Human airway tissue models (hATMs) have emerged as valuable tools for studying host-pathogen interactions involving airborne bacteria and viruses. Our human 3D tissue models of the conducting airways reflect the architecture of the conducting airways in humans. These hATMs consist of fibroblast-loaded connective tissue and a respiratory epithelial layer. The tissue models show the mucociliary phenotype and, thus, facilitate the mucus transport that is necessary to remove trapped pathogens.

Until recently, we built the respiratory tissue models on a 3D scaffold derived from decellularized porcine small intestine. In order to replace the associated animal experiments, the objective of this study was to substitute the biological scaffold with a synthetic polyamide 6 (PA6) matrix. Additionally, we evaluated the suitability of these models for investigating viral and bacterial infections.

To address this objective, both scaffold types were seeded with human respiratory fibroblasts and epithelial cells. The morphology of PA6- and aECM-based models was analyzed using histological methods. Furthermore, we measured the epithelial barrier and conducted RT-qPCR and immunofluorescent staining to study tissue model infection with influenza A virus (IAV). In addition, we investigated the infection of PA6-based hATMs with S. aureus with CFU assays and histological methods.

Comparing respiratory tissue models based on the biological and synthetic scaffold, respectively, no obvious differences concerning tissue model morphology, cell type composition, epithelial barrier properties and susceptibility to IAV infection were observed. Furthermore, PA6-based hATMs were successfully infected with S. aureus.

Our data show that PA6 fibers are suitable scaffolds for building human respiratory tissue models and can be used to replace biological scaffolds and associated animal experiments. The advanced features enable us to simulate the dynamics of infections and study the interactions between pathogens and human tissue in vitro. With their high in vitro-in vivo correlation, our models provide a promising platform for preclinical research and the investigation of infection mechanisms.