{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:00:45Z","timestamp":1790427645882,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":268,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007161","name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado, Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"publisher","award":["20250062"],"award-info":[{"award-number":["20250062"]}],"id":[{"id":"10.13039\/501100007161","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Toxicology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    The skeleton provides structural support, organ protection, and mineral storage, making the long\u2010term biocompatibility of orthopedic implants essential. Although stainless steel and cobalt\u2010based alloys are widely used in these devices, corrosion can release metal ions that induce inflammatory and cytotoxic responses in surrounding bone tissue. Because most in vitro studies rely on conventional two\u2010dimensional (2D) cultures, three\u2010dimensional (3D) spheroids offer a more physiologically relevant model for evaluating metal ion toxicity. In this study, human fetal osteoblast (hFOB) spheroids were exposed to CrCl\n                    <jats:sub>3<\/jats:sub>\n                    , CoCl\n                    <jats:sub>2<\/jats:sub>\n                    , or NiCl\n                    <jats:sub>2<\/jats:sub>\n                    at 100 or 500\u2009\u03bcM for 12\u2009days. Morphological alterations were evaluated by scanning electron microscopy and histology, while cytotoxicity and apoptosis were assessed using resazurin, live\/dead fluorescence, and annexin V\/propidium iodide staining. CrCl\n                    <jats:sub>3<\/jats:sub>\n                    caused minimal effects at 100\u2009\u03bcM and only moderate cytotoxicity at 500\u2009\u03bcM. In contrast, CoCl\n                    <jats:sub>2<\/jats:sub>\n                    and especially NiCl\n                    <jats:sub>2<\/jats:sub>\n                    significantly reduced spheroid growth, induced retraction of cytoplasmic extensions, membrane damage, and increased apoptosis, with the most severe effects observed at 500\u2009\u03bcM. Fluorescence and Annexin V staining confirmed a higher abundance of apoptotic bodies after CoCl\n                    <jats:sub>2<\/jats:sub>\n                    and NiCl\n                    <jats:sub>2<\/jats:sub>\n                    exposure than after CrCl\n                    <jats:sub>3<\/jats:sub>\n                    treatment. These findings demonstrate that 3D osteo\u2010spheroids provide a physiologically relevant platform for investigating the biological effects of metal ions released from orthopedic implants and reveal that nickel and cobalt ions exert substantially greater cytotoxicity than chromium under prolonged exposure conditions.\n                  <\/jats:p>","DOI":"10.1155\/jt\/1047932","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:31:53Z","timestamp":1790425913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morphological and Cytotoxic Effects of Metal Salts on Osteoblast Cells in Three\u2010Dimensional Spheroidal Cultures"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-8698","authenticated-orcid":false,"given":"Misael","family":"Vargas-L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-2808","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Castrej\u00f3n-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0275-9307","authenticated-orcid":false,"given":"\u00c1ngel Ernesto","family":"Ba\u00f1uelos-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2143","authenticated-orcid":false,"given":"Fernando","family":"G\u00f3mez-Ch\u00e1vez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-8581","authenticated-orcid":false,"given":"Ricardo","family":"Garc\u00eda-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma. 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