Mimicking bone microenvironment: 2D and 3D in vitro models of human osteoblasts

Ivan Yuste, Francis Christina Luciano, Katerina Lalatsa, Dolores Remedios Serrano

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Understanding the in vitro biology and behaviour of human osteoblasts is crucial for developing research models that reproduce closely the bone structure, its functions, and the cell-cell and cell-matrix interactions that occurs in vivo. Mimicking bone microenvironment is challenging, but necessary, to ensure the clinical translation of novel medicines to treat more reliable different bone pathologies. Currently, bone tissue engineering is moving from 2D cell culture models such as traditional culture, sandwich culture, micro-patterning, and altered substrate stiffness, towards more complex 3D models including spheroids, scaffolds, cell sheets, hydrogels, bioreactors, and microfluidics chips. There are many different factors, such cell line type, cell culture media, substrate roughness and stiffness that need consideration when developing in vitro models as they affect significantly the microenvironment and hence, the final outcome of the in vitro assay. Advanced technologies, such as 3D bioprinting and microfluidics, have allowed the development of more complex structures, bridging the gap between in vitro and in vivo models. In this review, past and current 2D and 3D in vitro models for human osteoblasts will be described in detail, highlighting the culture conditions and outcomes achieved, as well as the challenges and limitations of each model, offering a widen perpective on how these models can closely mimic the bone microenvironment and for which applications have shown more successful results.
Original languageEnglish
Article number105626
JournalPharmacological Research
Early online date21 Apr 2021
Publication statusPublished - 1 Jul 2021


  • bone regeneration
  • in vitro models
  • osteoblast
  • 3D bioprinting
  • microfluidics
  • tissue engineering
  • hydrogels


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