Nanomaterials are already part of everyday life in our modern society. New applications, along with continuously rising quantities being produced, have led to an increased exposure to nanomaterials for both people and the environment. Predicting the behaviour of nanomaterials in organisms and extensive risk assessments are currently difficult because we are missing prediction models.

How do these small particles with a size of only few millions of a millimetre overcome the protective layers of our body? How do the particles behave in the organism? Are the particles metabolised and are they dangerous? In order to find answers to these and other questions, 11 partners from business and science are developing new, innovative methods for precise detection of the behaviour of nanomaterials in the body and for better prediction and safe evaluation of the resulting risks for humans. This work is being done within the framework of the EU-project »HISENTS: High level integrated Sensor for Nanotoxicity Screening«.

Due to their small size and varied physical and chemical properties, nanoparticles can perform special functions and are today incorporated in a large number of everyday products. Nanoparticles are present in cosmetics, textiles, cleaning agents, sprays, packages as well as in food and dietary supplements and thus enter the human body day-to-day. Even the application of nanoscale particles in the pharma or medical sector is no longer a rarity. Therapeutics (e. g. drugs for chemo- or phototherapy) and diagnostics (e. g. contrast agents) as well as coatings of implants are increasingly based on nanomaterials.

Due to the numerous knowledge gaps and lack of model systems, so far only insufficient prediction of absorption, distribution, metabolism and excretion (ADME) of synthetic nanomaterials in the human organism is possible. In the pharmaceutical research and drug development industry the PBPK model (physiologically based pharmacokinetic model) is chosen as an established approach for the mathematical prediction of kinetic profiles of medical compounds regarding dose, route and species. In doing so the concentration in the tissues and toxic, as well as pharmacologic, effects are included. »Up to now only initial approaches of such models exist for nanomaterials«, explains Dr. Yvonne Kohl, Group Manager Nanotoxicology at the Fraunhofer Institute for Biomedical Engineering IBMT.

HISENTS: With a new multi-organ platform moves towards a safe evaluation of nano-effects in the body

In order to develop such a PBPK model for nanomaterials, data is required for »feeding« the mathematical model. By means of a multimodular microchip-based multi-organ platform, the pathway of the nanomaterial though the body is simulated and data is generated for developing a nanoPBPK model. »HISENTS« started in April 2016 to implement this platform and the nanoPBPK model. »HISENTS« is an international research project, receiving 6.3 Million Euro of funding from the European Commission (EU) within the framework of the »NanoSafetyCluster« program. »HISENTS« is an international, interdisciplinary research project with 11 partners, coordinated by Prof. Andrew Nelson of the University of Leeds. Besides the Fraunhofer Institute for Biomedical Engineering and the University of Leeds, universities from Austria, Israel and Slovakia, research institutions from Spain, Slovakia, Ireland and Norway as well as the company Blueprint Production Design Ltd. from the United Kingdom are involved. The project duration of »HISENTS« is 36 months.

The goal is to evaluate the effect of nanomaterials on molecular, cellular and organ-level. »The HISENTS-platform includes nine models, which can be freely interconnected to simulate realistic pathways of the nanomaterials through the human body«, explains Kohl. Each of these modules represents a barrier of the body (lung, gastrointestinal tract, placenta), an organ (liver, kidney, blood system) or subcellular compartments (bio-membrane, DNA, miRNA).

Fraunhofer IBMT is making a major contribution to this project by designing, fabricating and validating the microchip-based multi-organ platform. »The technological focus of the development work is on the miniaturized systems for cell cultivation to simulate the mentioned body barriers and organs as well as for investigating subcellular compartments. Instead of operating the modules in an incubator, we will equip each module with a miniaturized incubator making the application of the platform very flexible. Furthermore, we will integrate optical and electrical systems for cell characterization. To supply the individual modules and their interconnections, a suitable fluidic system has to be developed«, explains Thorsten Knoll, Group Manager Microfluidics and Microsensors.

In addition to the multimodular platform, Fraunhofer IBMT will develop new in vitro models for the investigation of human toxicologic effects (e. g. hepatotoxicity) of nanomaterials within the HISENTS-project. The researchers will study the barrier mobility of nanomaterials overcoming the lung- and intestine barrier, to understand the uptake in the body. »The cell models will be cultured in the newly developed microfluidic modules and interconnected with each other, enabling toxicological risk assessment of nanomaterials along the path through the body«, explains Dr. Yvonne Kohl.

The multidisciplinary formation of the »HISENTS« team and the variety of technical expertise enable the development of the urgently needed, interconnected organ modules, to generate the experimental data for »feeding« the mathematical models, which are essential for a safe and reliable risk assessment, risk prediction and evaluation of the behaviour of nanomaterials in the body.

For further information on the project, which is listed under the BMBF-funding code 685817, please refer to https://www.hisents.eu

Project duration : 01.04.2016 - 31.03.2019

Project partners:

University of Leeds (project coordinator, United Kingdom)
Tel-Aviv University (Israel)
Blueprint Production Design Ltd (United Kingdom)
Slovak University of Technology in Bratislava (Slovakia)
University Wien (Austria)
Universität des Saarlandes (Germany)
Cancer Research Institute Slovak Academy of Sciences (Slovakia)
Institut Catalá de Nanotecnologia (Spain)
Tyndall National Institute, University College Cork (Ireland)
Norwegian Institute for Air Pollution Research (Norway)