Human stem cell-based embryo models: from self-organization to recapitulating development

Human stem cell-based embryo models (hereafter referred to as embryo models) are a rapidly evolving field at the intersection of developmental biology and bioengineering. In this review, we examine design principles, material systems, and engineering approaches that enable the construction of models arising from pluripotent stem cells. We consider how three-dimensional environments, synthetic hydrogels, and spatiotemporal modulation of morphogenetic signals guide self-organization. Together, these factors enable the recapitulation of stages from blastocyst formation to early organogenesis. We then discuss opportunities of these engineered systems in disease modeling and developmental toxicity screening. We also address the scaling issues and biomanufacturing limitations that must be overcome to enable standardized, high-fidelity production.