Three-Dimensional Stiff Graphene Scaffold on Neural Stem Cells Behavior

Abstract

Physical cues of the scaffolds, elasticity, and stiffness significantly guide adhesion, proliferation, and differentiation of stem cells. In addressable microenvironments constructed by three-dimensional graphene foams (3D-GFs), neural stem cells (NSCs) interact with and respond to the structural geometry and mechanical properties of porous scaffolds. Our studies aim to investigate NSC behavior on the various stiffness of 3D-GFs. Two kinds of 3D-GFs scaffolds present soft and stiff properties with elasticity moduli of 30 and 64 kPa, respectively. Stiff scaffold enhanced NSC attachment and proliferation with vinculin and integrin gene expression were up-regulated by 2.3 and 1.5 folds, respectively, compared with the soft one. Meanwhile, up-regulated Ki67 expression and almost no variation of nestin expression in a group of the stiff scaffold were observed, implying that the stiff substrate fosters NSC growth and keeps the cells in an active stem state. Furthermore, NSCs grown on stiff scaffold exhibited enhanced differentiation to astrocytes. Interestingly, differentiated neurons on stiff scaffold are suppressed since growth associated protein-43 expression was significantly improved by 5.5 folds.

Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques

“…Surface chemistry, topography, chemical composition, wettability, stiffness, dimensionality, porosity, and degree of cross‐linking are fundamental parameters that must be taken into the account in the design of substitute for medical applications . By manipulating surface properties of implants such as surface charge, functional groups, and topography, initial cell attachment can be tuned in a controlled manner …”

“…Cells expanded more on substrates with stiffness of ≈24 kPa, whereas a highly elongated spindle‐like morphology was found with soft surfaces, ≈1 kPa ( Figure A) . Ma et al reported gene expression profile of NSCs onto the surface of graphene‐based substrates with different elastic moduli and assessed stem cell differentiation into various cell lineages (Figure B) . Vascular smooth muscle cells (SMCs) represented contractile phenotype in materials with lower elastic modulus (within the range of 0.38–12.70 N mm −2 of substrate stiffness) .…”

“…NSCs showed elongated and spreading protuberances on the surface of soft and stiff GF scaffolds, respectively. Reproduced with permission . Copyright 2016, American Chemical Society.…”

Nanomaterials in Neural‐Stem‐Cell‐Mediated Regenerative Medicine: Imaging and Treatment of Neurological Diseases

“…Further evidence showed that the stiffness of GO affects the adhesion, proliferation, and differentiation behaviors of stem cells. Ma et al discovered that, compared to soft GO, a stiff GO scaffold can better enhance the attachment and proliferation of NSCs, with the upregulation of vinculin and integrin gene expression …”

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

“…Indeed, 3D-GFs were shown to increase NSC differentiation compared to 2D graphene films and act as an electrically conductive scaffold [62]. In a follow-up study [63], stiffer 3D-GFs (64 kPa) promoted cell adhesion and proliferation compared to softer 3D-GFs (30 kPa), as measured by qPCR and western blotting (WB) of functional markers (e.g. vinculin and integrin for adhesion, Ki67 for proliferation).…”