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

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.