A 3D Human Bone and Bone Marrow-on-a-Chip Model for In Vitro Bone Remodeling and Immune Cell Maintenance

Area of Science:

• Biotechnology
• Immunology
• Orthopedics

Background:

• Existing in vitro models often focus narrowly on specific bone cell types.
• There is a need for more comprehensive models that integrate immune and bone cells.
• Current systems struggle to maintain mature immune cells and functional bone remodeling simultaneously.

Purpose of the Study:

• To develop a human Bone-on-a-Chip (BOAC) model integrating immune and bone cells.
• To create a xeno-free, perfused system that recapitulates bone remodeling.
• To enable long-term culture and functional assessment of immune cells within a bone microenvironment.

Main Methods:

• Integration of autologous primary immune and bone cells on native human bone scaffolds.
• Utilized a perfused environment with dynamic flow and sequential cell seeding.
• Employed controlled temperature modulation to optimize cell balance.
• Single-nucleus RNA sequencing for cellular population analysis.

Main Results:

• The BOAC model successfully recapitulated osteoclast-mediated resorption and osteoblast-driven matrix formation.
• Mature immune cells were maintained for up to 42 days with preserved functional responsiveness.
• Donor-specific immune profiles and key bone physiology features were sustained.
• The 3D architecture of decellularized human trabecular bone provided a physiologically relevant scaffold.

Conclusions:

• The developed human BOAC model offers a robust platform for studying bone remodeling and immune interactions.
• This system supports translational research and holds promise for personalized medicine applications.
• The model accurately preserves cellular heterogeneity and signaling pathways relevant to bone and bone marrow physiology.