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Author Notes:

Steven L. Goudy, Address: 2015 Uppergate Drive, Atlanta, GA, 30322, steven.goudy@emory.edu, Phone: (615)-715-3262

Subjects:

Research Funding:

This paper was supported by the Pediatric Technology Center Therapeutic Child Impact Grand Award from Georgia Tech and Children’s Healthcare of Atlanta.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Cleft palate
  • Wound healing
  • Oral cavity
  • Oronasal fistula
  • FTY720
  • ORONASAL FISTULAS
  • ANTIINFLAMMATORY MONOCYTES
  • REPAIR
  • RECRUITMENT
  • GROWTH
  • VEGF

Improving hard palate wound healing using immune modulatory autotherapies

Tools:

Journal Title:

ACTA BIOMATERIALIA

Volume:

Volume 91

Publisher:

, Pages 209-219

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Oral cavity wound healing occurs in an environment that sustains ongoing physical trauma and is rich in bacteria. Despite this, injuries to the mucosal surface often heal faster than cutaneous wounds and leave less noticeable scars. Patients undergoing cleft palate repair have a high degree of wound healing complications with up to 60% experiencing oronasal fistula (ONF) formation. In this study, we developed a mouse model of hard palate mucosal injury, to study the endogenous injury response during oral cavity wound healing and ONF formation. Immunophenotyping of the inflammatory infiltrate following hard palate injury showed delayed recruitment of non-classical LY6Clo monocytes and failure to resolve inflammation. To induce a pro-regenerative inflammatory response, delivery of FTY720 nanofiber scaffolds following hard palate mucosal injury promoted complete ONF healing and was associated with increased LY6Clo monocytes and pro-regenerative M2 macrophages. Alteration in gene expression with FTY720 delivery included increased Sox2 expression, reduction in pro-inflammatory IL-1, IL-4 and IL-6 and increased pro-regenerative IL-10 expression. Increased keratinocyte proliferation during ONF healing was observed at day 5 following FTY720 delivery. Our results show that local delivery of FTY720 from nanofiber scaffolds in the oral cavity enhances healing of ONF, occurring through multiple immunomodulatory mechanisms. Statement of Significance: Wound healing complications occur in up to 60% of patients undergoing cleft palate repair where an oronasal fistula (ONF) develops, allowing food and air to escape from the nose. Using a mouse model of palate mucosal injury, we explored the role of immune cell infiltration during ONF formation. Delivery of FTY720, an immunomodulatory drug, using a nanofiber scaffold into the ONF was able to attract anti-inflammatory immune cells following injury that enhanced the reepithelization process. ONF healing at day 5 following FTY720 delivery was associated with altered inflammatory and epithelial transcriptional gene expression, increased anti-inflammatory immune cell infiltration, and increased proliferation. These findings demonstrate the potential efficacy of immunoregenerative therapies to improve oral cavity wound healing.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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