<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

Abstract

During continuous innovation in the preparation, characterization and application of various bone repair materials for several decades, nanomaterials have exhibited many unique advantages. As a kind of representative two-dimensional nanomaterials, graphene and its derivatives (GDs) such as graphene oxide and reduced graphene oxide have shown promising potential for the application in bone repair based on their excellent mechanical properties, electrical conductivity, large specific surface area (SSA) and atomic structure stability. Herein, we reviewed the updated application of them in bone repair in order to present, as comprehensively, as possible, their specific advantages, challenges and current solutions. Firstly, how their advantages have been utilized in bone repair materials with improved bone formation ability was discussed. Especially, the effects of further functionalization or modification were emphasized. Then, the signaling pathways involved in GDs-induced osteogenic differentiation of stem cells and immunomodulatory mechanism of GDs-induced bone regeneration were discussed. On the other hand, their applications as contrast agents in the field of bone repair were summarized. In addition, we also reviewed the progress and related principles of the effects of GDs parameters on cytotoxicity and residues. At last, the future research was prospected.

Applications of Ceramic/Graphene Composites and Hybrids

“…Composite structures shaped either as 3D porous scaffolds, 2D planar coatings or barrier membranes have been developed ( Figure 16 ) to enhance the bone volume in bone defect zones [ 234 ]. The potential of graphene and GRM for the differentiation of various types of stem cells has captured remarkable attention [ 228 ]; actually, this ability has been ascribed to its peculiar noncovalent binding to different biomolecules that allows GRM to behave as pre-concentration platforms for osteogenic inducers, accelerating the differentiation of hMSC (Human Mesenchymal Stem Cells) into osteogenic cells.…”

“…Reinforcement has been observed also in printed bioactive glass scaffolds containing rGO [ 237 ]. In addition to BTE applications, graphene-based composites may be applied as the contrast agent in vivo imaging for real-time detection of the bone repair process, detecting structural changes, tumorigenicity, degradation and mineralization of the bone repair materials in complex environments (see review [ 234 ]).…”

“… Scheme showing the possible role of graphene-based materials (GDs) in BTE applications. Reprinted from reference [ 234 ]. …”

Biological Characterization of Polymeric Matrix and Graphene Oxide Biocomposites Filaments for Biomedical Implant Applications: A Preliminary Report

“…Recently, in order to improve these problems, carbon nanostructures such as graphene (Gr) and graphene oxide (GO) are providing new perspectives for TE. These can be applied in drugs and genes delivery of, as well as in the articular repair and bone defects [ 3 , 7 , 8 , 9 , 10 ] due to their physical characteristics such as mechanical strength, flexibility, elasticity [ 11 ], low density [ 12 ], structural support, self-lubricating properties and anti-wear due to its laminar structure which supports in the surface lubrication. Furthermore, these can be applied to mediate cell proliferation, differentiation and migration and improve the bone repair effect [ 7 , 13 , 14 , 15 , 16 ].…”

“…These can be applied in drugs and genes delivery of, as well as in the articular repair and bone defects [ 3 , 7 , 8 , 9 , 10 ] due to their physical characteristics such as mechanical strength, flexibility, elasticity [ 11 ], low density [ 12 ], structural support, self-lubricating properties and anti-wear due to its laminar structure which supports in the surface lubrication. Furthermore, these can be applied to mediate cell proliferation, differentiation and migration and improve the bone repair effect [ 7 , 13 , 14 , 15 , 16 ]. Additionally, GO plays an important role in stimulating cell functions and guiding tissue regeneration, as presented by Du et al [ 7 ], comparatively showing the osteogenic capacity of treated multiple-wall carbon nanotubes (MCNTs) and the inorganic component of natural bone.…”