title: Mutant CCL2 protein coating mitigates wear particle-induced bone loss in a murine continuous polyethylene infusion model.
abstract: Wear particle-induced osteolysis limits the long-term survivorship of total joint replacement (TJR). Monocyte/macrophages are the key cells of this adverse reaction. Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is the most important chemokine regulating trafficking of monocyte/macrophages in particle-induced inflammation. 7ND recombinant protein is a mutant of CCL2 that inhibits CCL2 signaling. We have recently developed a layer-by-layer (LBL) coating platform on implant surfaces that can release biologically active 7ND. In this study, we investigated the effect of 7ND on wear particle-induced bone loss using the murine continuous polyethylene (PE) particle infusion model with 7ND coating of a titanium rod as a local drug delivery device. PE particles were infused into hollow titanium rods with or without 7ND coating implanted in the distal femur for 4 weeks. Specific groups were also injected with RAW 264.7 as the reporter macrophages. Wear particle-induced bone loss and the effects of 7ND were evaluated by microCT, immunohistochemical staining, and bioluminescence imaging. Local delivery of 7ND using the LBL coating decreased systemic macrophage recruitment, the number of osteoclasts and wear particle-induced bone loss. The development of a novel orthopaedic implant coating with anti-CCL2 protein may be a promising strategy to mitigate peri-prosthetic osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Nabeshima
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gibon
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Chile, Santiago, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Córdova
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Florence
authors.initials: F
authors.lastname: Loi
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Eemeli
authors.initials: E
authors.lastname: Jämsen
authors.affiliation: Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: goodbone@stanford.edu.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage*; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D010014:Osteolysis / Q000139:chemically induced* / Q000517:prevention & control*; D020959:Polyethylene / Q000009:adverse effects* / Q000737:chemistry; D019736:Prostheses and Implants / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020099:Coated Materials, Biocompatible; D004343:Drug Implants; D020959:Polyethylene
keywords: Implant coating; Macrophage; Mutant CCL2 protein; Osteolysis; Total joint replacement