MiR-17-5p-engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21.

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  • Additional Information
    • Source:
      Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Weinheim : WILEY-VCH, [2014]-
    • Subject Terms:
      Diabetes Mellitus*/genetics ; Diabetes Mellitus*/metabolism ; Extracellular Vesicles*/genetics ; Gelatin* ; Methacrylates* ; MicroRNAs*/pharmacology ; MicroRNAs*/therapeutic use ; Wound Healing*/genetics; Humans ; Endothelial Cells ; Glucose ; Hydrogels ; PTEN Phosphohydrolase/antagonists & inhibitors ; PTEN Phosphohydrolase/genetics ; Diabetes Complications/therapy ; Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors ; Proto-Oncogene Proteins p21(ras)/genetics
    • Abstract:
      Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR-17-5p-engineered sEVs (sEVs 17-OE ) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs 17-OE are successfully fabricated with a 16-fold increase in miR-17-5p expression. SEVs 17-OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose-induced human umbilical vein endothelial cells (HG-HUVECs). Additionally, sEVs 17-OE also performs a promotive effect on high glucose-induced human dermal fibroblasts (HG-HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR-17-5p, are downregulated significantly by sEVs 17-OE . Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs 17-OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel-sEVs 17-OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs 17-OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.
      (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
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    • Grant Information:
      82172211 National Nature Science Foundation of China; 22205260 National Nature Science Foundation of China; 92268206 National Nature Science Foundation of China; 81830064 National Nature Science Foundation of China; 2022YFA1104303 National Key Research and Development Programs of China; CIFMS 2019-I2M-5-059 CAMS Innovation Fund for Medical Sciences; 2022-JCJQ-ZB-09600 Military Medical Research Projects; 2023-JSKY-SSQG-006 Military Medical Research Projects; 7242129 Natural Science Foundation of Beijing; ZYGD22008 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University
    • Contributed Indexing:
      Keywords: angiogenesis; collagen deposition; diabetic wounds; miR‐17‐5p; small extracellular vesicles
    • Accession Number:
      9000-70-8 (Gelatin)
      0 (gelatin methacryloyl)
      IY9XDZ35W2 (Glucose)
      0 (Hydrogels)
      0 (Methacrylates)
      0 (MicroRNAs)
      0 (MIRN17 microRNA, human)
      EC 3.1.3.67 (PTEN Phosphohydrolase)
      EC 3.1.3.67 (PTEN protein, human)
      EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
    • Publication Date:
      Date Created: 20240129 Date Completed: 20240404 Latest Revision: 20240415
    • Publication Date:
      20240416
    • Accession Number:
      PMC10987139
    • Accession Number:
      10.1002/advs.202307761
    • Accession Number:
      38286650