PF-PEG@ASIV-EXO Hydrogel Accelerates Diabetic Wound Healing by Ferroptosis Resistance and Promoting Angiogenesis.

IF 5.4 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Biomaterials Science & Engineering Pub Date : 2024-09-23 DOI:10.1021/acsbiomaterials.4c00692

Wu Xiong, Xi Zhang, Jinhui Hu, Xiaoling Zou, Hongyu Huang, Wenjing Qu, Shimin Cai, Chengyu Li, Yang Wei, Xingxing Zhong, Zhaoyang Cai, Zixin Huang

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Abstract

Astragaloside IV (ASIV) promotes the proliferation of key cells, endothelial progenitor cells (EPCs), during the wound healing process, while exosomes and hydrogels are ideal drug delivery carriers. This study aims to explore the mechanism of action of the "ROS-responsive hydrogel-engineered EPCs-targeted exosomes" composite ASIV delivery system (PF-PEG@ASIV-EXO) in diabetic wound healing. Surface markers of EPCs and PF-PEG@ASIV-EXO were detected separately. The degradation rate of PF-PEG@ASIV-EXO was assessed after coculturing with human dermal fibroblasts (HDF), immortalized human epidermal cells (HaCAT), and human EPCs, and the biocompatibility of EPCs and PF-PEG@ASIV-EXO was evaluated through exosome release and uptake. The effects of PF-PEG@ASIV-EXO on the viability, angiogenesis, ferroptosis, and mitochondria of high-glucose-treated EPCs (HS-EPCs) were investigated. A diabetic wound rat model was established, and the effects of PF-PEG@ASIV-EXO on diabetic wounds were evaluated through HE and Masson staining, as well as levels of VWF, CD31, and ferroptosis in the skin. EPCs were successfully isolated, and PF-PEG@ASIV-EXO was successfully constructed. PF-PEG@ASIV-EXO exhibited a high degradation rate within EPCs, and both EPCs and PF-PEG@ASIV-EXO showed good biocompatibility. PF-PEG@ASIV-EXO promoted the vitality and angiogenesis of EPCs, inhibited ferroptosis, and mitigated mitochondrial damage. Following treatment with PF-PEG@ASIV-EXO, the healing of diabetic rat skin accelerated, accompanied by elevated expression of VWF and CD31, and reduced ferroptosis levels. PF-PEG@ASIV-EXO hydrogel inhibits ferroptosis, promotes angiogenesis, and thereby accelerates the healing of diabetic wounds.

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PF-PEG@ASIV-EXO水凝胶通过抗铁蛋白沉积和促进血管生成加速糖尿病伤口愈合

黄芪甲苷IV（ASIV）能促进伤口愈合过程中的关键细胞--内皮祖细胞（EPCs）的增殖，而外泌体和水凝胶是理想的药物输送载体。本研究旨在探索 "ROS响应水凝胶-EPCs靶向外泌体 "复合ASIV递送系统（PF-PEG@ASIV-EXO）在糖尿病伤口愈合中的作用机制。分别检测了EPCs和PF-PEG@ASIV-EXO的表面标记物。与人真皮成纤维细胞（HDF）、永生化人表皮细胞（HaCAT）和人EPCs共培养后，评估了PF-PEG@ASIV-EXO的降解率，并通过外泌体的释放和吸收评估了EPCs和PF-PEG@ASIV-EXO的生物相容性。研究了PF-PEG@ASIV-EXO对高葡萄糖处理的EPCs（HS-EPCs）的活力、血管生成、铁突变和线粒体的影响。建立了糖尿病伤口大鼠模型，并通过 HE 和 Masson 染色以及皮肤中的 VWF、CD31 和铁蛋白沉积水平评估了 PF-PEG@ASIV-EXO 对糖尿病伤口的影响。EPCs 成功分离，PF-PEG@ASIV-EXO 成功构建。PF-PEG@ASIV-EXO在EPCs内表现出较高的降解率，EPCs和PF-PEG@ASIV-EXO均表现出良好的生物相容性。PF-PEG@ASIV-EXO促进了EPCs的活力和血管生成，抑制了铁变态反应，减轻了线粒体损伤。使用 PF-PEG@ASIV-EXO 治疗后，糖尿病大鼠皮肤愈合加快，同时 VWF 和 CD31 表达升高，铁蛋白沉积水平降低。PF-PEG@ASIV-EXO 水凝胶可抑制铁蛋白沉积，促进血管生成，从而加速糖尿病伤口的愈合。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

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