Afra Toma

BME PhD Proposal Presentation

Date: 2023-01-12
Time: 11:00am-12:00pm
Location / Meeting Link: Whitaker McIntire Conf Rm x.5-5043 (In person); https://emory.zoom.us/j/4721756407 (Virtual)

Committee Members:
Steven Goudy MD, MBA, FACS (Advisor) ; Nick J. Willett, Ph.D. ; Edward A. Botchwey, Ph.D. ; Andrés J. García, Ph.D. ; Ankur Singh, Ph.D.


Title: Enhancing Oral Tissue Regeneration Using FTY720-loaded Nanofibers as a Biomaterial-Based Immunotherapy

Abstract:
Orofacial clefts are the most common craniofacial congenital defect. These defects occur when the tissue of the lip or palate do not form properly. Up to 60% of cleft palate repair surgeries have wound healing complications leading to oronasal fistula (ONF), a persistent connection between the roof of mouth and the nasal cavity. The ONF affects the child’s ability to eat, talk, and thus, the overall quality of life. Current gold standard methods for ONF repair use human allograft tissues; however, these procedures have risks of infection or allograft rejection which then require further surgical revisions. Immunoregenerative therapies present a novel alternative approach as they can harness the body’s immune response to create a more favorable wound healing environment, one of which is immunomodulatory drug, FTY720. FTY720 is an FDA-approved drug to treat relapsing multiple sclerosis by reducing egress of lymphocytes and has been shown to induce macrophages and monocytes into pro-regenerative phenotypes. The overarching hypothesis is that delivery of FTY720-loaded nanofiber scaffolds in an ONF mouse model will enhance oral cavity wound healing by promoting pro-regenerative immune cell recruitment leading to improved vascularization, tissue remodeling and maturation. Therefore, the overall objective of this thesis is to repurpose a clinically available drug, FTY720, to harness the innate wound healing system as a novel form of biomaterial-based immunotherapy and enhance oral tissue regeneration during ONF healing. This will be achieved through two specific aims: 1) Engineering a bi-layered adhesive scaffold for FTY720 delivery and assessing tissue regeneration during ONF healing, 2) Investigating the contribution of pro-regenerative macrophages on oral wound healing following FTY720-NF treatment. Upon completion, this thesis will establish critical knowledge in the role of immunomodulation for oral wound healing and develop efficacious treatment options for pediatric patients following cleft palate surgery.