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Related Experiment Video

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Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture.

M A M Vis1, F Zhao2, E S R Bodelier1

  • 1Orthopaedic Biomechanics, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands.

Bone
|May 26, 2023
PubMed
Summary

Researchers developed a novel human 3D microfluidic bone-on-a-chip model. This scaffold-free system mimics bone remodeling, offering a promising alternative to animal testing for drug discovery and disease research.

Keywords:
Bone-on-chipCocultureLong-term cell cultureOsteoblastOsteoclastSelf-assembly

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Area of Science:

  • Biomaterials Engineering
  • Tissue Engineering
  • Microfluidics

Background:

  • Bone remodeling is vital for skeletal health; imbalances cause diseases like osteoporosis.
  • Animal models have limitations in predicting human clinical trial outcomes.
  • Human in vitro models are crucial for the 3Rs (reduction, refinement, replacement) in animal experimentation.

Purpose of the Study:

  • To develop a complete, scaffold-free, fully human in vitro model for bone remodeling.
  • To create a microfluidic coculture system that mimics in vivo bone formation and resorption.
  • To establish a platform for more accurate drug testing and disease modeling.

Main Methods:

  • A 3D microfluidic coculture system was engineered using human mesenchymal stromal cells and human monocytes.
  • Scaffold-free, bone-like tissues mimicking human trabeculae were self-assembled on-chip.
  • Computational modeling assessed fluid-induced shear stress and strain; a long-term culture setup (35 days) was established.

Main Results:

  • The system successfully generated scaffold-free, human bone-like tissues with trabecular dimensions.
  • Human monocytes differentiated into multinucleated osteoclast-like cells, enabling coculture and bone remodeling simulation.
  • The microfluidic setup facilitated long-term culture with continuous flow, low bubble risk, easy medium exchange, and live imaging.

Conclusions:

  • A novel, fully human, 3D microfluidic coculture model of bone remodeling was successfully developed.
  • This bone-on-a-chip system represents a significant advancement for in vitro bone research and drug testing.
  • The model addresses the need for human-relevant alternatives to animal studies in bone pathology research.