Next-generation brain organoids: neural complexity from cellular diversity to functional networks

Brain organoids, as pioneering three-dimensional (3D) in vitro platforms, have profoundly advanced our understanding of human brain development and disease mechanisms. This review summarizes recent progress in enhancing cellular diversity, structural organization, and functional complexity within brain organoids. A key application of these models lies in disease modelling, encompassing neurodevelopmental and neurodegenerative disorders as well as brain tumours, which enables personalized drug screening and mechanistic studies. Despite persistent challenges related to neuronal maturation, vascularization, reproducibility, and functional integration, we highlight emerging bioengineering strategies, multi-organ integration approaches, and ethical considerations that provide a roadmap for next-generation organoid platforms. Collectively, brain organoids hold transformative potential for both fundamental neuroscience and translational research, bridging critical gaps between conventional experimental models and human-specific pathophysiology.