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BME Seminar Series: Melinda Larsen, Ph.D.

Goergen Hall 101 (Sloan Auditorium)

"Constructing a Salivary Gland from the Outside In"

Melinda Larsen, Ph.D.
Associate Professor of Biological Sciences
SUNY College of Arts and Sciences
Albany, New York

Abstract: Biomimetic scaffolds for tissue engineering of salivary glands hold great promise for treatment of Xerostomia, or dry mouth, a condition caused by head and neck radiation therapy and Sjögren's syndrome. Salivary secretory acinar cells, the major producers of saliva, fail to function effectively in patients suffering from xerostomia. Although acinar cells cannot easily be cultured, we hypothesized that scaffolds that mimic specific properties of the microenvironment will support acinar cell differentiation and function ex vivo. We engineered micropatterned Poly Lactic-co-Glycolic Acid (PLGA) nanofiber scaffolds that promote cell-cell clustering and columnar morphology of epithelial cell lines. When conjugated with laminin, the scaffolds promote apicobasal polarization and when presented to the cell in a micropatterned array, the scaffolds further support apicobasal polarization. Primary salivary epithelial cells grown on the scaffolds were compared with cells grown in 3D Matrigel, a laminin-rich matrix. Immunocytochemistry and confocal imaging revealed that acinar marker proteins were rapidly lost while ductal cells increased through 10 days in culture in all conditions. The elastic modulus of the scaffold also impacted acinar differentiation in the context of the embryonic glands, with softer scaffold supporting normal development and differentiation. For application in regenerative therapies, salivary progenitor cells will be grown on scaffolds, and laminin-conjugated nanofiber scaffolds support maintenance of a kit+ progenitor cell population. Since kit+ cell populations are capable of differentiating into acinar populations, designing smart scaffolds will be a future goal to support acinar progenitor cell populations and promote their differentiation into secretory acinar cells.