{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:04:44Z","timestamp":1791324284930,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T00:00:00Z","timestamp":1117756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite reports associating tissue necrosis with implant failure, the degree to which processes, such as metal toxicity, negatively impact implant performance is unknown. We evaluated representative human peri\u2010implant cells (i.e., osteoblasts, fibroblasts, and lymphocytes) when challenged by Al<jats:sup>+3<\/jats:sup>, Co<jats:sup>+2<\/jats:sup>, Cr<jats:sup>+3<\/jats:sup>, Fe<jats:sup>+3<\/jats:sup>, Mo<jats:sup>+5<\/jats:sup>, Ni<jats:sup>+2<\/jats:sup>, and V<jats:sup>+3<\/jats:sup> chloride solutions (and Na<jats:sup>+2<\/jats:sup> as a control) over a wide range of concentrations (0.01\u201310.0 m<jats:italic>M<\/jats:italic>). Cell responses were measured using proliferation assays, viability assays, and microscopic cell morphology assessments. Differential effects were found to be less a function of the cell type than of the composition and concentration of metal challenge. No preferential immunosuppression was demonstrated. Below 0.01 m<jats:italic>M<\/jats:italic>, no metal was toxic. The most toxic metals (i.e., Co, Ni, and V) reduced proliferation (IC<jats:sub>50<\/jats:sub>), and viability (LC50) and cell morphology of osteoblasts, fibroblasts, and lymphocytes by &lt;50% at challenge concentrations &lt;1 m<jats:italic>M<\/jats:italic>. All other metals tested required &gt;5 m<jats:italic>M<\/jats:italic> to exact the same responses. Below 1 m<jats:italic>M<\/jats:italic>, these toxic metals also induced alterations in all cell morphology consisting of loss of filopodia or lamellipodia or changes in cell shape. Metals that were toxic at clinically relevant concentrations (less than previously reported values in peri\u2010implant tissues\/fluids) include Co (0.6 m<jats:italic>M<\/jats:italic>), Ni (0.8 m<jats:italic>M<\/jats:italic>), V (0.5 m<jats:italic>M<\/jats:italic>) for lymphocytes and Co (0.8 m<jats:italic>M<\/jats:italic>), V (0.3 m<jats:italic>M<\/jats:italic>), Al (1\u20135 m<jats:italic>M<\/jats:italic>), Fe (1\u20135 m<jats:italic>M<\/jats:italic>) for fibroblasts, and Co (0.8 m<jats:italic>M<\/jats:italic>), Ni (0.7 m<jats:italic>M<\/jats:italic>), V (0.1 m<jats:italic>M<\/jats:italic>) for osteoblasts. Only Co and V were toxic <jats:italic>in vitro<\/jats:italic> at concentrations below that detected <jats:italic>in vivo<\/jats:italic> in synovial fluid (V at 0.1 m<jats:italic>M<\/jats:italic> and Co at 0.8 m<jats:italic>M<\/jats:italic> for fibroblasts, and V at 0.4 m<jats:italic>M<\/jats:italic> and Co at 0.8 m<jats:italic>M<\/jats:italic> on osteoblasts). Thus, soluble Co and V released from Co\u2010 and Ti\u2010based alloys, respectively, could be implicated as the most likely to mediate cell toxicity in the periprosthetic milieu. \u00a9 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005<\/jats:p>","DOI":"10.1002\/jbm.a.30345","type":"journal-article","created":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T20:46:45Z","timestamp":1117831605000},"page":"124-140","source":"Crossref","is-referenced-by-count":107,"title":["Effects of soluble metals on human peri\u2010implant cells"],"prefix":"10.1002","volume":"74A","author":[{"given":"Nadim James","family":"Hallab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Caicedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amee","family":"Brasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Mikecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"402","volume-title":"Orthopedic basic science","author":"Jacobs J","year":"1999"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199608001-00017"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","unstructured":"CampbellPA McKellopH AlimR MirraJ NuttS AmstutzHC.Metal\u2010on\u2010metal hip replacements: Wear performance and cellular response to wear particles. In:DisegiR KennedyRL PilliarRM editors.Cobalt\u2010base alloys for biomedical applications ASTMSTP 1365.West Conshohocken PA:American Society for Testing and Materials;1999. p193\u2013200.","DOI":"10.1520\/STP14274S"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198870080-00017"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(20000305)49:3<353::AID-JBM8>3.0.CO;2-T"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199905010-00011"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199807000-00005"},{"key":"e_1_2_6_9_2","first-page":"157","article-title":"Metallic debris in femoral endosteolysis in failed cemented total hip arthroplasties","volume":"276","author":"Huo MH","year":"1992","journal-title":"Clin Orthop"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.76B1.8300684"},{"key":"e_1_2_6_11_2","volume-title":"Particulate\u2010associated endosteal osteolysis in titanium\u2010base alloy cementless total hip replacement. Particulate debris from medical implants","author":"Jacobs JJ","year":"1992"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199409000-00009"},{"key":"e_1_2_6_13_2","first-page":"1107","article-title":"Particles of metal alloys and their corrosion products in the liver, spleen and para\u2010aortic lymph nodes of patients with total hip replacement prosthesis","volume":"19","author":"Urban RM","year":"1996","journal-title":"Orthop Trans"},{"key":"e_1_2_6_14_2","first-page":"82","article-title":"Histologic, biochemical and ion analysis of tissue and fluids retrieved during total hip arthroplasty","volume":"261","author":"Dorr LD","year":"1990","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_6_15_2","first-page":"838","article-title":"Systemic distribution of metal degradation products from titanium alloy total hip replacements: an autopsy study","author":"Jacobs JJ","year":"1994","journal-title":"Trans Orthop Res Soc"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00393876"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jab.770050103"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199612000-00006"},{"key":"e_1_2_6_19_2","first-page":"94","article-title":"Local and distant products from modularity","volume":"319","author":"Jacobs J","year":"1995","journal-title":"Clin Orthop"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200004000-00002"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000237456"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(199701)34:1<29::AID-JBM5>3.0.CO;2-P"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0109-5641(94)90025-6"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.820280404"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0109-5641(93)90116-8"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(199705)35:2<265::AID-JBM14>3.0.CO;2-G"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(96)00009-9"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jab.770060406"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jab.770060205"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(199902)44:2<176::AID-JBM8>3.0.CO;2-6"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(97)00234-2"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(97)00149-X"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(19981205)42:3<443::AID-JBM14>3.0.CO;2-H"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2842.1998.00197.x"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199706000-00030"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.10106"},{"key":"e_1_2_6_37_2","first-page":"286","article-title":"Metal specific responses dominate in vitro hypersensitivity reactions in patients with total joint arthroplasty","volume":"28","author":"Hallab NJ","year":"2003","journal-title":"Transactions of the 49th Orthopaedic Research Society"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.10429"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199802000-00015"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100070302"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(83)90003-0"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1501"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1074>3.0.CO;2-C"},{"key":"e_1_2_6_44_2","series-title":"Advances in orthopaedic surgery","first-page":"279","author":"Jacobs JJ","year":"1994"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199901000-00021"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199810000-00006"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199405000-00011"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200112000-00008"},{"key":"e_1_2_6_49_2","unstructured":"HallabNJ MikeczK AkramiJ JacobsJ.Differential metal release and protein binding associated with titanium and cobalt\u2010chromium implant alloys. Trans 46th Orthop Res Soc2000 Orlando FL."},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(20000305)49:3<353::AID-JBM8>3.0.CO;2-T"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(86)90084-0"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbm.a.30345","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.30345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T04:58:37Z","timestamp":1697086717000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.30345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,3]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,7]]}},"alternative-id":["10.1002\/jbm.a.30345"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.30345","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,3]]}}}