Enhancing Oral Tissue Regeneration using FTY720-nanofibers as a Biomaterial-Based Immunotherapy
Author(s)
Toma, Afra I.
Advisor(s)
Willett, Nick J.
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Abstract
Orofacial clefts represent the most prevalent congenital craniofacial abnormality. Surgical complications in cleft palate repair can lead to postoperative oronasal fistula (ONF), a persistent communication between the oral and nasal cavities. ONF negatively impacts a child's eating and speaking abilities, consequently affecting their overall life quality. The current gold standard methods for ONF repair use human allograft tissues; however, these procedures have risks of graft infection and/or rejection. A promising regenerative therapy involves local delivery of FTY720, an FDA-approved immunomodulatory drug, to harness the body’s immune response to create a more favorable healing milieu. FTY720 reduces lymphocyte migration to inflammatory sites and promotes immune cell transition towards a pro-regenerative state. We hypothesize that local bilayer FTY720-NF delivery can accelerate oral cavity wound healing and modulate key lipids, genes, and proteins to reduce inflammation and promote tissue remodeling. This thesis aims to repurpose 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 FTY720-NF immunomodulation of key lipid, gene, and protein mediators to enhance ONF tissue regeneration. This research will establish critical insight in the role of immunomodulation for oral wound healing and develop an efficacious treatment alternative for pediatric patients following cleft palate surgery.
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Date
2024-10-16
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Text
Resource Subtype
Dissertation (PhD)