Liu Yumei, Shi Feng, Gong Kemeng, Liu Yang, Zhi Wei, Weng Jie, Qu Shuxin
Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
J Mater Sci Mater Med. 2017 Apr;28(4):56. doi: 10.1007/s10856-017-5865-z. Epub 2017 Feb 16.
The aim of this study was to investigate the in vitro release and the effect of RAW 264.7 macrophages of critical-sized wear particles of ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), one of the most effective drugs to treat osteoporosis in clinic. The critical-sized UHMWPE-ALN 0.5 wt.% wear particles were prepared by vacuum gradient filtration combined with Pluronic F-68. In vitro release of ALN from critical-sized UHMWPE-ALN wear particles was investigated in phosphate buffered saline (PBS) at 37 °C with a shaker. Cell morphology, proliferation, lactate dehydrogenase (LDH) leakage and secretions of cytokines were evaluated after co-cultured with critical-sized UHMWPE-ALN wear particles in vitro. Results showed that ALN released from critical-sized UHMWPE-ALN wear particles included burst release and slow release in vitro. Macrophages would be chemotaxis and aggregated around the critical-sized UHMWPE-ALN or UHMWPE wear particle, which was phagocytosed with time. The proliferation of macrophages co-cultured with critical-sized UHMWPE-ALN wear particles was significantly decreased compared with that of critical-sized UHMWPE group. Meanwhile, the critical-sized UHMWPE-ALN wear particles significantly induced the LDH leakage of macrophages, which indicated the cell death. The death of macrophages induced by ALN was one of pathways to inhibit their proliferation. The secretions of cytokines (interleukin-6 and tumor necrosis factor-alpha) in critical-sized UHMWPE-ALN group were significantly lower than those in critical-sized UHMWPE group due to the released ALN. The present results suggested that UHMWPE-ALN had the potential application in clinic to treat osteolysis induced by wear particles.
本研究的目的是研究载有阿仑膦酸钠（ALN，临床上治疗骨质疏松症最有效的药物之一）的超高分子量聚乙烯（UHMWPE）临界尺寸磨损颗粒的体外释放情况以及对RAW 264.7巨噬细胞的影响。通过真空梯度过滤结合普朗尼克F-68制备了临界尺寸的0.5 wt.% UHMWPE-ALN磨损颗粒。在37°C的磷酸盐缓冲盐水（PBS）中，使用振荡器研究了临界尺寸UHMWPE-ALN磨损颗粒中ALN的体外释放。在体外与临界尺寸UHMWPE-ALN磨损颗粒共培养后，评估细胞形态、增殖、乳酸脱氢酶（LDH）泄漏和细胞因子分泌情况。结果表明，临界尺寸UHMWPE-ALN磨损颗粒释放的ALN在体外包括突释和缓释。巨噬细胞会发生趋化作用并聚集在临界尺寸的UHMWPE-ALN或UHMWPE磨损颗粒周围，并随时间被吞噬。与临界尺寸UHMWPE组相比，与临界尺寸UHMWPE-ALN磨损颗粒共培养的巨噬细胞增殖显著降低。同时，临界尺寸UHMWPE-ALN磨损颗粒显著诱导巨噬细胞的LDH泄漏，这表明细胞死亡。ALN诱导的巨噬细胞死亡是抑制其增殖的途径之一。由于释放的ALN，临界尺寸UHMWPE-ALN组中细胞因子（白细胞介素-6和肿瘤坏死因子-α）的分泌显著低于临界尺寸UHMWPE组。目前的结果表明，UHMWPE-ALN在临床上有治疗磨损颗粒诱导的骨溶解的潜在应用价值。
