3D cocultures of osteoblasts and staphylococcus aureus on biomimetic bone scaffolds as a tool to investigate the host–pathogen interface in osteomyelitis

Raffaella Parente, Valentina Possetti, Maria Lucia Schiavone, Elisabetta Campodoni, Ciro Menale, Mattia Loppini, Andrea Doni, Barbara Bottazzi, Alberto Mantovani, Monica Sandri, Anna Tampieri, Cristina Sobacchi, Antonio Inforzato

Research output: Contribution to journalArticlepeer-review

Abstract

Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challenge pathogenetic hypotheses in controlled conditions, thus providing guidance and support to animal experimentation. In this regard, traditional 2D models of OM inherently lack the spatial complexity of bone architecture. Three-dimensional models of the disease overcome this limitation; however, they poorly reproduce composition and texture of the natural bone. Here, we developed a new 3D model of OM based on cocultures of SA and murine osteoblastic MC3T3-E1 cells on magnesium-doped hydroxyapatite/collagen I (MgHA/Col) scaffolds that closely recapitulate the bone extracellular matrix. In this model, matrix-dependent effects were observed in proliferation, gene transcription, protein expression, and cell–matrix interactions both of the osteoblastic cell line and of bacterium. Additionally, these had distinct metabolic and gene expression profiles, compared to conventional 2D settings, when grown on MgHA/Col scaffolds in separate monocultures. Our study points to MgHA/Col scaffolds as biocompatible and bioactive matrices and provides a novel and close-to-physiology tool to address the pathogenetic mechanisms of OM at the host–pathogen interface.

Original languageEnglish (US)
Article number837
JournalPathogens
Volume10
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • 3D models
  • Biomimetic bone scaffolds
  • Host–pathogen interface
  • Osteoblast-like cells
  • Osteomyelitis
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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