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Inhibition of aseptic loosening of artificial joints by graft polymerizaiton of a novel biocompatible polymer MPC

新型生物相容性聚合物MPC接枝聚合抑制人工关节无菌性松动

基本信息

批准号：
15390449
负责人：
TAKATORI Yoshio
金额：
$ 9.02万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390449/
关键词：
artificial joint aseptic loosening osteolysis biomaterial nanotechnology polymer

项目摘要

Despite improvements in techniques and materials, aseptic loosening of artificial hip joints remains as the most serious problem. This study investigated mechanical and biological effects of our original biocompatible phospholipid polymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) nano-graft onto artificial surface of polyethylene liner on prevention of aseptic loosening.To examine mechanical effects of MPC grafting of polyethylene liner, we performed hip simulator tests (3.0x10^6cycles) using cross-linked polyethylene (CL-PE) liners with or without nano-graft of MPC onto artificial surface (MPC liner/CL-PE liner) and PE liner. The friction torque was about 90% lower in MPC liners than control liners. Total amounts of wear produced from MPC liner was about 1/4 and 1/40 of those from GL-PE and PE liners, respectively. Three-dimensional morphometric analysis and SEM analysis of MPC liners revealed no or little wear. The effect of MPC grafting was maintained or pronounced … More after the test, because XPS analysis confirmed the remainder of the specific spectra of MPC on the liner surface.To examine biological responses of macrophages and osteoblasts, we prepared MPC nanoparticles (500nm). Using in vitro/vivo murine particle-induced osteolysis model, we examined biological effects of MPC nanoparticles on osteoclastogenesis. When nanoparticles were exposed to cultured mouse macrophages, MPC nanoparticles were hardly phagocytosed by macrophages and did not enhance the concentration of cytokines and PGE_2. Furthermore, the culture medium of macrophages exposed to MPC nanoparticles did not induce RANKL mRNA expression in osteoblasts and osteoclastogenesis from bone marrow cells. In vivo murine osteolysis model, particle-induced bone resorption was hardly observed in mice implanted MPC nanoparticles.Some medical devices grafted MPC onto its surface have been already used under authorization of the FDA. These results demonstrate that MPC polymer grafting decreases wear production and even if wear particles are produced, they are biologically inert, suggesting an epochal improvement of artificial hip joints preventing aseptic loosening. Less

尽管技术和材料有所改进，人工髋关节的无菌性松动仍然是最严重的问题。本研究研究了我们原创的由 2-甲基丙烯酰氧基乙基磷酰胆碱 (MPC) 纳米移植物组成的生物相容性磷脂聚合物在聚乙烯内衬人工表面上对防止无菌松动的机械和生物效应。为了检查聚乙烯内衬 MPC 移植的机械效果，我们进行了髋关节模拟器测试（3.0x10^6 次循环）使用交联聚乙烯 (CL-PE) 衬垫（带或不带 MPC 纳米接枝物到人造表面上）（MPC 衬垫/CL-PE 衬垫）和 PE 衬垫。 MPC 衬套中的摩擦扭矩比对照衬套低约 90%。 MPC 衬里产生的磨损总量分别约为 GL-PE 和 PE 衬里的 1/4 和 1/40。 MPC 衬里的三维形态分析和 SEM 分析显示没有磨损或磨损很小。测试后，MPC 接枝的效果得以维持或明显，因为 XPS 分析证实了 MPC 在内衬表面上剩余的特定光谱。为了检查巨噬细胞和成骨细胞的生物反应，我们制备了 MPC 纳米颗粒（500nm）。使用体外/体内小鼠颗粒诱导的骨溶解模型，我们检查了 MPC 纳米颗粒对破骨细胞生成的生物学效应。当纳米颗粒暴露于培养的小鼠巨噬细胞时，MPC纳米颗粒几乎不被巨噬细胞吞噬，并且不会增强细胞因子和PGE_2的浓度。此外，暴露于 MPC 纳米颗粒的巨噬细胞培养基不会诱导成骨细胞中 RANKL mRNA 的表达以及骨髓细胞的破骨细胞生成。在小鼠体内骨溶解模型中，植入MPC纳米颗粒的小鼠几乎没有观察到颗粒诱导的骨吸收。一些将MPC移植到其表面的医疗器械已经在FDA授权下使用。这些结果表明，MPC 聚合物接枝可减少磨损产生，即使产生磨损颗粒，它们也具有生物惰性，这表明人工髋关节在防止无菌性松动方面取得了划时代的改进。较少的