Abstract
Aim
Ultrahigh molecular weight polyethylene (UHMWPE) has been used for many years as a bearing surface in total joint replacement (TJR). However, late-state failure in TJR is predominantly caused by osteolysis mediated by wear particles. We tested our hypothesis that UHMWPE nanoparticles are important determinants in activating dendritic cells (DCs).
Methods
UHMWPE wear particles generated from a knee simulator were profiled using an atomic force microscopy and fractionated into six fractions: 0.05-0.2, 0.2-0.8, 0.8-1, 1-5, 5-10, and 10-20 micrometer. Effects of each fraction, a mixture of nano-sized fractions, and a mixture of all fractions on the activation of mice spleen DCs were determined using flow cytometry with specific antibodies of anti-CD11c-APC, anti-CD80-PE, anti-CD11b-PerCp, anti-CD86-Biotin and streptavidin-FITC. Supernatant from DCs treated with wear particles were assayed for IL-1beta, IL-6, IL-12/23, TNF-alpha and IFN-gamma. Activation of human osteoclasts (OCs) by wear particles were determined using TRAP stain.
Results
DCs treated with a mixture of nanoparticles showed a significant increase in CD80 expression. A similar trend was not observed when DCs were treated with solvent or media, suggesting that the increased expression of CD80 was UHMWPE nanoparticle specific. Macrophages treated with nanoparticles did not show a significant increase in the expression of CD80, suggesting that DCs may be more sensitive to activation than macrophages. These results were further supported by the increased production of cytokines, IL-1beta and IL-6. Furthermore, the mixture of nanoparticles and the mixture of all fractions directly stimulated maturation of OCs.
Conclusion
This study identifies a novel mechanism where UHMWPE nanoparticles activate DCs. The high proportion of nanoparticles from prosthetic joints would suggest this mechanism is a likely pathway for cytokine production and OCs maturation, all of which involve osteolysis. The nanoparticles as mediators of periprosthetic inflammation should be considered in developing biomaterials for bearing surfaces.
