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

尽管人工髋关节的技术和材料不断改进，但无菌性松动仍是最严重的问题。本研究探讨了我们原创的生物相容性磷脂聚合物（由2-甲基丙烯酰氧乙基磷酸胆碱（MPC）纳米接枝物组成）在聚乙烯内衬人工表面上预防无菌性松动的力学和生物学效应。我们使用交联聚乙烯（CL-PE）内衬进行髋关节模拟器测试（3.0 × 10^6次循环），在人工表面（MPC内衬/CL-PE内衬）和PE内衬上有或没有MPC纳米移植物。MPC内衬的摩擦扭矩比对照内衬低约90%。MPC内衬产生的磨损总量分别约为GL-PE和PE内衬的1/4和1/40。MPC内衬的三维形态测量分析和SEM分析显示没有磨损或磨损很小。MPC接枝的效果保持或显著 ...更多信息 为了检测巨噬细胞和成骨细胞的生物学反应，我们制备了MPC纳米颗粒（500 nm）。使用体外/体内小鼠颗粒诱导的骨溶解模型，我们研究了MPC纳米颗粒对破骨细胞生成的生物学效应。当MPC纳米粒暴露于培养的小鼠巨噬细胞时，MPC纳米粒几乎不被巨噬细胞吞噬，并且不增加细胞因子和PGE_2的浓度。此外，暴露于MPC纳米颗粒的巨噬细胞的培养基未诱导成骨细胞中RANKL mRNA表达和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，在其表面接枝MPC的一些医疗器械已经在FDA的授权下使用。这些结果表明，MPC聚合物接枝减少了磨损的产生，即使产生磨损颗粒，它们也是生物惰性的，这表明人工髋关节在预防无菌性松动方面取得了划时代的进步。少

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