Biomimetic Hydrogel Models of Early Development of the Placental Vasculature

Mentor: Michelle Oyen, Associate Professor, Department of Biomedical Engineering

Lab description: Our lab is developing engineering tools to understand and intervene into preterm birth, with a focus on the placenta and the maternal-fetal interface. The maternal and fetal vasculatures do not directly mix but the transport distances for oxygen and nutrients between them are small. One major cause of preterm birth is pre-eclampsia, when the placenta causes potentially fatally high blood pressure to develop in the mother. We use both experimental tools and computational modeling to try and understand the placenta’s role in this and related conditions.

Project: Both maternal and fetal outcomes in pregnancy are reliant on the first trimester development of the placenta, the maternal-fetal interface. Fetal trophoblast cells invade the maternal uterine lining and direct the remodeling of uterine spiral arteries. The signaling cues that direct this invasion are not fully known, nor are there diagnostic criteria to indicate that this process has been suboptimal. Poor outcomes in pregnancy, including pre-eclampsia and fetal growth restriction, occur when the placental vascular bed is insufficient for transport. Clinical signals of poor maternal and fetal outcomes may not appear until the third trimester, long after the early placental development has ceased. To study this process, we are developing assays using biomimetic hydrogels as an artificial extracellular matrix to model the physical and chemical environment during trophoblast invasion. The work is being conducted in collaboration with scientists in developmental biology, who derive trophoblast-like cells from induced pluripotent stem cells. The long-term goal of the project is to develop biomarker assays for signaling either poor or adequate trophoblast invasion, to allow for early diagnosis of future potential placental malfunction.