Müller Michelle, Drexel Roland, Burkhart Marie, Dähnhardt-Pfeiffer Stephan, Wien Lena, Herrmann Christine, Knoll Thorsten, Metzger Christoph, Briesen Heiko, Wagner Sylvia, Meier Florian, Kohl Yvonne
Department Bioprocessing & Bioanalytics, Fraunhofer Institute for Biomedical Engineering IBMT, Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach, Germany.
Postnova Analytics GmbH, Rankinestr. 1, 86899 Landsberg am Lech, Germany.
In Vitro Model. 2023 Aug 21;2(5):181-194. doi: 10.1007/s44164-023-00056-x. eCollection 2023 Nov.
Cellulose nanocrystals (CNC) play a promising role in the development of new advanced materials. The growing demand of CNC-containing products in the food industry will lead to an increased human exposure through oral uptake. To date, there is a dearth of studies reporting on the risks which CNC pose to human health following ingestion. In vitro models, which lack physiological accuracy, are often used to justify animal experiments in the field of nanosafety assessment. Nevertheless, ex vivo models of the intestine pose promising alternatives to in vivo experiments.
Two ex vivo models, a microfluidic chip based on porcine intestinal mucus and the Ussing chamber apparatus with tissue from abattoirs, which aim to complement in vitro models, are characterized by investigating the transport and toxicity of CNC through them in comparison to an in vitro triple co-culture model. Silver nanoparticles were included in this study as well-known and characterized nanomaterials for comparative purposes.
Study results show that CNC cross the intestinal mucus layer but do not pass the intestinal tissue barrier ex vivo and in vitro; furthermore, no toxic effects were observed under exposure conditions tested.
These ex vivo models present complementary methods to the existing standardized in vitro and in silico methods to support data generation under physiologically relevant conditions without the use of animals. This multi-model approach offers an enhanced understanding of the complex interaction between new materials and human tissue and aligns with the flexible approach of IATA (Integrated Approaches to Testing and Assessment) and NAMs (New Approach Methods) for chemical and drug safety assessment.
The online version contains supplementary material available at 10.1007/s44164-023-00056-x.
纤维素纳米晶体(CNC)在新型先进材料的开发中发挥着重要作用。食品工业中对含CNC产品的需求不断增长,这将导致人类通过口服摄入而增加接触。迄今为止,关于摄入后CNC对人类健康构成的风险的研究尚属匮乏。在纳米安全评估领域,缺乏生理准确性的体外模型常被用于证明动物实验的合理性。然而,肠道的离体模型为体内实验提供了有前景的替代方案。
两种离体模型,一种基于猪肠黏液的微流控芯片和一种带有屠宰场组织的尤斯灌流室装置,旨在补充体外模型,通过与体外三重共培养模型比较,研究CNC在其中的转运和毒性来对其进行表征。本研究还纳入了银纳米颗粒作为已知且已表征的纳米材料用于比较目的。
研究结果表明,CNC在体外和离体条件下均能穿过肠黏液层,但不会通过肠组织屏障;此外,在测试的暴露条件下未观察到毒性作用。
这些离体模型为现有的标准化体外和计算机模拟方法提供了补充方法,可以在不使用动物且生理相关条件下支持数据生成。这种多模型方法有助于增强对新材料与人体组织之间复杂相互作用的理解,并与国际航空运输协会(IATA)(测试与评估综合方法)和NAMs(新方法)在化学和药物安全评估中的灵活方法相一致。
在线版本包含可在10.1007/s44164-023-00056-x获取的补充材料。