NANO2021 RCN project "NanoBioreal"
A sound scientific basis is needed to assess the risks to workers and consumers, to inform regulatory bodies and to ensure a responsible development of nanotechnology. Most of the existing laboratory (in vitro) biological models, exposure systems and doses, as well data (in silico) models do not reflect the real-life exposure to nanomaterials (NMs). A significant source for unreliable results is represented by possible interactions of NMs with the reagents and detection systems for toxicity evaluation.
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The fast pace at which NMs enter the market requires a shift from expensive and ethically doubtful animal testing to innovative, reliable and socially acceptable in vitro and in silico test systems. The aim of NanoBioReal is to establish methods and biological models that reflect real-life exposure and which provide a reliable, robust and efficient platform to evaluate the effects of NMs on human health. Our testing system covers a wide area of biological models, from single cells to three-dimensional (3D) models that simulate tissues and organs. These include air-liquid interface (ALI) models for lung exposure, blood and «organ-on-a-chip» systems (lung and microvasculature-on-a-chip) that measure effects in real-time and can detect relevant effects after both short and longtime exposure.
To avoid interferences caused by NMs, we established in this project label-free impedance-based methods to evaluate cytotoxicity and cyclic voltammetry to assess oxidative stress caused by NMs. A set of representative NMs has been produced and physico-chemically characterized. Their in vitro cyto- and geno- toxicity was assessed in 2D cellular models and the results were compared to those obtained using the advanced 3D models and an animal model. Advanced models for lung, vasculature and whole blood exposure have been established and used for toxicity, inflammation, oxidative stress, and barrier integrity testing. A microfluidic setup for label-free live monitoring of cells and 3D biological models was established, optimized and its throughput has been increased. The results obtained in the NanoBioReal project deliver reliable, robust and relevant biological and in silico-models to support a “safe(r)-by-design” approach to the development of NMs and to address the needs of various stakeholders and regulators.
National partners: Coordinator - Dept. of Clinical Dentistry (IKO), Fac. of Medicine, Univ. of Bergen (UiB); Co-coordinator - National Inst. of Occupational Health (STAMI); the Norwegian Institute for Air Research (NILU); Centre of Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology (NTNU). Subcontractors: NorGenotech. International partners: Catalan Inst. of Nanoscience and Nanotechnology (ICN2) and the University of Gdansk. Collaborators: Dept. of Physics and Technology - NanoPhysics, Bodil Holst, Professor, Martin Greve, Associate Professor (UiB); Dept. of Electrical Engineering (HVL) - Emil Cimpan, Associate Professor; NIOM; TkVest; TkØst.
A Workshop “New Approach Methodologies for NanoSafety” and the “NanoBioReal” Project meeting were held in Bergen on March 30th and March 31st, 2023. The workshop and project meeting were organized by Mihaela R. Cimpan, Ivan Rios-Mondragon, Barbara Pekala, Sigrid Nævdal, the Department of Clinical Dentistry, Faculty of Medicine, University of Bergen.
Coordinator: Mihaela Roxana Cimpan, Professor; Researcher: Ivan Rios-Mondragon, PhD; Ole Bendik Hofshagen, MSc Nano; Marianne Stokka MSc Nano; Medusja Sritharan Nalliah MSC Nano