Abstract
The topographical interface of the extracellular environment has been appreciated as a principal biophysical regulator for modulating cell functions, such as adhesion, migration, proliferation, and differentiation. Despite the existed approaches that use two-dimensional nanomaterials to provide beneficial effects, opportunities evaluating their impact on stem cells remain open to elicit unprecedented cellular responses. Herein, we report an ultrathin cell-culture platform with potential-responsive nanoscale biointerfaces for monitoring mesenchymal stem cells (MSCs). We designed an intriguing nanostructured array through self-assembly of graphene oxide sheets and subsequent lithographical patterning method to produce chemophysically defined regions. MSCs cultured on anisotropic micro/nanoscale patterned substrate were spontaneously organized in a highly ordered configuration mainly due to the cell-repellent interactions. Moreover, the spatially aligned MSCs were spontaneously differentiated into smooth muscle cells upon the specific crosstalk between cells. This work provides a robust strategy for directing stem cells and differentiation, which can be utilized as a potential cell culture platform to understand cell–substrate or cell–cell interactions, further developing tissue repair and stem cell-based therapies.Graphical
Highlights
The ability to control cellular behavior at the cell-substrate interfaces has advanced in ex vivo biological studies through the surface chemistry and biophysical structures based on various topography, stiffness, or combinatorial properties [1,2,3]
We focused on the architecting of the ultrathin physicochemically defined cell-substrate and explored the related interactive responses of mesenchymal stem cells (MSCs) with tightly balanced cellular behaviors between self-restrained migration and differentiation into smooth muscle cells (SMCs) toward a highly aligned and stretched configuration
The alternately patterned surface area was defined by conventional photolithography on the reduced GO (rGO) film/glass substrate using a mask-aligner with a photomask of micron line/space pattern in a gradient configuration
Summary
The ability to control cellular behavior at the cell-substrate interfaces has advanced in ex vivo biological studies through the surface chemistry and biophysical structures based on various topography, stiffness, or combinatorial properties [1,2,3]. Regarding the topographic cues that promote specific interactions at the cell-substrate interfaces, the salient features of micro/nanoscale materials have become a promising toolbox for modulating the specified cellular processes [7,8,9]. A form of ultrathin cellsubstrates, including two-dimensional (2D) nanomaterials, has provided unprecedented topographical interfaces with biologically beneficial interactions owing to their unique chemical, mechanical, electrical, and optical properties [12,13,14,15] These materials have excellent capability as a cell culture platform because of their idiosyncratic modulatory effects, on the proliferation and differentiation of stem cells [16, 17]. The possible cell-repellent effects associated with the micro/nanostructured features of 2D materials in directing cell migration and aligned cell organization have received little attention
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