{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T01:17:34Z","timestamp":1784423854695,"version":"3.55.0"},"reference-count":91,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["CG2015 seed funding"],"award-info":[{"award-number":["CG2015 seed funding"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Titanium has been used in osteosynthesis for decades and its compatibility and safety is unquestioned. Studies have shown that there is release and collection of titanium in the organ systems with little note of toxicity. The gold standard is considered to be titanium osteosynthesis plate produced by milling methods. The use of customized titanium plates produced with 3D printing, specifically direct metal laser sintering, have found increasing use in recent years. It is unknown how much titanium is released in these printed titanium implants, which is known to be potentially porous, depending on the heat settings of the printer. We hypothesize that the amount of titanium released in printed titanium implants may be potentially more or equal compared to the gold standard, which is the implant produced by milling. Methods: We studied the biosafety of this technology and its products by measuring serum and organ titanium levels after implantation of 3D-printed versus traditionally fabrication titanium plates and screws in a pilot study using the rabbit model. A total of nine rabbits were used, with three each in the control, milled and printed titanium group. The animals were euthanized after six months. Serum and organs of the reticuloendothelial system were harvested, digested and assayed for titanium levels. Results: Organ and serum titanium levels were significantly higher in rabbit subjects implanted with titanium implants (milled and printed) compared to the control group. However, there was no significant difference in organ and serum titanium levels of subjects implanted with milled and traditionally fabricated titanium implants. Conclusions: The biosafety of use of 3D-printed titanium implants and traditionally fabricated titanium implants are comparable. With this in mind, 3D-printed custom implants can not only replace, but will very possibly surpass traditionally fabricated titanium implants in the mode and extent of use.<\/jats:p>","DOI":"10.3390\/ijms22168480","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T08:01:42Z","timestamp":1628236902000},"page":"8480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Benefits and Biosafety of Use of 3D-Printing Technology for Titanium Biomedical Implants: A Pilot Study in the Rabbit Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Sabrina Livia","family":"Ng","sequence":"first","affiliation":[{"name":"Department Oral and Maxillofacial Surgery, National Dental Centre Singapore, Singapore 168938, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhabrata","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-2435","authenticated-orcid":false,"given":"Yen-Peng","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8877-1584","authenticated-orcid":false,"given":"Raymond Chung Wen","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattharee","family":"Chanchareonsook","sequence":"additional","affiliation":[{"name":"Department Oral and Maxillofacial Surgery, National Dental Centre Singapore, Singapore 168938, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1177\/154405910308200510","article-title":"The use of small titanium screws for orthodontic anchorage","volume":"82","author":"Deguchi","year":"2003","journal-title":"J. Dent. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0921-5093(96)10243-4","article-title":"The use of titanium for medical applications in the USA","volume":"213","author":"Wang","year":"1996","journal-title":"Mater. Sci. Eng. A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0901-5027(99)80160-X","article-title":"The use of titanium mandibular reconstruction plates in patients with oral cancer","volume":"28","author":"Spencer","year":"1999","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_4","first-page":"86","article-title":"A retrospective study of osseointegrated skin-penetrating titanium fixtures used for retaining facial prostheses","volume":"7","author":"Jacobsson","year":"1992","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Brunette, D.M., Tengvall, P., Textor, M., and Thomsen, P. (2001). Titanium in Medicine: Material Science, Surface Science, Engineering, Biological Responses and Medical Applications, Springer Science & Business Media.","DOI":"10.1007\/978-3-642-56486-4"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ratner, B.D. (2001). A perspective on titanium biocompatibility. Titanium in Medicine, Springer.","DOI":"10.1007\/978-3-642-56486-4_1"},{"key":"ref_7","unstructured":"Blackburn, M., and Williams, J. (1969). Strength, Deformation Modes and Fracture in Titanium-Aluminum Alloys, Boeing Scientific Research Labs Seattle Wash Solid State Physics Lab."},{"key":"ref_8","unstructured":"Welsch, G., Boyer, R., and Collings, E. (1993). Materials Properties Handbook: Titanium Alloys, ASM international."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0921-5093(97)00806-X","article-title":"Mechanical properties of biomedical titanium alloys","volume":"243","author":"Niinomi","year":"1998","journal-title":"Mater. Sci. Eng. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4103\/2231-0746.133065","article-title":"3D modeling, custom implants and its future perspectives in craniofacial surgery","volume":"4","author":"Parthasarathy","year":"2014","journal-title":"Ann. Maxillofac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5999\/aps.2015.42.3.267","article-title":"Clinical application of three-dimensional printing technology in craniofacial plastic surgery","volume":"42","author":"Choi","year":"2015","journal-title":"Arch. Plast. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s11548-010-0476-x","article-title":"3D printing based on imaging data: Review of medical applications","volume":"5","author":"Rengier","year":"2010","journal-title":"Int. J. Comput. Assist. Radiol. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/0022-3913(83)90359-1","article-title":"Biocompatibility of titanium implants: Surface science aspects","volume":"49","author":"Kasemo","year":"1983","journal-title":"J. Prosthet. Dent."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7306","DOI":"10.1021\/es048982l","article-title":"Functionalized TiO2 nanoparticles for use for in situ anion immobilization","volume":"39","author":"Mattigod","year":"2005","journal-title":"Environ. Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1079\/PNS2001134","article-title":"Fine and ultrafine particles of the diet: Influence on the mucosal immune response and association with Crohn\u2019s disease","volume":"61","author":"Lomer","year":"2002","journal-title":"Proc. Nutr. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7594","DOI":"10.1021\/ac8012626","article-title":"TiO2 in commercial sunscreen lotion: Flow field-flow fractionation and ICP-AES together for size analysis","volume":"80","author":"Contado","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1039\/b006285p","article-title":"Determination of titanium dioxide in foods using inductively coupled plasma optical emission spectrometry","volume":"125","author":"Lomer","year":"2000","journal-title":"Analyst"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/0021-9681(62)90114-5","article-title":"Abnormal trace metals in man\u2014Chromium","volume":"15","author":"Schroeder","year":"1962","journal-title":"J. Chronic Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6757","DOI":"10.1021\/es901102n","article-title":"Titanium nanomaterial removal and release from wastewater treatment plants","volume":"43","author":"Kiser","year":"2009","journal-title":"Environ. Sci. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.envpol.2008.08.004","article-title":"Synthetic TiO2 nanoparticle emission from exterior facades into the aquatic environment","volume":"156","author":"Ulrich","year":"2008","journal-title":"Environ. Pollut."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1021\/am201842n","article-title":"High-performance plastic dye-sensitized solar cells based on low-cost commercial P25 TiO2 and organic dye","volume":"4","author":"Yin","year":"2012","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_22","first-page":"615","article-title":"Recyclable rubber sheets impregnated with potassium oxalate doped TiO2 and their uses in decolorization of dye-polluted waters","volume":"4","author":"Suwanchawalit","year":"2010","journal-title":"Int. J. Environ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9216","DOI":"10.1021\/es9015553","article-title":"Modeled environmental concentrations of engineered nanomaterials (TiO2, ZnO, Ag, CNT, fullerenes) for different regions","volume":"43","author":"Gottschalk","year":"2009","journal-title":"Environ. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1021\/es103040t","article-title":"Evidence for negative effects of TiO2 and ZnO nanoparticles on soil bacterial communities","volume":"45","author":"Ge","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1021\/es405596y","article-title":"Release of TiO2 nanoparticles from sunscreens into surface waters: A one-year survey at the old Danube recreational Lake","volume":"48","author":"Gondikas","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6705","DOI":"10.1021\/es204530n","article-title":"Development of Environmental Fate Models for Engineered Nanoparticles\u2014A Case Study of TiO2 Nanoparticles in the Rhine River","volume":"46","author":"Praetorius","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sillanp\u00e4\u00e4, M., Paunu, T.-M., and Sainio, P. (2011). Aggregation and deposition of engineered TiO2 nanoparticles in natural fresh and brackish waters. J. Phys. Conf. Ser., 304.","DOI":"10.1088\/1742-6596\/304\/1\/012018"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1021\/es301487s","article-title":"Fate of zinc oxide nanoparticles during anaerobic digestion of wastewater and post-treatment processing of sewage sludge","volume":"46","author":"Lombi","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Golanski, L., Gaborieau, A., Guiot, A., Uzu, G., Chatenet, J., and Tardif, F. (2011). Characterization of abrasion-induced nanoparticle release from paints into liquids and air. J. Phys. Conf. Ser., 304.","DOI":"10.1088\/1742-6596\/304\/1\/012062"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1708-8208.2011.00340.x","article-title":"Clinical Evaluation of Split-Crest Technique with Ultrasonic Bone Surgery for Narrow Ridge Expansion: Status of Soft and Hard Tissues and Implant Success","volume":"15","author":"Anitua","year":"2013","journal-title":"Clin. Implant Dent. Relat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/030919099294401","article-title":"Medical rapid prototyping and 3D CT in the manufacture of custom made cranial titanium plates","volume":"23","author":"Winder","year":"1999","journal-title":"J. Med. Eng. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.dental.2011.10.014","article-title":"The future of dental devices is digital","volume":"28","year":"2012","journal-title":"Dent. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1108\/13552540610682714","article-title":"Fabrication of customised maxillo-facial prosthesis using computer-aided design and rapid prototyping techniques","volume":"12","author":"Singare","year":"2006","journal-title":"Rapid Prototyp. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1016\/j.biomaterials.2008.05.032","article-title":"Porous titanium scaffolds fabricated using a rapid prototyping and powder metallurgy technique","volume":"29","author":"Ryan","year":"2008","journal-title":"Biomaterials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"061016","DOI":"10.1115\/1.4025773","article-title":"Electron beam additive manufacturing of titanium components: Properties and performance","volume":"135","author":"Edwards","year":"2013","journal-title":"J. Manuf. Sci. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e247","DOI":"10.1016\/j.bjps.2007.12.020","article-title":"Correction of a mandibular asymmetry using a custom-made titanium onlay","volume":"62","author":"Yates","year":"2009","journal-title":"J. Plast. Reconstr. Aesthetic Surg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mangano, F., Chambrone, L., Van Noort, R., Miller, C., Hatton, P., and Mangano, C. (2014). Direct metal laser sintering titanium dental implants: A review of the current literature. Int. J. Biomater., 2014.","DOI":"10.1155\/2014\/461534"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/jbm.b.31219","article-title":"Selective Laser Melting: A regular unit cell approach for the manufacture of porous, titanium, bone in-growth constructs, suitable for orthopedic applications","volume":"89","author":"Mullen","year":"2009","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1007\/s10856-009-3763-8","article-title":"The development of a scanning strategy for the manufacture of porous biomaterials by selective laser melting","volume":"20","author":"Stamp","year":"2009","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.biomaterials.2005.07.041","article-title":"Structural, mechanical and in vitro characterization of individually structured Ti\u20136Al\u20134V produced by direct laser forming","volume":"27","author":"Hollander","year":"2006","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/jbm.a.32033","article-title":"Stereo imaging and cytocompatibility of a model dental implant surface formed by direct laser fabrication","volume":"88","author":"Mangano","year":"2009","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/jbm.b.31682","article-title":"Highly porous titanium scaffolds for orthopaedic applications","volume":"95","author":"Dabrowski","year":"2010","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jmbbm.2009.10.006","article-title":"Mechanical evaluation of porous titanium (Ti6Al4V) structures with electron beam melting (EBM)","volume":"3","author":"Parthasarathy","year":"2010","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0267-6605(93)90006-S","article-title":"Clinical and animal experiments on stress corrosion of titanium miniplates","volume":"14","author":"Bessho","year":"1993","journal-title":"Clin. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1067\/moe.2000.107224","article-title":"Release of metal in vivo from stressed and nonstressed maxillofacial fracture plates and screws","volume":"90","author":"Matthew","year":"2000","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1010-5182(96)80049-7","article-title":"Immuno-inflammatory responses in the tissue adjacent to titanium miniplates used in the treatment of mandibular fractures","volume":"24","author":"Katou","year":"1996","journal-title":"J. Cranio-Maxillo-Facial Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.ijom.2009.02.016","article-title":"The fate of titanium miniplates and screws used in maxillofacial surgery: A 10 year retrospective study","volume":"38","author":"Murphy","year":"2009","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1108\/13552540510573365","article-title":"Binding mechanisms in selective laser sintering and selective laser melting","volume":"11","author":"Kruth","year":"2005","journal-title":"Rapid Prototyp. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/sj.bjc.6600758","article-title":"Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells","volume":"88","author":"Coen","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1834-7819.2002.tb00331.x","article-title":"A study of titanium release into body organs following the insertion of single threaded screw implants into the mandibles of sheep","volume":"47","author":"Frisken","year":"2002","journal-title":"Aust. Dent. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1600-0501.2010.01980.x","article-title":"Peripheral quantitative computer tomographic, histomorphometric, and removal torque analyses of two different non-coated implants in a rabbit model","volume":"22","author":"Shin","year":"2011","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_52","first-page":"206","article-title":"Systemic metal ion levels in dental implant patients","volume":"12","author":"Smith","year":"1997","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/00000478-199401000-00008","article-title":"Sinus Histiocytosis of Pelvic Lymph Nodes after Hip Replacement: A Histiocytic Proliferation Induced by Cobalt-Chromium and Titanium","volume":"18","author":"Vuitch","year":"1994","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_54","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":"JBJS"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1302\/0301-620X.86B4.14368","article-title":"Wear debris from hip or knee replacements causes chromosomal damage in human cells in tissue culture","volume":"86","author":"Daley","year":"2004","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s13191-012-0139-4","article-title":"Hypersensitivity to titanium: A less explored area of research","volume":"12","author":"Vijayaraghavan","year":"2012","journal-title":"J. Indian Prosthodont. Soc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0041-008X(85)90339-4","article-title":"Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years","volume":"79","author":"Lee","year":"1985","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0013-9351(86)80177-3","article-title":"Pulmonary response to impaired lung clearance in rats following excessive TiO2 dust deposition","volume":"41","author":"Lee","year":"1986","journal-title":"Environ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nordberg, G.F., Fowler, B.A., and Nordberg, M. (2014). Handbook on the Toxicology of Metals, Academic Press.","DOI":"10.1016\/B978-0-444-59453-2.00001-9"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.etp.2006.06.001","article-title":"Pulmonary tumor types induced in Wistar rats of the so-called \u201c19-dust study\u201d","volume":"58","author":"Mohr","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1034\/j.1600-0536.2000.043006344.x","article-title":"Exposure to metallic gold in patients with contact allergy to gold sodium thiosulfate","volume":"43","author":"Ahnlide","year":"2000","journal-title":"Contact Dermat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2106\/00004623-200103000-00017","article-title":"Metal sensitivity in patients with orthopaedic implants","volume":"83","author":"Hallab","year":"2001","journal-title":"JBJS"},{"key":"ref_63","unstructured":"Schramm, M., and Pitto, R. (2000). Clinical relevance of allergological tests in total hip joint replacement. Proceedings 5th International CeramTec Symposium, Bioceramics in Hip Joint Replacement, 18\u201319 February 2000, Georg Thieme Verlag."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/0003-4975(94)90228-3","article-title":"Pacemaker contact sensitivity: Clinical recognition and management","volume":"57","author":"Abdallah","year":"1994","journal-title":"Ann. Thorac. Surg."},{"key":"ref_65","first-page":"53","article-title":"Yellow nail syndrome in patients with titanium and gold implants","volume":"1","author":"Berglund","year":"1999","journal-title":"Toxicol. Lett."},{"key":"ref_66","first-page":"25","article-title":"Sensitivity to titanium. A cause of implant failure?","volume":"73","author":"Lalor","year":"1991","journal-title":"Bone Jt. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1600-0536.1984.tb00986.x","article-title":"Pacemaker contact sensitivity","volume":"11","author":"Peters","year":"1984","journal-title":"Contact Dermat."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/BF02967485","article-title":"A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy","volume":"8","author":"Tamai","year":"2001","journal-title":"Breast Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1600-0536.1985.tb01089.x","article-title":"Pacemaker contact sensitivity","volume":"12","author":"Verbov","year":"1985","journal-title":"Contact Dermat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1600-0536.1995.tb02089.x","article-title":"Granulomatous dermatitis after implantation of a titanium-containing pacemaker","volume":"33","author":"Viraben","year":"1995","journal-title":"Contact Dermat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/0142-9612(91)90144-Y","article-title":"Effect of surface treatment on the dissolution of titanium-based implant materials","volume":"12","author":"Wisbey","year":"1991","journal-title":"Biomaterials"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/0142-9612(96)00023-3","article-title":"Titanium serum and urine levels in rabbits with a titanium implant in the absence of wear","volume":"17","author":"Bianco","year":"1996","journal-title":"Biomaterials"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/jor.1100010411","article-title":"Metal ion release from titanium-based prosthetic segmental replacements of long bones in baboons: A long-term study","volume":"1","author":"Woodman","year":"1983","journal-title":"J. Orthop. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1016\/j.actbio.2012.12.001","article-title":"In vivo serum titanium ion levels following modular neck total hip arthroplasty\u201410 year results in 67 patients","volume":"9","author":"Omlor","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1054\/bjom.1998.0264","article-title":"Metallic fragments on the surface of miniplates and screws before insertion","volume":"37","author":"Ray","year":"1999","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Suito, H., Iwawaki, Y., Goto, T., Tomotake, Y., and Ichikawa, T. (2013). Oral factors affecting titanium elution and corrosion: An in vitro study using simulated body fluid. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066052"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/jbm.820290716","article-title":"Experimental long-term study of titanium ions eluted from pure titanium miniplates","volume":"29","author":"Bessho","year":"1995","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0026-265X(02)00059-0","article-title":"The role of analytical methods for the determination of trace elements in environmental biomonitors","volume":"73","author":"Bettinelli","year":"2002","journal-title":"Microchem. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1017\/S1751731114000068","article-title":"A comparison of two methods for determining titanium dioxide marker content in broiler digestibility studies","volume":"8","author":"Morgan","year":"2014","journal-title":"Animal"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.chemosphere.2013.01.065","article-title":"A simplified method for determining titanium from TiO2 nanoparticles in fish tissue with a concomitant multi-element analysis","volume":"92","author":"Shaw","year":"2013","journal-title":"Chemosphere"},{"key":"ref_81","first-page":"81","article-title":"Accurate determination of titanium as titanium dioxide for limited sample size digestibility studies of feed and food matrices by inductively coupled plasma optical emission spectrometry with real-time simultaneous internal standardization","volume":"31","author":"Kerkhof","year":"2010","journal-title":"At. Spectrosc."},{"key":"ref_82","unstructured":"Grosser, Z.A., Neubauer, K., Thompson, L., and Davidowski, L. (2021, June 05). A Comparison of ICP-OES and ICP-MS for the Determination of Metals in Food. Available online: https:\/\/www.spectroscopyonline.com\/view\/comparison-icp-oes-and-icp-ms-determination-metals-food."},{"key":"ref_83","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":"1998","journal-title":"Periodontology 2000"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1023\/A:1018590513178","article-title":"Systemic titanium levels in rabbits with a titanium implant in the absence of wear","volume":"8","author":"Bianco","year":"1997","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v013a01","article-title":"Animal models for implant biomaterial research in bone: A review","volume":"13","author":"Pearce","year":"2007","journal-title":"Eur Cell Mater."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1039\/C6MT00110F","article-title":"Toxicological aspects of soluble titanium\u2013a review of in vitro and in vivo studies","volume":"8","author":"Golasik","year":"2016","journal-title":"Metallomics"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12989-018-0251-7","article-title":"Detection of titanium particles in human liver and spleen and possible health implications","volume":"15","author":"Heringa","year":"2018","journal-title":"Part. Fibre Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtemb.2019.09.005","article-title":"Blood and plasma titanium levels associated with well-functioning hip implants","volume":"57","author":"Swiatkowska","year":"2020","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"L975","DOI":"10.1152\/ajplung.1999.277.5.L975","article-title":"Induction of fibrogenic mediators by fine and ultrafine titanium dioxide in rat tracheal explants","volume":"277","author":"Churg","year":"1999","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.arth.2004.09.013","article-title":"Accumulation in liver and spleen of metal particles generated at nonbearing surfaces in hip arthroplasty","volume":"19","author":"Urban","year":"2004","journal-title":"J. Arthroplast."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.toxlet.2006.12.001","article-title":"Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration","volume":"168","author":"Wang","year":"2007","journal-title":"Toxicol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8480\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:47Z","timestamp":1760164907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":91,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168480"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168480","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}