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Impact of simulated biological aging on physicochemical and biocompatibility properties of cyclic olefin copolymers

机译:模拟生物老化对环烯烃共聚物理化和生物相容性的影响

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We study the effect of simulated biological aging on the properties of cyclic olefin copolymers and particularly their biocompatibility. Already reported as biocompatible polymers according to ISO/EN 10993 guidelines, COC are good candidates for medical devices. The influence of two major additives (antioxidants and lubricants) was investigated and comparison with non-aging COC was done.Four in vitro simulated biological conditions were tested: 2 extreme pH (1 and 9) to simulate digestive tract environment; THP-1-derived macrophages contact and pro-oxidant medium with hypochlorite solution simulating the oxidative attack during the foreign body reaction. After one month of incubation with the different media at 37 degrees C, surface topography was studied by atomic force microscopy (AFM) and IR spectroscopy. Extracts of incubated media were also analysed in chromatography to investigate potential degradation products. Cytotoxicity (MTT and LDH) of the materials was evaluated using cell culture methods with L929 fibroblasts. Oxidative stress (ROS and SOD analysis) and two inflammatory biomarkers (Il-6 and TNF-alpha secretion) were explored on THP-1-derived macrophages in direct contact with aged COC.Surface topography of COC was modified by aging conditions with an influence of antioxidant presence and under some conditions. HPLC analysis realized on freeze-dried solutions issued from the different incubations showed the presence of traces of low molecular weight compounds issued from polyphenolic antioxidant and from COC degradation. GC MS analysis carried out directly on the different incubated COC, showed no detectable leachable molecules.No cytotoxicity has been observed with the different aged COC. However, results show that the pH environment had an influence on the cytotoxicity tests with a protecting effect of antioxidant presence; and pro oxidant incubating conditions decreased cellular viability on COC. pH 1 and pH 9 conditions also induced an increase of ROS production which was partially reduced for COC containing an antioxidant or a lubricant. Il-6 production was globally more important for aged COC compared with basal condition and particularly for oxidative simulated environment.Those results indicate that physiological factors like pH or oxidant conditions have an impact on surface topography and on COC interaction with the biological environment but without compromising their biocompatibility. Antioxidant or lubricant presence could modulate these variations pointing out the necessity of a thoroughly investigation for biocompatibility assessment of COC as a component of implantable devices. COCs show a good biocompatibility even after accelerated aging under extreme biological conditions.
机译:我们研究了模拟生物老化对环烯烃共聚物性能,特别是其生物相容性的影响。根据ISO / EN 10993指南,COC已经被报告为生物相容性聚合物,它是医疗器械的理想选择。研究了两种主要添加剂(抗氧化剂和润滑剂)的影响,并与未老化的COC进行了比较。测试了四种体外模拟的生物学条件:2个极端pH(1和9)以模拟消化道环境; THP-1衍生的巨噬细胞与次氯酸盐溶液接触促氧化剂介质,模拟异物反应过程中的氧化攻击。在37摄氏度下与其他培养基孵育一个月后,通过原子力显微镜(AFM)和红外光谱研究了表面形貌。还对孵育培养基的提取物进行了色谱分析,以研究潜在的降解产物。使用具有L929成纤维细胞的细胞培养方法评估了材料的细胞毒性(MTT和LDH)。在与老化的COC直接接触的THP-1来源的巨噬细胞上探索了氧化应激(ROS和SOD分析)和两个炎性生物标志物(Il-6和TNF-α分泌).COC的表面形貌因老化条件而受到影响在某些条件下抗氧化剂的存在对来自不同孵育过程的冻干溶液进行的HPLC分析表明,存在痕量的多酚类抗氧化剂和COC降解产生的低分子量化合物。直接在不同的温育COC上进行的GC MS分析表明,没有可检测到的可浸出分子。但是,结果表明,pH环境对细胞毒性测试有影响,并具有抗氧化剂的保护作用。和促氧化剂孵育条件会降低细胞对COC的活力。 pH 1和pH 9条件也引起ROS产生的增加,对于含有抗氧化剂或润滑剂的COC,ROS产生的部分减少。与基础条件相比,Il-6的产生对于老化的COC而言在全球范围内更为重要,尤其是对于氧化模拟环境而言。它们的生物相容性。抗氧化剂或润滑剂的存在可能会调节这些变化,从而指出了对彻底调查COC作为可植入设备的组成部分进行生物相容性评估的必要性。即使在极端生物学条件下加速老化后,COC仍具有良好的生物相容性。

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