Enhanced osteogenic commitment of mesenchymal stem cells on graphene oxide-incorporated biomaterials

Abstract

Tissue engineering is an interdisciplinary field that has attempted to restore or regenerate tissues and organs by biomimetic fabrication of scaffolds with functionality. Graphene oxide (GO) is considered as an enormously potential biomaterial due to its nontoxicity, high dispersity and hydrophilic interaction, which characteristics can stimulate the interaction between substrate and cells. In chapter 1, we utilized GO substrates to observe its effect on the osteogenic responses of mouse mesenchymal-like stem cells, C3H10T1/2, GO substrates were fabricated via chemically immobilizing GO at 1.0 mg/ml on glass slides. C3H10T1/2 cells on GO substrates resulted in increased cell surface area and enhanced both cellular adhesions and osteogenic differentiation. Priming C3H10T1/2 cells with chondrocyte-conditioned medium (CM) could further induce a synergistic effect of osteogenesis on GO substrates. All these data suggested that GO substrate along with CM is suitable for upregulating osteogenic responses of mesenchymal stem cells. In chapter 2, we fabricated GO incorporated 3D scaffold to observe effects on the osteogenic responses of human tonsil derived mesenchymal stem cells at 3D environment. Polyethylene glycol (PEG)-based cryogels are attractive biomaterials for stem cell culture due to their tunable material properties and porous structures. In this study, compared to unmodified hydrogel, Graphene oxide (GO) embedded polyethylene glycol cryogel showed not only improved cell attachment, focal adhesion, and focal adhesion kinase (FAK) signaling activation, but also enhanced cell viability and survival. As a result, we demonstrated that PEG-GO cryogel can stimulate osteogenic differentiation under osteo-inductive condition and can enhance osteogenic phenotypes compared to the PEG cryogel group. All these data suggested that, GO could serve as an effective bio-functionalizing agent for hydrogels to control stem cell behaviors and lineage commitment.