Regulation of substrate surface topography on differentiation of mesenchymal stem cells
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REVIEW PAPER
Regulation of substrate surface topography on differentiation of mesenchymal stem cells Bo Huo1 · Yang Zhao1 · Xue Bai1 · Qing Sun1 · Fei Jiao1 Received: 6 May 2020 / Revised: 4 July 2020 / Accepted: 28 July 2020 © The Chinese Society of Theoretical and Applied Mechanics and Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Mesenchymal stem cells (MSCs) have been extensively used in the field of tissue engineering and regenerative medicine. The effect of surface properties on the differentiation of MSCs is a very important issue for the design and fabrication of scaffolds or biomaterials. This review is mainly focused on the morphological or topographic characteristics of cell adhesion substrate, i.e. cell area and shape for individual cell, cell density and cell–cell contact for multiple cells, substrate roughness, ridge width, micropillar height, nanoparticle diameter and aspect ratio of nanowire. The results from different studies were quantitatively analyzed using comparable or unified parameters and definitions under the specific experimental conditions such as cell source, culture time, induction medium, matrix material and differentiation marker. Some interesting phenomena and properties were discovered by this integrated and systematic analysis, which might give insights into the regulatory mechanism of surface morphology or topography on MSCs differentiation. Keywords Mesenchymal stem cell · Adhesion morphology · Surface topography · Differentiation · Biomaterial
1 Introduction Mesenchymal stem cells (MSCs) are the only reminiscence of mesenchyme still present in adult organisms [1]. They have high capability of self-renewal and differentiation into multiple lineages, including neurons, myoblasts, osteoblasts, chondrocytes and so on. Because of the extensive differentiation capabilities, MSCs have been widely used as the candidates of seed cells in tissue engineering or regeneration medicine [2]. MSCs differentiation responds to both chemical and physical cues generated in the extracellular environment [3]. Since 1990s, the interaction between stem cells and biomaterials has been extensively investigated. It has been well recognized that extracellular microenvironment plays important roles in growth and differentiation of stem cells. Apart from soluble chemical factor in the extracellular solution [4] and chemical composition of the substrate where cells adhere to also gets involved with the differentiation of MSCs [5, 6], physical and geometric properties of
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substrate surface influence MSC differentiation. One milestone of the fundamental works on physical properties of substrate is the discovery in 2006 performed by Discher et al., i.e. that substrate stiffness significantly regulates MSCs differentiation [7]. In addition, a number of researches showed that the geometric factors such as intercellular connection [8, 9], cell shape [9–11], cell area [9, 12–14] and substrate morphology [15–19] are also able to modulate the differentiation of MSCs. Along with the conti
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