Continuous Infusion of UHMWPE Particles Induces Increased Bone Macrophages and Osteolysis
Aseptic loosening and periprosthetic osteolysis resulting from wear debris are major complications of total joint arthroplasty. Monocyte/macrophages are the key cells related to osteolysis at the bone-implant interface of joint arthroplasties. Whether the monocyte/macrophages found at the implant interface in the presence of polyethylene particles are locally or systemically derived is unknown.
We therefore asked (1) whether macrophages associated with polyethylene particle-induced chronic inflammation are recruited locally or systemically and (2) whether the recruited macrophages are associated with enhanced osteolysis locally.
Noninvasive in vivo imaging techniques (bioluminescence and microCT) were used to investigate initial macrophage migration systemically from a remote injection site to polyethylene wear particles continuously infused into the femoral canal. We used histologic and immunohistologic staining to confirm localization of migrated macrophages to the polyethylene particle-treated femoral canals and monitor cellular markers of bone remodeling.
The values for bioluminescence were increased for animals receiving UHMWPE particles compared with the group in which the carrier saline was infused. At Day 8, the ratio of bioluminescence (operated femur divided by nonoperated contralateral femur of each animal) for the UHMWPE group was 13.95 ± 5.65, whereas the ratio for the saline group was 2.60 ± 1.14. Immunohistologic analysis demonstrated the presence of reporter macrophages in the UHMWPE particle-implanted femora only. MicroCT scans showed the bone mineral density for the group with both UHMWPE particles and macrophage was lower than the control groups.
Infusion of clinically relevant polyethylene particles, similar to the human scenario, stimulated systemic migration of remotely injected macrophages and local net bone resorption.
KeywordsBone Mineral Density UHMWPE Wear Debris Wear Particle Total Joint Arthroplasty
We thank Dr Afraaz Irani for performing the bone mineral density analysis of the microCT scans. We thank Dr Gobalakrishnan Sundaresan who supplied the Fluc and GFP expressing RAW264.7 macrophage cell line, Dr Timothy Wright (Hospital for Special Surgery, New York, NY) who supplied the UHMWPE particles, and Stephanie Byun for sectioning of samples used in this study. We also thank Dr Lane Smith, Dr Sam Gambhir, and Dr Chris Contag for their helpful advice.
- 8.Dean DD, Schwartz Z, Blanchard CR, Liu Y, Agrawal CM, Lohmann CH, Sylvia VL, Boyan BD. Ultrahigh molecular weight polyethylene particles have direct effects on proliferation, differentiation, and local factor production of MG63 osteoblast-like cells. J Orthop Res. 1999;17:9–17.CrossRefPubMedGoogle Scholar
- 11.Doorn PF, Campbell PA, Worrall J, Benya PD, McKellop HA, Amstutz HC. Metal wear particle characterization from metal on metal total hip replacements: transmission electron microscopy study of periprosthetic tissues and isolated particles. J Biomed Mater Res. 1998;42:103–111.CrossRefPubMedGoogle Scholar
- 43.Suchard SJ, Stetsko DK, Davis PM, Skala S, Potin D, Launay M, Dhar TG, Barrish JC, Susulic V, Shuster DJ, McIntyre KW, McKinnon M, Salter-Cid L. An LFA-1 (αLβ2) small-molecule antagonist reduces inflammation and joint destruction in murine models of arthritis. J Immunol. 2010;184:3917–3926.CrossRefPubMedGoogle Scholar