Microengineered bone models: advances and applications of bone-on-a-chip technology

Bone-on-a-Chip (BoC) platforms are emerging microphysiological systems designed to recapitulate the complex cellular, structural, and mechanical microenvironments of human bone. These microfluidic-based models provide enhanced physiological relevance for studying bone remodeling dynamics, disease progression, and drug responses compared to traditional 2D cultures. This review discusses the anatomical and pathophysiological features of bone that must be replicated in vitro, highlighting recent advances in BoC platforms and their applications in regenerative medicine, drug discovery, and personalized therapy. However, despite their potential, current BoC technologies still face significant challenges, including the simplified representation of the extracellular matrix, incomplete recapitulation of the dense osteocyte network, and partial reproduction of native biomechanical stimuli. Furthermore, integrating vascularization, immune components, and ensuring scalability remain critical hurdles. Future directions focus on developing multi-tissue interfaces, advanced biomaterials, real-time sensing technologies, and AI-assisted data analysis. While still evolving, BoC technology serves as a promising tool for bridging the gap between in vitro models and clinical applications in translational bone research.