-title":"Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity","volume":"492","author":"Hattori","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1073\/pnas.0903269107","article-title":"Geometric cues for directing the differentiation of mesenchymal stem cells","volume":"107","author":"Kilian","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10856-009-3834-x","article-title":"Microscopic observations and inflammatory cytokine productions of human macrophage phagocytising submicron titanium particles","volume":"21","author":"Taira","year":"2010","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"39612","DOI":"10.1038\/srep39612","article-title":"Scaling of titanium implants entrains inflammation-induced osteolysis","volume":"7","author":"Eger","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/jre.12364","article-title":"Titanium ions form particles that activate and execute interleukin-1\u03b2 release from lipopolysaccharide-primed macrophages","volume":"52","author":"Pettersson","year":"2017","journal-title":"J. Periodontal Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Delgado-Ruiz, R., and Romanos, G. (2018). Potential Causes of Titanium Particle and Ion Release in Implant Dentistry: A Systematic Review. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113585"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.dental.2016.05.012","article-title":"Analysis of titanium and other metals in human jawbones with dental implants\u2014A case series study","volume":"32","author":"He","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.nantod.2015.06.006","article-title":"Nanoparticle uptake: The phagocyte problem","volume":"10","author":"Gustafson","year":"2015","journal-title":"Nano Today"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/cid.12711","article-title":"On inflammation-immunological balance theory-A critical apprehension of disease concepts around implants: Mucositis and marginal bone loss may represent normal conditions and not necessarily a state of disease","volume":"21","author":"Albrektsson","year":"2018","journal-title":"Clin. Implant Dent. Relat. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ivanovski, S., Bartold, P.M., and Huang, Y.S. (2022). The role of foreign body response in peri-implantitis: What is the evidence?. Periodontology 2000.","DOI":"10.1111\/prd.12456"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1111\/clr.12718","article-title":"Metal elements in tissue with dental peri-implantitis: A pilot study","volume":"27","author":"Fretwurst","year":"2016","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/joor.12735","article-title":"Titanium release in peri-implantitis","volume":"46","author":"Pettersson","year":"2019","journal-title":"J. Oral Rehabil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/clr.13928","article-title":"Study on the immunopathological effect of titanium particles in peri-implantitis granulation tissue: A case\u2013control study","volume":"33","author":"Rakic","year":"2022","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1600-0501.2004.01053.x","article-title":"Titanium release from implants prepared with different surface roughness. An in vitro and in vivo study","volume":"15","author":"Wennerberg","year":"2004","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1177\/0022034518765751","article-title":"Reduction of Tribocorrosion Products When Using the Platform-Switching Concept","volume":"97","author":"Alrabeah","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8704896","DOI":"10.1155\/2020\/8704896","article-title":"Response of Human Mesenchymal Stromal Cells from Periodontal Tissue to LPS Depends on the Purity but Not on the LPS Source","volume":"2020","author":"Behm","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/odi.13768","article-title":"Anti-apoptotic effects of human gingival mesenchymal stromal cells on polymorphonuclear leucocytes","volume":"28","author":"Blufstein","year":"2021","journal-title":"Oral Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Andrukhov, O., Andrukhova, O., \u00d6zdemir, B., Haririan, H., M\u00fcller-Kern, M., Moritz, A., and Rausch-Fan, X. (2016). Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to P. gingivalis Lipopolysaccharide. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160848"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, F., \u00d6zdemir, B., Nguyen, P.Q., Andrukhov, O., and Rausch-Fan, X. (2020). Methanandamide diminish the Porphyromonas gingivalis lipopolysaccharide induced response in human periodontal ligament cells. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01087-6"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nemec, M., Bartholomaeus, H.M., Bertl, M.H., Behm, C., Shokoohi-Tabrizi, H.A., Jonke, E., Andrukhov, O., and Rausch-Fan, X. (2020). Behaviour of Human Oral Epithelial Cells Grown on Invisalign\u00ae SmartTrack\u00ae Material. Materials, 13.","DOI":"10.3390\/ma13235311"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10022\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:22:17Z","timestamp":1760142137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":56,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231710022"],"URL":"https:\/\/doi.org\/10.3390\/ijms231710022","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]}}}