Engineering Bone Organoids to Model Development and Disease

Organoids are 3D miniature tissue models that recapitulate the spatial organization and function of living cells in native tissues. They have become powerful tools for studying human development and disease in vitro. Despite remarkable progress, most existing organoid models are restricted to epithelial tissues such as the intestine, brain, and liver. However, generating human bone organoids remains a major challenge because (1) native bone tissue contains a complex network of cavities and fluid-filled tunnels within a mineralized matrix, and (2) current in vitro techniques largely fail to differentiate precursor cells into osteocytes within simple hydrogels. In this seminar, I will first introduce the structure–function relationships of native bone, as well as existing animal models of bone diseases and their limitations. I will then present several engineered bone organoid models developed in my group at ETH Zurich, which combine patient-derived cells, microarchitected biomaterials, light-based bioprinting, and organ-on-chip technologies. Finally, I will discuss the current challenges and future outlook for advancing bone organoid models toward more physiologically relevant systems and in vitro drug discovery.