| Tissue engineering has been considered an alternative to animal research. Recently, pharmaceutical companies renewed interests in inhaled drug development. These interests prompted a study into an engineered model of the bronchial mucosa. Cell lines and primary cells (fibroblast and epithelial cells) were used in the development of the engineered tissue. Parameters such as cell viability, seeding density, and extracellular matrix protein production were considered. The resulting tissue resembled the normal human bronchial mucosa physiologically and morphologically. The tissue model was used to elucidate fibroblast modulation of epithelial cell permeability. The permeability of the epithelium when cultured over a fibroblast-embedded collagen I gel was only 17.3%, 17.2%, and 2.7% of the permeability of the epithelium when cultured over a collagen I coated polycarbonate membrane for sucrose, HP228, and inulin, respectively. In addition, the model was used to examine the long term effects of insulin on airway mucosa. High insulin concentrations increased the contraction of these collagen gels. The mechanism is likely to be extra a-actin production with decreased tissue inhibitor of metalloproteinase (TIMP-1) expression. We conclude that the engineered model of the bronchial mucosa can be used to accelerate the development of drugs for inhalation. |
