Emerging engineering strategies in bone organoids: From biomimetic scaffolds to dynamic microenvironmental stimulation

Bone organoids have emerged as transformative models for studying bone development and disease by recapitulating complex cellular ecosystems in vitro . However, unlike soft tissues, the unique mineralized matrix and highly dynamic mechanical environment of bone pose significant challenges to classical self-assembly strategies. Consequently, engineering strategies are not merely auxiliary but essential for constructing functional bone organoids. This review provides a comprehensive overview of advanced engineering strategies designed to overcome these biological hurdles. We critically examine the integration of dynamic mechanical microenvironments and the design of biomimetic topologies for guiding cell fate. Furthermore, we explore the application of bone organoids in disease modeling while addressing inherent limitations. Potential solutions based on the convergence of 3D bioprinting, microfluidic organ-on-a-chip systems, and artificial intelligence are proposed. We anticipate that deep interdisciplinary collaboration will accelerate the transition of bone organoids from theoretical exploration to clinical personalized medicine, bridging the gap between basic research and regenerative therapies. • Engineering strategies are defined as essential for structural bone organoids. • Biomimetic scaffolds with TPMS and hierarchical topology guide cell fate. • Stimuli-responsive materials enable dynamic mechanical microenvironments. • Integrated bone-on-a-chip platforms facilitate vascularization and disease modeling.