Enhanced Migration of Neural Stem Cells by Microglia Grown on a Three-Dimensional Graphene Scaffold

Abstract

One of the key challenges in engineering neural tissues for cell-based therapies is to develop a biocompatible scaffold material to direct neural stem cell (NSC) behaviors. One great advantage for a scaffold would be to induce NSC migration toward pathological sites during regeneration and repair. In particular, the inflammatory responses in the pathological zone, which are mainly mediated by microglia in the central nervous system, affect the repair capacity of NSCs through NSC migration. Recently, graphene was used as a neural interface and scaffold material, but few studies have addressed the relationship between microglia and NSCs in a graphene culture system. In this study, we used a combination of immunofluorescence, Western blotting, enzyme-linked immunosorbent assays, and scanning electron microscopy to investigate how conditioned medium (CM) produced from microglia grown on two-dimensional graphene (2D-G) films or three-dimensional graphene (3D-G) foams govern NSC migration. The results revealed that the CM produced by microglia grown in 3D-G cultures could promote neurosphere formation, facilitate NSC migration from the neurospheres, and increase single cell polarization by activating the stromal cell-derived factor 1 α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) signaling pathway and enhancing cell adhesion on the substrate. By contrast, the 2D-G CM failed to achieve these results. Our study suggests the great potential of 3D-G as a neural scaffold for NSC-based therapy in tissue engineering and regenerative medicine.

Multivalent Interactions between 2D Nanomaterials and Biointerfaces

“…Various 2D and 3D architectures such as graphene nanofibers or foams have also displayed promise for neural tissue engineering . 3D GO nanofibers (GO‐NFs) have shown greatly enhanced growth and development of primary motor neurons, assisted by electrical stimulation of the cells via the conductive GO‐NFs .…”

“…3D GO nanofibers (GO‐NFs) have shown greatly enhanced growth and development of primary motor neurons, assisted by electrical stimulation of the cells via the conductive GO‐NFs . Microglia grown in 3D graphene foams produced conditioned medium (CM) that promoted cell adhesion and neurosphere formation, which does not occur when microglia are grown on 2D graphene films . 3D structures present many properties that are uniquely different than their 2D counterparts and could be even better for neural tissue engineering and regenerative medicine.…”

In vitro effect of graphene structures as an osteoinductive factor in bone tissue engineering: A systematic review

“…14 Researchers have demonstrated that 3D structured graphene, compared to 2D, provides larger accessible specific surface areas, interconnected conductive structure and unique surface microstructure, 120,121 which might improve cell growth and differentiation. 122,123 To further compare the compatibility of 3D and 2D structured graphene, Jiang et al 124 synthesized 2D films and 3D foams of graphene and reported that 3D structured foams are more beneficial for migration of neural stem cells. Indeed, the 3D graphene foam could enhance cell migration through stromal-cell derived factor-1α/CXCR4 signaling pathway, which is essential for the cell migration.…”

Application of Nanowires for Retinal Regeneration

“…Nanostructures have evolved as multidisciplinary applications by combination with materials as an advanced architecture to develop functional substitutes for various proposes such as wound dressing [4][5][6], tissue engineering [7][8][9][10][11], and biomedical applications [12][13][14]. Neuroscience, related to the retina is one of the most exciting fields where nanostructures with modified properties serve as scaffolds to promote and facilitate the migration and adhesion of the cells [15].…”