Organ-On-Chip Technology: The Future of Feto-Maternal Interface Research?

The placenta and fetal membrane act as a protective barrier throughout pregnancy while maintaining communication and nutrient exchange between the baby and the mother. Disruption of this barrier leads to various pregnancy complications, including preterm birth, which can have lasting negative consequences. Thus, understanding the role of the feto-maternal interface during pregnancy and parturition is vital to advancing basic and clinical research in the field of obstetrics. However, human subject studies are inherently difficult, and appropriate animal models are lacking. Due to these challenges, in vitro cell culture-based studies are most commonly utilized. However, the structure and functions of conventionally used in vitro 2D and 3D models are vastly different from the in vivo environment, making it difficult to fully understand the various factors affecting pregnancy as well as pathways and mechanisms contributing to term and preterm births. This limitation also makes it difficult to develop new therapeutics. The emergence of in vivo-like in vitro models such as organ-on-chip (OOC) platforms can better recapitulate in vivo functions and responses and has the potential to move this field forward significantly. OOC technology brings together two distinct fields, microfluidic engineering and cell/tissue biology, through which diverse human organ structures and functionalities can be built into a laboratory model that better mimics functions and responses of in vivo tissues and organs. In this review, we first provide an overview of the OOC technology, highlight two major designs commonly used in achieving multi-layer co-cultivation of cells, and introduce recently developed OOC models of the feto-maternal interface. As a vital component of this review, we aim to outline progress on the practicality and effectiveness of feto-maternal interface OOC (FM-OOC) models currently used and the advances they have fostered in obstetrics research. Lastly, we provide a perspective on the future basic research and clinical applications of FM-OOC models, and even those that integrate multiple organ systems into a single OOC system that may recreate intrauterine architecture in its entirety, which will accelerate our understanding of feto-maternal communication, induction of preterm labor, drug or toxicant permeability at this vital interface, and development of new therapeutic strategies.