Ultrasound-Activated GelMA Hydrogel Loaded with MSC-EVs Promotes Functional Regeneration of Skin Vasculature, Nerves, and Appendages.

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2025-07-02 DOI:10.1021/acsami.5c07357

Bingyang Yu,Chao Zhang,Dongzhen Zhu,Yanlin Su,Xu Guo,Feng Tian,Jianjun Li,Zhao Li,Wei Song,Yi Kong,Jinpeng Du,Mengde Zhang,Yuyan Huang,Liting Liang,Qinghua Liu,Yaxin Tan,Yue Kong,Yuzhen Wang,Linhao Hou,Sha Huang

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引用次数: 0

Abstract

Severe skin injuries often lead to dysfunctional healing marked by fibrosis and loss of vascular, neural, and appendage structures. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer regenerative potential, their therapeutic efficacy is limited by poor delivery efficiency. Here, we present a bioengineered strategy combining ultrasound stimulation with a gelatin methacryloyl (GelMA) hydrogel-EV delivery platform to address these challenges. Ultrasound serves as a mechanobiological primer, enhancing MSC-EVs internalization via calcium-dependent cytoskeletal remodeling, thereby amplifying pro-regenerative pathways such as angiogenesis (such as VEGF), matrix modulation (such as TGF-β/Smad), and neural repair (such as NGF). In vitro, ultrasound (420 kHz, 5 V) synergized with MSC-EVs (60 μg/mL) significantly boosted fibroblast viability, migration, and secretory functions. In a murine full-thickness wound model, the ultrasound-activated GelMA-EV system accelerated re-epithelialization (90% closure by Day 14), induced robust neovascularization and neurogenesis, and facilitated unprecedented hair follicle regeneration. Mechanistic studies revealed ultrasound-driven calcium in-flow and actin depolymerization as key mediators of enhanced MSC-EVs uptake. This synergistic integration of physical and biochemical cues establishes a transformative paradigm for functional skin regeneration, bridging a critical gap in regenerative therapeutics.

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装载msc - ev的超声激活凝胶水凝胶促进皮肤血管系统、神经和附属物的功能再生。

严重的皮肤损伤常常导致以纤维化和血管、神经和附属物结构丧失为特征的功能失调愈合。虽然间充质干细胞衍生的细胞外囊泡（msc - ev）具有再生潜力，但其治疗效果受到输送效率低的限制。在这里，我们提出了一种生物工程策略，将超声刺激与明胶甲基丙烯酰（GelMA）水凝胶- ev递送平台相结合，以解决这些挑战。超声作为机械生物学引物，通过钙依赖性细胞骨架重塑增强MSC-EVs内化，从而放大促再生途径，如血管生成（如VEGF）、基质调节（如TGF-β/Smad）和神经修复（如NGF）。在体外，超声（420 kHz, 5 V）与msc - ev （60 μg/mL）协同作用可显著提高成纤维细胞的活力、迁移和分泌功能。在小鼠全层伤口模型中，超声激活的GelMA-EV系统加速了再上皮化（第14天闭合90%），诱导了强大的新生血管和神经发生，并促进了前所未有的毛囊再生。机制研究表明，超声驱动的钙流入和肌动蛋白解聚是msc - ev摄取增强的关键介质。这种物理和生化线索的协同整合建立了功能性皮肤再生的变革范例，弥合了再生治疗的关键空白。

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

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.