Development of Nanofiber Scaffolds for Engineering an Artificial Salivary Gland

There is currently a significant clinical need for artificial salivary glands as a therapeutic option for patients suffering from xerostomia. To achieve unidirectional fluid secretion, the epithelial acinar cells must establish and maintain polarity by partitioning the plasma membrane into distinct apical and basolateral membrane surfaces to achieve unidirectional fluid secretion. Establishment and maintenance of epithelial acinar cell polarity has been difficult to achieve in vitro, and yet is critical saliva secretion in an engineered salivary gland. Physical properties of the scaffold provided to epithelial cells will likely influence their ability to differentiate and achieve apical-basal polarity. We have engineered nanofiber matrices using the biocompatible polymer, PLGA (poly-L-lactic-co-glycolic acid) having differing topology and organization and documented the structure of these scaffolds using SEM. We evaluated the effects of several factors on epithelial cell attachment, self-organization, and apico-basal polarity on the scaffolds using confocal microscopy to examine expression and organization of apical tight junction proteins, ZO-1 and claudins, and basal markers, such as integrin α6 and the ECM protein fibronectin. The surface of the nanofiber matrix was functionalized with chemically-linked ligands to further optimize apical-basal polarity. These studies will identify an optimal scaffold for future use in an engineered functional salivary gland construct.