Mutant CCL2 protein coating mitigates wear particle-induced bone loss in a murine continuous polyethylene infusion model

Akira Nabeshima, Jukka Pajarinen, Tzu hua Lin, Xinyi Jiang, Emmanuel Gibon, Luis A. Córdova, Florence Loi, Laura Lu, Eemeli Jämsen, Kensuke Egashira, Fan Yang, Zhenyu Yao, Stuart B. Goodman

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1-9
    Number of pages9
    JournalBiomaterials
    Volume117
    DOIs
    Publication statusPublished - Feb 1 2017

    All Science Journal Classification (ASJC) codes

    • Bioengineering
    • Ceramics and Composites
    • Biophysics
    • Biomaterials
    • Mechanics of Materials

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