A Topographically Optimized Substrate with Well‐Ordered Lattice Micropatterns for Enhancing the Osteogenic Differentiation of Murine Mesenchymal Stem Cells

Seo, Chang Ho; Furukawa, Katsuko; Suzuki, Yuji; Kasagi, Nobuhide; Ichikı, Takanori; Ushida, Takashi

doi:10.1002/mabi.201000477

Cited by 23 publications

(21 citation statements)

References 55 publications

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“…Development of in vitro topographical cues provides a rapid and inexpensive alternative to better recapitulate the in vivo microenvironment and guide stem cell differentiation [87,152-157]. For instance, in a study by Seo et al, enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) was observed on geometrically ordered lattice micropatterns [158]. An interval pattern of 3 μm showed significant upregulation of alkaline phosphatase after 6 days and type-I collagen and osteocalcin after 12 days, compared to flat surfaces.…”

Section: Stem Cell Differentiationmentioning

confidence: 99%

Engineering microscale topographies to control the cell–substrate interface

et al. 2012

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Cells in their in vivo microenvironment constantly encounter and respond to a multitude of signals. While the role of biochemical signals has long been appreciated, the importance of biophysical signals has only recently been investigated. Biophysical cues are presented in different forms including topography and mechanical stiffness imparted by the extracellular matrix and adjoining cells. Microfabrication technologies have allowed for the generation of biomaterials with microscale topographies to study the effect of biophysical cues on cellular function at the cell–substrate interface. Topographies of different geometries and with varying microscale dimensions have been used to better understand cell adhesion, migration, and differentiation at the cellular and sub-cellular scales. Furthermore, quantification of cell-generated forces has been illustrated with micropillar topographies to shed light on the process of mechanotransduction. In this review, we highlight recent advances made in these areas and how they have been utilized for neural, cardiac, and musculoskeletal tissue engineering application.

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Section: Stem Cell Differentiationmentioning

confidence: 99%

Engineering microscale topographies to control the cell–substrate interface

et al. 2012

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“…The physical features of the ECM (e.g., stiffness [1–6], viscoelasticity [7] and topography [8–10]) play pivotal roles in governing cell behavior. In particular, ECM stiffness is a key regulator of cellular morphology [11–13], migration [14–16], proliferation [17–19], gene expression [20–22] and differentiation [23–25]. The elastic modulus of native ECM varies among different tissue types, ranging from 0.5 to 1 kPa in brain to 10-20 GPa in bone.…”

Section: Introductionmentioning

confidence: 99%

Mechanically dynamic PDMS substrates to investigate changing cell environments

et al. 2017

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Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ~1300 to 1900 μm2 and from ~2700 to 4600 μm2 for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ~2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.

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“…Thus, the topographical feature of the scaffold surface to which cells adhere is an important characteristics for cell differentiation and tissue regeneration. A number of topographies, such as grooved, grid or pillar substrates have been designed in the in vitro studies to mimic the physiological niche . To date, little is known about the underlying intracellular mechanisms of the topography‐mediated cell responses.…”

Section: Introductionmentioning

confidence: 99%

Enhanced osteogenic differentiation of MC3T3‐E1 cells on grid‐topographic surface and evidence for involvement of YAP mediator

Zhang

Gong

Sun

et al. 2016

J Biomedical Materials Res

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Numerous studies have shown that surface topography can promote cell-substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering.

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A Topographically Optimized Substrate with Well‐Ordered Lattice Micropatterns for Enhancing the Osteogenic Differentiation of Murine Mesenchymal Stem Cells

Cited by 23 publications

References 55 publications

Engineering microscale topographies to control the cell–substrate interface

Engineering microscale topographies to control the cell–substrate interface

Mechanically dynamic PDMS substrates to investigate changing cell environments

Enhanced osteogenic differentiation of MC3T3‐E1 cells on grid‐topographic surface and evidence for involvement of YAP mediator

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