Sequential alendronate delivery by hydroxyapatite-coated maghemite for enhanced bone fracture healing

Accelerating the healing of bone fractures in the presence of infection is a serious challenge that has increased hopes for reducing this challenge by using nanotechnology. This study tried to effectively reduce bacterial infection by producing alendronate (An)-maghemite nanosphere-hydroxyapatite (An-MNS-HA) through co-precipitation, in addition to increasing the rate of proliferation and differentiation of human primary osteoblasts cells. After production of An-MNS-HA, their physicochemical properties were investigated by TEM, DLS and FTIR methods as well as the level of An release. The toxicity of An-MNS-HA was determined by MTT assay and the antibacterial activities of An-MNS-HA were also performed on both Gram-negative and Gram-positive bacteria. In addition, cell differentiation markers including ALP, OC, ODF, OPG and RANKL genes were analyzed by real time PCR technique. The results revealed that An-MNS-HA is spherical with a rough surface with a size of around 105.5 ± 2.08 nm. Also, DLS and FTIR results confirmed the potential loading of HA and An on MNS with a drug loading efficiency of 55.39 ± 4.68% and a drug release rate of 80.93 ± 5.28% from An-MNS-HA. The antibacterial activity of An-MNS-HA on both Gram-negative and Gram-positive bacteria exhibited a significant reduction in infection, despite a greater effect on Gram-negative bacteria. Also, cell proliferation and differentiation in the presence of An-MNS-HA were observed which were associated with an increase in the expression of the ALP, OC, ODF and OPG mRNA as well as decreased expression of RANKL gene. Finally, An-MNS-HA with high biological compatibility, antibacterial activity and induction of ossification, has a good ability to accelerate and repair bone defects.