Bioengineering gradients for controlled embryo and organ modeling

Symmetry breaking and tissue patterning are fundamental processes in mammalian development. Understanding these events is essential not only for advancing mammalian developmental biology but also for the ongoing efforts to create in vitro models of mammalian embryogenesis and organogenesis using stem cells. This review highlights recent bioengineering innovations designed to control exogenous and endogenous gradients of soluble biochemical signals and insoluble biophysical cues, effectively guiding cell differentiation and spatial organization in embryo and organ modeling. Specifically, we discuss microfluidics- and micropatterning-based multicellular culture systems, as well as approaches that use porous beads loaded with soluble factors and engineered cells as synthetic signaling centers to replicate dynamic in vivo signaling. We evaluate the effectiveness and limitations of each technique in influencing cell fate decisions, morphogenesis, and patterning, and explore their applications in modeling mammalian development. Finally, we outline emerging approaches that leverage bioengineered tools to construct mammalian embryo and organ models for both basic research and translational applications.