Functionalizing PLGA Nanofiber Scaffolds to Regulate Salivary Gland Cell Behavior

Xerostomia (dry mouth) due to salivary gland hypofunction is a condition that decreases quality of life and affects millions of people. Xerostomia can be caused by Sjogren’s syndrome, radiation therapy for head and neck cancers, or result as a side effect from many medications.  Current treatments consist of replacement therapies that are inadequate as long-term treatments and are dependent upon a functional secretory cell population in the patient. Since salivary hypofunction can result from either loss of secretory acinar cells or loss of function by these cells, one therapeutic approach could be replacement of these cells in an artificial salivary gland.  However, it is difficult to maintain an epithelial cell secretory phenotype outside of the native cell environment. To mimic the structure of the extracellular matrix, we previously generated polymeric, nanofiber scaffolds composed of poly(lactic-co-glycolic acid) (PLGA), and found that the nanofiber scaffolds partially stimulate apicobasal polarity. Objectives: In the current study, we fictionalized nanofiber scaffolds with bioactive materials to stimulate apicobasal polarization. Methods:  Nanofiber scaffolds were chemically modified to covalently attach chitosan and laminin-111 to them. Trypan blue assays were used to evaluate cell viability and proliferation. Immunoblotting was used to quantify levels of tight junction proteins and immunocytochemistry to localize proteins in cells using confocal imaging. Results:   The unmodified nanofiber scaffolds promote some apicobasal polarity in salivary gland cell lines as observed with apical restriction of ZO-1, a tight junction (TJ) protein, relative to flat surfaces. Modification of nanofiber scaffolds with chitosan promotes salivary gland cell proliferation but inhibits apicobasal polarity. Fictionalization of these scaffolds with laminin-111 enhances apicobasal polarity by apically restricting a second TJ protein, occludin. Conclusion: Functionalizing PLGA nanofiber scaffolds with bioactive molecules allows for improved regulation of salivary gland epithelial cell structure, as progress towards replicating the epithelial cell secretory phenotype in vitro.

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This abstract is based on research that was funded entirely or partially by an outside source: NIH1DE019197, NIHRC1DE020402, NIHDE01919702S1

Keywords: Biomaterials, Extracellular matrix molecules and Salivary glands

See more of: Salivary Gland Structure and Function
See more of: Salivary Research

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