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一种具有活性氧响应释放模式的工程强化细胞外囊泡整合水凝胶可减轻脊髓损伤。

An engineering-reinforced extracellular vesicle-integrated hydrogel with an ROS-responsive release pattern mitigates spinal cord injury.

作者信息

Cao Jian, Zhang Xunqi, Guo Jing, Wu Jiahe, Lin Lingmin, Lin Xurong, Mu Jiafu, Huang Tianchen, Zhu Manning, Ma Lan, Zhou Weihang, Jiang Xinchi, Wang Xuhua, Feng Shiqing, Gu Zhen, Gao Jian-Qing

机构信息

State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Sci Adv. 2025 Apr 4;11(14):eads3398. doi: 10.1126/sciadv.ads3398. Epub 2025 Apr 2.

DOI:10.1126/sciadv.ads3398
PMID:40173229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11963969/
Abstract

The local delivery of mesenchymal stem cell-derived extracellular vesicles (EVs) via hydrogel has emerged as an effective approach for spinal cord injury (SCI) treatment. However, achieving on-demand release of EVs from hydrogel to address dynamically changing pathology remains challenging. Here, we used a series of engineering methods to further enhance EVs' efficacy and optimize their release pattern from hydrogel. Specifically, the pro-angiogenic, neurotrophic, and anti-inflammatory effects of EVs were reinforced through three-dimensional culture and dexamethasone (Dxm) encapsulation. Then, the prepared Dxm-loaded 3EVs (3EVs-Dxm) were membrane modified with ortho-dihydroxy groups (-2OH) and formed an EV-integrated hydrogel (3EVs-Dxm-Gel) via the cross-link with phenylboronic acid-modified hyaluronic acid and tannic acid. The phenylboronic acid ester in 3EVs-Dxm-Gel enabled effective immobilization and reactive oxygen species-responsive release of EVs. Topical injection of 3EVs-Dxm-Gel in SCI rats notably mitigated injury severity and promoted functional recovery, which may offer opportunities for EV-based therapeutics in central nervous system injury.

摘要

通过水凝胶局部递送间充质干细胞衍生的细胞外囊泡(EVs)已成为治疗脊髓损伤(SCI)的一种有效方法。然而,实现EVs从水凝胶中的按需释放以应对动态变化的病理状况仍然具有挑战性。在此,我们使用了一系列工程方法来进一步提高EVs的疗效,并优化其从水凝胶中的释放模式。具体而言,通过三维培养和地塞米松(Dxm)包封增强了EVs的促血管生成、神经营养和抗炎作用。然后,将制备的载有Dxm的3EVs(3EVs-Dxm)用邻二羟基(-2OH)进行膜修饰,并通过与苯基硼酸修饰的透明质酸和单宁酸交联形成EV整合水凝胶(3EVs-Dxm-Gel)。3EVs-Dxm-Gel中的苯基硼酸酯能够有效固定EVs并实现活性氧响应性释放。在SCI大鼠中局部注射3EVs-Dxm-Gel可显著减轻损伤严重程度并促进功能恢复,这可能为中枢神经系统损伤的基于EVs的治疗提供机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/5bc858037ef9/sciadv.ads3398-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/82f845561cec/sciadv.ads3398-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/138a7b260e0b/sciadv.ads3398-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/cd05b1036fce/sciadv.ads3398-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/a7b310061f5d/sciadv.ads3398-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/5bc858037ef9/sciadv.ads3398-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/82f845561cec/sciadv.ads3398-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/3daa03b794aa/sciadv.ads3398-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/138a7b260e0b/sciadv.ads3398-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd6/11963969/cd05b1036fce/sciadv.ads3398-f4.jpg
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