title: Effects of prosthetic materials on the host immune response: evaluation of polymethyl-methacrylate (PMMA), polyethylene (PE), and polystyrene (PS) particles.
abstract: The main causes for the long-term prosthetic implants' failure are the body's reaction to the implanted material or mechanical stress on the device resulting in the formation of wear particles. Particulate wear debris attracts macrophages, and depending on the chemical composition of the material and particle size, various levels of inflammatory response may occur. While transient inflammation is common, development of chronic inflammation may have serious consequences, leading to implant failure. Such a process may also cause systemic changes to immune functions and long-term effects on the host immune responses. In this study, we evaluated the effects of polystyrene (PS), polyethylene (PE), and polymethylmethacrylate (PMMA) particles on macrophage function and the generation of T-cell responses. Particles of various diameters were injected intraperitoneally into Balb/c mice, and immune functions were examined at 3, 10, and 21 days after the injection. The intensity of phagocytosis by peritoneal exudate cells (PECs) and the proliferative response of spleen cells from treated mice were evaluated. Enumeration of PECs revealed an increase in the total number of cells. Mice injected with PS or PE particles had a higher percentage of cells containing particles than PMMA-injected mice. Macrophages with PS or PE particles tended to adhere to and/or infiltrate peritoneal fibro-fatty tissues surrounding the spleen and pancreas, while the PMMA-carrying macrophages infiltrated the spleen, resulting in an increase of spleen size and "weight. The spleen cell proliferation assay revealed only mild and transient effects on the mitogen response in both PE and PS particle-injected mice. However, in the PMMA-injected mice we observed a lasting increase of the Con A response and a decrease of the LPS response. In vitro exposure of PECs from untreated mice showed a dose-response pattern in nitric oxide (NO) and TNFalpha production. While exposure to either PMMA or PE induced comparable levels of NO, exposure to PMMA induced a markedly higher production of TNFalpha than exposure to PE. The results indicate that particulate biomaterials may, in addition to the initial activation of phagocytes, significantly affect immune functions and compromise the host response to other antigenic stimuli.
authors.affiliation: Marquette University, Department of Biomedical Engineering, Milwaukee, WI, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Frick
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dietz
authors.forename: Katharine
authors.initials: K
authors.lastname: Merritt
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Umbreit
authors.forename: Vesna J
authors.initials: VJ
authors.lastname: Tomazic-Jezic
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005260:Female; D007109:Immunity / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020959:Polyethylene / Q000276:immunology / Q000494:pharmacology*; D019904:Polymethyl Methacrylate / Q000494:pharmacology*; D011137:Polystyrenes / Q000276:immunology / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D001672:Biocompatible Materials; D011137:Polystyrenes; D020959:Polyethylene; D019904:Polymethyl Methacrylate