BMECHE Research Seminar - Danielle Benoit (University of Rochester)

Danielle Benoit, Ph.D.
Director, Materials Science Program
Professor, Department of Biomedical Engineering
Center for Musculoskeletal Research and Center for Oral Biology
University of Rochester

Salivary Gland Microphysiological Systems for Radioprotective Drug Discovery
Approximately 80% of the 700,000 head and neck cancer patients diagnosed worldwide annually receive therapeutic radiation therapy. Radiation therapy in the head and neck region results in off-target salivary gland dysfunction due to loss of salivary gland acinar cell secretory function, culminating in chronic dry mouth or xerostomia in >50% of patients. Patients afflicted with xerostomia experience chronic sore throat, excruciating burning sensations, loss of teeth, dysphagia, and chronic oral infections. Existing treatments for salivary gland dysfunction are palliative and there is no cure. Thus, the development of radioprotective drugs is imperative for the prevention of this highly debilitating condition. Progress in this area has been stifled by a lack of models, as salivary gland cells (SGCs) rapidly lose secretory acinar phenotype in vitro. This is due in part to disruption of the extracellular matrix (ECM) during dissociation, contributing to reduced intracellular signaling and eliminating cues required for proper cell function. To address this issue, we developed a salivary gland microphysiological system to culture SGCs in engineered extracellular matrices based on poly(ethylene glycol) (PEG) hydrogels. This system provides tunable control of the matrix microenvironment by alteration of enzymatically responsive peptide crosslinkers and presentation of cell adhesive peptide matrix cues. To develop a high throughput drug screening platform, we combine our hydrogel technology with microbubble (MB) array technology, wherein cells are seeded in high density arrays of 50 nL spherical cavities molded in polydimethylsiloxane (PDMS). Within the MB-gel microenvironment, SGCs organize into tissue mimetic structures which morphologically and functionally resemble acinar units of the salivary gland. This platform is currently being exploited to screen drug libraries to identify novel radioprotective candidates. Additionally, the microbubble microenvironment, namely hydrogel biochemical cues and degradation and media supplements, is being explored to further enhance longitudinal SGC function.

Biography
Danielle Benoit is the James P. Wilmot Distinguished Professor within the Department of Biomedical Engineering with appointments also in chemical engineering and the Center for Musculoskeletal Research. Her research specializes in the rational design of polymeric materials for regenerative medicine and drug delivery applications. Her work has provided insights into the translation of tissue engineering strategies for bone allograft repair, development of pH-responsive nanoparticles for nucleic acid and small molecule delivery, and novel targeting strategies for bone-specific delivery of therapeutics.
https://www.hajim.rochester.edu/bme/people/faculty/benoit_danielle/

In-person 73-1180 and Zoom: https://rit.zoom.us/j/96134371398