Graphene oxide-collagen composite scaffold for osteogenic differentiation of human mesenchymal stem cells

Abstract

It is known that mesenchymal stem cells (MSCs) preferentially undergo osteogenic differentiation when cultured on mechanically stiff substrate. Here we demonstrate that covalent conjugation of mechanically stiff graphene oxide (GO) flakes to the pore of relatively soft, three-dimensional (3D) collagen scaffolds improves the mechanical property of the scaffolds and promotes osteogenic differentiation of MSCs that adhere to the pore of the scaffolds and are cultured. The covalent conjugation of GO flakes (average 6 μm in size) to the pore of collagen sponges increased the scaffold stiffness by 3 folds and did not cause cytotoxicity. Culture of human MSCs on the GO-collagen scaffolds significantly enhanced osteogenic differentiation compared to culture on non-modified collagen scaffolds. The enhanced osteogenic differentiation was likely mediated by hMSCs' mechanosensing of stiff substrate, since molecules that are related to cell adhesion to stiff substrates were up-regulated or activated. Since 3D scaffolds can be used to improve the cell-cell and cell-matrix interactions, mimic the microenvironment of native tissue, and regenerate neo-tissues, the 3D GO-collagen scaffolds could offer a powerful platform for stem cell research and orthopedic regenerative medicine.