title: A 3D vascularized bone remodeling model combining osteoblasts and osteoclasts in a CaP nanoparticle-enriched matrix.
abstract: OBJECTIVE
  We aimed to establish a 3D vascularized in vitro bone remodeling model.
  
  
  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.
  
  
  CONCLUSIONS
  We successfully developed a vascularized 3D bone remodeling model, whereby cells interacted and exerted their specific function.
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bongio
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lopa
authors.affiliation: 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.
authors.forename: Mara
authors.initials: M
authors.lastname: Gilardi
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bersini
authors.affiliation: 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.
authors.forename: Matteo
authors.initials: M
authors.lastname: Moretti
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: D002130:Calcium Phosphates; D020100:Hydrogels; C020243:calcium phosphate
keywords: 3D model; bone remodeling; vascularization