Nanofibrillated cellulose (NFC) is a renewable nanomaterial that has beneficial uses in various applications such as packaging materials and paper. Like carbon nanotubes (CNT), NFCs have high aspect ratio and favorable mechanical properties. The aspect ratio also rises a concern whether NFC could pose a health risk and induce pathologies, similar to those triggered by multi-walled CNT. In this study, we explored the immunomodulatory properties of four NFCs in vitro and in vivo, and compared the results with data on bulk-sized cellulose fibrils and rigid multi-walled CNT (rCNT). Two of the NFCs were non-functionalized and two were carboxymethylated or carboxylated. We investigated the production of pro-inflammatory cytokines in differentiated THP-1 cells, and studied the pulmonary effects and biopersistence of the materials in mice. Our results demonstrate that one of the non-functionalized NFCs tested reduced cell viability and triggered pro-inflammatory reactions in vitro. In contrast, all cellulose materials induced innate immunity response in vivo 24 h after oropharyngeal aspiration, and the non-functionalized NFCs additionally caused features of Th2-type inflammation. Modest immune reactions were also seen after 28 days, however, the effects were markedly attenuated as compared with the ones after 24 h. Cellulose materials were not cleared within 1 month, as demonstrated by their presence in the exposed lungs. All effects of NFC were modest as compared with those induced by rCNT. NFC-induced responses were similar or exceeded those triggered by bulk-sized cellulose. These data provide new information about the biodurability and pulmonary effects of different NFCs; this knowledge can be useful in the risk assessment of cellulose materials.

中文翻译：

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纳米原纤化纤维素会导致急性肺部炎症，并在一个月内消退

纳米原纤化纤维素（NFC）是一种可再生纳米材料，在包装材料和纸张等各种应用中具有有益的用途。与碳纳米管（CNT）一样，NFC具有高长宽比和良好的机械性能。长宽比也引起了人们的担忧，即NFC是否会构成健康风险并诱发病理，类似于多壁CNT触发的那些。在这项研究中，我们探讨了四种NFC在体外和体内的免疫调节特性。，并将结果与​​散装纤维素原纤维和刚性多壁CNT（rCNT）的数据进行了比较。NFC中有两个未官能化，而两个则被羧甲基化或羧化。我们研究了分化的THP-1细胞中促炎细胞因子的产生，并研究了该物质在小鼠中的肺部影响和生物持久性。我们的研究结果表明，测试的一种非功能化NFC降低了细胞活力并触发了体外促炎性反应。相反，所有纤维素材料都可以在体内诱导先天免疫应答口咽抽吸后24小时，未官能化的NFC还会引起Th2型炎症。在28天后也观察到了适度的免疫反应，但是与24小时后相比，免疫反应明显减弱。纤维素材料在1个月内未清除，这通过暴露在肺中的纤维素证明。与rCNT诱导的相比，NFC的所有作用均不明显。NFC诱导的反应与散装纤维素触发的反应相似或超过。这些数据提供了有关不同NFC的生物耐久性和肺部影响的新信息；该知识可用于纤维素材料的风险评估。