{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:49:00Z","timestamp":1764784140739,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T00:00:00Z","timestamp":1541462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BA 3347\/12-1"],"award-info":[{"award-number":["BA 3347\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The evaluation of the biological effects of endoprosthetic wear particles on cells in vitro relies on a variety of test assays. However, most of these methods are susceptible to particle-induced interferences; therefore, label-free testing approaches emerge as more reliable alternatives. In this study, impedance-based real-time monitoring of cellular viability and metabolic activity were performed following exposure to metallic and ceramic wear particles. Moreover, label-free imaging of particle-exposed cells was done by high-resolution darkfield microscopy (HR-ODM) and field emission scanning electron microscopy (FESEM). The isolated human fibroblasts were exposed to CoCr28Mo6 and alumina matrix composite (AMC) ceramic particles. HR-ODM and FESEM revealed ingested particles. For impedance measurements, cells were seeded on gold-plated microelectrodes. Cellular behavior was monitored over a period of 48 h. CoCr28Mo6 and AMC particle exposure affected cell viability in a concentration-dependent manner, i.e., 0.01 mg\/mL particle solutions led to small changes in cell viability, while 0.05 mg\/mL resulted in a significant reduction of viability. The effects were more pronounced after exposure to CoCr28Mo6 particles. The results were in line with light and darkfield microcopy observations indicating that the chosen methods are valuable tools to assess cytotoxicity and cellular behavior following exposure to endoprosthetic wear particles.<\/jats:p>","DOI":"10.3390\/ijms19113486","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T03:45:22Z","timestamp":1541562322000},"page":"3486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Label-Free Monitoring of Uptake and Toxicity of Endoprosthetic Wear Particles in Human Cell Cultures"],"prefix":"10.3390","volume":"19","author":[{"given":"Anika","family":"Jonitz-Heincke","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, Rostock University Medical Center, Doberaner Strasse 142, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Tillmann","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, Rostock University Medical Center, Doberaner Strasse 142, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Ostermann","sequence":"additional","affiliation":[{"name":"Biomaterials\u2014Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Aarstadveien 19-21, 5009 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Springer","sequence":"additional","affiliation":[{"name":"Medical Biology and Electron Microscopy Center, Rostock University Medical Center, Strempelstrasse 14, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, Rostock University Medical Center, Doberaner Strasse 142, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-7891","authenticated-orcid":false,"given":"Paul","family":"H\u00f8l","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Bergen, Jonas Lies vei 87, N-5021 Bergen, Norway"},{"name":"Department of Orthopaedic Surgery, Biomatlab, Haukeland University Hospital, Jonas Lies vei 87, N-5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Cimpan","sequence":"additional","affiliation":[{"name":"Biomaterials\u2014Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Aarstadveien 19-21, 5009 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.arth.2013.01.012","article-title":"Revision surgery after total joint arthroplasty: A complication-based analysis using worldwide arthroplasty registers","volume":"28","author":"Sadoghi","year":"2013","journal-title":"J. Arthroplasty"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.5435\/00124635-200800001-00011","article-title":"How has the biologic reaction to wear particles changed with newer bearing surfaces?","volume":"16","author":"Jacobs","year":"2008","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bonr.2017.07.003","article-title":"Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening","volume":"7","author":"Amirhosseini","year":"2017","journal-title":"Bone Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wirtz, D.C., Rader, C.P., and Reichel, H. (2008). Partikelkrankheit. Revisionsendoprothetik der H\u00fcftpfanne, Springer.","DOI":"10.1007\/978-3-540-75649-1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/jor.1100140318","article-title":"Bone formation and bone resorption in failed total joint arthroplasties: Histomorphometric analysis with histochemical and immunohistochemical technique","volume":"14","author":"Kadoya","year":"1996","journal-title":"J. Orthop. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0142-9612(00)00181-2","article-title":"In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery","volume":"22","author":"Trindade","year":"2001","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1302\/0301-620X.94B1.28047","article-title":"Current concepts in osteolysis","volume":"94","author":"Ollivere","year":"2012","journal-title":"J. Bone Joint Surg. Br."},{"key":"ref_8","first-page":"182","article-title":"Biologic effects of implant debris","volume":"67","author":"Hallab","year":"2009","journal-title":"Bull. NYU Hosp. Jt. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jacobs, J.J., Roebuck, K.A., Archibeck, M., Hallab, N.J., and Glant, T.T. (2001). Osteolysis: Basic science. Clin. Orthop. Relat. Res., 71\u201377.","DOI":"10.1097\/00003086-200112000-00008"},{"key":"ref_10","first-page":"201","article-title":"The basic science of periprosthetic osteolysis","volume":"62","author":"Goodman","year":"2013","journal-title":"Instr. Course Lect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.molmed.2011.12.002","article-title":"Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty","volume":"18","author":"Gill","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cellimm.2013.04.003","article-title":"Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles","volume":"282","author":"Potnis","year":"2013","journal-title":"Cell Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1016\/j.biomaterials.2011.04.046","article-title":"Role of the Toll-like receptor pathway in the recognition of orthopedic implant wear-debris particles","volume":"32","author":"Pearl","year":"2011","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1615\/JLongTermEffMedImplants.2014010562","article-title":"Role of macrophages in the biological reaction to wear debris from joint replacements","volume":"24","author":"Nich","year":"2014","journal-title":"J. Long Term. Eff. Med. Implants"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"596870","DOI":"10.1155\/2012\/596870","article-title":"The role of TLR and chemokine in wear particle-induced aseptic loosening","volume":"2012","author":"Gu","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0142-9612(99)00211-2","article-title":"Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition","volume":"21","author":"Lohmann","year":"2000","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/S0142-9612(01)00312-X","article-title":"Ceramic and PMMA particles differentially affect osteoblast phenotype","volume":"23","author":"Lohmann","year":"2002","journal-title":"Biomaterials"},{"key":"ref_18","first-page":"1055","article-title":"The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles","volume":"28","author":"Lochner","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3389\/fimmu.2018.00831","article-title":"Inflammatory response of human PBMCs and osteoblasts incubated with metallic and ceramic submicron particles","volume":"9","author":"Klinder","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12026","DOI":"10.1088\/1742-6596\/429\/1\/012026","article-title":"An impedance-based high-throughput method for evaluating the cytotoxicity of nanoparticles","volume":"429","author":"Cimpan","year":"2013","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.tiv.2012.01.019","article-title":"Role of physicochemical characteristics in the uptake of TiO2 nanoparticles by fibroblasts","volume":"26","author":"Allouni","year":"2012","journal-title":"Toxicol. In Vitro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s12393-010-9019-z","article-title":"Bioimpedance: A review for food processing","volume":"2","author":"Pliquett","year":"2010","journal-title":"Food Eng. Rev."},{"key":"ref_23","first-page":"204","article-title":"Contact-dependent transfer of TiO2 nanoparticles between mammalian cells","volume":"10","author":"Schoelermann","year":"2016","journal-title":"Nanotoxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.3892\/mmr.2016.5415","article-title":"Contribution of human osteoblasts and macrophages to bone matrix degradation and proinflammatory cytokine release after exposure to abrasive endoprosthetic wear particles","volume":"14","author":"Lochner","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3892\/ijmm.2013.1383","article-title":"Cell viability, collagen synthesis and cytokine expression in human osteoblasts following incubation with generated wear particles using different bone cements","volume":"32","author":"Schulze","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.dental.2009.08.007","article-title":"Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts","volume":"26","author":"Urcan","year":"2010","journal-title":"Dent. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1016\/j.transproceed.2010.05.059","article-title":"Validation of xCELLigence real-time cell analyzer to assess compatibility in xenotransplantation with pig-to-baboon model","volume":"42","author":"Quereda","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jonitz-Heincke, A., Tillmann, J., Klinder, A., Krueger, S., Kretzer, J.P., Hol, P.J., Paulus, A.C., and Bader, R. (2017). The impact of metal ion exposure on the cellular behavior of human osteoblasts and PBMCs: In vitro analyses of osteolytic processes. Materials, 10.","DOI":"10.3390\/ma10070734"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, L., and Fan, Y. (2016). Adverse biological effect of TiO(2) and hydroxyapatite nanoparticles used in bone repair and replacement. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060798"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11420-006-9003-6","article-title":"The central role of wear debris in periprosthetic osteolysis","volume":"2","author":"Purdue","year":"2006","journal-title":"HSS J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5312\/wjo.v6.i2.172","article-title":"Biological response to prosthetic debris","volume":"6","author":"Bitar","year":"2015","journal-title":"World J. Orthop."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12026","DOI":"10.1039\/C4NR02535K","article-title":"Peptide modified gold nanoparticles for improved cellular uptake, nuclear transport, and intracellular retention","volume":"6","author":"Yang","year":"2014","journal-title":"Nanoscale"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"014022","DOI":"10.1117\/1.2837450","article-title":"Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles","volume":"13","author":"Curry","year":"2008","journal-title":"J. Biomed. Opt."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"015023","DOI":"10.1088\/1748-605X\/aa5aa2","article-title":"Engulfment of ceramic particles by fibroblasts does not alter cell behavior","volume":"12","author":"Faye","year":"2017","journal-title":"Biomed. Mater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:28:12Z","timestamp":1760196492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,6]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["ijms19113486"],"URL":"https:\/\/doi.org\/10.3390\/ijms19113486","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,11,6]]}}}