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

With the increasing importance of preclinical evaluation of newly developed drugs or treatments, in vitro organ or disease 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 recapitulate the bone microenvironment have been less developed or reviewed compared with other OOCs. The bone is one of the most dynamic organs and undergoes continuous remodeling throughout its lifetime. The aging population is growing worldwide, and healthcare costs are rising rapidly. Since in vitro BOC models that recapitulate native bone niches and pathological features can be important for studying the underlying mechanism of orthopedic diseases and predicting drug responses in preclinical trials instead of in animals, the development of biomimetic BOCs with high efficiency and fidelity will be accelerated further. Here, we review recently engineered BOCs developed using various microfluidic technologies 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 of BOCs. Finally, we addressed the limitations and challenging issues of current BOCs that should be overcome to obtain more acceptable BOCs in the biomedical and pharmaceutical industries.