Microfluidic organ-on-chip device: a unique platform for investigating implantation and placentation

Disruption of critical processes during early placentation is associated with several pregnancy disorders, leading to high rates of morbidity and mortality globally. However, we are unable to detect or modify the course of these disorders because the fundamental mechanisms underlying their development remain incompletely described. This stems from an inability to ethically study these processes in vivo and a lack of technology to model early placentation in vitro in a physiologically relevant manner. Recent advances in bioengineering have resulted in the development of organ-on-chip devices-novel 3-dimensional cell culture models that use microchip technology to mimic key functional aspects of specific tissue/organ systems. We leveraged organ-on-chip technology to develop a human implantation-on-a-chip device, enabling in vitro modeling of two processes essential to early pregnancy-trophoblast invasion and maternal vascular remodeling. This microengineered platform emulates the 3-dimensional microarchitecture, tissue compartmentalization, and cellular heterogeneity of the maternal-fetal interface during implantation. Additionally, the device enables simulation, direct visualization, and quantitative analysis of dynamic events that occur during early pregnancy, representing a major advance from existing systems. In this manuscript, we explain the importance of human-specific research platforms for the study of implantation and placentation, describe the development and unique applications of the implantation-on-a-chip device to study human pregnancy, and highlight improvements to the device currently in progress.