MukoBact – In vitro biofilm models of human mucosa in the gut and lungs for basic research and drug testing


Predictive test models for investigating the fundamental mechanisms of mucosal infections are urgently needed. Bacterial tissue infections of skin wounds and mucous membranes pose a major problem due to the rise in resistant pathogens and the lack of effective medicines. Although the transferability of animal data to the human body is limited and tissue infection models are very stressful for laboratory animals, animal models are still primarily used in research into fundamental issues.


In a previous project, we successfully developed an in vitro model of persistent wound infections. However, this model cannot be readily transferred to the intestine and lung, as the mucus layer covering the epithelium plays a crucial role in biofilm formation and drug transport, amongst other things. Corresponding intestinal and lung models in the literature also neglect the specialised niche of the mucous membranes or imitate it only inadequately.

For this reason, the aim of this project is to develop an in vitro model of bacterial biofilms associated with mucous membranes. To this end, a matrix of electrospun fibres is used to mimic both the three-dimensional microstructure and the mechanical characteristics of native mucus. This is followed by colonisation with relevant bacterial strains to form visible biofilms. The use of the electrospun matrix subsequently enables the transfer of the pre-matured biofilms onto 3D models of various epithelia in order to characterise interactions (see Fig. 1).

The model opens up the possibility of conducting detailed research into the individual stages of biofilm formation ((ir)reversible adhesion, maturation, dispersion) within the specialized environment of mucous membranes, as well as modeling various pathologies through the customized design of mucosa-mimetic fiber networks by modifying the properties of mucus (thickness, viscosity, composition). Furthermore, the newly designed biofilm models can be used in the development and testing of new therapies to combat overt bacterial infections. Since bacterial resistance is greatly increased within the biofilm matrix, the biofilm model proposed here offers a promising approach for creating more physiologically relevant conditions for testing new drugs.