AUTHOR=Rufaihah Abdul Jalil , Cheyyatraivendran Suganya , Mazlan Muhammad Danial Mohd , Lim Kenrich , Chong Mark Seow Khoon , Mattar Citra Nurfarah Zaini , Chan Jerry Kok Yen , Kofidis Theodoros , Seliktar Dror TITLE=The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells JOURNAL=Frontiers in Physiology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01555 DOI=10.3389/fphys.2018.01555 ISSN=1664-042X ABSTRACT=Hydrogel materials have been successfully used as matrices to explore the role of biophysical and biochemical stimuli in directing stem cell behavior. Here, we present our findings on the role of stiffness in guiding fetal mesenchymal stem cell (fMSC) fate determination using semi-synthetic hydrogels made from PEG-fibrinogen (PF). The fMSCs were cultivated in the PF for up to two weeks to study the influence of matrix modulus (i.e., cross-linking density of the PF) on fMSC proliferation, morphology and integrin expression. Both two-dimensional (2D) and three-dimensional (3D) culture conditions were employed to examine the fMSCs as single cells or as cell spheroids. The hydrogel modulus affected the rate of fMSC proliferation, the integrin expression levels and the cell morphology, both as single cells and as spheroids. The cell seeding density was also found to be an important parameter of the system in that high densities were favorable in facilitating more cell-to-cell contacts that direct stem cell fate. Our findings provide important insight about rational design of a hydrogel cell culture matrix and other cell culture conditions that can be used to optimize the biological response of fMSCs for various tissue engineering applications.