Improving Human Respiratory Mucosa Tissue Models with Polyamide 6 Scaffolds

Abstract

Advanced tissue-engineered respiratory models are essential for studying drug or cosmetic toxicity, infection biology and xenobiotic metabolism. Here, we investigated a polyamide 6 (PA6)-based electrospun stromal scaffold as a substitute for porcine-derived small intestinal submucosa (SIS) to build human airway mucosa tissue models at the air-liquid interface. We demonstrate that the porous PA6 scaffold supports extracellular matrix production by human nasal fibroblasts and facilitates the complete differentiation of respiratory epithelial cells to the mucociliary phenotype. These models reduce reliance on animal-derived materials, improve reproducibility, and minimize potential interference from animal-derived antigens and pathogens. Both PA6- and SIS-based models promote fibroblast migration, epithelial differentiation, and the expression of key xenobiotic metabolizing enzymes. They exhibit comparable epithelial barrier integrity and susceptibility to influenza A virus infections. These findings establish PA6 scaffolds as a suitable, animal-free alternative to the SIS to build human airway mucosa tissue models.

Impact Statement

To minimize the usage of animal-components to build tissue-engineered models of the human respiratory mucosa, we replaced the porcine-derived small intestinal submucosa (SIS) by a polyamide 6 (PA6)-based electrospun scaffold. The PA6 scaffold supports extracellular matrix production by human nasal fibroblasts and facilitates the differentiation of respiratory epithelial cells to the mucociliary phenotype. SIS- and PA6-based respiratory tissue models exhibit comparable epithelial barrier integrity, abundance of xenobiotic metabolizing enzymes, and susceptibility to influenza A virus infections. These findings establish PA6 scaffolds as a suitable, animal-free alternative to SIS for generating human airway mucosa tissue models.