Spatial confinement toward creating artificial living systems.

Lifeforms are regulated by many physicochemical factors, and these factors could be controlled to play a role in the construction of artificial living systems. Among these factors, spatial confinement is an important one, which mediates biological behaviors at multiscale levels and participates in the biomanufacturing processes accordingly. This review describes how spatial confinement, as a fundamental biological phenomenon, provides cues for the construction of artificial living systems. Current knowledge about the role of spatial confinement in mediating individual cell behavior, collective cellular behavior, and tissue-level behavior are categorized. Endeavors on the synthesis of biomacromolecules, artificial cells, engineered tissues, and organoids in spatially confined bioreactors are then emphasized. After that, we discuss the cutting-edge applications of spatially confined artificial living systems in biomedical fields. Finally, we conclude by assessing the remaining challenges and future trends in the context of fundamental science, technical improvement, and practical applications.