{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:51:21Z","timestamp":1786866681222,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union Seventh Framework Programme ([FP7\/2007\u20132013] [FP7\/2007\u20132011])","award":["n\u00b0 [318553]"],"award-info":[{"award-number":["n\u00b0 [318553]"]}]},{"name":"EPSRC Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine","award":["EP\/L014823\/1"],"award-info":[{"award-number":["EP\/L014823\/1"]}]},{"name":"UK-China Science Bridge Award and Changzhou Science and Technology Bureau","award":["102178"],"award-info":[{"award-number":["102178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>The use of total hip arthroplasties (THA) has been continuously rising to meet the demands of the increasingly ageing population. To date, this procedure has been highly successful in relieving pain and restoring the functionality of patients\u2019 joints, and has significantly improved their quality of life. However, these implants are expected to eventually fail after 15\u201325 years in situ due to slow progressive inflammatory responses at the bone-implant interface. Such inflammatory responses are primarily mediated by immune cells such as macrophages, triggered by implant wear particles. As a result, aseptic loosening is the main cause for revision surgery over the mid and long-term and is responsible for more than 70% of hip revisions. In some patients with a metal-on-metal (MoM) implant, metallic implant wear particles can give rise to metal sensitivity. Therefore, engineering biomaterials, which are immunologically inert or support the healing process, require an in-depth understanding of the host inflammatory and wound-healing response to implanted materials. This review discusses the immunological response initiated by biomaterials extensively used in THA, ultra-high-molecular-weight polyethylene (UHMWPE), cobalt chromium (CoCr), and alumina ceramics. The biological responses of these biomaterials in bulk and particulate forms are also discussed. In conclusion, the immunological responses to bulk and particulate biomaterials vary greatly depending on the implant material types, the size of particulate and its volume, and where the response to bulk forms of differing biomaterials are relatively acute and similar, while wear particles can initiate a variety of responses such as osteolysis, metal sensitivity, and so on.<\/jats:p>","DOI":"10.3390\/jfb8030033","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T03:30:06Z","timestamp":1501558206000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Immunological Responses to Total Hip Arthroplasty"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-9375","authenticated-orcid":false,"given":"Kenny","family":"Man","sequence":"first","affiliation":[{"name":"Biomaterials and Tissue Engineering Group, School of Dentistry, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-0411","authenticated-orcid":false,"given":"Lin-Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Foster","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-2826","authenticated-orcid":false,"given":"Xuebin","family":"Yang","sequence":"additional","affiliation":[{"name":"Biomaterials and Tissue Engineering Group, School of Dentistry, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Medical College and the First Affiliated Hospital, Henan University of Science and Technology, Henan 471023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.2106\/00004623-198971100-00007","article-title":"Charnley total hip arthroplasty with cement. Fifteen-year results","volume":"71","author":"Kavanagh","year":"1989","journal-title":"J. Bone Jt. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"h756","DOI":"10.1136\/bmj.h756","article-title":"Setting benchmark revision rates for total hip replacement: Analysis of registry evidence","volume":"350","author":"Kandala","year":"2015","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2106\/00004623-200704000-00012","article-title":"Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030","volume":"89","author":"Kurtz","year":"2007","journal-title":"J. Bone Jt. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/000164700317413067","article-title":"Long-term registration has improved the quality of hip replacement\u2014A review of the Swedish THR Register comparing 160,000 cases","volume":"71","author":"Herberts","year":"2000","journal-title":"Acta Orthop. Scand."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00264-007-0364-3","article-title":"Total hip arthroplasties: What are the reasons for revision?","volume":"32","author":"Ulrich","year":"2008","journal-title":"Int. Orthop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"515","DOI":"10.5301\/hipint.5000444","article-title":"Revision rates for metal-on-metal hip resurfacing and metal-on-metal total hip arthroplasty\u2014A systematic review","volume":"26","author":"Jorgensen","year":"2016","journal-title":"Hip Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1753425912451779","article-title":"Particle disease: Biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty","volume":"19","author":"Gallo","year":"2013","journal-title":"Innate Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.2106\/JBJS.H.01220","article-title":"The epidemiology of bearing surface usage in total hip arthroplasty in the United States","volume":"91A","author":"Bozic","year":"2009","journal-title":"J. Bone Jt. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1586\/17434440.5.3.383","article-title":"Current state and future of joint replacements in the hip and knee","volume":"5","author":"Lee","year":"2008","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bordini, B., Stea, S., De Clerico, M., Strazzari, S., Sasdelli, A., and Toni, A. (2007). Factors affecting aseptic loosening of 4750 total hip arthroplasties: Multivariate survival analysis. BMC Musculoskelet. Disord., 8.","DOI":"10.1186\/1471-2474-8-69"},{"key":"ref_11","unstructured":"Dotinga, R. (2015). Number of Hip Replacements Has Skyrocketed: Report, WebMD, LLC."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15040","DOI":"10.1038\/boneres.2015.40","article-title":"Current research on pharmacologic and regenerative therapies for osteoarthritis","volume":"4","author":"Zhang","year":"2016","journal-title":"Bone Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/185150","article-title":"The pathology of orthopedic implant failure is mediated by innate immune system cytokines","volume":"2014","author":"Landgraeber","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nrrheum.2011.128","article-title":"Mediators of the inflammatory response to joint replacement devices","volume":"7","author":"Cobelli","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chun, A.L. (2016). Implant materials: Reducing wear debris. Nat. Nanotechnol.","DOI":"10.1038\/nnano.2016.12"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.1016\/j.biomaterials.2004.01.023","article-title":"Biomaterial-associated thrombosis: Roles of coagulation factors, complement, platelets and leukocytes","volume":"25","author":"Gorbet","year":"2004","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4103\/0019-5413.77129","article-title":"The basic science of peri-implant bone healing","volume":"45","author":"Kuzyk","year":"2011","journal-title":"Indian J. Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1016\/0142-9612(95)00311-8","article-title":"Platelet binding and protein adsorption to titanium and gold after short time exposure to heparinized plasma and whole blood","volume":"17","author":"Kanagaraja","year":"1996","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6692","DOI":"10.1016\/j.biomaterials.2011.05.078","article-title":"Immune responses to implants\u2014A review of the implications for the design of immunomodulatory biomaterials","volume":"32","author":"Franz","year":"2011","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.matsci.31.1.81","article-title":"Biological responses to materials","volume":"31","author":"Anderson","year":"2001","journal-title":"Ann. Rev. Mater. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/1043-6618(92)90214-V","article-title":"Platelet-dependent modulation of neutrophil function","volume":"26","author":"Bazzoni","year":"1992","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12S","DOI":"10.1097\/01.prs.0000225430.42531.c2","article-title":"The basic science of wound healing","volume":"117","author":"Broughton","year":"2006","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.4049\/jimmunol.158.7.3385","article-title":"Interleukin-13 induces human monocyte\/macrophage fusion and macrophage mannose receptor expression","volume":"158","author":"DeFife","year":"1997","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1002\/jbm.820291014","article-title":"Role for interleukin-4 in foreign-body giant-cell formation on a poly(etherurethane urea) in vivo","volume":"29","author":"Kao","year":"1995","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nbt.2600","article-title":"All charged up about implanted biomaterials","volume":"31","author":"Grainger","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10195-008-0038-y","article-title":"Uhmwpe for arthroplasty: Past or future?","volume":"10","author":"Bistolfi","year":"2009","journal-title":"J. Orthop. Traumatol."},{"key":"ref_28","unstructured":"Liao, Y.-S., Greer, K., Hanes, M., and McNulty, D. (2004, January 17\u201321). Effects of resin and dose on wear and mechanical properties of cross-linked thermally stabilized uhmwpe. Proceedings of the 7th World Biomaterials Congress-2004, Sydney, Australia."},{"key":"ref_29","first-page":"1","article-title":"Current research in the pathogenesis of aseptic implant loosening associated with particulate wear debris","volume":"79","author":"Jiang","year":"2013","journal-title":"Acta Orthop. Belg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biomaterials.2016.10.038","article-title":"Macrophage integrins modulate response to ultra-high molecular weight polyethylene particles and direct particle-induced osteolysis","volume":"115","author":"Zaveri","year":"2017","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.2106\/00004623-199411000-00010","article-title":"Isolation and characterization of debris in membranes around total joint prostheses","volume":"76A","author":"Margevicius","year":"1994","journal-title":"J. Bone Jt. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1179\/1751584X12Y.0000000005","article-title":"Biological effects of wear particles generated in total joint replacements: Trends and future prospects","volume":"6","author":"Tipper","year":"2012","journal-title":"Tribol. Mater. Surf. Interfaces"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1016\/j.actbio.2012.03.042","article-title":"Revision joint replacement, wear particles, and macrophage polarization","volume":"8","author":"Rao","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1243\/0954411001535219","article-title":"Biological reactions to wear debris in total joint replacement","volume":"214","author":"Ingham","year":"2000","journal-title":"Proc. Inst. Mech. Eng. Part H"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.4049\/jimmunol.0803007","article-title":"The mechanism of osteoclast differentiation induced by il-1","volume":"183","author":"Kim","year":"2009","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1111\/j.1365-2362.2012.02717.x","article-title":"The osteoclast, bone remodelling and treatment of metabolic bone disease","volume":"42","author":"Boyce","year":"2012","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/jor.21548","article-title":"Selective inhibition of the mcp-1-ccr2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of uhmwpe particles","volume":"30","author":"Gibon","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8046","DOI":"10.1016\/j.actbio.2013.05.005","article-title":"Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms","volume":"9","author":"Gallo","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1002\/art.22134","article-title":"The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis","volume":"54","author":"Koreny","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1172\/JCI45913","article-title":"Oscar is a collagen receptor that costimulates osteoclastogenesis in dap12-deficient humans and mice","volume":"121","author":"Barrow","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2198914","article-title":"Histopathological analysis of peek wear particle effects on the synovial tissue of patients","volume":"2016","author":"Paulus","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/(SICI)1097-4636(199810)42:1<103::AID-JBM13>3.0.CO;2-M","article-title":"Metal wear particle characterization from metal on metal total hip replacements: Transmission electron microscopy study of periprosthetic tissues and isolated particles","volume":"42","author":"Doorn","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1243\/09544119JEIM99","article-title":"Wear and biological activity of highly crosslinked polyethylene in the hip under low serum protein concentrations","volume":"221","author":"Galvin","year":"2007","journal-title":"Proc. Inst. Mech. Eng. Part H"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1243\/095441105X69123","article-title":"Clinical experience with metal-on-metal total joint replacements: Indications and results","volume":"220","author":"Learmonth","year":"2006","journal-title":"Proc. Inst. Mech. Eng. Part H"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"457","DOI":"10.2106\/00004623-200004000-00002","article-title":"Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement","volume":"82","author":"Urban","year":"2000","journal-title":"J. Bone Jt. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/jat.3039","article-title":"Toxicology-based cancer causation analysis of cocr-containing hip implants: A quantitative assessment of genotoxicity and tumorigenicity studies","volume":"34","author":"Christian","year":"2014","journal-title":"J. Appl. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.biomaterials.2016.04.023","article-title":"Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro","volume":"98","author":"Rakow","year":"2016","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s11095-008-9562-y","article-title":"Role of particle size in phagocytosis of polymeric microspheres","volume":"25","author":"Champion","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.ejps.2010.09.006","article-title":"Particle size affects the cellular response in macrophages","volume":"41","author":"Yue","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1016\/S0142-9612(99)00044-7","article-title":"Effects of metallic ion toxicity on human gingival fibroblasts morphology","volume":"20","author":"Messer","year":"1999","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00244-017-0377-x","article-title":"Toxicity of chromium (vi) to two mussels and an amphipod in water-only exposures with or without a co-stressor of elevated temperature, zinc, or nitrate","volume":"72","author":"Wang","year":"2017","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_52","first-page":"231","article-title":"Generation of hydroxyl radical by chromate in biologically relevant systems: Role of cr(v) complexes versus tetraperoxochromate(v)","volume":"102","author":"Shi","year":"1994","journal-title":"Environ. Health Perspect."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1039\/an9952000931","article-title":"Uptake of chromate in human red blood cells and isolated rat liver cells: The role of the anion carrier","volume":"120","author":"Alexander","year":"1995","journal-title":"Analyst"},{"key":"ref_54","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_55","unstructured":"International Agency for Research on Cancer (1999). Surgical Implants and Other Foreign Bodies, The International Agency for Research on Cancer (IARC)."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1302\/0301-620X.83B7.0831075","article-title":"Increased chromosome translocations and aneuploidy in peripheral blood lymphocytes of patients having revision arthroplasty of the hip","volume":"83","author":"Doherty","year":"2001","journal-title":"J. Bone Jt. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1302\/0301-620X.87B10.16541","article-title":"Metal-specific differences in levels of DNA damage caused by synovial fluid recovered at revision arthroplasty","volume":"87B","author":"Davies","year":"2005","journal-title":"J. Bone Jt. Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2106\/JBJS.F.01435","article-title":"Chromosomal aberrations in the peripheral blood of patients with metal-on-metal hip bearings","volume":"90A","author":"Dunstan","year":"2008","journal-title":"J. Bone Jt. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1243\/095441105X63282","article-title":"Cancer incidence and causes of death among total hip replacement patients: A review based on nordic cohorts with a special emphasis on metal-on-metal bearings","volume":"220","author":"Visuri","year":"2006","journal-title":"Proc. Inst. Mech. Eng. Part H"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/00003086-200105000-00020","article-title":"Osteolysis in a cementless, second generation metal-on-metal hip replacement","volume":"386","author":"Beaule","year":"2001","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.2106\/JBJS.I.00695","article-title":"Postmortem study of femoral osteolysis associated with metal-on-metal articulation in total hip replacement an analysis of nine cases","volume":"92A","author":"Huber","year":"2010","journal-title":"J. Bone Jt. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ocl.2014.11.001","article-title":"Modes of failure in metal-on-metal total hip arthroplasty","volume":"46","author":"Fehring","year":"2015","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00428-008-0659-9","article-title":"Necrotic granulomatous pseudotumours in bilateral resurfacing hip arthoplasties: Evidence for a type iv immune response","volume":"453","author":"Pandit","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5301\/hipint.5000293","article-title":"A 5-year survival analysis of 160 biomet magnum m2 metal-on-metal total hip prostheses","volume":"26","author":"Koper","year":"2016","journal-title":"Hip Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1007\/s11999-010-1372-y","article-title":"Histological features of pseudotumor-like tissues from metal-on-metal hips","volume":"468","author":"Campbell","year":"2010","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1023\/A:1017979710992","article-title":"Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation","volume":"222","author":"Hallab","year":"2001","journal-title":"Mol. Cell. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.arth.2004.09.012","article-title":"Immune responses correlate with serum-metal in metal-on-metal hip arthroplasty","volume":"19","author":"Hallab","year":"2004","journal-title":"J. Arthroplast."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0142-9612(02)00351-4","article-title":"Tnf-alpha secretion and macrophage mortality induced by cobalt and chromium ions in vitro-qualitative analysis of apoptosis","volume":"24","author":"Catelas","year":"2003","journal-title":"Biomaterials"},{"key":"ref_69","first-page":"1171","article-title":"Loosening and osteolysis associated with metal-on-metal bearings: A local effect of metal hypersensitivity?","volume":"88A","author":"Jacobs","year":"2006","journal-title":"J. Bone Jt. Surg."},{"key":"ref_70","first-page":"297","article-title":"Ceramic biomaterials: An introductory overview","volume":"21","author":"Brostow","year":"1999","journal-title":"J. Mater. Educ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/00003086-200010000-00008","article-title":"Evolution of alumina-on-alumina implants-a review","volume":"379","author":"Sedel","year":"2000","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1016\/S0142-9612(02)00047-9","article-title":"Alumina-alumina artificial hip joints. Part I: A histological analysis and characterisation of wear debris by laser capture microdissection of tissues retrieved at revision","volume":"23","author":"Hatton","year":"2002","journal-title":"Biomaterials"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1016\/S0142-9612(02)00048-0","article-title":"Alumina-alumina artificial hip joints. Part II: Characterisation of the wear debris from in vitro hip joint simulations","volume":"23","author":"Tipper","year":"2002","journal-title":"Biomaterials"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.2106\/JBJS.F.00970","article-title":"The squeaking hip: A phenomenon of ceramic-on-ceramic total hip arthroplasty","volume":"91A","author":"Jarrett","year":"2009","journal-title":"J. Bone Jt. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0142-9612(98)00214-2","article-title":"Induction of macrophage apoptosis by ceramic and polyethylene particles in vitro","volume":"20","author":"Catelas","year":"1999","journal-title":"Biomaterials"},{"key":"ref_76","first-page":"819","article-title":"Characterisation of wear particles produced by metal on metal and ceramic on metal hip prostheses under standard and microseparation simulation","volume":"18","author":"Brown","year":"2007","journal-title":"J. Mater. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1016\/S0142-9612(03)00120-0","article-title":"Biological reaction to alumina, zirconia, titanium and polyethylene particles implanted onto murine calvaria","volume":"24","author":"Warashina","year":"2003","journal-title":"Biomaterials"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Christel, P.S. (1992). Biocompatibility of surgical-grade dense polycrystalline alumina. Clin. Orthop. Relat. Res., 10\u201318.","DOI":"10.1097\/00003086-199209000-00003"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0142-9612(02)00360-5","article-title":"Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro","volume":"24","author":"Germain","year":"2003","journal-title":"Biomaterials"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/01.blo.0000149996.91974.83","article-title":"Ceramics in total hip replacement","volume":"430","author":"Hannouche","year":"2005","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2010.01.012","article-title":"The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (cocr alloy) particles","volume":"697","author":"Tsaousi","year":"2010","journal-title":"Mutat. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0736-0266(01)00077-8","article-title":"Differential apoptotic response of j774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles","volume":"20","author":"Petit","year":"2002","journal-title":"J. Orthop. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/S0142-9612(02)00510-0","article-title":"Effects of clinically relevant alumina ceramic wear particles on tnf-alpha production by human peripheral blood mononuclear phagocytes","volume":"24","author":"Hatton","year":"2003","journal-title":"Biomaterials"}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/8\/3\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:44:42Z","timestamp":1760208282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/8\/3\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,1]]},"references-count":83,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,9]]}},"alternative-id":["jfb8030033"],"URL":"https:\/\/doi.org\/10.3390\/jfb8030033","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,1]]}}}