Biomimetic micropatterned adhesive surfaces to mechanobiologically regulate placental trophoblast fusion

The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure and regulates transport between mother and baby during development. It is maintained throughout pregnancy by continuous fusion of trophoblast cells, and disruptions in fusion are associated with considerable adverse health effects including diseases such as preeclampsia. Developing predictive control over cell fusion in culture models is hence of critical importance in placental drug discovery and transport studies; but this can currently be only partially achieved with biochemical factors. Here, we investigate whether biophysical signals associated with budding morphogenesis during development of the placental villous tree can synergistically direct and enhance cultured trophoblast fusion. We use micropatterning techniques to manipulate physical stresses in engineered microtissues, and demonstrate that biomimetic geometries simulating budding robustly enhances fusion and alter spatial patterns of synthesis o...