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

• Published in: Advanced science 2024-04, Vol.11 (13), p.e2307761-n/a
• Main Authors: Wei, Qian, Su, Jianlong, Meng, Sheng, Wang, Yaxi, Ma, Kui, Li, Bingmin, Chu, Ziqiang, Huang, Qilin, Hu, Wenzhi, Wang, Zihao, Tian, Lige, Liu, Xi, Li, Tanshi, Fu, Xiaobing, Zhang, Cuiping
• Format: Article
• Language: English
• Subjects: Angiogenesis; Cell cycle; collagen deposition; Diabetes; Diabetes Complications - therapy; Diabetes Mellitus - genetics; Diabetes Mellitus - metabolism; diabetic wounds; Endoplasmic reticulum; Endothelial Cells; Extracellular vesicles; Extracellular Vesicles - genetics; Fibroblasts; Gelatin; Glucose; Humans; Hydrogels; Methacrylates; MicroRNAs; MicroRNAs - pharmacology; MicroRNAs - therapeutic use; miR‐17‐5p; Phosphatase; Proteins; Proto-Oncogene Proteins p21(ras) - antagonists & inhibitors; Proto-Oncogene Proteins p21(ras) - genetics; PTEN Phosphohydrolase - antagonists & inhibitors; PTEN Phosphohydrolase - genetics; Senescence; small extracellular vesicles; Stem cells; Wound healing; Wound Healing - genetics
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202307761

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 (sEVs17‐OE) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs17‐OE are successfully fabricated with a 16‐fold increase in miR‐17‐5p expression. SEVs17‐OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, sEVs17‐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 sEVs17‐OE. Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs17‐OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel‐sEVs17‐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 sEVs17‐OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated. miR‐17‐5p‐engineered sEVs (sEVs17‐OE) can restore cellular functions of skin repair cells in diabetic wounds by inhibiting senescence and promoting angiogenesis and collagen deposition. Furthermore, a functional wound dressing by loading sEVs17‐OE into GelMA hydrogel is developed, accelerating the diabetic wound healing process and offering an option for chronic wound management.