The applications of buckminsterfullerene C60 and derivatives in orthopaedic research

Abstract

Abstract Buckminsterfullerene C60 and derivatives have been extensively explored in biomedical research due to their unique structure and unparalleled physicochemical properties. C60 is characterized as a "free radical sponge" with an anti-oxidant efficacy several hundred-fold higher than conventional anti-oxidants. Also, the C60 core has a strong electron-attracting ability and numerous functional compounds with widely different properties can be added to this fullerene cage. This review focused on the applications of C60 and derivatives in orthopaedic research, such as the treatment of cartilage degeneration, bone destruction, intervertebral disc degeneration (IVDD), vertebral bone marrow disorder, radiculopathy, etc., as well as their toxicity in vitro and in vivo. We suggest that C60 and derivatives, especially the C60 cores coupled with functional groups presenting new biological and pharmacological activities, are advantageous in orthopaedic research and will be promising in clinical performance for musculoskeletal disorders treatment; however, the pharmacokinetics and toxicology of these agents as local/systemic administration need to be carefully determined.

Figure 1

The structure of buckminsterfullerene C₆₀.

Figure 2

Possible mechanisms under which C₆₀ acts as an efficient free radical scavenger. C₆₀ removes free radicals potentially by direct quenching of NO, neutralization of singlet oxygen, enzyme-like dismutation of superoxide radicals, as well as trapping and inactivation of hydroxyl radicals.

Figure 3

The strategy to treat cartilage degeneration with C₆₀ and derivatives. C₆₀ and derivatives enhance cellular chondrogenesis working as polyanionic substances and polyanionic substance concentrators, suppress cartilage inflammation by scavenging free radicals, and promote joint lubricity as a “molecular bearing”.

Figure 4

The strategy to treat bone destruction with C₆₀ and derivatives. C₆₀ and derivatives enhance osteogenesis by increasing osteogenic gene expression, and suppress osteoclastogenesis through inhibition of receptor activator of NFκB (RANK)-RANK ligand (RANKL) signaling pathway by direct removal of ROS as well as suppressing the production of proinflammatory cytokines.

Figure 5

The general strategy to treat IVDD, vertebral bone marrow lesion and radiculopathy, with C₆₀ and derivatives, against low back pain. The “free radical sponge” C₆₀ and derivatives suppress disc tissue inflammation, promote disc tissue regeneration, prevent vertebral bone marrow edema and fatty degeneration and inhibit DRG inflammatory responses under high oxidative stress.