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 coprecipitation, 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-MNSHA. 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, AnMNS-HA with high biological compatibility, antibacterial activity and induction of ossification, has a good ability to accelerate and repair bone defects.

Automated summary

The study utilized An-MNS-HA nanomaterial to effectively reduce bacterial infection and increase proliferation and differentiation of human primary osteoblasts cells. This nanomaterial displayed antibacterial activity, low toxicity, and ability to induce ossification, showing promise for accelerating bone fracture healing and repair of bone defects.