Organoids are widely considered to be ideal in vitro models that have been widely applied in many fields, including regenerative medicine, disease research and drug screening. It is distinguished from other three-dimensional in vitro culture model systems by self-organization and sustainability in long-term culture. The three core components of organoid culture are cells, exogenous factors, and culture matrix. Due to the complexity of bone tissue, and heterogeneity of osteogenic stem/progenitor cells, it is challenging to construct organoids for modeling skeletal systems. In this study, we examine current progress in the development of skeletal system organoid culture systems and analyze the current research status of skeletal stem cells, their microenvironmental factors, and various potential organoid culture matrix candidates to provide cues for future research trajectory in this field. Impact Statement The emergence of organoids has brought new opportunities for the development of many biomedical fields. The bone organoid field still has much room for exploration. This review discusses the characteristics distinguishing organoids from other three-dimensional model systems and examines current progress in the organoid production of skeletal systems. In addition, based on core elements of organoid cultures, three main problems that need to be solved in bone organoid generation are further analyzed. These include the heterogeneity of skeletal stem cells, their microenvironmental factors, and potential organoid culture matrix candidates. This information provides direction for the future research of bone organoids.
Keywords: 3D model systems; organoids; pluripotent stem cells; skeletal stem cells; skeletal systems.