<br>封装在 GelMA 水凝胶中的 MiR-17-5p 工程 sEV 通过靶向 PTEN 和 p21 促进糖尿病伤口愈合,Advanced Science

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封装在 GelMA 水凝胶中的 MiR-17-5p 工程 sEV 通过靶向 PTEN 和 p21 促进糖尿病伤口愈合
Advanced Science ( IF 14.3 ) Pub Date : 2024-01-29 , DOI: 10.1002/advs.202307761
Qian Wei _{1,

2} , Jianlong Su _{1,

3} , Sheng Meng _{1,

3} , Yaxi Wang ₁ , Kui Ma _{1,

2} , Bingmin Li ₁ , Ziqiang Chu ₁ , Qilin Huang ₁ , Wenzhi Hu ₁ , Zihao Wang _{1,

3} , Lige Tian ₁ , Xi Liu _{1,

2} , Tanshi Li _{1,

2,

4,

5} , Xiaobing Fu _{1,

2,

3,

5,

6} , Cuiping Zhang _{1,

2,

5,

6}

Affiliation

伤口愈合延迟是糖尿病的主要并发症，并且与细胞功能受损有关。目前的治疗效果并不令人满意。根据之前关于小细胞外囊泡（sEV）中 microRNA 表达的报道，制备了 miR-17-5p 工程化的 sEV（sEVs ^17-OE ）并将其封装在明胶甲基丙烯酰（GelMA）水凝胶中用于糖尿病伤口治疗。成功制备了 SEV ^17-OE ，miR-17-5p 表达增加了 16 倍。 SEVs ^17-OE抑制衰老并促进高糖诱导的人脐静脉内皮细胞 (HG-HUVEC) 的增殖、迁移和管形成。此外，sEVs ^17-OE还对高糖诱导的人真皮成纤维细胞 (HG-HDF) 具有促进作用。机制分析表明，sEVs ^17-OE显着下调 miR-17-5p 靶基因 p21 和磷酸酶和张力蛋白同源物 (PTEN) 的表达。因此，p21 和 PTEN 的下游基因和途径被激活。接下来，将 sEV ^17-OE加载到 GelMA 水凝胶中，以制造新型生物活性伤口敷料并评估其对糖尿病伤口愈合的影响。 Gel-sEVs ^17-OE通过促进血管生成和胶原蛋白沉积有效加速伤口愈合。其细胞机制可能与局部细胞增殖有关。因此，通过在 GelMA 水凝胶中负载 sEVs ^17-OE成功制造了一种新型生物活性伤口敷料，为慢性伤口管理提供了一种选择。

"点击查看英文标题和摘要"

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

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.

更新日期：2024-01-29

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