Antioxidant flavonoid-loaded nano-bioactive glass bone paste: in vitro apatite formation and flow behavior

Non-cement pastes in the form of injectable materials have gained considerable attention in non-invasive regenerative medicine. Different osteoconductive bioceramics have been used as the solid phase of these bone pastes. Mesoporous bioactive glass can be used as an alternative bioceramic for paste preparation because of its osteogenic qualities. Plant-derived osteogenic agents can also be used in paste formulation to improve osteogenesis; however, their side effects on physical and physicochemical properties should be investigated. In this study, nano-bioactive glass powder was synthesized by a sol-gel method, loaded with different amounts of quercetin (0, 100, 150, and 200 μM), an antioxidant flavonoid with osteogenesis capacity. The loaded powder was then homogenized with a mixture of hyaluronic acid and sodium alginate solution to form a paste. We subsequently evaluated the rheological behavior, injectability, washout resistance, and in vitro bioactivity of the quercetin-loaded pastes. The washout resistance was found to be more than 96% after 14 days of immersion in simulated body fluid (SBF) as well as tris-buffered and citric acid-buffered solutions at 25 °C and 37 °C. All pastes exhibited viscoelastic behavior, in which the elastic modulus exceeded the viscous modulus. The pastes displayed shear-thinning behavior, in which viscosity was more influenced by angular frequency when the quercetin content increased. Results indicated that injectability was much improved using quercetin and the injection force was in the range 20-150 N. Following 14 days of SBF soaking, the formation of a nano-structured apatite phase on the surfaces of quercetin-loaded pastes was confirmed through scanning electron microscopy, X-ray diffractometry, and Fourier-transform infrared spectroscopy. Overall, quercetin, an antioxidant flavonoid osteogenic agent, can be loaded onto the nano-bioactive glass/hyaluronic acid/sodium alginate paste system to enhance injectability, rheological properties, and bioactivity.