Bone-on-a-Chip: Biomimetic Models Based on Microfluidic Technologies for Biomedical Applications

Withthe increasing importance of preclinical evaluation of newlydeveloped drugs or treatments, in vitro organ ordisease models are necessary. Although various organ-specific on-chip(organ-on-a-chip, or OOC) systems have been developed as emerging in vitro models, bone-on-a-chip (BOC) systems that recapitulatethe bone microenvironment have been less developed or reviewed comparedwith other OOCs. The bone is one of the most dynamic organs and undergoescontinuous remodeling throughout its lifetime. The aging populationis growing worldwide, and healthcare costs are rising rapidly. Since in vitro BOC models that recapitulate native bone nichesand pathological features can be important for studying the underlyingmechanism of orthopedic diseases and predicting drug responses inpreclinical trials instead of in animals, the development of biomimeticBOCs with high efficiency and fidelity will be accelerated further.Here, we review recently engineered BOCs developed using various microfluidictechnologies and investigate their use to model the bone microenvironment.We have also explored various biomimetic strategies based on biological,geometrical, and biomechanical cues for biomedical applications ofBOCs. Finally, we addressed the limitations and challenging issuesof current BOCs that should be overcome to obtain more acceptableBOCs in the biomedical and pharmaceutical industries.