Research progress on graphene and its derivatives modulating the bone regeneration microenvironment

Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.