Release of exosomes from injectable silk fibroin and alginate composite hydrogel for treatment of myocardial infarction

IF 2.3 4区医学 Q3 ENGINEERING, BIOMEDICAL Journal of Biomaterials Applications Pub Date : 2024-04-30 DOI:10.1177/08853282241251610

Yunjie Ni, Yinjian Hua, Zhengfei He, Weilv Hu, Zhiyun Chen, Diqing Wang, Xintong Li, Yanfang Sun, Guohua Jiang

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Abstract

Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-β1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.

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从注射用丝纤维素和海藻酸盐复合水凝胶中释放外泌体，用于治疗心肌梗死

心肌梗死（MI）被认为是全球死亡的重要原因。外泌体（EXOs）对多种心血管疾病的细胞间通信和病理生理学至关重要。然而，外泌体的半衰期短、清除快，导致输送到病变区域的治疗剂量不足。因此，我们开发了一种可注射的蚕丝纤维素和海藻酸盐（SF/Alg）复合水凝胶，用于结合来自 H9C2 细胞的叶酸受体靶向 EXOs（FA-EXOs），治疗心肌梗塞-缺血/再灌注（MI-I/R）后的心肌损伤。由此产生的复合材料具有多种特性，包括可调节的凝胶化动力学、剪切稀化注射性、适应心跳的柔软性和动态稳定性以及出色的细胞相容性。将 SF/Alg + FA-EXOs 注入受损的大鼠心脏后，射血分数、分数缩短率和纤维化面积均有所改善，从而显著增强了心脏功能。实时 PCR 和免疫荧光染色结果显示，与心脏相关的蛋白质（CD31）和基因（VWF 和 Serca2a）的表达明显上调。相反，纤维化相关基因（TGF-β1）的表达则明显下降。因此，所获得的 SF/Alg + FA-EXOs 系统能明显增强细胞间的相互作用，促进细胞增殖和血管生成，对心肌梗死有很好的治疗效果。

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 Biomaterials Applications 工程技术-材料科学：生物材料

CiteScore

5.10

自引率

3.40%

发文量

144

审稿时长

1.5 months

期刊介绍： The Journal of Biomaterials Applications is a fully peer reviewed international journal that publishes original research and review articles that emphasize the development, manufacture and clinical applications of biomaterials. Peer-reviewed articles by biomedical specialists from around the world cover: New developments in biomaterials, R&D, properties and performance, evaluation and applications Applications in biomedical materials and devices - from sutures and wound dressings to biosensors and cardiovascular devices Current findings in biological compatibility/incompatibility of biomaterials The Journal of Biomaterials Applications publishes original articles that emphasize the development, manufacture and clinical applications of biomaterials. Biomaterials continue to be one of the most rapidly growing areas of research in plastics today and certainly one of the biggest technical challenges, since biomaterial performance is dependent on polymer compatibility with the aggressive biological environment. The Journal cuts across disciplines and focuses on medical research and topics that present the broadest view of practical applications of biomaterials in actual clinical use. The Journal of Biomaterial Applications is devoted to new and emerging biomaterials technologies, particularly focusing on the many applications which are under development at industrial biomedical and polymer research facilities, as well as the ongoing activities in academic, medical and applied clinical uses of devices.