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

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.