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用于增强血管生成和心肌细胞保护的具有外泌体释放功能的3D打印导电壳聚糖-聚苯胺支架的评估

evaluation of 3D-printed conductive chitosan-polyaniline scaffolds with exosome release for enhanced angiogenesis and cardiomyocyte protection.

作者信息

Hashemi Amir, Ezati Masoumeh, Zumberg Inna, Chmelíková Larisa, Fohlerová Zdenka, Provazník Valentýna

机构信息

Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology Technicka 3082/12 61600 Brno Czech Republic

Department of Microelectronics, Faculty of Electrical Engineering and Communication, Brno University of Technology Technicka 3082/12 61600 Brno Czech Republic.

出版信息

RSC Adv. 2025 May 20;15(21):16826-16844. doi: 10.1039/d5ra02940f. eCollection 2025 May 15.


DOI:10.1039/d5ra02940f
PMID:40395791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12090194/
Abstract

Myocardial infarction (MI) often results in significant damage to heart tissues, leading to cardiac dysfunction, fibrosis, and diminished cell-cell communication. Exosomes (EXOs) from stem cells show great potential in promoting tissue repair and angiogenesis, but their rapid clearance and degradation limit therapeutic efficacy. Here, we introduce a 3D-printed scaffold using a conductive biomaterial ink composed of chitosan (CS) and polyaniline (PANI). This scaffold combines the bioactivity of EXOs with the conductive properties of PANI to protect cardiac cells under ischemic stress. Using an hypoxia/reoxygenation (H/R) model with HL-1 cardiomyocytes, we simulated key aspects of myocardial ischemia-reperfusion injury. The addition of PANI improved the electrical conductivity of the scaffold, which was essential for enhancing cardiomyocyte viability and intercellular connectivity under hypoxic conditions. EXOs significantly promoted angiogenic activity , as evidenced by enhanced human umbilical vein endothelial cell (HUVEC) migration and robust tube formation, highlighting their role in stimulating new blood vessel growth. Molecular analyses revealed that EXOs positively influence processes such as angiogenesis and inflammation regulation in HL-1 cells. Additionally, EXOs improved HUVEC migration, emphasizing their pro-angiogenic role. These findings indicate that combining PANI and EXOs in a 3D-printed scaffold yields synergistic benefits, improving cardiomyocyte function and promoting endothelial angiogenesis , thereby providing insights for future cardiac repair strategies.

摘要

心肌梗死(MI)常导致心脏组织严重受损,进而引发心脏功能障碍、纤维化以及细胞间通讯减弱。干细胞来源的外泌体(EXOs)在促进组织修复和血管生成方面具有巨大潜力,但其快速清除和降解限制了治疗效果。在此,我们介绍一种使用由壳聚糖(CS)和聚苯胺(PANI)组成的导电生物材料墨水3D打印的支架。这种支架将外泌体的生物活性与聚苯胺的导电特性相结合,以保护缺血应激下的心脏细胞。我们使用HL-1心肌细胞的缺氧/复氧(H/R)模型模拟了心肌缺血再灌注损伤的关键方面。聚苯胺的添加提高了支架的电导率,这对于在缺氧条件下提高心肌细胞活力和细胞间连接至关重要。外泌体显著促进了血管生成活性,人脐静脉内皮细胞(HUVEC)迁移增强和强大的管腔形成证明了这一点,突出了它们在刺激新血管生长中的作用。分子分析表明,外泌体对HL-1细胞中的血管生成和炎症调节等过程产生积极影响。此外,外泌体改善了HUVEC迁移,强调了它们的促血管生成作用。这些发现表明,在3D打印支架中结合聚苯胺和外泌体可产生协同效益,改善心肌细胞功能并促进内皮血管生成,从而为未来的心脏修复策略提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/57141505f37e/d5ra02940f-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/0b78c2e2be55/d5ra02940f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/41223c4bec0a/d5ra02940f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/9b7b2290d599/d5ra02940f-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/b198e10f2f25/d5ra02940f-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/b9b75757fddf/d5ra02940f-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/452f604f198a/d5ra02940f-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/57141505f37e/d5ra02940f-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/0b78c2e2be55/d5ra02940f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/41223c4bec0a/d5ra02940f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/9b7b2290d599/d5ra02940f-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/b198e10f2f25/d5ra02940f-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/b9b75757fddf/d5ra02940f-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/452f604f198a/d5ra02940f-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4606/12090194/57141505f37e/d5ra02940f-f7.jpg

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本文引用的文献

[1]
Stem cells derived exosome laden oxygen generating hydrogel composites with good electrical conductivity for the tissue-repairing process of post-myocardial infarction.

J Nanobiotechnology. 2025-3-17

[2]
Injectable pH Responsive Conductive Hydrogel for Intelligent Delivery of Metformin and Exosomes to Enhance Cardiac Repair after Myocardial Ischemia-Reperfusion Injury.

Adv Sci (Weinh). 2025-2-18

[3]
Black-Phosphorus-Reinforced Injectable Conductive Biodegradable Hydrogel for the Delivery of ADSC-Derived Exosomes to Repair Myocardial Infarction.

ACS Appl Mater Interfaces. 2024-10-30

[4]
Chitosan alchemy: transforming tissue engineering and wound healing.

RSC Adv. 2024-6-17

[5]
Electrically Conductive Collagen-PEDOT:PSS Hydrogel Prevents Post-Infarct Cardiac Arrhythmia and Supports hiPSC-Cardiomyocyte Function.

Adv Mater. 2024-7

[6]
Role of extracellular vesicles in insulin resistance: Signaling pathways, bioactive substances, miRNAs, and therapeutic potential.

Cell Biochem Funct. 2024-4

[7]
A New Strategy for the Regulation of Neuroinflammation: Exosomes Derived from Mesenchymal Stem Cells.

Cell Mol Neurobiol. 2024-2-19

[8]
Priming and Combined Strategies for the Application of Mesenchymal Stem Cells in Ischemic Stroke: A Promising Approach.

Mol Neurobiol. 2024-9

[9]
Conducting polymer scaffolds: a new frontier in bioelectronics and bioengineering.

Trends Biotechnol. 2024-6

[10]
A Novel Conductive Polypyrrole-Chitosan Hydrogel Containing Human Endometrial Mesenchymal Stem Cell-Derived Exosomes Facilitated Sustained Release for Cardiac Repair.

Adv Healthc Mater. 2024-4

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