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用于减轻无菌性骨溶解的双金属金属有机框架

Bimetallic Metal-Organic Framework for Mitigating Aseptic Osteolysis.

作者信息

Pan Huajun, Miao Xinxin, Deng Jianjian, Pan Chongzhi, Cheng Xigao, Wang Xiaolei

机构信息

Department of Orthopedics, the Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi330006, P. R. China.

National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi330088, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2023 Feb 1;15(4):4935-4946. doi: 10.1021/acsami.2c19449. Epub 2023 Jan 19.

Abstract

The disability rate of joint diseases can be reduced by the use of artificial joints, but joint loosening at a late state limits the lifespan and surgical efficacy of the joints. Wear particles can be recognized by macrophages and induce cells to produce reactive oxygen species (ROS) and inflammatory factors, causing persistent inflammation and decreased osteogenic activity, which ultimately leads to loosening of joint prostheses. Here, the platinum (Pt) nanozymes with excellent ROS scavenging and anti-inflammatory capabilities were encapsulated in zinc imidazolium zeolite framework-8 (ZIF-8), and then the osteogenic active element lanthanum (La) was introduced through ion exchange to finally construct a bimetallic metal-organic framework (Pt@ZIF-8@La). and experiments demonstrated that this multifunctional nanoplatform possessed the functions of efficient scavenging of ROS, immune regulation, and promotion of osteogenic differentiation. Meanwhile, the mechanism is explored that Pt@ZIF-8@La can also promote osteogenic mineralization by upregulating the ratio of the osteoprotegerin (OPG)/receptor activator of the NF-κB ligand (RANKL), which can achieve a synergistic therapeutic effect of immunomodulation and osteogenesis, thereby realizing the purpose of relieving aseptic osteolysis.

摘要

人工关节的使用可降低关节疾病的致残率,但晚期关节松动限制了关节的使用寿命和手术疗效。磨损颗粒可被巨噬细胞识别并诱导细胞产生活性氧(ROS)和炎性因子,导致持续性炎症和骨生成活性降低,最终导致关节假体松动。在此,将具有优异ROS清除和抗炎能力的铂(Pt)纳米酶封装在咪唑锌沸石骨架-8(ZIF-8)中,然后通过离子交换引入成骨活性元素镧(La),最终构建双金属金属有机框架(Pt@ZIF-8@La)。实验表明,这种多功能纳米平台具有高效清除ROS、免疫调节和促进成骨分化的功能。同时,探究了Pt@ZIF-8@La还可通过上调骨保护素(OPG)/核因子κB受体激活因子配体(RANKL)的比值促进成骨矿化,从而实现免疫调节与成骨的协同治疗效果,进而实现缓解无菌性骨溶解的目的。

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