A high-throughput 3D bioprinted human placenta as a novel predictive platform to study drug safety and pathological conditions during pregnancy

Authors

• C Antich
• J Noel
• Y Qu
• D Tao
• E Radnaa
• J Jacob
• R Menon
• MJ Song
• M Ferrer

Abstract

During pregnancy, impaired maternal health or fetal exposure to xenobiotics can lead to gestational complications and long-term health consequences. Unfortunately, due to the limited ability to monitor the human maternofetal interface and the lack of physiologically relevant in vitro models, the underlying mechanisms behind gestational pathologies and the downstream effects remain poorly understood. Therefore, we developed a novel biomimetic in vitro human placenta (hPB) model at various gestational phases in a high throughput format using 3D bioprinting technology, to study placenta physiology, pathology, and pharmacology. To replicate the key elements of the hPB, we bioprinted trophoblast cells and fetal vasculature cells on opposite sides of transwell inserts on a 96-well format platform. In particular, we constructed a trophoblast bilayer comprising syncytiotrophoblasts, cytotrophoblasts, and subjacent fetal vasculature for the early-stage model, which was exposed to hypoxic conditions. Conversely, for the late-stage model, we utilized syncytiotrophoblasts with subjacent fetal vasculature exposed to normoxia conditions. The anatomical similarity in structure to the human placenta was verified using gene expression, proteomic analysis, and immunostaining experiments. The barrier integrity of hPB at various phases was confirmed by TEER and paracellular transport experiments. Fluorescent intensity measurements were used to investigate activities such as nutrients uptake and drug efflux activity, while ELISA assays were employed to evaluate hormones synthesis. This new platform will provide a powerful tool for understanding the relationships between prenatal exposure to pathological conditions and developmental outcomes, and will ultimately serve as the foundation for establishing global public health guidelines to prevent pregnancy complications.

Scientific Focus Area: Biomedical Engineering and Biophysics

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