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Front Physiol. 2018 Dec 21;9:1555. doi: 10.3389/fphys.2018.01555. eCollection 2018.

The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells.

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Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
Department of Obstretics and Gynaecology, National University of Singapore, Singapore, Singapore.
Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre Singapore, National University Health System, Singapore, Singapore.
Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore, Singapore.
Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel.


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 modulus in guiding bone marrow fetal mesenchymal stem cell (BMfMSC) fate determination using semi-synthetic hydrogels made from PEG-fibrinogen (PF). The BMfMSCs were cultivated in the PF for up to 2 weeks to study the influence of matrix modulus (i.e., cross-linking density of the PF) on BMfMSC survival, morphology and integrin expression. Both two-dimensional (2D) and three-dimensional (3D) culture conditions were employed to examine the BMfMSCs as single cells or as cell spheroids. The hydrogel modulus affected the rate of BMfMSC metabolic activity, 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 favored higher metabolic activity. Our findings provide important insight about design of a hydrogel scaffold that can be used to optimize the biological response of BMfMSCs for various tissue engineering applications.


PEGylated fibrinogen; biomaterials; hydrogel; matrix stiffness; scaffold; tissue engineering

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