Synergistic effect of cell-derived extracellular matrix and topography on osteogenesis of mesenchymal stem cells

Yang, L., Ge, L. & van Rijn, P., 2020, In : ACS Applied Materials & Interfaces.

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Cell-derived matrices (CDM) are an interesting alternative to the conventional sources of extracellular matix (ECM) as CDM mimics better the natural ECM composition and are therefore attractive as a scaffolding material to be used for regulating the functions of stem cells. Previous research on stem cell differentiation has demonstrated that both surface topography and CDM have a significant influence. However, not much focus has been placed on elucidating possible synergistic effects of CDM and topography on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this study, Polydimethylsiloxane (PDMS)-based anisotropic topographies (wrinkles) with various topography dimensions were prepared and subsequently combined with native ECM produced by human fibroblasts that remained onto the surface topography after decellularization. The synergistic effect of CDM combined with topography on osteogenic differentiation of hBM-MSCs was investigated. The results showed that substrates with specific topography dimensions, coated with aligned CDM, dramatically enhanced the capacity of osteogenesis as investigated using immunofluorescent staining for identifying osteopontin (OPN) and mineralization. Furthermore, the hBM-MSCs on the substrates decorated with CDM exhibited higher percentage of YAP inside the nucleus, stronger cell contractility, and more formation of focal adhesion, illustrating that enhanced osteogenesis is partly mediated by cellular tension and mechanotransduction following the YAP pathway. Taken together, our findings highlight the importance of ECM mediating the osteogenic differentiation of stem cells, and the combination of CDM and topography will be a powerful approach for material-driven osteogenesis.

Original languageEnglish
JournalACS Applied Materials & Interfaces
Publication statusE-pub ahead of print - 2020

ID: 125785869