制备具有抗菌和骨传导性能的 3D 打印 PLGA/Cu(I)@ZIF-8 纳米复合材料支架，用于感染性骨修复。
Preparation of antibacterial and osteoconductive 3D-printed PLGA/Cu(I)@ZIF-8 nanocomposite scaffolds for infected bone repair.
机构信息
Department of Orthopaedics, Huashan Hospital, Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai, 200040, China.
出版信息
J Nanobiotechnology. 2020 Feb 27;18(1):39. doi: 10.1186/s12951-020-00594-6.
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 HO, 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.
背景
修复大骨缺损是临床实践中的一大挑战。在本研究中，采用铜负载 ZIF-8 纳米粒子和聚乳酸-羟基乙酸共聚物（PLGA），结合三维打印技术制备多孔 PLGA/Cu（I）@ZIF-8 支架，用于感染性骨修复。
方法
通过透射电子显微镜和扫描电子显微镜观察 PLGA/Cu（I）@ZIF-8 支架的表面形态。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（MSCs）共培养，以探索其生物相容性和骨诱导性能。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%，具有良好的机械性能。当与 HO 孵育时，Cu（I）@ZIF-8 纳米粒子产生了活性氧，这有助于其抗菌性能。在 PLGA/Cu（I）@ZIF-8 支架表面培养的 mMSCs 铺展良好，贴壁且增殖率高，碱性磷酸酶和茜素红染色较纯 PLGA 支架增加。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，培养在 PLGA/Cu（I）@ZIF-8 支架上的金黄色葡萄球菌几乎全部死亡，而在体内感染大鼠植入 PLGA/Cu@ZIF-8 支架后，炎性细胞浸润和细菌数量明显减少。
结论
所有这些发现表明，PLGA/Cu（I）@ZIF-8 支架具有优异的抗菌和骨诱导性能，以及良好的生物相容性和高生物活性。本研究表明，PLGA/Cu（I）@ZIF-8 支架可作为骨组织工程的一种有前途的生物材料，特别是用于感染性骨修复。
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