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Bifunctional Borate Bioactive Glass (B-BG) Spontaneously Inhibits Bone Tumor and Time-Sequentially Promotes Bone
Renxian Wang1, Songxia Xia2,3, Zhuoyu Li4
1JST sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Abstract:
Post-operative treatment of bone tumors faces a critical clinical dilemma: the need to simultaneously inhibit the tumor while promoting bone regeneration. For this purpose, a multifunctional borate bioactive glass (B-BG) with dynamic pH was designed. In vitro studies indicated, within 2 days, a significant increase in pH up to ∼8.3 was generated to inhibit tumor cells. In the meantime, the increase of surrounding pH generated the formation of apatite-like minerals on the glass surface due to higher supersaturation with respect to hydroxyapatite, thus slow down the degradation rate of B-BG to generate the second stage, a moderate pH range between 7.5 and 8.0, thus increasing the expression of angiogenic genes in HUVECs at 2 days to 2 weeks, and then osteogenic genes in hADSCs after 2 weeks. Such results were further confirmed by implanting B-BG in a mouse CDX osteosarcoma model, a rabbit tumor metastatic model, and a rabbit femoral condyle defect model. The intelligence of such composition indicates the ability to spontaneously meet the surrounding environment respectively tumor inhibition and bone formation. In summary, multifunctional borate bioactive glass (B-BG) may provide a promising strategy for the treatment of bone tumors and the repair of bone defects.
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