Induction of Bone Remodeling by Raloxifene-Doped Iron Oxide Functionalized with Hydroxyapatite to Accelerate Fracture Healing

Abstract

Repairing fractures in the presence of infection is a major challenge that is currently declining using nanotechnology. By producing iron oxide nanoparticles (NPs) containing hydroxyapatite and Raloxifene (R-IONPs-HA), this study tries to target drug delivery, control infection and promotion of the cells proliferation/differentiation to repair damaged tissue. After the production of R-IONPs-HA through co-precipitation, the physicochemical features of the NPs were considered by SEM, TEM, DLS and XRD methods, and the possibility of drug release. The effect of R-IONPs-HA on MC3T3-E1 cell proliferation/differentiation was determined by CCK-assay and microscopic observations. Also, Gram-negative and -positive bacteria were applied to evaluate the antibacterial activity. Finally, cell differentiation biomarkers like an ALP, OCN, and RUNX-2 genes were examined by real time (RT)-PCR. The results showed that R-IONPs-HA was spherical with dimensions of 98.1 ± 1.17 nm. In addition, the results of Zeta and XRD confirmed the loading HA and R on IONPs. Also, the release rate of R and HA in 64 h with pH 6 reached 61.4 and 30.4%, respectively. The anti-bacterial activity of R-IONPs-HA on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacteria showed a significant reduction in infection. Also, MC3T3-E1 cells showed greater proliferation and differentiation by R-IONPs-HA compared to other groups. Increased expression of ossification genes such as OCN, and RUNX-2 confirmed this claim. Finally, R-IONPs-HA with good biocompatibility, antibacterial activity and ossification induction has great potential to repair bone fractures and prevent infection.