NAMs Use of New NAM's Approach Methodologies (NAMs) for the hazard assessment of nanofibers. (DSB.AD006.319)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute for Genetic and Biomedical Research (IRGB)

Project manager

MARIANNA PAULIS
Phone number: 0282245153
Email: barbara.cassani@irgb.cnr.it

Abstract

The present proposal aims to improve our understanding of human health impacts of cellulose
nanofibers (NCF) ingestion, addressing some key challenges set by the European Safety Authority.
NCF will be examined upon exposure to digestive fluids, interaction with oro-gastro-intestinal
enzymes and final effects on human gut tissues. The specific focus will be on immune reactivity at
the intestinal barrier site. The project will use and compare advanced in vitro models of the human
intestine, both static and in tubular microfluidic format, improved by complementation with relevant
innate immune cells. The NCF effects will be assessed in terms of changes in tissue permeability,
toxicity (necrosis, programmed cell death, oxidative stress) and activation of immune/inflammationrelated
pathways. Besides knowledge advancement, the proposal intends to provide predictive in
vitro assays and contribute to regulatory assessment frameworks.

Goals

The specific objectives are the following:
- assessing the impact of NCF, transformed upon in vitro ingestion/digestion simulation (e.g.
exposure to digestive enzymes), in advanced human intestinal tissue models;
- comparing the current gut-on-chip models with advanced complex in vitro systems (from
primary and iPSC-derived human cells), to validate the reliability of the models;
- evaluating the impact of ingested NCF on human gut-associated immunity, in health and
disease/inflammatory conditions (IBD-like disease), using appropriate tissues and
microenvironmental conditions in the in vitro models;
- refining/simplifying the methodological platform to ensure reliability and replicability, and use
it for drafting a preliminary expert opinion report as a basis of guidance documents for regulatory
adoption.

Start date of activity

15/03/2021

Keywords

nanocellulose, gut-on-a-chip models

Last update: 23/04/2024