Abstract

Background: Malignant bone tumors usually occur in young people and have a high mortality and disability rate. Surgical excision commonly results in residual bone tumor cells and large bone defects, and conventional radiotherapy and chemotherapy may cause significant side effects. In this study, a bifunctional Bi-BG scaffold for near-infrared (NIR)-activated photothermal ablation of bone tumors and enhanced bone defect regeneration is fabricated. Methods: In this study, we prepared the Bi-BG scaffold by in-situ generation of NIR-absorbing Bi coating on the surface of a 3D-printing bioactive glass (BG) scaffold. SEM was used to analyze the morphological changes of the scaffolds. In addition, the temperature variation was imaged and recorded under 808nm NIR laser irradiation in real time by an infrared thermal imaging system. Then, the proliferation of rat bone mesenchymal stem cells (rBMSCs) and Saos-2 on the scaffolds was examined by CCK-8 assay. ALP activity assay and RT-PCR were performed to test the osteogenic capacity. For in vivo experiments, the nude rat tumor-forming and rat calvarial defect models were established. At 8weeks after surgery, micro-CT, and histological staining were performed on harvested calvarial samples. Results: The Bi-BG scaffolds have outstanding photothermal performance under the irradiation of 808nm NIR at different power densities, while no photothermal effects are observed for pure BG scaffolds. The photothermal temperature of the Bi-BG scaffold can be effectively regulated in the range 26-100°C by controlling the NIR power density and irradiation duration. Bi-BG scaffolds not only significantly induces more than 95% of osteosarcoma cell death (Saos-2) in vitro, but also effectively inhibit the growth of bone tumors in vivo. Furthermore, they exhibit excellent capability in promoting osteogenic differentiation of rBMSCs and finally enhance new bone formation in the calvarial defects of rats. Conclusion: The Bi-BG scaffolds have bifunctional properties of photothermal antitumor therapy and bone regeneration, which offers an effective method to ablate malignant bone tumors based on photothermal effect.

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