A Human Bone Defect‐on‐a‐Chip Model for Studying Bone Regeneration

Biomimetic in vitro models to study tissue (patho)physiology are increasingly important to complement or replace animal experiments. In recent years, various organ‐on‐chip models have been developed, resembling specific structural and functional aspects of human tissues and organs. This study presents a novel human bone defect‐on‐a‐chip (BDOC) model, aiming to recapitulate selected key processes during the early post‐injury phase of bone healing, incorporating bone graft substitutes. Such models minimize cell and reagent use, lowering experimental costs. Additionally, they provide an alternative to animal models. Using human cells provides translatable data unaffected by interspecies differences, narrowing the gap between proof‐of‐concept and clinical application. Moreover, these models offer excellent observational capability, enabling high‐resolution analysis of cellular behavior. The BDOC features two diverging host bone‐mimicking side compartments defining a triangular defect‐like inner chamber with different gap sizes. Over 21 days, human mesenchymal stem/stromal cells (HMSCs) and human primary macrophages are co‐cultured in the BDOC together with calcium phosphate microparticles. The HMSCs’ gap size‐dependent migration, osteogenic differentiation, and mineralization are assessed inside the inner chamber. The HMSCs travel from the side compartments to the defect‐like area, express key osteogenic markers, and deposit mineral. Similar models could help develop biomaterial‐based bone regenerative therapies one day.