Nano-Spatiotemporal Programming in Organoid Engineering: From Stochastic Self-Organization to Controllable...

Organoids are widely used for in vitro modeling of human organogenesis and disease, yet their reliance on stochastic self-organization limits reproducibility, standardization, and translational applications. Nanotechnology provides tools to guide organoid self-organization toward more controllable developmental outcomes. Specifically, nano-spatiotemporal programming enables modulation of extracellular architecture and dynamic morphogen presentation, supporting more interpretable organoid development. In this Review, we discuss the intersection of nanomaterials and organoid engineering. We summarize how nanoengineered matrices, spatiotemporal cue delivery vehicles, and stimuli-responsive nanoscaffolds regulate structural patterning, lineage-specific differentiation, and functional maturation. By synthesizing these advances, this Review outlines design principles for developmentally programmable human organoids and their potential use in regenerative medicine, tissue engineering, and fundamental embryology.