Tissue Engineering the Next Generation Endometrium-on-Chip

Kevin Osteen of Vanderbilt University Medical Center in the U.S. is developing a three-dimensional cell model that mimics the lining of the human uterus (endometrium), including different cell types and a vascular system, that can be used for affordable medium-to-high-throughput compound screening to discover new contraceptives with minimal adverse side effects. The endometrium is a multi-layered tissue that supports embryo implantation and maintains pregnancy and responds to hormonal cues to undergo renewal during each menstrual cycle. Recapitulating this environment in vitro could provide a valuable, contraceptive screening platform to identify new contraceptives. In Phase I, they built a compartmentalized two-chamber device to model the cross-talk between two endometrial cell layers. They showed that this EndoChip was able to mimic the process of decidualization that is critical for establishing pregnancy. In Phase II, they will refine a second-generation EndoChip to include an epithelial component in the form of organoids by incorporating a three-dimensional synthetic hydrogel and complete endometrial microenvironment for in vitro contraceptive screens. This will be validated with existing drugs known to affect endometrial function. They will also incorporate microfluidic platforms and existing in vitro organ models to establish a multi-organ system that mimics the effect of the liver or gut for analyzing candidate drug efficacy and safety.