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用于伤口管理的生物工程化细胞外囊泡水凝胶调节炎症微环境

Bioengineered Extracellular Vesicle Hydrogel Modulating Inflammatory Microenvironment for Wound Management.

作者信息

Mu Yunfei, Ma Liwen, Yao Jia, Luo Dan, Ding Xianguang

机构信息

State Key Laboratory of Organic Electronics and Information Displays, Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

The First College of Clinical Medicine, Nanjing Medical University, Nanjing 211100, China.

出版信息

Int J Mol Sci. 2024 Dec 5;25(23):13093. doi: 10.3390/ijms252313093.

DOI:10.3390/ijms252313093
PMID:39684803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642447/
Abstract

Chronic wounds, frequently arising from conditions like diabetes, trauma, or chronic inflammation, represent a significant medical challenge due to persistent inflammation, heightened infection risk, and limited treatment solutions. This study presents a novel bioengineered approach to promote tissue repair and improve the healing environment. We developed a bioactive hydrogel patch, encapsulated zeolitic imidazolate framework-8 (ZIF-8) into extracellular vesicles (EVs) derived from anti-inflammatory M2 macrophages, and synthesized ZIF@EV, then embedded it in the sodium alginate matrix. This hydrogel structure enables the controlled release of therapeutic agents directly into the wound site, where it stimulates endothelial cell proliferation and promotes new blood vessel formation. These processes are key components of effective tissue regeneration. Crucially, the EV-infused patch influences the immune response by polarizing macrophages towards an M2 phenotype, shifting the wound environment from inflammation toward regenerative healing. When applied in a murine model of chronic wounds, the EV hydrogel patch demonstrated notable improvements in healing speed, quality, and tissue integration compared to traditional approaches such as growth factor therapies and foam dressings. These promising findings suggest that this bioactive hydrogel patch could serve as a versatile, practical solution for chronic wound management, providing an adaptable platform that addresses both the biological and logistical needs of wound care in clinical settings.

摘要

慢性伤口通常由糖尿病、创伤或慢性炎症等病症引起,由于持续炎症、感染风险增加以及治疗方案有限,构成了重大的医学挑战。本研究提出了一种新型生物工程方法,以促进组织修复并改善愈合环境。我们开发了一种生物活性水凝胶贴片,将沸石咪唑酯骨架-8(ZIF-8)封装到源自抗炎M2巨噬细胞的细胞外囊泡(EVs)中,合成ZIF@EV,然后将其嵌入海藻酸钠基质中。这种水凝胶结构能够将治疗剂直接可控地释放到伤口部位,在那里它刺激内皮细胞增殖并促进新血管形成。这些过程是有效组织再生的关键组成部分。至关重要的是,注入EV的贴片通过使巨噬细胞向M2表型极化来影响免疫反应,将伤口环境从炎症转变为再生愈合。当应用于慢性伤口的小鼠模型时,与生长因子疗法和泡沫敷料等传统方法相比,EV水凝胶贴片在愈合速度、质量和组织整合方面表现出显著改善。这些有前景的发现表明,这种生物活性水凝胶贴片可以作为慢性伤口管理的一种通用、实用的解决方案,提供一个适应临床环境中伤口护理的生物学和后勤需求的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/b86e317214c7/ijms-25-13093-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/8a0c427ff2f8/ijms-25-13093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/c09aea3bb4cc/ijms-25-13093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/36b606d463e0/ijms-25-13093-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/d94ba678741f/ijms-25-13093-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/b86e317214c7/ijms-25-13093-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/8a0c427ff2f8/ijms-25-13093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/c09aea3bb4cc/ijms-25-13093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/36b606d463e0/ijms-25-13093-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/d94ba678741f/ijms-25-13093-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e801/11642447/b86e317214c7/ijms-25-13093-g005.jpg

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本文引用的文献

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Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation.机械电子刺激自体细胞外囊泡生物合成植入物以调节肠道微生物群。
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Paintable Bioactive Extracellular Vesicle Ink for Wound Healing.可喷涂生物活性细胞外囊泡墨水用于伤口愈合。
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The roles of extracellular vesicles in the immune system.细胞外囊泡在免疫系统中的作用。
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Chronic wounds.慢性创面。
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Emerging treatment strategies in wound care.伤口护理的新兴治疗策略。
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