Continuous Infusion of UHMWPE Particles Induces Increased Bone Macrophages and Osteolysis

Abstract

Background 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. Questions/purposes 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.Methods 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.Results 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. Conclusions Infusion of clinically relevant polyethylene particles, similar to the human scenario, stimulated systemic migration of remotely injected macrophages and local net bone resorption.

Exogenous MC3T3 Preosteoblasts Migrate Systemically and Mitigate the Adverse Effects of Wear Particles

“…To confirm the specificity of the antiluciferase antibody, an identical staining protocol was repeated on control femora from a prior experiment from our laboratory, in which no cells were injected and either saline or UHMWPE was infused from the pump. 12 No luciferasepositive cell staining was seen in these sections.…”

“…Additionally, previous work by Ren et al demonstrated that there was no increase in bioluminescence (reflecting systemic exogenous reporter cell trafficking) if reporter cells were not injected. 12 Injecting cells into a small, rapidly beating heart is more difficult than injecting cells into the tail vein, which is visible and remains still. We used the presence of blood in the syringe to indicate correct placement of the needle, but its placement throughout the duration of the injection is difficult to confirm.…”

“…This occurs primarily through the MCP-1-CCR2 ligand receptor axis. 12,43 These cells become activated, further releasing chemokines for macrophages and reparative cells, such as preosteoblasts, and also stimulate osteoclast differentiation and maturation. Osteoclasts locally resorb bone, thereby releasing other chemotactic substances, such as osteocalcin, and may make the bony matrix available as a scaffold for the injected MC3T3 cells to increase bone mass and mitigate wear particle-induced bone loss.…”

“…[4][5][6][7][8][9][10] This recruitment of macrophages is not just local, but systemic in nature. [10][11][12] The increased number of macrophages and osteoclasts increase bone resorption, leading to osteolysis.…”

“…A significant problem of this method remains the accumulation of the cells in the lungs during the cells' first pass from venous to arterial circulation. 11,12,26,27 Intracardiac injection (ICI) into the left ventricle, on the other hand, directly introduces the cells into systemic circulation. Cancer researchers have explored this method of cell delivery as a model for metastasis, but its utility in other fields has not been established.…”