A 3D human placenta-on-a-chip model to probe nanoparticle exposure at the placental barrier

With the commercialization of nanomaterials, environmental exposure to nanoparticles (NPs) has raised great concerns due to the long-term effects to human body, particularly to pregnant women. Previous studies found that NPs had an adverse impact on placenta in mice, but care must be taken when extrapolating the results to human pregnancy in consideration of the great difference between species. Here, we proposed a microengineered 3D placental barrier-on-a-chip microdevice and further explored complicated placental responses to NPs exposure in vitro. The microdevice recreated near-physiological 3D microenvironment and dynamic conditions in fetal maternal circulation combined with the extracellular matrix and flow. With the exposure to titanium dioxide nanoparticles (TiO₂-NPs), a common nanomaterial, a series of placental responses were investigated, including oxidative stress, cell apoptosis, barrier permeability, and maternal immune cell behavior. By contrast to oxidative stress and cell apoptosis, placental barrier integrity and maternal immune cells were greatly influenced even with low concentrated NPs, suggesting the potential damages triggered by NPs in our daily life. Collectively, this in vitro experimental model of human placenta provides a simple platform to study environmental exposure to NPs, and might be potential for a wide range of applications in biological study, disease treatment and drug assessment.