title: Orthopedic implant cobalt-alloy particles produce greater toxicity and inflammatory cytokines than titanium alloy and zirconium alloy-based particles in vitro, in human osteoblasts, fibroblasts, and macrophages.
abstract: The performance of total joint arthroplasty (TJA) depends on the size/shape, material, and amounts of implant debris. Much remains unknown in terms of which types of debris are most reactive. We compared the responses of human periimplant cells, osteoblasts, fibroblasts, and macrophages, exposed to particles of different metal-based particles (i.e., cobalt-chromium-molybdenum (CoCrMo) alloy, titanium (Ti) alloy, zirconium (Zr) oxide, and Zr alloy. CoCrMo-alloy particles were by far the most toxic (p < 0.05) and decreased viability and proliferation of human osteoblasts, fibroblasts, and macrophages by >50% at a dose of only 50 particles per cell. All particle types induced the production of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8 by osteoblasts, fibroblasts, and monocytes/macrophages. However, the greatest cytokine responses of macrophages were to CoCrMo alloy (TNF-α and IL-8) and Ti alloy (IL-1β). Likewise, the greatest responses of fibroblasts and osteoblasts were to CoCrMo alloy (IL-6 and TNF-α) (i.e., IL-6 300 pg/mL; 30-fold max, TNF-α 150 pg/mL; 15-fold max) versus controls. For macrophages, CoCrMo particles induced IL-8 (> 2000 pg/mL; approx 100-fold max) above controls and were also significantly elevated above levels produced by Zr-based particles. Submicron sized (0.2-0.9 μm) Zr-based particles (originally presumed to be more reactive) induced less toxicity and inflammatory responses when compared with larger (approx 1 μm) CoCrMo-alloy and Ti-alloy particles.
authors.affiliation: Department of Orthopedic Surgery, University of Illinois in Chicago, Chicago, Illinois, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Dalal
authors.forename: Vivek
authors.initials: V
authors.lastname: Pawar
authors.forename: Kyron
authors.initials: K
authors.lastname: McAllister
authors.forename: Carolyn
authors.initials: C
authors.lastname: Weaver
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Hallab
mesh_terms: D000497:Alloys / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008027:Light; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D019736:Prostheses and Implants / Q000009:adverse effects*; D012542:Scattering, Radiation; D014025:Titanium / Q000633:toxicity; D015040:Zirconium / Q000633:toxicity
chemical_list: D000497:Alloys; D016207:Cytokines; D003035:Cobalt; D015040:Zirconium; D014025:Titanium