The effect of local IL-4 delivery or CCL2 blockade on implant fixation and bone structural properties in a mouse model of wear particle induced osteolysis.
Modulation of macrophage polarization and prevention of CCL2-induced macrophage chemotaxis are emerging strategies to reduce wear particle induced osteolysis and aseptic total joint replacement loosening. In this study, the effect of continuous IL-4 delivery or bioactive implant coating that constitutively releases a protein inhibitor of CCL2 signaling (7ND) on particle induced osteolysis were studied in the murine continuous femoral intramedullary particle infusion model. Polyethylene particles with or without IL-4 were infused into mouse distal femurs implanted with hollow titanium rods using subcutaneous infusion pumps. In another experimental group, particles were infused into the femur through a 7ND coated rod. After 4 weeks, fixation of the implant was assessed using a pullout test. The volume of trabecular bone and the geometry of the local cortical bone were assessed by µCT and the corresponding structural properties of the cortical bone determined by torsional testing. Continuous IL-4 delivery led to increased trabecular bone volume as well as enhanced local bone geometry and structural properties, while 7ND implant coating did not have effect on these parameters. The results suggest that local IL-4 treatment is a promising strategy to mitigate wear particle induced osteolysis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2255-2262, 2016.
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Taishi
T
Sato
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Jukka
J
Pajarinen
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Anthony
A
Behn
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Xinyi
X
Jiang
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Tzu-Hua
TH
Lin
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Florence
F
Loi
Department of Orthopaedic Surgery, Stanford University, Stanford, California.
Zhenyu
Z
Yao
Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Kensuke
K
Egashira
Department of Orthopaedic Surgery, Stanford University, Stanford, California.|Department of Bioengineering, Stanford University, Stanford, California.
Fan
F
Yang
Department of Orthopaedic Surgery, Stanford University, Stanford, California.|Department of Bioengineering, Stanford University, Stanford, California.
Stuart B
SB
Goodman
D000818:Animals; D000069343:Bone-Implant Interface; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D005269:Femur / Q000378:metabolism* / Q000473:pathology; D020007:Implants, Experimental / Q000009:adverse effects*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020959:Polyethylene / Q000009:adverse effects / Q000494:pharmacology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015847:Interleukin-4; D020959:Polyethylene
CCL2; aseptic loosening; bone structural properties; interleukin-4; macrophage