What is graphene doing in the lungs?

Graphene is considered the material of the future. However, little is known so far about whether and how graphene affects our health should it enter the body. A team of researchers from Empa and the Adolphe Merkle Institute (AMI) in Fribourg have now conducted studies on a three-dimensional lung model for the first time to investigate the behavior of graphene and graphene-like materials after inhalation.

Graphene is considered the material of the future. However, little is known so far about how this material affects our health. (Image: depositphotos)

The material graphene is made of is tensile and tear resistant, highly elastic and electrically conductive. Graphene has many extraordinary properties, which enables revolutionary applications in a wide variety of fields. It is not for nothing that the EU has launched the "Graphene Flagship", which is supported with one billion euros and is thus considered the largest European research initiative. As part of this huge project, Empa is also contributing its know-how, as possible health aspects and effects on the human organism play an essential role in the context of Europe-wide graphene research.

These activities have now given rise to an additional project funded by the Swiss National Science Foundation (SNSF), which has recently been launched at Empa and AMI. This involves the use of a cellular 3-D lung model, with which the researchers want to find out what effects graphene and graphene-like materials can have on the human lung - and under conditions that are as close to reality as possible. This is a challenge, because not all graphene is the same. Depending on the production method and processing, a wide variety of shapes and qualities of the material are produced, which in turn can trigger different reactions in the lungs.

Three-dimensional cell cultures "breathe in" particles

The research team of Peter Wick, Tina Bürki and Jing Wang from Empa and Barbara Rothen-Rutishauser and Barbara Drasler from AMI recently published their first results in the scientific journal "Carbon". With the 3-D lung model, the researchers have succeeded in realistically recreating the actual conditions at the air-blood barrier as well as the effect of graphene in lung tissue - without experiments on animals or humans. This involves a cell model that replicates the lung alveoli. Conventional in vitro tests work with cell cultures from only one cell type - the established lung model, on the other hand, consists of three different cell types that simulate the conditions inside the lung, namely alveolar epithelial cells as well as two types of immune cells - macrophages and dendritic cells.

Another factor that has hardly been considered so far in in vitro experiments is the contact of the graphene particles via the air. Usually, cells are cultivated in a culture dish in a nutrient solution and exposed to materials, for example graphene, in this form. In reality, however, i.e. at the lung barrier, this is different.

"The human organism is most likely to come into contact with graphene particles through the air we breathe," says Tina Bürki from Empa's Particles-Biology Interactions research department. The particles are therefore inhaled and come into direct contact with the lung tissue. The new lung model is set up so that the cells are located on a porous filter membrane at the air-liquid interface, and the researchers spray the graphene particles onto the lung cells using an atomizer to mimic the process in the body as closely as possible. The three-dimensional cell culture virtually "inhales" the graphene dusts.

No acute damage detected

These experiments in the 3-D lung model have now yielded initial results. The researchers were able to demonstrate that no acute damage forms in the lung when lung epithelial cells come into contact with graphene oxide (GO) or so-called graphene nanoplatelets (GNP). This includes reactions such as sudden cell death, oxidative stress or inflammation.

In order to also detect chronic changes in the body, the SNSF project will run for three years; the next step will be long-term studies with the lung model. Wick and his team are exposing the lung cells not only to pure graphene particles but also to abraded graphene particles from composite materials, which are classically used to reinforce polymers. Jing Wang from Empa's Advanced Analytical Technologies department is involved in the project.
Again, to estimate as realistically as possible the amount of graphene particles to which people are exposed, Wang is studying and quantifying the abrasion of the composite materials. Using this data, the team exposes the 3-D lung model to realistic conditions and is able to make longer-term predictions about the toxicity of graphene and graphene-like materials.
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