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

被引：19

作者：

Wei, Qian ^{[1
,2
]}

Su, Jianlong ^{[1
,3
]}

Meng, Sheng ^{[1
,3
]}

Wang, Yaxi ^{[1
]}

Ma, Kui ^{[1
,2
]}

Li, Bingmin ^{[1
]}

Chu, Ziqiang ^{[1
]}

Huang, Qilin ^{[1
]}

Hu, Wenzhi ^{[1
]}

Wang, Zihao ^{[1
,3
]}

Tian, Lige ^{[1
]}

Liu, Xi ^{[1
,2
]}

Li, Tanshi ^{[1
,2
,4
,5
,6
]}

Fu, Xiaobing ^{[1
,2
,3
,5
,6
,7
]}

Zhang, Cuiping ^{[1
,2
,5
,6
,7
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Res Ctr Tissue Repair & Regenerat, Affiliated Med Innovat Res Div, Beijing 100048, Peoples R China

[2] Chinese Acad Med Sci, Res Unit Trauma Care, Tissue Repair & Regenerat, 2019RU051, Beijing 100048, Peoples R China

[3] Chinese PLA Med Sch, Beijing 100853, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Emergency, Beijing 100853, Peoples R China

[5] PLA Key Lab Tissue Repair & Regenerat Med, Beijing 100048, Peoples R China

[6] Beijing Key Res Lab Skin Injury Repair & Regenerat, Beijing 100048, Peoples R China

[7] Sichuan Univ, West China Hosp, Innovat Ctr Wound Repair, Chengdu 610041, Sichuan, Peoples R China

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 13期

关键词：

miR-17-5p; angiogenesis; collagen deposition; diabetic wounds; small extracellular vesicles; SMALL EXTRACELLULAR VESICLES; SENESCENCE; CANCER; CELLS; MICRORNA-17-5P; MECHANISMS; EXOSOMES; STRATEGY; INJURY;

D O I：

10.1002/advs.202307761

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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. image

引用

页数：17