Background/Objectives

Advanced thermoplastic materials, such as polyether-ether-ketone (PEEK) and highly cross-linked polyethylene (HXLPE), have been increasingly used as orthopaedic implant materials. Similar to other implants, PEEK-on-HXLPE prostheses produce debris from polymer wear that may activate the immune response, which can cause osteolysis, and ultimately implant failure. In this study, we examined whether the anti-inflammatory properties of zinc oxide nanoparticles (ZnO NPs) could attenuate polymer wear particle-induced inflammation.

Methods

RAW264.7 ​cells were cultured with PEEK or PE particles and gradient concentrations of ZnO NPs. Intracellular mRNA expression and protein levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6 were detected. An air pouch mouse model was constructed to examine the inflammatory response and expression of pro-inflammatory factors in vivo. Furthermore, an osteolysis rat model was used to evaluate the activation of osteoclasts and destruction of bone tissue induced by polymer particles with or without ZnO NPs. Protein expression of the MEK-ERK-COX-2 pathway was also examined by western blotting to elucidate the mechanism underlying particle-induced anti-inflammatory effects.

Results

ZnO NPs (≤50 ​nm, 5 ​μg/mL) showed no obvious cytotoxicity and attenuated PEEK or PE particle-induced inflammation and inflammatory osteolysis by reducing MEK and ERK phosphorylation and decreasing COX-2 expression.

Conclusion

ZnO NPs (≤50 ​nm, 5 ​μg/mL) attenuated polymer wear particle-induced inflammation via regulation of the MEK-ERK-COX-2 axis. Further, ZnO NPs reduced bone tissue damage caused by particle-induced inflammatory osteolysis.

The translational potential of this article

Polymer wear particles can induce inflammation and osteolysis in the body after arthroplasty. ZnO NPs attenuated polymer particle-induced inflammation and inflammatory osteolysis. Topical use of ZnO NPs and blended ZnO NP/polymer composites may provide promising approaches for inhibiting polymer wear particle-induced inflammatory osteolysis, thus expanding the range of polymers used in joint prostheses.

中文翻译：

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ZnO 纳米颗粒通过调节 MEK-ERK-COX-2 轴减轻聚合物磨损颗粒诱导的炎症性骨溶解

背景/目标

先进的热塑性材料，例如聚醚醚酮 (PEEK) 和高度交联聚乙烯 (HXLPE)，已越来越多地用作骨科植入材料。与其他植入物类似，PEEK-on-HXLPE 假体产生的聚合物磨损碎片可能会激活免疫反应，从而导致骨溶解，并最终导致植入物失败。在这项研究中，我们检查了氧化锌纳米颗粒 (ZnO NPs) 的抗炎特性是否可以减轻聚合物磨损颗粒引起的炎症。

方法

RAW264.7 细胞与 PEEK 或 PE 颗粒和梯度浓度的 ZnO NP 一起培养。检测细胞内促炎因子TNF-α、IL-1β和IL-6的mRNA表达和蛋白水平。构建气囊小鼠模型以检查体内炎症反应和促炎因子的表达。此外，溶骨大鼠模型用于评估由含有或不含 ZnO NPs 的聚合物颗粒诱导的破骨细胞活化和骨组织破坏。还通过蛋白质印迹检查 MEK-ERK-COX-2 途径的蛋白质表达，以阐明颗粒诱导的抗炎作用的机制。

结果

ZnO NPs (≤50 nm, 5 μg/mL) 没有显示出明显的细胞毒性，并通过降低 MEK 和 ERK 磷酸化和降低 COX-2 表达来减弱 PEEK 或 PE 颗粒诱导的炎症和炎症性骨溶解。

结论

ZnO NPs (≤50 nm, 5 μg/mL) 通过调节 MEK-ERK-COX-2 轴减轻聚合物磨损颗粒引起的炎症。此外，ZnO NPs 减少了由颗粒诱导的炎症性骨溶解引起的骨组织损伤。

本文的翻译潜力

聚合物磨损颗粒可在关节成形术后引起体内炎症和骨质溶解。ZnO NPs 减弱了聚合物颗粒诱导的炎症和炎症性骨溶解。局部使用 ZnO NPs 和混合 ZnO NP/聚合物复合材料可能为抑制聚合物磨损颗粒引起的炎症性骨溶解提供有前景的方法，从而扩大用于关节假体的聚合物的范围。