An Integrated Organoid-on-a-Chip Platform for Modeling the Human Placental Barrier.

The placental barrier plays a critical role in protecting the fetus from xenobiotics and regulating the maternal-fetal exchange. However, conventional trophoblast cell lines and animal models often fail to accurately recapitulate the key structural and functional features of the human placental barrier. In this study, a novel organ-on-a-chip (OOC) model was developed that integrated human JEG-3 trophoblast organoids with human umbilical vein endothelial cells under combined fluid shear stress and mechanical strain. This configuration supports the self-assembly of a three-dimensional, functional placental barrier. The engineered tissue exhibited essential physiological characteristics, including syncytiotrophoblast marker expression, human chorionic gonadotropin secretion, and enhanced glucose transport activity. This model was used to assess the transbarrier transport of several flavonoid compounds. The results indicated that permeation occurred primarily via passive diffusion, with permeability differences governed mainly by physicochemical properties, such as lipophilicity, rather than molecular size. This integrated OOC platform establishes a biomimetic human placental model that provides a reliable tool for evaluating placental permeability and the potential toxicity risks of complex compounds.