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Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis
Pei-Gen Ren1, Afraaz Irani, Zhinong Huang
1Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
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.
Insights
Systemic macrophages migrate to polyethylene particles, causing bone loss in joint replacements. This study tracked macrophage movement and confirmed their role in periprosthetic osteolysis, a key complication.
Area of Science:
- Biomedical Engineering
- Immunology
- Orthopedic Surgery
Background:
- Aseptic loosening and periprosthetic osteolysis are major complications of total joint arthroplasty, driven by wear debris.
- Monocyte/macrophages are critical cells mediating osteolysis at the bone-implant interface.
Purpose of the Study:
- To determine if macrophages involved in polyethylene particle-induced inflammation are recruited systemically or locally.
- To investigate the association between recruited macrophages and local osteolysis.
Main Methods:
- Noninvasive in vivo imaging (bioluminescence, microCT) tracked systemic macrophage migration to infused polyethylene particles.
- Histologic and immunohistologic staining confirmed macrophage localization and monitored bone remodeling markers.
Main Results:
- Bioluminescence imaging showed significantly increased macrophage migration to polyethylene particles compared to saline controls.
- Immunohistology confirmed reporter macrophages were present only in polyethylene particle-implanted femora.
- MicroCT scans revealed reduced bone mineral density in femora with both polyethylene particles and macrophages.
Conclusions:
- Clinically relevant polyethylene particles stimulate systemic macrophage migration from remote sites.
- This systemic macrophage recruitment contributes to local net bone resorption, exacerbating periprosthetic osteolysis.
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