TY - JOUR
KW - animal alternative
KW - bone marrow
KW - Bone Remodeling
KW - disease modeling
KW - human microfluidic culture
KW - organ-on-a-chip
KW - xeno-free 3D in vitro system
AU - Nina Stelzer
AU - Melanie-Jasmin Ort
AU - Kristian Händler
AU - Emely Bortel
AU - Ioanna Maria Dimitriou
AU - Martin Textor
AU - Georg N. Duda
AU - Janosch Schoon
AU - Uwe Marx
AU - Uwe Kornak
AU - Annika Winter
AU - Bernhard Hesse
AU - Stefanie Donner
AU - Sebastian Hardt
AU - Oliver Klein
AU - Simon Reinke
AU - Malte Spielmann
AU - Sven Geißler
AB - We developed a human Bone-on-a-Chip (BOAC) model that integrates autologous primary immune and bone cells on native human bone substrates within a xeno-free, perfused environment. In contrast to existing models, which focus primarily on hematopoietic or stromal compartments, our system recapitulates key aspects of functional bone remodeling and enables the maintenance of mature immune cells (up to 42 days), with preserved functional responsiveness at defined time points during culture. Dynamic flow and sequential cell seeding facilitated osteoclast-mediated resorption, osteoblast-driven matrix formation, and the maintenance of donor-specific immune profiles over extended culture periods. The balance between bone cell activity and immune cell persistence 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. The bone scaffold provides a physiologically relevant 3D architecture derived from decellularized human trabecular bone. Single-nucleus RNA sequencing confirmed the presence of major donor-specific immune and bone cell populations. This 3D human in vitro system provides a robust platform for translational research and personalized medicine.
BT - Advanced Science
DO - 10.1002/advs.202518224
IS - n/a
LA - en
N2 - We developed a human Bone-on-a-Chip (BOAC) model that integrates autologous primary immune and bone cells on native human bone substrates within a xeno-free, perfused environment. In contrast to existing models, which focus primarily on hematopoietic or stromal compartments, our system recapitulates key aspects of functional bone remodeling and enables the maintenance of mature immune cells (up to 42 days), with preserved functional responsiveness at defined time points during culture. Dynamic flow and sequential cell seeding facilitated osteoclast-mediated resorption, osteoblast-driven matrix formation, and the maintenance of donor-specific immune profiles over extended culture periods. The balance between bone cell activity and immune cell persistence 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. The bone scaffold provides a physiologically relevant 3D architecture derived from decellularized human trabecular bone. Single-nucleus RNA sequencing confirmed the presence of major donor-specific immune and bone cell populations. This 3D human in vitro system provides a robust platform for translational research and personalized medicine.
EP - e18224
T2 - Advanced Science
TI - A 3D Human Bone and Bone Marrow-on-a-Chip Model for In Vitro Bone Remodeling and Immune Cell Maintenance
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202518224
VL - n/a
Y2 - 2026-07-10
SN - 2198-3844
ER -