Ex vivo models for intestinal translocation studies of cellulose nanocrystals

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. Supplementary Information: The online version contains supplementary material available at 10.1007/s44164-023-00056-x.