Bone-on-a-chip platforms and integrated biosensors: Towards advanced in vitro bone models with real-time biosensing

Bone diseases, such as osteoporosis and bone defects, often lead to structural and functional deformities of the patient's body. Understanding the complicated pathophysiology and finding new drugs for bone diseases are in dire need but challenging with the conventional cell and animal models. Bone-on-a-chip (BoC) models recapitulate key features of bone at an unprecedented level and can potentially shift the paradigm of future bone research and therapeutic development. Nevertheless, current BoC models predominantly rely on off-chip analysis which provides only endpoint measurements. To this end, integrating biosensors within the BoC can provide non-invasive, continuous monitoring of the experiment progression, significantly facilitating bone research. This review aims to summarize research progress in BoC and biosensor integrations and share perspectives on this exciting but rudimentary research area. We first introduce the research progress of BoC models in the study of bone remodeling and bone diseases, respectively. We then summarize the need for BoC characterization and reported works on biosensor integration in organ chips. Finally, we discuss the limitations and future directions of BoC models and biosensor integrations as next-generation technologies for bone research.