Osteoinductive and antimicrobial mechanisms of graphene-based materials for enhancing bone tissue engineering.

Graphene-based materials (GMs) have great application prospects in bone tissue engineering due to their osteoinductive ability and antimicrobial activity. GMs induce osteogenic differentiation through several mechanisms and pathways in bone tissue engineering. First of all, the surface and high hardness of the porous folds of graphene or graphene oxide (GO) can generate mechanical stimulation to initiate a cascade of reactions that promote osteogenic differentiation without any chemical inducers. In addition, change of the extracellular matrix (ECM), regulation of macrophage polarization, the oncostatin M (OSM) signaling pathway, the MAPK signaling pathway, the BMP signaling pathway, the Wnt/β-catenin signaling pathway, and other pathways are involved in GMs' regulation of osteogenesis. In bone tissue engineering, GMs prevent the formation of microbial biofilms mainly through preventing microbial adhesion and killing them. The former is mainly achieved by reducing surface free energy (SFE) and increasing hydrophobicity. The latter mainly includes oxidative stress and photothermal/photodynamic effects. Graphene and its derivatives (GDs) are mainly combined with bioactive ceramic materials, metal materials and macromolecular polymers to play an antimicrobial effect in bone tissue engineering. Concentration, number of layers, and type of GDs often affect the antimicrobial activity of GMs. In this paper, we reviewed relevant osteoinductive and antimicrobial mechanisms of GMs and their applications in bone tissue engineering.