Osteolysis remains the most important problem in orthopedic implant failure. Wear debris from the implant contains polyethylene (PE) particulate which has been shown to activate monocyte-derived macrophages (MDM). Although the response of MDM has been shown to be influenced by the size, shape, and chemical type of PE, the effect of chemically altered PE on MDM has not been studied. In this study, human MDM were seeded onto glass coverslips coated with virgin high density (HD)PE and chemically modified HDPE (impregnated with ppm levels of CoCl(2) and oxidized by heat) mixed with type I collagen and cultured for 96 h. Light microscopic evaluation demonstrated consistent phagocytosis of the HDPE particulate that was confirmed by scanning electron and transmission electron microscopy with little evidence of cytotoxicity. Evaluation of pro-inflammatory mediator secretion by MDMs in response to the virgin and chemically modified HDPE revealed significant differences in interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6 secretion. A significant elevation of IL-1 secretion was observed after initial exposure to virgin HDPE particles compared with controls (p = 0.001). IL-1 secretion was also elevated in the low oxidized particle groups (p = 0.001), whereas the highly oxidized particles were not different than controls. Secretion of both IL-6 (p = 0.03) and TNF-alpha (p = 0.007) were significantly elevated by the low oxidized HDPE particles whereas the virgin and highly oxidized groups showed no difference. The different effects on MDM activation when HDPE surface chemistry was altered, highlight the importance of defining the particle properties when studying the role of MDM activation in in vitro systems and extrapolating these observations to the in vivo situation.
Controversy remains regarding the ability of silicone materials to induce a specific immune reaction versus a nonspecific inflammatory response. Histopathological analysis of the tissue around failed breast implants reveals chronic inflammation with silicone gel droplets either surrounded by giant cells or engulfed by macrophages, areas of fibrosis, and necrosis. Macrophages are the key cells engulfing or forming foreign body giant cells. To address the mechanisms of silicone-induced inflammation a model of human monocyte-derived macrophages (MDMs) was developed. After sonication of silicone gel, the silicone droplets were embedded in Type I collagen and used to coat glass coverslips; human MDMs were subsequently seeded on the coverslips and maintained in culture for up to 7 days. The advantage of the model was that human macrophages could be studied histologically, and cytochemically as they interacted with well-characterized silicone materials. Initial analysis of the human macrophages shows phagocytosis of the silicone gel within hours of exposure to the material. Analysis for pro-inflammatory cytokines reveals significant transient secretion of IL-1 (p < 0.01) over controls by human macrophages upon exposure to silicone gel at 24 h.
The interaction of macrophages and ultra-high molecular weight polyethylene (PE) wear plays an important role in perpetuating chronic inflammation at the bone implant interface, leading to peri-implant osteolysis and mechanical failure of the implant. A model to study the interaction of human mature macrophages with orthopaedic biomaterial wear has been previously developed. With the use of the model, in this study, the mature human monocyte-derived macrophages (MDMs) were observed with light, fluorescent, and scanning electron microscopy (SEM), as well as transmission electron microscopy (TEM). The cell viability was investigated using calcein and ethidium staining. Following exposure to PE particulate, the morphology of the human MDMs was heterogeneous: rounded, flattened, and elongated. There was no morphological evidence of cytotoxicity or apoptosis. The MDM viability was not influenced by phagocytosis of PE particulate in a negative fashion. In fact, more prolonged cell viability was observed in the human MDMs exposed to PE particulate when compared to controls.
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