含有一氧化氮释放氧化锌和褪黑素调节细胞外囊泡的多重聚乳酸乙烯-丙烯酸酯（PLGA）支架，用于治疗严重慢性肾病。

IF 11.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2025-03-01 DOI:10.1016/j.jare.2024.03.018

Won-Kyu Rhim , Jiwon Woo , Jun Yong Kim , Eun Hye Lee , Seung-Gyu Cha , Da-Seul Kim , Seung-Woon Baek , Chun Gwon Park , Bum Soo Kim , Tae Gyun Kwon , Dong Keun Han

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引用次数: 0

摘要

导言：随着慢性肾脏病（CKD）在全球的流行，通过组织再生恢复肾功能的策略可替代肾脏替代疗法。然而，由于肾基底细胞的可重复性相对较低，植入生物材料的生物活性有限，加上物质诱发炎症和免疫原性的可能性较高，肾组织再生可能具有挑战性：方法：基于可生物降解的多孔聚乳酸（PLGA）平台，成功制备了含有重要生物活性成分（如蓖麻油酸接枝镁（OH）2（M）、细胞外基质（E）和α-硫辛酸共轭氧化锌（Z））的混合PMEZ支架。此外，为了改善功能，还将在无血清杂质的化学定义培养基中提取的人脐带间充质干细胞的褪黑素调节细胞外小泡（mEVs）加载到PMEZ支架上，构建了多重PMEZ/mEV支架：结果：在Mg(OH)2和细胞外基质负载PLGA支架的功能作用下，改性ZnO的一氧化氮持续释放特性和mEVs的再生功能显著提高，肾脏再生活性明显增强。在此基础上，5/6 肾切除小鼠模型（模拟严重的人类 CKD）已实现了结构和功能的恢复：我们的研究证明了基于可降解聚乳酸（PLGA）的多重支架在代表严重慢性肾功能衰竭模型的 5/6 肾切除小鼠中用于肾组织再生的综合生物活性。肾组织形态形成和功能恢复的最佳微环境成功实现了 PMEZ/mEV 重要成分的生物活性组合，这可能是治疗 CKD 的一种有前途的替代疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease

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Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease

Introduction

With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging.

Objectives

To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds.

Methods

Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)₂ (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold.

Results

With functionalities of Mg(OH)₂ and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD.

Conclusion

Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

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来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.