title: Ceramic and PMMA particles differentially affect osteoblast phenotype.
abstract: There is increasing evidence that wear debris particles present in periprosthetic tissues have direct effects on osteoblasts. The nature of the cell response varies with the chemistry of the particle and the number of particles. Most studies have used Ti, Ti-6Al-4V, and ultrahigh molecular weight polyethylene (UHMWPE) particles since these materials are most frequently used in implants and as a result, these particles predominate in peri-prosthetic tissues. Ceramics have also been used successfully as load-bearing surfaces in implants for years, although it is unknown how wear debris from these surfaces may contribute to aseptic bone loss. Further, particles resulting from polymethylmethacrylate (PMMA) cements used for fixation may also be involved in aseptic loosening of implants, but how these particles may affect bone formation is unknown. In the present study, we examined whether aluminum oxide (Al2O3), zirconium oxide (ZrO2), and PMMA particles exert effects on osteoblast proliferation, phenotypic expression, and local factor production, and if so, whether the effects were specific to the particle type. ZrO2 particles were produced in a custom-made axial mixer in which ZrO2 containers were filled with ZrO2 bars and 95% ethanol and then rotated continuously at room temperature. PMMA particles were prepared in a ZrO2 roller mill. Al2O3 was produced and provided by Aesculap AG. Particles were endotoxin-free with equivalent circle diameters <3 microm; Al2O3 particles were significantly smaller than ZrO2 or PMMA particles. Particle suspensions were added to confluent cultures of MG63 osteoblast-like cells after diluting them 1:100, 1:10, and 1:1 with culture medium. Cells were incubated with the particles for 24 h. Transmission electron microscopy showed that MG63 cells phagocytosed Al2O3 particles and exhibited ultrastructural changes consistent with cytotoxicity. This was supported by biochemical changes as well. Proliferation, alkaline phosphatase activity, and TGF-beta1 levels were decreased. ZrO2 and PMMA particles increased proliferation and alkaline phosphatase specific activity. The effect of ZrO2 on alkaline phosphatase was targeted to matrix vesicles, the effect of PMMA was greater on the cells. All particles increased prostaglandin E2 production. These results show that Al2O3, ZrO2, and PMMA particles elicit direct effects on osteoblasts and that cell response depends on the particle type. None of the particles tested had the same effect as noted previously for UHMWPE: increased proliferation and decreased alkaline phosphatase. These results may indicate that the response of peri-prosthetic tissues to wear particles may be modulated by the relative contributions of the various particle types present.
authors.affiliation: Department of Orthopaedics, University of Texas Health Science Center at San Antonio, 78229-3900, USA.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Lohmann
authors.forename: David D
authors.initials: DD
authors.lastname: Dean
authors.forename: Georg
authors.initials: G
authors.lastname: Köster
authors.forename: David
authors.initials: D
authors.lastname: Casasola
authors.forename: Gottfried H
authors.initials: GH
authors.lastname: Buchhorn
authors.forename: Ulrich
authors.initials: U
authors.lastname: Fink
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000537:Aluminum Oxide / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D001843:Bone Cements / Q000494:pharmacology*; D002455:Cell Division; D002516:Ceramics / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008854:Microscopy, Electron; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis; D010641:Phenotype; D019904:Polymethyl Methacrylate / Q000494:pharmacology*; D019736:Prostheses and Implants; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D015034:Zinc Oxide / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019904:Polymethyl Methacrylate; D000469:Alkaline Phosphatase; D015232:Dinoprostone; D000537:Aluminum Oxide; D015034:Zinc Oxide