title: The biological response to nanometre-sized polymer particles.
abstract: Recently, nanometre-sized UHMWPE particles generated from hip and knee replacements have been identified in vitro and in vivo. UHMWPE particles in the 0.1-1.0μm size range have been shown to be more biologically active than larger particles, provoking an inflammatory response implicated in late aseptic loosening of total joint replacements. The biological activity of nanometre-sized particles has not previously been studied. The biological response to clinically-relevant UHMWPE wear particles including nanometre-sized and micrometre-sized, along with polystyrene particles (FluoSpheres 20nm, 60nm, 200nm and 1.0μm), and nanometre-sized model polyethylene particles (Ceridust 3615®), was determined in terms of osteolytic cytokine release from primary human peripheral blood mononuclear cells (PBMNCs). Nanometre-sized UHMWPE wear particles, nanometre-sized Ceridust 3615® and 20nm FluoSpheres had no significant effect on TNF-α, IL-1β, IL-6 and IL-8 release from PBMNCs at a concentration of 100μm(3) particles per cell after 12 and 24h. The micrometre-size UHMWPE wear particles (0.1-1.0μm) and 60nm, 200nm and 1.0μm FluoSpheres caused significantly elevated osteolytic cytokine release from PBMNCs. These results indicated that particles below circa 50nm fail to activate PBMNCs and that particle size, composition and morphology played a crucial role in cytokine release by particle stimulated macrophages.
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK. Electronic address: A.Liu@leeds.ac.uk.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Liu
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Richards
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Bladen
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Eileen
authors.initials: E
authors.lastname: Ingham
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: John
authors.initials: J
authors.lastname: Fisher
authors.affiliation: Institute of Medical and Biological Engineering, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Tipper
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure*; D010316:Particle Size; D011095:Polyethylenes / Q000633:toxicity*; D055815:Young Adult
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene
keywords: Bioactivity; Joint replacement; Nanoparticle; Osteolysis; Polyethylene