Bone Organoids: Current Approaches, Challenges, and Potential Applications

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Organoids are complex three-dimensional microtissues formed by the selforganization of stem cells and aimed to mimic the structural and functional characteristics of human tissues. Bone comprises multiple cells with a mechanically rigid extracellular matrix (ECM). The diversity of a bone in terms of structure and complexity demands an ideal bone model with limited control of physico-chemical parameters. Potential applications of bone organoids can be seen in bone regeneration, and regulation mechanism studies and to address various bone-related disorders and defects. Approaches to creating bone organoids may include using mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), osteoblasts, and osteoclasts in addition to endothelial cells for the vasculature generation. Moreover, in bone organoids, ECM of biological origin materials that display close resemblance with the native bone ECM are preferred or may be generated using scaffold-free methods. The mechanical load should be the primary parameter that should be considered in the model. Since bone is considered hypoxic, organoid-based bone models should include an O2 regulation mechanism to achieve a physiologic hypoxic environment. Advanced cell isolation, tissue culture, and cell differentiation techniques, along with microfluidics and tissue engineering strategies, might lead to the production of physiologically relevant bone organoids. This chapter outlines prerequisites for bone organoid development and the potential applications of bone organoid-based models in various biomedical research domains. Additionally, their limitations and future perspectives are also explored.