01505nas a2200205   4500000000100000008004100001260001500042653001500057653002600072653002500098653001800123653001300141653002200154100002500176700001900201245006500220856007200285520092800357022001401285       2026                            d  c2026-06-0810aAssembloid10aDevelopmental biology10aengineering organoid10aOrganogenesis10aorganoid10aself-organization1 aJonathan A. Brassard1 aJames M. Wells00aDesigning complex organoids through developmental principles  uhttps://www.sciencedirect.com/science/article/pii/S19345909260019673 aPrinciples of developmental biology have inspired efforts for directed differentiation of human pluripotent stem cells (hPSCs), leading to the first generation of organoids that are now well established as models of human development and disease. However, first-generation organoid models were missing many cell types that would be needed to study normal and pathological processes. Here, we discuss how designing next-generation organoids with increased cellular complexity has been possible by better reproducing developmental processes in play during organogenesis in vivo. We focus on recent conceptual and technical advances in reconstructing appropriate cellular diversity in organoids, dissecting the importance of tissue-tissue interactions and specialized cell addition, and how engineering technologies can further enhance our ability to control how cells are brought together to mimic human development in vitro.  a1934-5909