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

In contrast to existing models, which focus primarily on hematopoietic or stromal compartments, our system mimics functional bone remodeling and enables the long-term maintenance of mature immune cells. Dynamic flow and sequential cell seeding facilitated osteoclast-mediated resorption, osteoblast-driven matrix formation, and the preservation of donor-specific immune profiles over several weeks.

The balance between bone cell activity and immune cell maintenance was further optimized by controlled temperature modulation. The BOAC model preserves key features of bone and bone marrow physiology, including extracellular matrix formation, soluble factor signaling, and cellular heterogeneity. Single-nucleus RNA sequencing confirmed the sustained presence of donor-specific immune and bone cell populations.