Afra I. Toma
BME PhD Defense Presentation

Date: 2024-08-29
Time: 2:00PM
Location / Meeting Link: Emory Musculoskeletal Institute 6th Floor Conference Room (in-person); https://emory.zoom.us/j/4721756407 (virtual)

Committee Members:
Steven Goudy, MD, MBA; Nick Willett, PhD; Edward Botchwey, PhD; Andrés J. García, PhD; Ankur Singh, PhD


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

Abstract:
Orofacial clefts are the most common craniofacial congenital defect, occurring when the tissue of the lip or palate does not form properly. Complications in cleft palate repair surgeries can result in postoperative 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 uses human allograft tissues. However, these procedures have risks of infection or allograft rejection which can require surgical revisions. Immunoregenerative therapies present a novel alternative approach for oral wound healing as they can harness the body’s immune response to create a more favorable healing milieu. A promising treatment option for oral wound healing can be a biomaterial-based delivery of immunomodulatory drug, FTY720. FTY720 is an FDA-approved drug used to reduce egress of lymphocytes from secondary lymphoid organs and has shown to induce immune cell transition towards a pro-regenerative phenotype. The central hypothesis of our studies is that local FTY720-NF delivery will enhance ONF wound healing through regenerative macrophage regulation of key lipids and genes to resolve inflammation and improve tissue remodeling. Therefore, the overall objective of this thesis is to repurpose a clinically available drug, FTY720, to harness the reparative wound healing system as a biomaterial-based, pro-regenerative immunotherapy following cleft palate and ONF repair. This will be achieved through two specific aims: 1) engineering a bilayer, biomaterial scaffold to deliver FTY720-NF, modulate immune cell recruitment, and promote a regenerative oral wound healing environment, 2) investigating the contribution of pro-regenerative macrophages to the regulation of key lipid and gene mediators following FTY720-NF immunomodulation. This thesis will establish critical knowledge in the role of immunomodulation for oral wound healing and provide an efficacious treatment alternative for pediatric patients following cleft palate surgery.