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

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Zhaoyan Xu, Wanzi Hong, Yuanxi Mo, Fen Shu, Yaoxin Liu, Yuqi Cheng, Ning Tan, Lei Jiang
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Abstract

Acute myocardial infarction (AMI) destroys heart cells by disrupting the oxygen supply. Improving oxygen delivery to the injured area may avoid cell death and regenerate the heart. We present the creation of oxygen-producing injectable bio-macromolecular hydrogels using catalase (CAT) loaded alginate (Alg) and fibrin (Fib) incorporated with the Mesenchymal stem cells (MSCs) derived exosomes (Exo). The composite hydrogel additionally incorporates electrical stimulating qualities from gold nanoparticles (AuNPs). In vitro experiments showed that this composite hydrogel (Exo/Hydro/AuNPs/CAT) exhibits electrical conductivity similar to an actual heart and effectively releases CAT. The O2-generating hydrogel released oxygen for almost 5 days under hypoxia conditions. We showed that after 7 days of in vitro cell culture, produces the same paracrine factors as rat neonatal cardiomyocytes (RNCs), rat cardiac fibroblasts (RCFs), and Human Umbilical Vein Endothelial Cells (HUVECs), imitating capillary architecture and function. Our work demonstrated that the injectable conductive hydrogel loaded with CAT and AuNPs reduced left ventricular remodeling and myocardial dysfunction in rats after MI. Exo/Hydro/AuNPs/CAT boosted infarct margin angiogenesis, decreased cell apoptosis, and necrosis, and elevated Connexm43 (Cx43) expression. The therapeutic benefits and the ease of production of oxygen make this bioactive injectable conductive hydrogel an effective therapeutic agent for MI.

干细胞衍生的外泌体载氧水凝胶复合材料在心肌梗死后的组织修复过程中的良好导电性。
急性心肌梗死(AMI)通过破坏氧气供应来破坏心脏细胞。改善对受伤部位的氧气输送可以避免细胞死亡并使心脏再生。我们提出了利用负载海藻酸盐(Alg)和纤维蛋白(Fib)的过氧化氢酶(CAT)与间充质干细胞(MSCs)衍生的外泌体(Exo)结合制备可注射的产氧生物大分子水凝胶。复合水凝胶还含有来自金纳米颗粒(AuNPs)的电刺激特性。体外实验表明,这种复合水凝胶(Exo/Hydro/AuNPs/CAT)具有与实际心脏相似的导电性,并能有效释放CAT。生成o2的水凝胶在缺氧条件下释放氧气近5天。我们发现,经过7天的体外细胞培养,产生与大鼠新生心肌细胞(RNCs)、大鼠心脏成纤维细胞(rfc)和人脐静脉内皮细胞(HUVECs)相同的旁分泌因子,模仿毛细血管的结构和功能。我们的研究表明,载CAT和AuNPs的可注射导电水凝胶可减少心肌梗死后大鼠左心室重构和心肌功能障碍。Exo/Hydro/AuNPs/CAT可促进梗死边缘血管生成,减少细胞凋亡和坏死,并提高Connexm43 (Cx43)的表达。治疗的好处和易于生产氧气使这种生物活性可注射导电水凝胶成为心肌梗死的有效治疗剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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