Functionalizing PLGA nanofiber scaffolds to regulate salivary gland cell behavior

Date of Award




Document Type

Master's Thesis

Degree Name

Master of Science (MS)


Department of Biological Sciences

Content Description

1 online resource (vii, 94 pages) : illustrations.

Dissertation/Thesis Chair

Melinda Larsen

Committee Members

James Castracane, Ben Szaro


Apicobasal Polarity, Chitosan, Epithelial Cells, Laminin, Salivary Gland, Tissue Engineering, Salivary glands, Tissue scaffolds, Epithelial cells, Cells, Growth factors, Nanofibers, Nanobiotechnology

Subject Categories



Xerostomia (dry mouth) due to salivary gland hypofunction is a condition affecting millions of people that has multiple causes and results in a decreased quality of life by causing dental caries, difficulties swallowing, loss of taste, and pain. Salivary hypofunction is typified by loss of acinar cells that produce saliva or a loss of function of these cells. Current treatments consist of replacement therapies including artificial stimulants of salivation which are inadequate as a long-term therapy as they are dependent upon a functional, secretory cell population in the patient. One therapeutic approach could be replacement of acinar and ductal, saliva-transporting cells in an artificial salivary gland as both cell types are needed for production of functional saliva; however, it is difficult to maintain an epithelial cell secretory phenotype outside the native cell environment. We previously generated polymeric, nanofiber scaffolds composed of poly(lactic-co-glycolic acid) (PLGA) that mimic the structure of the basement membrane, a specialized extracellular matrix, that provides many growth and differentiation supporting signals to epithelial cells. Two functions that the scaffold could provide to the cells are stimulation of cell proliferation to populate the scaffold and stimulation of apicobasal polarity. Although the nanofiber scaffolds provide a modest stimulation of apicobasal polarity, they do not significantly affect proliferation. Functionalization of the scaffolds with bioactive materials could stimulate the desired cell responses. A derivative of the polysaccharide chitin, chitosan is a biologically active, widely used biomaterial that is structurally similar to glycosaminoglycans (GAGs), natural components of the BM and laminin-111, a heterotrimeric, glycoprotein that is a major component of the basement membrane, were covalently coupled to the nanofiber scaffolds. We found that chitosan-coupled nanofiber scaffolds stimulated proliferation of both salivary gland acinar and ductal cells, while laminin-111-modified nanofiber scaffolds promoted a polarized cell phenotype in salivary epithelial cells, which may be necessary for subsequent differentiation and function of these cells. Addition of such modifications effectively enhances the nanofiber scaffolds as they more closely resemble the functional basement membrane.


Requested ProQuest takedown; no end date

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