Synergistic Effect of Cell-Derived Extracellular Matrices and Topography on Osteogenesis of Mesenchymal Stem Cells

Abstract

Cell-derived matrices (CDMs) are an interesting alternative to conventional sources of extracellular matrices (ECMs) as CDMs mimic the natural ECM composition better and are therefore attractive as a scaffolding material for regulating the functions of stem cells. Previous research on stem cell differentiation has demonstrated that both surface topography and CDMs have a significant influence. However, not much focus has been devoted to elucidating possible synergistic effects of CDMs 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 ECMs produced by human fibroblasts that remained on the surface topography after decellularization. The synergistic effect of CDMs combined with topography on osteogenic differentiation of hBM-MSCs was investigated. The results showed that substrates with specific topography dimensions, coated with aligned CDMs, dramatically enhanced the capacity of osteogenesis as investigated using immunofluorescence staining for identifying osteopontin (OPN) and mineralization. Furthermore, the hBM-MSCs on the substrates decorated with CDMs exhibited a higher percentage of (Yes-associated protein) YAP inside the nucleus, stronger cell contractility, and greater formation of focal adhesions, illustrating that enhanced osteogenesis is partly mediated by cellular tension and mechanotransduction following the YAP pathway. Taken together, our findings highlight the importance of ECMs mediating the osteogenic differentiation of stem cells, and the combination of CDMs and topography will be a powerful approach for material-driven osteogenesis.

Self-agglomerated collagen patterns govern cell behaviour

“…The topographies on the collagen stains are at nano-level and forced tenocytes to form an elongated shape. This result is also supported by Yang et al where they show that nano topographies as small as 50 nm led elongation and orientation of human dermal fibroblasts 37 , and human bone marrow-derived mesenchymal stem cells 38 . However, characteristics (pitch, ridge, and groove dimensions) of the nano-groove surface topography matter and can either result in elongated cell shape or lead to the formation of spherical aggregates of human tenocytes 39 .…”

Dual anisotropicity comprising 3D printed structures and magnetic nanoparticle assemblies: towards the promotion of mesenchymal stem cell osteogenic differentiation

“…At the current stage, although the role of magnetic properties and anisotropicity in the induction of ADSC osteogenic differentiation should be fully elucidated before considering animal-based validation experiments, it is still suitable in vitro platform for mechanistic studies and therapeutic candidate testing. In addition, we believe that combination with cell-derived ECM will improve the cell-composite interaction and further promote the osteogenesis of stem cells [32][33][34] .…”

Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine

“…Mechano-physical re-engineering could be achieved by culturing ECM-secreting cells in 3D sacrificial hydrogels (Yuan et al, 2018), on micro-molds (Schell et al, 2016), and micro-and nano-grooves (Ozguldez et al, 2018;Almici et al, 2020;Yang et al, 2020), forcing cell reorganization and leading to ECM assemblies with unique architectures (i.e., parallel fiber alignment). ECM postprocessing, such as cross-linking, could further alter ECM stiffness (Subbiah et al, 2016) or the overall presentation of CD-ECM.In particular, cross-linking of pepsin-solubilized CD-ECM with genipin resulted in the formation of hydrogels (Nyambat et al, 2020), Changes in biochemical and mechano-physical properties of the ECM let to changes in gene expression and behavior of reseeded cells (Kim et al, 2015;Ozguldez et al, 2018;Sart et al, 2020).…”

“…Mechano-physical re-engineering could be achieved by culturing ECM-secreting cells in 3D sacrificial hydrogels ( Yuan et al, 2018 ), on micro-molds ( Schell et al, 2016 ), and micro- and nano-grooves ( Ozguldez et al, 2018 ; Almici et al, 2020 ; Yang et al, 2020 ), forcing cell reorganization and leading to ECM assemblies with unique architectures (i.e., parallel fiber alignment). ECM postprocessing, such as cross-linking, could further alter ECM stiffness ( Subbiah et al, 2016 ) or the overall presentation of CD-ECM.…”