Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Suzhou Medical College of Soochow University, Soochow University, Suzhou, 215007, P. R. China.
Department of Thoracic and Cardiovascular Surgery, Baotou Central Hospital, Baotou, 014040, P. R. China.
Adv Healthc Mater. 2023 May;12(13):e2202959. doi: 10.1002/adhm.202202959. Epub 2023 Feb 5.
Myocardial infarction (MI) is a cardiovascular disease that poses a serious threat to human health. Uncontrolled and excessive cardiac fibrosis after MI has been recognized as a primary contributor to mortality by heart failure. Thus, prevention of fibrosis or alleviation of fibrosis progression is important for cardiac repair. To this end, a biocompatible microneedle (MN) patch based on gelatin is fabricated to load exosomes containing microRNA-29b (miR-29b) mimics with antifibrotic activity to prevent excessive cardiac fibrosis after MI. Exosomes are isolated from human umbilical cord mesenchymal stem cells and loaded with miR-29b mimics via electroporation, which can be internalized effectively in cardiac fibroblasts to upregulate the expression of miR-29b and downregulate the expression of fibrosis-related proteins. After being implanted in the infarcted heart of a mouse MI model, the MN patch can increase the retention of loaded exosomes in the infarcted myocardium, leading to alleviation of inflammation, reduction of the infarct size, inhibition of fibrosis, and improvement of cardiac function. This design explored the MN patch as a suitable platform to deliver exosomes containing antifibrotic biomolecules locally for the prevention of cardiac fibrosis, showing the potential for MI treatment in clinical applications.
心肌梗死（MI）是一种对人类健康构成严重威胁的心血管疾病。研究发现，MI 后不受控制和过度的心脏纤维化是心力衰竭导致死亡的主要原因。因此，预防纤维化或减轻纤维化进展对于心脏修复至关重要。为此，我们设计了一种基于明胶的生物相容性微针（MN）贴片，用于装载具有抗纤维化活性的 microRNA-29b（miR-29b）模拟物的外泌体，以预防 MI 后过度的心脏纤维化。外泌体从小鼠脐带间充质干细胞中分离出来，并通过电穿孔装载 miR-29b 模拟物，可有效被心脏成纤维细胞内化，上调 miR-29b 的表达并下调纤维化相关蛋白的表达。将 MN 贴片植入 MI 小鼠模型的梗死心脏后，可增加负载的外泌体在梗死心肌中的保留，从而减轻炎症、减少梗死面积、抑制纤维化并改善心功能。该设计探索了 MN 贴片作为一种局部递送含抗纤维化生物分子的外泌体的合适平台，用于预防心脏纤维化，显示出在临床应用中治疗 MI 的潜力。
