Improving hard palate wound healing using immune modulatory autotherapies
| Autor: | Samir A. Ballestas, Yvonne C. Stephenson, Archana Kamalakar, Thomas C. Turner, Nick J. Willett, Edward A. Botchwey, Steven L. Goudy |
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| Rok vydání: | 2019 |
| Předmět: |
Palate
Hard Pathology medicine.medical_specialty 0206 medical engineering Nanofibers Biomedical Engineering Scars Inflammation 02 engineering and technology Biochemistry Article Immunomodulation Biomaterials Mice Immune system Immunophenotyping medicine Animals Molecular Biology Nose Wound Healing Fingolimod Hydrochloride business.industry Macrophages SOXB1 Transcription Factors General Medicine 021001 nanoscience & nanotechnology 020601 biomedical engineering medicine.anatomical_structure Gene Expression Regulation Cytokines Hard palate medicine.symptom 0210 nano-technology Keratinocyte Wound healing business Biotechnology |
| Zdroj: | Acta Biomater |
| ISSN: | 1742-7061 |
| DOI: | 10.1016/j.actbio.2019.04.052 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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