Tantalum (Ta) is gaining attention as a biomaterial in bone tissue engineering. Although the clinical advantage of Ta-based implants for primary and revision total joint replacement (TJA) has been well documented, few studies investigated the effect of wear products of Ta implants on peri-implant cells, and their potential contribution to aseptic implant loosening. This study is aimed at examining the cytotoxicity, oxidative stress, and proinflammatory potential of Ta and TiO₂ nanoparticles (NPs) on macrophages in vitro. NPs were characterized using scanning electron microscopy, dynamic light scattering, and energy-dispersive X-ray. To test the NP-mediated cellular response in macrophages, THP-1-derived macrophages were challenged with both NPs, and cytotoxicity was analyzed using CCK-8 and LDH assays. Flow cytometry was used to investigate particle uptake and their internalization routes. NP-mediated oxidative stress was investigated by measuring the production of reactive oxygen species, and their proinflammatory potential was determined by quantifying the production of TNFα and IL-1β in cell culture supernatants using ELISA. We found that both Ta and TiO₂ NPs were taken up through actin-dependent phagocytosis, although TiO₂ NPs did also show some involvement of macropinocytosis and clathrin-mediated endocytosis. Ta NPs caused no apparent toxicity, while TiO₂ NPs demonstrated significant cytotoxicity at a concentration of over 100μg/mL at 24 h. Ta NPs induced negligible ROS generation and proinflammatory cytokines (TNFα, IL-1β) in macrophages. In contrast, TiO₂ NPs markedly induced these effects in a dose-dependent manner. Our findings indicate that Ta NPs are inert, nontoxic, and noninflammatory. Therefore, Ta could be considered an excellent biomaterial in primary and revision joint arthroplasty implants.

中文翻译：

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钽纳米颗粒在 THP-1 衍生巨噬细胞中的细胞毒性、氧化应激和炎症反应的研究

钽 (Ta) 作为骨组织工程中的生物材料正受到关注。尽管 Ta 基种植体在初次和翻修全关节置换 (TJA) 中的临床优势已得到充分证明，但很少有研究调查 Ta 种植体的磨损产物对种植体周围细胞的影响，以及它们对无菌种植体松动的潜在贡献。本研究旨在检测 Ta 和 TiO ₂纳米颗粒 (NPs)在体外对巨噬细胞的细胞毒性、氧化应激和促炎潜力。. 使用扫描电子显微镜、动态光散射和能量色散 X 射线对纳米颗粒进行表征。为了测试巨噬细胞中 NP 介导的细胞反应，用两种 NP 攻击 THP-1 衍生的巨噬细胞，并使用 CCK-8 和 LDH 测定分析细胞毒性。流式细胞术用于研究颗粒摄取及其内化途径。通过测量活性氧的产生来研究 NP 介导的氧化应激，并通过使用 ELISA量化细胞培养上清液中 TNF α和 IL-1 β的产生来确定它们的促炎潜力。我们发现 Ta 和 TiO ₂ NPs 都通过肌动蛋白依赖性吞噬作用被吸收，尽管 TiO ₂NPs 也确实显示出一些参与巨胞饮作用和网格蛋白介导的内吞作用。Ta NPs 没有引起明显的毒性，而 TiO ₂ NPs在 24 h浓度超过 100 μg /mL 时表现出显着的细胞毒性。Ta NPs在巨噬细胞中诱导可忽略不计的 ROS 生成和促炎细胞因子（TNF α、IL-1 β）。相比之下，TiO ₂ NPs 以剂量依赖性方式显着诱导这些效应。我们的研究结果表明，Ta NPs 是惰性、无毒和非炎症的。因此，Ta 可以被认为是初次和翻修关节置换术植入物的优良生物材料。