Harnessing Advances in Bone Tissue Engineering for Design of Bone-on-Chip Systems

Organ-on-Chip systems demonstrate significant potential as next-generation models to study human (patho)physiology and to assess new therapies. Whereas on-chip models of soft tissues and organs have progressed substantially over the past decade, the development of bone-on-chip (BoC) systems remains comparatively slower. This slower progress stems from the structural and functional complexity of bone tissue, which hampers efforts to recapitulate bone (patho)physiology on-chip. Advances in bone tissue engineering (BTE) now provide opportunities regarding i) innovative biomaterials design strategies and ii) advanced bioengineering tools, enabling a closer replication of the architectural and functional complexity of native bone. However, these technological advances have primarily resulted in improved regenerative therapies, while also offering opportunities for innovative BoC designs. This perspective article identifies key requirements for BoCs, explores existing models and their respective advantages and limitations. Subsequently, opportunities derived from BTE are highlighted to accelerate the development of BoCs which more accurately capture crucial features of in vivo bone (patho)physiology. Finally, key considerations for BoC design are discussed, and an outlook for further developments in this emerging field is provided.