BME PhD Proposal Seminar: Andrew Shubin

Goergen Hall 101 (Sloan Auditorium)

"Poly(ethylene glycol) Hydrogels for Salivary Gland Regeneration"

Supervised by Prof. Danielle Benoit

Abstract:

Over 40,000 patients in the U.S. are diagnosed with head and neck cancers annually. Radiation therapy for these cancers can cause damage to the salivary glands resulting in permanent dry mouth or xerostomia. Xerostomia significantly detracts from patient quality of life by limiting dietary options, impairing speech production, adversely impacting oral hygiene. Current treatments rely on maximizing function out of residual tissue and no regenerative options exist that can restore function on irreparably damaged glands. However, direct cellular injections of submandibular gland cells have been shown to lead to modest but inconsistent recovery of salivary gland function after radiation injury in mouse models. This project aims to develop a biomaterials approach to enhance the ability of cell-based therapies. In particular, we are interested in exploring hydrogels to aid in cell transplantation as their hydrophilicity and stiffness can be made to match the ECM of soft tissues; however, very little work had been published regarding the use of hydrogels with salivary gland cells and tissues.

We propose the use of poly(ethylene glycol) (PEG) hydrogels as a means to regenerate and transplant functional salivary tissue. PEG hydrogels are bio-inert and non-immunogenic providing a bottom-up approach to the development of a biomaterial scaffold. PEG hydrogels can be easily functionalized with both degradable and bioactive moieties giving PEG hydrogels the ability to be adapted to multiple different tissue types. We aim to develop permissive encapsulation methods of primary salivary gland cells through the use of cytocompatible photopolymerization strategies and cell-cell interactions to promote the viability of encapsulated cell populations. We will functionalize the hydrogel scaffold with cell adhesion motifs and matrix metalloproteinase-degradability to mimic the salivary gland extracellular matrix as a means to improve encapsulated cell survival, proliferation, and secretion of factors commonly found in saliva. Finally, we will use promising hydrogel formulations to transplant salivary gland cells through in situ hydrogel formation as a means to regenerate salivary gland tissues and restore saliva secretion after radiation treatment. Successful design and implementation of PEG hydrogels for regeneration of salivary tissue will lead to novel therapeutic interventions for those who develop severe xerostomia due to radiation therapy.