Development of a 3D Printed, Bioengineered Placenta Model to Evaluate the Role of Trophoblast Migration in Preeclampsia.

Abstract

Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality. Current research suggests that the impaired trophoblastic invasion of maternal spiral arteries contributes significantly to the development of PE. However, the pathobiology of PE remains poorly understood, and there is a lack of treatment options largely due to ineffective experimental models. Utilizing the capability of bioprinting and shear wave elastography, we developed a 3D, bioengineered placenta model (BPM) to study and quantify cell migration. Through BPM, we evaluated the effect of epidermal growth factor (EGF) on the migratory behavior of trophoblast and human mesenchymal stem cells. Our results demonstrate a positive correlation between cell migration rates and EGF concentration. These results indicate that a feasible ex vivo placental model can be bioprinted to examine cellular, molecular, and pharmacologic interactions. In addition, EGF clearly affects the celluar migration, a potential therapeutic agent to treat preeclampsia. We envision that our ex vivo tissue modeling approach can be readily transferred to study other normal biologic and abnormal pathologic processes such as fibroblast migration in wound healing and stem cell homing.