Evidence map›Paper›PMID 39665738›Full record

ArticleCytotherapy2025

FTY720P-treated macrophages in PEG-4MAL hydrogels promote oral wound healing.

Andre J Burnham, Afra I Toma, Daniel Shah, Tim Cha, Sundus Kaimari, Monica Behara, Keerthi Priya Chinniampalayam Sekar, Archana Kamalakar, Nick Willett, Edward Botchwey and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cytotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Biomaterials strategy for promoting palatal wound healing.Frontiers in bioengineering and biotechnology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Andre J BurnhamDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA; Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Afra I TomaDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Daniel ShahDepartment of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Tim ChaDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Sundus KaimariDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Monica BeharaDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Keerthi Priya Chinniampalayam SekarDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Archana KamalakarDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Nick WillettDepartment of Bioengineering, University of Oregon, Eugene, Oregon, USA.
Edward BotchweyDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Steven L GoudyDepartment of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; Department of Otolaryngology, Children's Healthcare of Atlanta, Atlanta, Georgia, USA. Electronic address: steven.goudy@emory.edu.

Funding

An immunomodulatory approach to improve oral cavity wound healingR01DE028905 · NIDCR · EMORY UNIVERSITY · PI GOUDY, STEVEN L · 2020 to 2024
$2.7M
T32 CTEng (Cellular and Tissue Engineering) Training ProgramT32GM145735 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI Edward A. Botchwey, Andres J Garcia · 2022 to 2026
$2.3M
NIDCR NIH HHS R01 DE028905NIGMS NIH HHS T32 GM145735
6 · The paper itself

Abstract

BACKGROUND

aimsOral wound healing involves hemostasis, inflammation, proliferation and tissue remodeling. The oral cavity is a complex wound healing environment because of the presence of saliva, a high bacterial burden and ongoing physical trauma from eating. The inflammatory component of wound healing balances the polarization of macrophages in healing tissues between M1 inflammatory macrophages and M2 anti-inflammatory macrophages. M2 macrophages secrete anti-inflammatory and pro-regenerative cytokines and chemokines, which aid wound healing. Fingolimod, or FTY720, a Food and Drug Administration-approved sphingosine-1-phosphate modulator, has been implicated in inducing the polarization of macrophages to the M2 phenotype. In this study, we investigated whether macrophage pre-treatment with phosphorylated FTY720 (FTY720P), the bioactive form of the drug, in a PEG-4MAL hydrogel promotes improved oral wound healing in a critically sized oral mucosal defect model. METHODS AND

resultsUsing cytokine dot blots and Luminex cytokine assays (MilliporeSigma, Burlington, MA, USA), FTY720P-treated murine RAW 264.7 and human THP1-differentiated macrophages in PEG-4MAL hydrogels secreted chemokines and cytokines known to regulate inflammation (e.g., interleukin [IL] 4, IL-13) and induce M2 macrophage polarization (e.g., CCL6, CCL22), leukocyte migration (e.g., CXCL2, CCL2, CCL12, CCL22), angiogenesis (e.g., vascular endothelial growth factor) and epithelialization (e.g., IL-1, IL-17, IL-22). In vitro, FTY720P-treated cells induced chemotaxis of macrophages and fibroblasts in Transwell assays (Corning, Corning, NY, USA) and oral epithelial scratch wound closure. In a murine oronasal fistula (ONF) model of oral wound healing, the local application of FTY720P-treated macrophages in PEG-4MAL hydrogels significantly increased wound closure (75% closure) relative to non-treated cells (40% closure) and blank hydrogel controls (25% closure) (P < 0.0001). Flow cytometry of mouse palatal tissue showed that application of FTY720P-treated macrophage hydrogels to ONFs significantly increased day 7 percentage of M1 and M2 macrophages, mesenchymal stromal cells and CD19+ B cells. Significantly fewer neutrophils, monocytes, CD4+/CD8+ T cells and endothelial cells were observed in the FTY720P-treated macrophage defects, suggesting that FTY720P-treated macrophages in hydrogels promote oral wound healing via suppression of granulation and resolution of inflammation and promotion of tissue maturation.

conclusionsOur data provide new insights into the use of potential FTY720P-treated macrophage therapies for oral wound healing and have clinical implications for cleft palate and oral surgery.

Indexed as

Fingolimod HydrochlorideHydrogelsMacrophagesWound HealingAnimalsCytokinesHumansMiceMouth MucosaPolyethylene GlycolsRAW 264.7 CellsCytokinesFingolimod HydrochlorideHydrogelsPolyethylene Glycolscell therapycleft palate surgeryFTY720head and neck surgeryhydrogelmacrophages

Identifiers

PMID39665738
PMCPMC11810592

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.