Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis.
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.


OBJECTIVE
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.
Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
Pei-Gen
PG
Ren
Afraaz
A
Irani
Zhinong
Z
Huang
Ting
T
Ma
Sandip
S
Biswal
Stuart B
SB
Goodman
D000818:Animals; D019643:Arthroplasty, Replacement / Q000009:adverse effects / Q000295:instrumentation; D015519:Bone Density / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D007595:Joint Prosthesis; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010014:Osteolysis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000276:immunology; D010316:Particle Size; D011095:Polyethylenes / Q000008:administration & dosage* / Q000633:toxicity; D011474:Prosthesis Design; D013997:Time Factors; D014162:Transfection; D055114:X-Ray Microtomography
D008164:Luminescent Proteins; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene