AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-06-11 DOI:10.1016/j.bioactmat.2025.06.013

Wenzhang Liu , Hongchao Huang , Futing Shu , Yingying Liu , Jiezhi Lin , Lu Yang , Wei Zhang , Luofeng Jiang , Tianyi Liu , Chaoran Xie , Lei Li , Yin He , Shichu Xiao , Yongjun Zheng , Zhaofan Xia

{"title":"AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4","authors":"Wenzhang Liu , Hongchao Huang , Futing Shu , Yingying Liu , Jiezhi Lin , Lu Yang , Wei Zhang , Luofeng Jiang , Tianyi Liu , Chaoran Xie , Lei Li , Yin He , Shichu Xiao , Yongjun Zheng , Zhaofan Xia","doi":"10.1016/j.bioactmat.2025.06.013","DOIUrl":null,"url":null,"abstract":"<div><div>Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired keratinocyte function, both of which are key factors contributing to delayed healing. In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing. We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues, with detrimental effects on keratinocyte proliferation, migration, and apoptosis. Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4 (OLFM4), a key gene associated with cell proliferation, adhesion and migration. To optimize delivery and therapeutic efficacy, we engineered MSC-derived exosomes loaded with antagomiR-192-5p (ant-192; Final content: 2 nmol per wound; Loading efficiency: 35.22 ± 0.34 %) and then encapsulated into a composite hydrogel composed of GelMA and MXene (Ti<sub>3</sub>C<sub>2</sub>Tx) nanosheets, forming a multifunctional dressing (Exo-ant-192@M-Gel). It achieved sustained release of ant-192, delay its degradation, and exert anti-inflammatory properties, thus promoting epithelization and burn wound healing. This study offered a novel therapeutic approach for burn wound closure.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"52 ","pages":"Pages 318-337"},"PeriodicalIF":18.0000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioactive Materials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452199X25002361","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired keratinocyte function, both of which are key factors contributing to delayed healing. In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing. We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues, with detrimental effects on keratinocyte proliferation, migration, and apoptosis. Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4 (OLFM4), a key gene associated with cell proliferation, adhesion and migration. To optimize delivery and therapeutic efficacy, we engineered MSC-derived exosomes loaded with antagomiR-192-5p (ant-192; Final content: 2 nmol per wound; Loading efficiency: 35.22 ± 0.34 %) and then encapsulated into a composite hydrogel composed of GelMA and MXene (Ti₃C₂Tx) nanosheets, forming a multifunctional dressing (Exo-ant-192@M-Gel). It achieved sustained release of ant-192, delay its degradation, and exert anti-inflammatory properties, thus promoting epithelization and burn wound healing. This study offered a novel therapeutic approach for burn wound closure.

查看原文本刊更多论文

包裹在mxene修饰的GelMA水凝胶中的antagomir -192-5p工程外泌体通过靶向OLFM4促进烧伤创面上皮的形成

烧伤创面愈合是一个多方面的过程，通常会因过度炎症和角化细胞功能受损而复杂化，这两者都是导致愈合延迟的关键因素。在这项研究中，我们通过高通量测序筛选氧化应激条件下调节上皮化过程的关键miRNA。我们发现miR-192-5p在角质形成细胞和烧伤创面组织的氧化应激模型中均显著上调，对角质形成细胞的增殖、迁移和凋亡有不利影响。抑制miR-192-5p通过上调olfactomedin-4 （OLFM4）来增强表皮细胞功能，OLFM4是与细胞增殖、粘附和迁移相关的关键基因。为了优化递送和治疗效果，我们设计了msc衍生的外泌体，装载了antagomiR-192-5p(抗-192；最终含量：2nmol /伤口；负载效率：35.22±0.34%)，然后包封成由GelMA和MXene （Ti3C2Tx）纳米片组成的复合水凝胶，形成多功能填料（Exo-ant-192@M-Gel）。它实现了抗192的持续释放，延缓其降解，并发挥抗炎特性，从而促进上皮和烧伤创面愈合。本研究为烧伤创面愈合提供了一种新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.