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Research Article

A 3D vascularized bone remodeling model combining osteoblasts and osteoclasts in a CaP nanoparticle-enriched matrix

    Matilde Bongio

    Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy

    Authors contributed equally

    Search for more papers by this author

    ,
    Silvia Lopa

    Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy

    Authors contributed equally

    Search for more papers by this author

    ,
    Mara Gilardi

    Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy

    PhD School in Life Sciences, Department of Biotechnology & Biosciences, University of Milano–Bicocca, 20126 Milan, Italy

    ,
    Simone Bersini

    Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy

    &
    Matteo Moretti

    *Author for correspondence:

    E-mail Address: matteo.moretti@grupposandonato.it

    Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy

    Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland

    Swiss Institute of Regenerative Medicine (SIRM), 6900 Lugano, Switzerland

    Fondazione Cardiocentro Ticino, 6900 Lugano, Switzerland

    Published Online:https://doi.org/10.2217/nnm-2015-0021

    Aim: We aimed to establish a 3D vascularized in vitro bone remodeling model. Materials & methods: Human umbilical endothelial cells (HUVECs), bone marrow mesenchymal stem cells (BMSCs), and osteoblast (OBs) and osteoclast (OCs) precursors were embedded in collagen/fibrin hydrogels enriched with calcium phosphate nanoparticles (CaPn). We assessed vasculogenesis in HUVEC-BMSC coculture, osteogenesis with OBs, osteoclastogenesis with OCs, and, ultimately, cell interplay in tetraculture. Results: HUVECs developed a robust microvascular network and BMSCs differentiated into mural cells. Noteworthy, OB and OC differentiation was increased by their reciprocal coculture and by CaPn, and even more by the combination of the tetraculture and CaPn. Conclusion: We successfully developed a vascularized 3D bone remodeling model, whereby cells interacted and exerted their specific function.

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