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Biologic reactivity to orthopedic implant debris mediates long-term clinical performance of total joint arthroplasty implants. However, the reasons that some facets of implant debris (e.g., particle size, shape, base material, etc.) are more pro-inflammatory remain controversial. This precludes accurate prediction and optimal design of modern total joint replacements. We hypothesized that debris particle size can influence adsorbed protein film composition and affect subsequent bioreactivity. We measured size-dependent proteinfilm adsorption, and adsorbed protein-film-dependent cytokine release using equal surface areas of different sized cobalt-chromium alloy (CoCr-alloy) particles and in vitro challenge of human macrophages (THP-1 and human primary). Smaller (5 μm diameter) versus larger (70 μm diameter) particles preferentially adsorbed more serum protein in general (p&lt;0.03), where higher molecular weight serum proteins consistent with IgG were identified. Additionally, 5-μm CoCr-alloy particles pre-coated with different protein biofilms (IgG vs. albumin) resulted in a difference in cytokine expression in which albumin-coated particles induced more TNF-α release and IgG-coated particles induced more IL-1β release from human monocytes/macrophages. In these preliminary in vitro studies, we have demonstrated the capability of equal surface areas of different particle sizes to influence adsorbed protein composition and that adsorbed protein differences on identical particles can translate into complex differences in bioreactivity. Together, these findings suggest that adsorbed protein differences on different-sized particles of the same material may be a contributing mechanism by which certain particles induce different reactivities.

Implant Debris Particle Size Affects Serum Protein Adsorption Which May Contribute to Particle Size-Based Bioreactivity Differences