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具有良好导电性的干细胞衍生外泌体负载产氧水凝胶复合材料用于心肌梗死后的组织修复过程。

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

作者信息

Xu Zhaoyan, Hong Wanzi, Mo Yuanxi, Shu Fen, Liu Yaoxin, Cheng Yuqi, Tan Ning, Jiang Lei

机构信息

Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.

Department of Cardiology, The First People's Hospital of Foshan, Foshan, 528000, China.

出版信息

J Nanobiotechnology. 2025 Mar 17;23(1):213. doi: 10.1186/s12951-025-03289-y.

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 Ogenerating 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.

摘要

急性心肌梗死(AMI)通过中断氧气供应来破坏心脏细胞。改善向受损区域的氧气输送可能会避免细胞死亡并使心脏再生。我们展示了利用负载过氧化氢酶(CAT)的海藻酸盐(Alg)和与间充质干细胞(MSCs)衍生外泌体(Exo)结合的纤维蛋白(Fib)制备可注射产氧生物大分子水凝胶。该复合水凝胶还具有来自金纳米颗粒(AuNPs)的电刺激特性。体外实验表明,这种复合水凝胶(Exo/Hydro/AuNPs/CAT)表现出与实际心脏相似的导电性,并能有效释放CAT。在缺氧条件下,产氧水凝胶释放氧气近5天。我们表明,体外细胞培养7天后,它产生与大鼠新生心肌细胞(RNCs)、大鼠心脏成纤维细胞(RCFs)和人脐静脉内皮细胞(HUVECs)相同的旁分泌因子,模仿毛细血管结构和功能。我们的工作表明,负载CAT和AuNPs的可注射导电水凝胶可减轻心肌梗死后大鼠的左心室重构和心肌功能障碍。Exo/Hydro/AuNPs/CAT促进梗死边缘血管生成,减少细胞凋亡和坏死,并提高连接蛋白43(Cx43)的表达。这种生物活性可注射导电水凝胶的治疗益处和易于制备使其成为治疗心肌梗死的有效治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea5e/11912659/d15c4cfd76de/12951_2025_3289_Fig1_HTML.jpg

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