Abstract
The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 μm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving α2 and α5 integrins. Further silencing either α2 or α5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the α2 and α5 integrins as mechano-sensitive molecules mediate MSCs’ ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues.
Highlights
The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis
Since morphological changes of Mesenchymal stromal cells (MSCs) and enhancement of interface interaction between MSCs and the surrounding matrix in response to different spherical SBCs were associated with accelerated osteogenesis (Figs 3 and 4), we investigated the relationships between the actin cytoskeleton, focal adhesion (FA), and osteogenic differentiation ability of MSCs under these conditions
Since the gene expressions of α 2 and α 5 integrins were upregulated in Groups II and III (Fig. 6), and integrins are the fundamental components in FA as well as the essential elements for mechanosensing and mechanotransduction[32], we further investigated whether the spherical SBCs-mediated differentiation was regulated by α 2 and α 5 integrins
Summary
The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Organ or tissue architectures serve as structure-based scaffolding and provide a source of natural mechanical cues for cells. At the single cell level, the spatial boundary condition (SBC) determined by the spatial presentation of extracellular matrix (ECM) and surrounding cells imposes a unique structural geometry and spatial constraint that affects stem cell self-renewal and differentiation, in mesenchymal[3], hematopoietic[4], cardiac[5], keratinocytic[6], and hair follicle stem cells[7]. Mechanical forces can be directionally summed, amplifying the net effect of mechanotransduction by increasing the magnitude of the optimal force applied[8] For this reason, the mechanical properties of microenvironments have been explored as another regulatory factor to precisely control stem cell fate and function in situ. The bionic materials used in the above mentioned studies have a wide range of pore sizes, irregular spatial boundaries, and various porosities and have limited the investigation of how SBC influences stem cell behaviors
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