Mini-bones: miniaturized bone in vitro models.

In bone tissue engineering (TE) and regeneration, miniaturized, (sub)millimeter-sized bone models have become a popular trend since they bring about physiological biomimicry, precise orchestration of concurrent stimuli, and compatibility with high-throughput setups and high-content imaging. They also allow efficient use of cells, reagents, materials, and energy. In this review, we describe the state of the art of miniaturized in vitro bone models, or 'mini-bones', describing these models based on their characteristics of (multi)cellularity and engineered extracellular matrix (ECM), and elaborating on miniaturization approaches and fabrication techniques. We analyze the performance of 'mini-bone' models according to their applications for studying basic bone biology or as regeneration models, disease models, and screening platforms, and provide an outlook on future trends, challenges, and opportunities.