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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

In vivo detection of extracellular vesicles by flexible needle-type microbiosensor

Min Luo,Yuxin Lou,Yingqi Liang,Jiangang Mei,Di Zhang,Fei Lan,Junfang Zhu,Yuxin Fang,Lei Zheng,Shihua Luo,Ye Zhang

Extracellular vesicles (EVs) contain a wealth of biological information and hold great value for disease diagnosis. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency, reduce external interferences and enable continuous or real-time dynamic monitoring. However, developing a simple and accurate in vivo assay for EVs remains challenging. In this study, we constructed an allosteric aptamer-based flexible microneedle biosensor capable of measuring disease-associated EVs in vivo. Firstly, the aptamer binding to CD63 captures EVs and immobilizes it on the electrode, and then the aptamer binding to EGFR contacts the EVs, which results in a change in redox current, due to the proximity of the reporter molecule to the electrode surface decreases electron efficiency. Continuous monitoring of tumor-derived EVs revealed significant variations in EVs concentrations across different tumor stages, which exhibited a strong correlation with tumor volume. This flexible microneedle sensor offers the advantages of selectivity, biocompatibility, and analytical performance, presenting a promising approach for tumor monitoring in vivo .

CAS / MDL: 16961-25-4
研究领域: 生物传感器 · 纳米技术 · 癌症研究 · 分子诊断学 · 生物医学工程
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Nanomaterials · 2026 ·Vol. 16 ·期 18 ·1171 · IF 4.8

Multifunctional Hydrogel Dressing Loaded with DH-EVs Promotes Healing of Bacteria-Infected Diabetic Wounds

Jiemin Dai,Wenwen Zhao,Xin Ma,Wantong Lu,Wentao Zhou,Kan Yin,Meng Zhao

Background: Persistent inflammation and excessive neutrophil extracellular trap (NET) formation hinder the healing of bacteria-infected diabetic wounds. The Salvia miltiorrhiza – Astragalus membranaceus herb pair possesses anti-inflammatory activity, but its poor solubility, rapid metabolic clearance, and unclear material basis limit direct wound application. Extracellular vesicles (DH-EVs) isolated from this herb pair may improve local delivery and stability. Therefore, this work constructs a DH-EV-incorporated hydrogel dressing aimed at inhibiting NET formation and facilitating diabetic wound healing. Methods: DH-EVs were isolated from the Salvia miltiorrhiza – Astragalus membranaceus pair, characterized by lipidomics and small-RNA sequencing, and incorporated into a hydrogel. The dressing was evaluated for physicochemical properties, mechanical performance, biocompatibility, NET inhibition, anti-inflammatory activity, and therapeutic efficacy in vitro and in bacteria-infected diabetic wounds. Results: DH-EVs were isolated, and sequencing identified miRNAs potentially regulating inflammation- and NET-related pathways. Incorporation into hydrogel did not significantly alter mechanical integrity or biocompatibility. In vitro and in vivo, the DH-EV-loaded hydrogel suppressed excessive NET formation, reduced local inflammation, and improved wound closure and tissue regeneration in bacteria-infected diabetic wounds. Conclusions: The DH-EV-loaded hydrogel promotes bacteria-infected diabetic wound repair by suppressing excessive NET formation and inflammation, providing a promising strategy for localized wound treatment.

✓ 已验证 DOI PubMed 高影响因子
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Small · 2026 · IF 11.8

Engineering EVs Via ZnBGs-Integrated 3D Dynamic Culture for Type II Diabetic Pressure Ulcer Therapy

Zhipeng Sun,Yilin Ding,Xiaolin Chen,Zilin Wu,Yue Huang,Huitong Luo,Xiaodong Cao

Pressure ulcers (PUs) under type II diabetic conditions pose a significant clinical challenge due to damage to the vascular and neural networks, a situation further complicated by sustained mechanical pressure resulting from prolonged patient immobility. While engineered extracellular vesicles (EVs) hold therapeutic potential, conventional production methods face limitations such as rapid drug inactivation, compromised EV structural integrity, and poor scalability. Metal-doped bioactive glass (mBGs) extract induces cellular phenotypic changes through continuous ion release and nanoparticle mineralization, employing a non-genetic, non-destructive approach that preserves the integrity of EVs and enables more stable, directed functional induction. To further facilitate scalable manufacturing without compromising directed functional induction, we coupled ZnBGs extract with 3D dynamic cell culture technology for enhanced EVs production. The resulting 3D-ZnBG-EVs significantly increased protein yield and demonstrated enhanced angiogenic and neurogenic functions, which are mediated via the PI3K-AKT-HIF-1α axis. In a Sprague-Dawley (SD) rat model of type II diabetic pressure ulcers, ZnBG-EVs significantly improved vascular and neural repair, extracellular matrix deposition, collagen maturation, and overall wound closure. This integrated strategy provides a scalable, function-directed platform for EVs-based PUs therapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Mitochondrial energy reprogramming via dECM/GP@EVs@Gpnmb to prevent post-myocardial infarction heart failure

Na Li,Ying Wang,Ling Yuan,Shuang Peng,Zhansheng Hu,Baoquan Wang,Dan Zhang,Longxiang Su,Huiping Wu

Heart failure following myocardial infarction (MI) remains a major cause of mortality. This study aimed to prevent post-MI heart failure by facilitating macrophage mitochondrial transfer through Engineered Extracellular Vesicles-Dextran-Peptide Hydrogel (dECM/GP@EVs@Gpnmb) to induce reprogramming of myocardial mitochondrial energy metabolism. Key macrophage subsets in MI progression were identified using single-cell RNA sequencing data. A mouse model with Gpnmb knockout in macrophages was developed, showing exacerbated myocardial injury. In vitro experiments demonstrated that Gpnmb+ macrophages could transfer “healthy” mitochondria to cardiomyocytes, regulating mitochondrial energy metabolism. The dECM/GP@EVs@Gpnmb promoted a reparative macrophage phenotype, improving mitochondrial energy metabolism in cardiomyocytes and reducing myocardial damage. In vivo , dECM/GP@EVs@Gpnmb treatment enhanced the accumulation of EVs@Gpnmb in infarcted areas, improving cardiac function in MI mice. Overall, this approach holds promise for preventing and treating post-MI heart failure by mediating macrophage mitochondrial transfer and reprogramming myocardial mitochondrial function.

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Stem Cells International · 2025 ·Vol. 2025 ·期 1 ·5243270 · IF 3.3

Therapeutic Potential of hucMSC-EVs in Diabetic Kidney Disease via Regulating the miR-146b-5p/Merlin/YAP Axis

Bei Li,Qiongni Wang,Linru Shi,Qifeng Liu,Hui Qian,Lixia Yu,Cheng Ji

Diabetic kidney disease (DKD) is characterized by a continuous decline in renal function and progressive fibrosis, making it a leading cause of end-stage kidney disease with limited therapeutic options. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown great potential in tissue regeneration and repair, offering a new avenue for the treatment of DKD. The purpose of this study is to explore the function and mechanism of action of EVs derived from human umbilical cord MSCs (hucMSC-EVs) in the development of DKD. Our findings show that under high-glucose (HG) conditions, miR-146b-5p is highly expressed in glomerular mesangial cells, downregulating the target protein Merlin, which promotes the activation of the YAP signaling pathway and induces mesangial cell fibrotic-like changes, leading to a significant deposition of collagen and interstitial fibrosis in the kidney. In vivo and in vitro experimental findings reveal that hucMSC-EVs can significantly inhibit miR-146b-5p, upregulate Merlin expression, prevent the nuclear translocation of YAP, improve renal function, and reduce collagen deposition, demonstrating a significant antifibrotic effect. The findings of this study emphasize the central role of the miR-146b-5p/Merlin/YAP axis in hucMSC-EVs-mediated inhibition of renal fibrosis and highlight the potential of MSC-EVs as a targeted nanotherapeutic strategy for DKD.

CAS / MDL: 69-65-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Healthcare Materials · 2023 · IF 10

Sustained Release of BMSC-EVs from 3D Printing Gel/HA/nHAP Scaffolds for Promoting Bone Regeneration in Diabetic Rats

Tingting Yang,Yunsheng Dong,Jinpeng Wan,Xiangsheng Liu,Yufei Liu,Jiaxing Huang,Jie Zhou,Hui Xiao,Lizong Tang,Yanying Wang,Shufang Wang,Hong Cai

Extracellular vesicles (EVs) play an important role in intercellular communication, and the function of EVs mainly depends on the state of source cells. To determine the effect of diabetic microenvironment on EVs secreted by bone marrow mesenchymal stem cells (BMSCs), this work explores the effect of normal glucose (5.5 m m ) cultured BMSCs derived EVs (NG-EVs) and high glucose (30 m m ) cultured BMSCs derived EVs (HG-EVs) in regulating the migration, proliferation and osteoblastic differentiation of BMSCs in vitro. In order to improve the bioavailability of EVs, this work constructs a sustained release system of polydopamine (PDA) functionalized 3D printing gelatin/hyaluronic acid/nano-hydroxyapatite (Gel/HA/nHAP) scaffolds (S/PDA) and verifies its function in the calvarial defect model of diabetic rats. This work confirms that both NG-EVs and HG-EVs can promote proliferation and migration, inhibit apoptosis and promote osteogenic differentiation, but the function of HG-EVs is weaker than that of NG-EVs. Therefore, EVs secreted by autologous cells of diabetic patients are not suitable for self-repair. This work hopes that the 3D printing scaffold designed for sustained-release EVs will provide a new strategy for acellular tissue engineering bone repair in diabetic patients.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 组织工程 · 生物医学工程 · 再生医学 · 细胞生物学 · 材料科学
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CELLULAR AND MOLECULAR LIFE SCIENCES · 2026 ·Vol. 83 ·期 1 ·141 · IF 6.5

Atherosclerotic plaque-derived extracellular vesicles mediate smooth muscle cell phenotypic switching and promote vascular remodeling: EVs promote VSMC phenotypic switching

Jia Wang,Xuan Shi,Di Wang,Jie Gao,Kangmo Huang,Juanji Li,Weichen Dong,Yunzi Li,Hongquan Guo,Yi Wang,Zhenqian Huang,Zhihui Liu,Li Huang,Liangyuan Pan,Xinfeng Liu,Wusheng Zhu,Mengna Peng,Gelin Xu

Background Despite the use of lipid-lowering and anti-inflammatory treatments, the progression of atherosclerosis is relentless in most patients. This suggests the presence of in situ pathological factors that continuously exacerbate lesions. We hypothesized that extracellular vesicles (EVs) within the atherosclerotic microenvironment might act as in situ stimulatory factors on vascular smooth muscle cells (VSMCs), thereby exacerbating atherosclerosis. Methods and results A local atherosclerosis model was induced using Ldlr knockout ( Ldlr KO) rats fed a high-cholesterol diet and subjected to partial carotid ligation. Immunofluorescence, Western blot (WB), and single-cell sequencing confirmed the phenotypic switching of VSMCs in atherosclerotic plaques from both rats and humans. The phenotypic switching of VSMCs in atherosclerotic rats was characterized by reduced expression of VSMC contraction markers and increased expression of LGALS3, PDGFRB, and SCA1. GW4869 inhibited the phenotypic switching of VSMCs in atherosclerotic plaques in a rat model. EVs were extracted from atherosclerotic carotid tissues using differential centrifugation. Chitosan thermosensitive hydrogels were used for in situ delivery of EVs into the arterial wall of the carotid artery. Immunofluorescence staining revealed that atherosclerotic plaque-derived EVs (AS-EVs) promoted VSMC phenotypic switching and downregulated the expression of VSMC contractile markers in vitro. miRNA analysis of EVs derived from atherosclerotic plaques of rats identified miR-23a-3p and its target gene Myl12b . To investigate the underlying mechanisms, engineered EVs loaded with miR-23a-3p were used to mimic AS-EVs. AS-EVs potentially regulate MRTFA nuclear translocation via miR-23a-3p/ Myl12b , inhibit contractile marker expression, promote VSMC phenotypic switching, and further promote carotid artery remodelling. Conclusion We conclude that AS-EVs promote VSMC phenotypic switching and exacerbate atherosclerosis. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-026-06094-4.

CAS / MDL: 13408-09-8 9012-76-4
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JOURNAL OF NANOBIOTECHNOLOGY · 2026 · IF 15

Single-cell transcriptomics-guided dynamic hydrogel delivery of artemisia argyi-derived EVs relieves ER stress and promotes diabetic wound regeneration

Miao Dazhuang,Suo Xiaopeng,Geng Xinqian,Yang Ying,Wang Gaoming,Zhou Yang,Jia Yunhe,Yang Shuofei,Li Heping,Li Gaohua

Diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, and delayed tissue regeneration, yet effective strategies to regulate the pathological immune microenvironment remain limited. Here, integrated single-cell transcriptomics and multi-omics analyses revealed significant enrichment of endoplasmic reticulum stress (ERS)-related signaling in pro-inflammatory macrophages within diabetic wounds, suggesting a potential mechanism driving chronic inflammation. To target this process, we developed an injectable dynamic hydrogel (GPOK-2@EVs) incorporating Artemisia argyi-derived extracellular vesicles (EVs) for localized immunomodulatory therapy. The hydrogel was formed through dual dynamic crosslinking between phenylboronic acid-modified gelatin and oxidized konjac glucomannan, providing self-healing capability, injectability, tissue adhesion, and pH/ROS-responsive degradation for sustained EV release. In vitro experiments demonstrated that GPOK-2@EVs exhibited excellent biocompatibility and effectively reprogrammed macrophages toward an anti-inflammatory phenotype, accompanied by reduced inflammatory cytokine secretion, alleviated ERS activation, decreased ROS accumulation, and improved mitochondrial integrity. GPOK-2@EVs significantly enhanced endothelial angiogenic activities, including cytoskeletal remodeling, tube formation, and migration. In a diabetic mouse wound model, GPOK-2@EVs accelerated wound closure, promoted granulation tissue formation and collagen deposition, enhanced vascularization, and suppressed inflammatory and ERS responses. These findings demonstrate that EV-loaded dynamic hydrogels can modulate the inflammatory microenvironment and promote diabetic wound regeneration, providing a promising biomaterial strategy for chronic wound therapy. Graphical GPOK-2@EVs hydrogel promotes wound healing through ROS-responsive EV release, macrophage modulation, inflammatory cytokine reduction, and enhanced angiogenesis.

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Advanced Science · 2025 · IF 14.1

Treatment of Denervated Muscle Atrophy by Injectable Dual-Responsive Hydrogels Loaded with Extracellular Vesicles

Ziheng Bu,Jianxing Jing,Wei Liu,Zhen Fan,Junchao Huang,Zheng Zhou,Jianhai Hu,Jinxi An,Jiachang Hong,Jianing Yu,Daolin Tang,Min Sun,Jianzhong Du,Peng Wu

Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by challenges in delivery and bioactivity within the complex microenvironment of the injury site. To address this issue, an injectable hydrogel is developed that is responsive to both ultrasound and pH, with inherent anti-inflammatory and antioxidant properties, designed to improve the targeted delivery of stem cell-derived EVs. This hydrogel system allows for controlled release of EVs from human umbilical cord mesenchymal stem cells (HUC-MSCs), adapting to the specific conditions of the injury environment. In vivo studies using a rat model of nerve injury demonstrated that the EV-loaded hydrogel (EVs@UR-gel) significantly preserved muscle function. Six weeks post-nerve reconstruction, treated rats exhibited muscle strength, circumference, and wet weight reaching 89.53 ± 0.96%, 76.02 ± 7.49%, and 88.0 ± 2.65% of healthy controls, respectively, alongside an improvement in the sciatic nerve index (−0.11±0.09). This platform presents a novel therapeutic approach by maintaining EV bioactivity, enabling tunable release based on the disease state, and facilitating the restoration of muscle structure and function.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 肌肉骨骼疾病
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Journal of Extracellular Vesicles · 2023 ·Vol. 12 ·期 2 ·e12310 · IF 16

Hypoxia promotes EV secretion by impairing lysosomal homeostasis in HNSCC through negative regulation of ATP6V1A by HIF-1α

Xiaoning Wang,Ruoyi Wu,Peisong Zhai,Zheqi Liu,Ronghui Xia,Zhen Zhang,Xing Qin,Chuwen Li,Wantao Chen,Jiang Li,Jianjun Zhang

Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome-derived EVs are the main subtype affected by insufficient O 2 . The accumulation of hypoxia-inducible factor-1α (HIF-1α) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes. Subsequently, impaired lysosomal degradation contributes to the reduced fusion of multivesicular bodies (MVBs) with lysosomes and enables the secretion of intraluminal vesicles (ILVs) as EVs. These findings establish a HIF-1α-regulated lysosomal dysfunction-EV release axis and provide an exquisite framework to better understand EV biogenesis.

CAS / MDL: 111-30-8
研究领域: 癌症生物学 · 细胞生物学 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Dynamic hydrogel-integrated microneedle patch with extracellular vesicles encapsulation for wound healing

Dan Wu,Xiangyi Wu,Qichen Luan,Qing Tang,Lu Fan,Xin Shou,Xia Gao,Xiaoyun Qian,Yuanjin Zhao

Excessive reactive oxygen species (ROS) generated by wounds and bacterial infection are the great obstacles for diabetic wound closure. Here, we present a novel dual ROS-scavenging and antibacterial microneedle array patch with M2 macrophage-derived extracellular vesicles (M2-EVs) encapsulation for diabetic wound healing. The microneedle patch with a core–shell structure is composed of hyaluronic acid (HA) and PFP hydrogel crosslinked by polyvinyl alcohol (PVA)/2-formylphenylboronic acid (2-FPBA)/polyetherimide (PEI). When exposed to high levels of ROS existed in the wound, the dynamic covalent bonds of the hydrogel network can dissociate and subsequently release M2-EVs from the HA core. Benefitting from ROS-scavenging properties, antibacterial activities, and macrophage polarization driven by M2-EVs, the microneedle patch could effectively promote wound closure in diabetic animal models. These results indicated that the proposed ROS-scavenging microneedle patches with EVs delivery are promising for variety of difficult-to-heal wounds in clinical application.

CAS / MDL: 9002-89-5
研究领域: 生物医学工程 · 伤口愈合 · 材料科学 · 药学
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Journal of Inflammation Research · 2025 · IF 4.1

Cucurbitacin IIa Alleviates Colitis via Promoting the Release of Host-Derived Extracellular Vesicles Encapsulating microRNA-30b-5p

Yinyin Zhao,Binyuan Jiang,Shengnan Zuo

Purpose Cucurbitacins have demonstrated anti-inflammatory effects and show promise for inflammatory bowel diseases. However, the underlying mechanisms by which cucurbitacins affect colitis remain largely unknown.Methods In this study, we investigated the impact of cucurbitacin IIa on dextran sulfate sodium (DSS)-induced colitis in rats and the alterations in intestinal extracellular vesicles (EVs). EVs were isolated and characterized, followed by analysis of the small RNAs and proteins encapsulated within them using small RNA sequencing and proteomics, respectively.Results Our results revealed that cucurbitacin IIa alleviated colitis symptoms in DSS-treated rats, along with changes in the morphology and composition of intestinal EVs. Notably, EVs from cucurbitacin IIa-treated rats also mitigated colitis symptoms in DSS-treated rats. Further analysis showed that cucurbitacin IIa modified the protein profiles and microRNA composition of EVs extracted from the feces of colitis rats. Specifically, microRNA-30b-5p, significantly increased by cucurbitacin IIa, was found to alleviate colitis symptoms in DSS-treated rats. In conclusion, cucurbitacin IIa appears to alleviate colitis by promoting the release of microRNA-30b-5p from host-derived extracellular vesicles.Conclusion These findings enhance our understanding of cucurbitacin IIa’s effects on intestinal health and offer potential new therapeutic targets for inflammatory bowel disease treatment.

CAS / MDL: 58546-34-2
研究领域: 药理学 · 胃肠病学 · 分子生物学
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