GelMA hydrogel-loaded extracellular vesicles derived from keratinocytes promote skin microvasculature regeneration and wound healing in diabetic mice through activation of the PDGF-induced PI3K/AKT pathway.

IF 5.3 2区医学 Q2 CELL BIOLOGY

Cell Biology and Toxicology Pub Date : 2025-06-14 DOI:10.1007/s10565-025-10062-2

Qian Li, Leilei Zhou, Wenqiang Li, Weiheng Zhao, Weimin Chen, Mohammed S AlQranei, Jiarui Bi, Ping Huang

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引用次数: 0

Abstract

Objective: This study explores how extracellular vesicles (EVs) derived from keratinocytes cultured in Gelatin Methacryloyl (GelMA) hydrogels facilitate microvascular regeneration and enhance wound repair in diabetic skin ulcers.

Methods: EVs were harvested from keratinocyte cultures via ultracentrifugation and ultrafiltration, followed by characterization. Their uptake and angiogenic effects on human umbilical vein endothelial cells (HUVECs) were assessed in the following experimentations. Transcriptomic profiling of EV-treated HUVECs identified angiogenesis-related gene expression changes. A diabetic murine wound model was established and validated via glycemic profiling and pancreatic histology. In vivo effects of GelMA-EVs were evaluated through wound closure rates, histology (re-epithelialization, vascularization, collagen deposition), CD31 staining, and microvascular imaging.

Results: Keratinocyte-derived EVs significantly enhanced HUVEC proliferation, migration, and tube formation. Mechanistic studies reported elevated PDGF expression, activating the PI3K/AKT pathway. In vivo experiments validated that GelMA hydrogel-loaded EVs increased PDGF expression in wound tissues, promoting microvascular reconstruction and accelerating wound healing in diabetic mouse skin ulcers.

Conclusion: GelMA hydrogel-loaded EVs derived from keratinocytes upregulate PDGF, activating the PI3K/AKT pathway to promote microvascular network reconstruction and enhance wound healing in diabetic mouse skin ulcers.

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来源于角质形成细胞的GelMA水凝胶负载细胞外囊泡通过激活pdgf诱导的PI3K/AKT通路促进糖尿病小鼠皮肤微血管再生和伤口愈合。

目的：探讨明胶甲基丙烯酰（GelMA）水凝胶培养的角质形成细胞的细胞外囊泡（EVs）如何促进微血管再生和促进糖尿病性皮肤溃疡的伤口修复。方法：从角质细胞培养物中通过超离心和超滤收集ev，然后进行表征。在接下来的实验中，我们评估了它们对人脐静脉内皮细胞（HUVECs）的摄取和血管生成作用。ev处理的HUVECs的转录组学分析鉴定了血管生成相关的基因表达变化。建立了糖尿病小鼠伤口模型，并通过血糖谱和胰腺组织学进行了验证。通过伤口愈合率、组织学（再上皮化、血管化、胶原沉积）、CD31染色和微血管成像来评估gelma - ev的体内效果。结果：角化细胞来源的EVs显著增强HUVEC的增殖、迁移和管状形成。机制研究报告PDGF表达升高，激活PI3K/AKT通路。体内实验证实，装载GelMA水凝胶的ev增加了糖尿病小鼠皮肤溃疡创面组织中PDGF的表达，促进微血管重建，加速创面愈合。结论：来自角质形成细胞的GelMA水凝胶负载ev上调PDGF，激活PI3K/AKT通路，促进糖尿病小鼠皮肤溃疡微血管网络重建，促进创面愈合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.