{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:38:28Z","timestamp":1768509508574,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,23]]},"group-title":"Bioengineering","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Orofacial clefts are the most common craniofacial congenital anomaly. Following cleft palate repair, up to 60% of surgeries have wound healing complications leading to oronasal fistula (ONF), a persistent connection between the roof of the mouth and the nasal cavity. The current gold standard methods for ONF repair use human allograft tissues; however, these procedures have risks of graft infection and\/or rejection, requiring surgical revisions. Immunoregenerative therapies present a novel alternative approach to harness the body\u2019s immune response and enhance the wound healing environment. We utilized a repurposed FDA-approved immunomodulatory drug, FTY720, to reduce the egress of lymphocytes and induce immune cell fate switching toward pro-regenerative phenotypes. Here, we engineered a bilayer biomaterial system using Tegaderm\u2122, a liquid-impermeable wound dressing, to secure and control the delivery of FTY720- nanofiber scaffolds (FTY720-NF). We optimized release kinetics of the bilayer FTY720-NF to sustain drug release for up to 7d with safe, efficacious transdermal absorption and tissue biodistribution. Through comprehensive immunophenotyping, our results illustrate a pseudotime pro-regenerative state transition in recruited hybrid immune cells to the wound site. Additional histological assessments established a significant difference in full thickness ONF closure in mice on Day 7 following treatment with bilayer FTY720-NF, compared to controls. These findings demonstrate the utility of immunomodulatory strategies for oral wound healing, better positing the field to develop more efficacious treatment options for pediatric patients.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Local delivery of bilayer FTY720-nanofiber scaffolds in an ONF mouse model promotes complete wound closure through modulation of pro-regenerative immune and stromal cells.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.22.573096","type":"posted-content","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T20:20:19Z","timestamp":1703362819000},"source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Bilayer Biomaterial Delivery of FTY720 as an Immunotherapy to Accelerate Oral Wound Healing"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-046X","authenticated-orcid":false,"given":"Afra 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