A bifunctional zoledronate sustained-release system in scaffold: Tumor therapy and bone repair

Abstract

It is of great challenges to repair bone defect and prevent tumor recurrence in bone tumors postoperative treatment. Bone scaffolds loaded with zoledronate (ZOL) are expected to solve these issues due to its osteogenesis and anti-tumor ability. Furthermore, ZOL needs to be sustained release to meet the requirement of long-term therapy. In this study, ZOL was loaded into amination functionalized mesoporous silicon (SBA15NH2), and then incorporated into poly (L-lactic acid) to prepare PLLA/SBA15NH2-ZOL scaffold via selective laser sintering technology. On one hand, ZOL of local release not only can inhibit growth and proliferation of bone tumor cells but also inhibit osteoclast differentiation through competitive binding of receptor activator of nuclear factor (NF)-kB (RANK) in osteoclast precursors. On the other hand, amination function could change the surface charge of mesoporous silica to positive charge to enhance the absorption of ZOL, mesoporous structure and abundant amino groups of SBA15NH2 play a barrier role and form hydrogen bond with phosphate groups of ZOL, respectively, thereby achieving its sustained release. The results showed that the loading amount of ZOL was 236.53 mg/g, and the scaffold could sustainedly release ZOL for more than 6 weeks. The scaffold inhibited proliferation of osteosarcoma cells through inducing apoptosis and cell cycle arrest. TRAP staining and F-actin ring formation experiment showed the scaffold inhibited differentiation and mature of osteoclast. Pit formation assay indicated that bone resorption activity was inhibited strongly.