Tan Ying, Nie Yali, ZhengWen Lei, Zheng Zhi
Hunan Provincial Key Laboratory of Multi-omics And Artificial Intelligence of Cardiovascular Diseases &Department of Cardiology, The First Affiliated Hospital, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study & School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Department of Cardiothoracic Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
J Mater Chem B. 2024 Jun 19;12(24):5838-5847. doi: 10.1039/d4tb00573b.
In cardiac tissue engineering, myocardial surface patches and hydrogel intramyocardial injections represent the two primary hydrogel-based strategies for myocardial infarction (MI) treatment. However, the comparative effectiveness of these two treatments remains uncertain. Therefore, this study aimed to compare the effects of the two treatment modalities by designing a simple and reproducible hydrogel cross-linked with γ-PGA and 4-arm-PEG-SG. To improve mitochondrial damage in cardiomyocytes (CMs) during early MI, we incorporated the mitochondria-targeting antioxidant MitoQ into the hydrogel network. The hydrogel exhibited excellent biodegradability, biocompatibility, adhesion, and injectability . The hydrogel was utilized for rat MI treatment through both patch adhesion and intramyocardial injections. results demonstrated that the slow release of MitoQ peptide from the hydrogel hindered ROS production in CM, alleviated mitochondrial damage, and enhanced CM activity within 7 days, effectively inhibiting MI progression. Both hydrogel intramyocardial injections and patches exhibited positive therapeutic effects, with intramyocardial injections demonstrating superior efficacy in terms of cardiac function and structure in equivalent treatment cycles. In conclusion, we developed a MitoQ/hydrogel system that is easily prepared and can serve as both a myocardial patch and an intramyocardial injection for MI treatment, showing significant potential for clinical applications.
在心脏组织工程中，心肌表面贴片和水凝胶心肌内注射是基于水凝胶治疗心肌梗死（MI）的两种主要策略。然而，这两种治疗方法的相对有效性仍不确定。因此，本研究旨在通过设计一种与γ-聚谷氨酸（γ-PGA）和四臂聚乙二醇琥珀酰亚胺戊二酸酯（4-arm-PEG-SG）交联的简单且可重复的水凝胶，比较这两种治疗方式的效果。为改善心肌梗死早期心肌细胞（CMs）中的线粒体损伤，我们将线粒体靶向抗氧化剂MitoQ纳入水凝胶网络。该水凝胶具有优异的生物降解性、生物相容性、粘附性和可注射性。通过贴片粘附和心肌内注射两种方式将该水凝胶用于大鼠心肌梗死治疗。结果表明，水凝胶中MitoQ肽的缓慢释放可在7天内阻碍心肌细胞中活性氧（ROS）的产生，减轻线粒体损伤并增强心肌细胞活性，有效抑制心肌梗死进展。水凝胶心肌内注射和贴片均显示出积极的治疗效果，在相同治疗周期内，心肌内注射在心脏功能和结构方面表现出更优的疗效。总之，我们开发了一种易于制备的MitoQ/水凝胶系统，它既可以作为心肌贴片，也可以作为心肌内注射剂用于心肌梗死治疗，具有显著的临床应用潜力。
