Graphene-Based Nanomaterials as Bioactive Agents and Drug Delivery Systems for Bone Tissue Engineering.

Graphene-based nanomaterials (GBNs), such as graphene oxide and reduced graphene oxide, have been considered as promising functional materials for bone tissue engineering due largely to their intrinsic biological functions and great drug delivery capacity. As bioactive materials, GBNs possess antibacterial activity, photothermal effect, and the ability to regulate immune microenvironment and osteogenesis-related signaling pathways such as Wnt/β-catenin, MAPK, and BMP/Smad. As drug delivery systems, the large surface area and multiple functionalization sites allow GBNs to have great potential in loading and delivering various active agents, such as drugs, genes, and growth factors. Based on these properties, GBNs prevent infections, facilitate stem cell adhesion, proliferation, and osteogenic differentiation, and ultimately promote bone regeneration. In the past few years, reports regarding the applications of GBNs in bone tissue engineering have been well documented, but the clinical translation is still limited. Herein, on the basis of the two major roles of GBNs (bioactive agents and drug delivery systems), we aim to provide a comprehensive understanding of the multiple functions and mechanisms of GBNs in promoting bone tissue regeneration. The progress and challenges in clinical translation are also discussed.