Microengineered hiPSC-Derived 3D Amnion Tissue Model to Probe Amniotic Inflammatory Responses under Bacterial Exposure.

Intra-amniotic infection is a common cause of preterm birth that can lead to adverse neonatal outcomes. Despite the basic and clinical significance, the study in normal and diseased human amnion is highly challenging due to the limited use of human primary tissues and the distinct divergence between animal models and human. Here, we established a microengineered hiPSC-derived amnion tissue model on a chip to investigate the inflammatory responses of amnion tissues to bacterial exposure. The microdevice consisted of two parallel channels with a middle matrix channel, creating a permissive microenvironment for amnion differentiation. Dissociated hiPSCs efficiently self-organized into cell cavity and finally differentiated into a polarized squamous amniotic epithelium on the chip under perfused 3D culture. When exposed to E. coli, amnion tissue exhibited significant functional impairments compared to the control, including induced cell apoptosis, disrupted cell junction integrity, and increased inflammatory factor secretion, recapitulating a series of characteristic clinical signs of intra-amniotic infection at an early stage. Together, this amnion-on-a-chip model provides a promising platform to investigate intrauterine inflammation in early gestation, indicating its potential applications in human embryology and reproductive medicine.