Polarization of organoids by bioengineered symmetry breaking

Symmetry breaking leading to axis formation and spatial patterning is crucial for achieving more accurate recapitulation of human development in organoids. While these processes can occur spontaneously by self-organizing capabilities of pluripotent stem cells, they can often result in variation in structure and composition of cell types within organoids. To address this limitation, bioengineering techniques that utilize geometric, topological and stiffness factors are increasingly employed to enhance control and consistency. Here, we review how spontaneous manners and engineering tools such as micropattern, microfluidics, biomaterials, etc. can facilitate the process of symmetry breaking leading to germ layer patterning and the formation of anteroposterior and dorsoventral axes in blastoids, gastruloids, neuruloids and neural organoids. Furthermore, brain assembloids, which are composed of multiple brain regions through fusion processes are discussed. The overview of organoid polarization in terms of patterning tools can offer valuable insights for enhancing the physiological relevance of organoid system.