Development of a biomaterial model of the decidualized endometrium

Statement of Purpose: The endometrium, the site of embryo implantation, is a unique, dynamic tissue that undergoes rapid vascular remodeling over the course of the menstrual cycle and pregnancy. Endometrial models are crucial for understanding reproductive disorders, including preeclampsia and endometriosis. They also provide a platform to examine mechanisms underlying vascular remodeling that takes place within the endometrium. While animal models can be used to study dynamic endometrial processes, physiological differences in placentation between animals and humans call into question the relevance of such models. Traditional 2D in vitro models allow researchers to study the endometrium using human cells; however, they do not capture cellular crosstalk in complex microenvironments. Tissue engineered 3D endometrial models would provide new avenues to recapitulate aspects of the in vivo environment while retaining the capability to study cell-cell and cell-matrix interactions in a highly tunable manner. Herein, we describe an adaptable 3D hydrogel model of the endometrium consisting of a coculture of human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs) within a methacrylamide-functionalized gelatin (GelMA) hydrogel. We demonstrate the ability to form vessel structures within this model as well as study the kinetics of trophoblast invasion in 3D. The GelMA hydrogel provides a platform to integrate additional signals from the native tissue microenvironment of the endometrium, namely sex steroid hormones, to examine how the role played by endometrial stromal cell decidualization status (specialized decidual endometrial stromal cells play a critical role in embryo implantation and placentation) affects endothelial cell network formation.