Imitating the microenvironment of native biofilms using nanofibrous scaffolds to emulate chronic wound infections

Three-dimensional scaffolds of electrospun fibers are widely investigated for in vitro human tissue engineering, but to date, their application in the cultivation of bacterial biofilms has been neglected. In contrast, in a clinical setting, biofilms have received increasing recognition as major determinants of severe and chronic tissue infections, illustrating their immense threat to global public health. Their complex three-dimensional structure enables their persistence in harsh infection environments, tight attachment to human tissue and reduced susceptibility to antimicrobials. For the investigation of biofilm formation and persistence and for the development of novel infection therapies, mimicking the complex biofilm architecture with adequate in vitro models is essential. In this study, electrospun nanofibers were designed to simulate the matrix of native biofilms to serve as scaffolds for a novel biofilm model, which provides an in vivo-like growth environment and comprises biofilm-tissue interfaces. The three-dimensional scaffolds closely imitate the composition and structure of the matrix, while providing high mechanical support. The specific material properties of the developed scaffolds promote bacterial adhesion, infiltration, and homogenous distribution throughout the fiber network. Furthermore, matrix production and increased tolerance against antibiotics were proven, verifying adequate biofilm formation and maturation. In combination with human ex vivo wound models, the chronic state of infected wounds could be emulated allowing for investigation of biofilm-tissue interfaces and biofilm-host interactions. The here-described biofilm model based on nanofibers represents a valuable tool for simulating biofilm-associated infections in a pathophysiologically relevant manner paving new grounds for a multitude of possible applications beyond infection research.