After bone tumor resection, the large bony deficits are commonly reconstructed with Ti‐based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant‐relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma‐induced acidic condition, naringin and Zn²⁺ can be released easily from the functional Ti substrate. The anti‐osteosarcoma and antibacterial assay showed the delivered naringin and Zn²⁺ can induce a remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos‐2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal‐regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti‐based implants for the reconstruction of large bony after osteosarcoma resection.

中文翻译：

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具有 pH 响应性柚皮苷-ZnO 纳米颗粒的 Ti 基底的功能化，用于骨肉瘤切除术后大骨的重建。

骨肿瘤切除后，大的骨缺损通常用钛基金属假体重建，可提供即时稳定的固定，并允许早期下地和负重。然而，当用于骨肉瘤切除术时，钛种植体相关感染和肿瘤复发被认为是种植失败的两个关键因素。因此，在这项工作中，制备了一种用柚皮苷装饰的新型氧化锌纳米颗粒并将其固定在钛基底上。药物递送曲线证明，在骨肉瘤诱导的酸性条件下的细菌感染和 Warburg 效应中，柚皮苷和 Zn ²⁺可以很容易地从功能性钛基质中释放出来。抗骨肉瘤和抗菌试验显示传递的柚皮苷和 Zn ²⁺可以诱导细菌（大肠杆菌和金黄色葡萄球菌）的氧化应激显着增加) 和骨肉瘤 (Saos-2 细胞) 通过产生活性氧 (ROS)。ROS 的积累导致细菌生物膜和细菌膜的损伤，导致细菌 RNA 和 DNA 的泄漏。同时，ROS的增加通过激活ROS/细胞外信号调节激酶信号通路诱导骨肉瘤细胞凋亡。此外，体外细胞实验，包括细胞活力、碱性磷酸酶活性、胶原蛋白分泌、细胞外基质矿化水平，表明功能性钛底物对成骨细胞增殖和分化具有巨大潜力。因此，本研究为开发多功能钛基植入物用于骨肉瘤切除术后大骨的重建提供了一种简单而有前景的策略。