Bone-on-chip models

Bone is a highly dynamic organ, whose functions include structural and protective support, mobility, and hormone regulation. This active tissue is under continuous remodeling, balancing synthesis, and resorption to enable growth and repair. Imbalances in bone remodeling are characteristic of several diseases, such as osteoporosis and (metastatic) cancers. Conventionally, research on (patho-)physiology of bone is conducted using oversimplistic two-dimensional (2D) in vitro models or nonhuman representative in vivo models, which deliver limited predictive power. Organs-on-chips are in vitro model alternatives that circumvent these limitations by providing high spatiotemporal control over cellular, (bio-)chemical, and/or physical gradients, enabling high surface-to-volume ratios and mechanical stimulation. In particular, applications of bone-on-chip models allow: (1) generating fundamental knowledge on bone biology, (2) development of regenerative approaches, (3) modeling of disease stages, (4) drug screening, and (5) mimicry of the interplay between organs in complex diseases. This chapter comprises a comprehensive overview of current developments and trends in bone-on-chip platforms. Bone is a highly dynamic organ, responsible for fundamental functions, including structural and protective support for soft tissues and bone marrow, respectively, hormone regulation, and, importantly, mobility. This active tissue is under continuous remodeling, balancing synthesis and resorption, to enable growth, mechanical adaptation, and repair. Imbalances may lead to severe and tremendously debilitating bone diseases. Conventionally, research on bone (path-)physiology is conducted using oversimplistic 2D in vitro models or nonrepresentative in vivo models, which typically fail to reproduce the complexity of the human bone microenvironment. Model alternatives that circumvent these limitations are on the rise, delivering on the promise to mimic human-relevant (patho-)physiological microenvironments. In particular the organ-on-chip field is gaining increasing attention, due to the intrinsic ability of these microfluidic models to provide high control over cellular, (bio-)chemical, and/or physical cues, enable high surface-to-volume ratios, and allow for mechanical cue tailoring, at the microscale, in a spatiotemporal orchestrated manner. To date, several bone-on-chip models have contributed to generating fundamental knowledge on bone biology, in both healthy and disease conditions. Moreover, many successful examples illustrate their ability to assist in the development of regenerative approaches, serve as models of disease stages to screen for therapies, and mimic the interplay between organs, simulating systemic-like connections. In this chapter, we report on organ-on-a-chip technologies with a focus on bone research. We describe the application of these organotypic models in combination with advanced technologies. Finally, we report on current trends, expected to bring forward bone-on-chip platforms as enablers of precision medicine, thereby paving the way to establish a paradigm shift in the development of more effective bone therapeutics.