Incorporating the Antioxidant Fullerenol into Calcium Phosphate Bone Cements Increases Cellular Osteogenesis without Compromising Physical Cement Characteristics

Abstract

Herein, fullerenol (Ful), a highly water‐soluble derivative of C60 fullerene with demonstrated antioxidant activity, is incorporated into calcium phosphate cements (CPCs) to enhance their osteogenic ability. CPCs with added carboxymethyl cellulose/gelatin (CMC/Gel) are doped with biocompatible Ful particles at concentrations of 0.02, 0.04, and 0.1 wt v%−1 and evaluated for Ful‐mediated mechanical performance, antioxidant activity, and in vitro cellular osteogenesis. CMC/gel cements with the highest Ful concentration decrease setting times due to increased hydrogen bonding from Ful's hydroxyl groups. In vitro studies of reactive oxygen species (ROS) scavenging with CMC/gel cements demonstrate potent antioxidant activity with Ful incorporation and cement scavenging capacity is highest for 0.02 and 0.04 wt v%−1 Ful. In vitro cytotoxicity studies reveal that 0.02 and 0.04 wt v%−1 Ful cements also protect cellular viability. Finally, increase of alkaline phosphatase (ALP) activity and expression of runt‐related transcription factor 2 (Runx2) in MC3T3‐E1 preosteoblast cells treated with low‐dose Ful cements demonstrate Ful‐mediated osteogenic differentiation. These results strongly indicate that the osteogenic abilities of Ful‐loaded cements are correlated with their antioxidant activity levels. Overall, this study demonstrates exciting potential of Fullerenol as an antioxidant and proosteogenic additive for improving the performance of calcium phosphate cements in bone reconstruction procedures.

Calcium Orthophosphate (CaPO4) Containing Composites for Biomedical Applications: Formulations, Properties, and Applications

“…Unfortunately, self-hardening CaPO 4 formulations with ceramic properties become brittle after setting, while the hardening time may not be suitable for clinical procedures [478]. Therefore, several attempts have been made to transform them into biocomposites to improve their properties, for example, by adding PEG [479,480], polylactide [481], PLGA [482], gelatin [414,[483][484][485][486], osteocalcin/collagen [487], alginic acid [488], chitin [489], chitosan [451,490], fibrin glue [491], silk fibroin [492,493], silanized HPMC [494], CMC [495], PVA fibers with CMC [496] and without CMC [497], CMC/gelatin/fullerenol [498], bioactive glass [499][500][501][502], bioactive glass functionalized with hypoxia conditioned medium [503], calcium silicate [504][505][506], cockle shell powders [507], metals [508], magnetic nanoparticles [509], and so on. Light-curing formulations have also been prepared [510,511].…”

“…To conclude the carbon issue, carbon fibers of very small sizes [1113][1114][1115], as well as diamonds [1116,1117], graphene and graphene oxide [171,177,178,197,689,885,1118,1119], fullerenes [848] and their derivatives [498,1120], carbon quantum dots [672,673], and other allotropes of the nanosized carbons were used to reinforce the CaPO 4 bioceramics [1092]. More complicated multicomponent formulations, such as HA nanobelts/carbon nanotubes constructed into carbon fiber/DCPA/epoxy biocomposites, have been developed as well [1121].…”