BACKGROUND The repair of large bone defects is a great challenge in clinical practice. In this study, copper-loaded-ZIF-8 nanoparticles and poly (lactide-co-glycolide) (PLGA) were combined to fabricate porous PLGA/Cu(I)@ZIF-8 scaffolds using three-dimensional printing technology for infected bone repair. METHODS The surface morphology of PLGA/Cu(I)@ZIF-8 scaffolds was investigated by transmission electron microscopy and scanning electron microscopy. The PLGA/Cu(I)@ZIF-8 scaffolds were co-cultured with bacteria to determine their antibacterial properties, and with murine mesenchymal stem cells (MSCs) to explore their biocompatibility and osteoconductive properties. The bioactivity of the PLGA/Cu(I)@ZIF-8 scaffolds was evaluated by incubating in simulated body fluid. RESULTS The results revealed that the PLGA/Cu(I)@ZIF-8 scaffolds had porosities of 80.04 ± 5.6% and exhibited good mechanical properties. When incubated with H2O2, Cu(I)@ZIF-8 nanoparticles resulted generated reactive oxygen species, which contributed to their antibacterial properties. The mMSCs cultured on the surface of PLGA/Cu(I)@ZIF-8 scaffolds were well-spread and adherent with a high proliferation rate, and staining with alkaline phosphatase and alizarin red was increased compared with the pure PLGA scaffolds. The mineralization assay showed an apatite-rich layer was formed on the surface of PLGA/Cu(I)@ZIF-8 scaffolds, while there was hardly any apatite on the surface of the PLGA scaffolds. Additionally, in vitro, Staphylococcus aureus cultured on the PLGA/Cu(I)@ZIF-8 scaffolds were almost all dead, while in vivo inflammatory cell infiltration and bacteria numbers were dramatically reduced in infected rats implanted with PLGA/Cu@ZIF-8 scaffolds. CONCLUSION All these findings demonstrate that PLGA/Cu(I)@ZIF-8 scaffolds possess excellent antibacterial and osteoconductive properties, as well as good biocompatibility and high bioactivity. This study suggests that the PLGA/Cu(I)@ZIF-8 scaffolds could be used as a promising biomaterial for bone tissue engineering, especially for infected bone repair.

中文翻译：

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抗菌和骨传导性3D打印PLGA / Cu（I）@ ZIF-8纳米复合支架的制备，用于感染的骨修复。

背景技术大骨缺损的修复是临床实践中的巨大挑战。在这项研究中，载有铜的ZIF-8纳米颗粒和聚丙交酯-乙交酯共聚物（PLGA）结合使用三维印刷技术制造多孔PLGA / Cu（I）@ ZIF-8支架，用于感染的骨修复。方法采用透射电子显微镜和扫描电子显微镜研究PLGA / Cu（I）@ ZIF-8支架的表面形貌。将PLGA / Cu（I）@ ZIF-8支架与细菌共培养以确定其抗菌性能，并与鼠间充质干细胞（MSC）共培养以探索其生物相容性和骨传导特性。通过在模拟体液中孵育来评估PLGA / Cu（I）@ ZIF-8支架的生物活性。结果结果表明，PLGA / Cu（I）@ ZIF-8支架的孔隙率为80.04±5.6％，并具有良好的机械性能。当与过氧化氢一起孵育时，Cu（I）@ ZIF-8纳米颗粒产生了活性氧，这有助于它们的抗菌性能。与纯PLGA支架相比，在PLGA / Cu（I）@ ZIF-8支架表面上培养的mMSC可以很好地扩散和粘附，并具有较高的增殖速率，并且碱性磷酸酶和茜素红的染色增加。矿化试验表明，PLGA / Cu（I）@ ZIF-8支架表面形成了富含磷灰石的层，而PLGA支架表面几乎没有磷灰石。此外，在体外，在PLGA / Cu（I）@ ZIF-8支架上培养的金黄色葡萄球菌几乎全部死亡，而植入PLGA / Cu @ ZIF-8支架的受感染大鼠体内的炎性细胞浸润和细菌数量显着减少。结论所有这些发现表明PLGA / Cu（I）@ ZIF-8支架具有出色的抗菌和骨传导特性，以及良好的生物相容性和高生物活性。这项研究表明PLGA / Cu（I）@ ZIF-8支架可用作骨组织工程，尤其是感染的骨修复的有前途的生物材料。