Department of Cardiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, No. 2, Sipailou, Nanjing 210096, China.
ACS Appl Mater Interfaces. 2022 Sep 14;14(36):40491-40500. doi: 10.1021/acsami.2c05352. Epub 2022 Aug 29.
Uncontrolled and excessive fibrosis after myocardial infarction (MI) in the peri-infarct zone leads to left ventricular remodeling and deterioration of cardiac function. Inhibiting fibroblast activation during the mature phase of cardiac repair improves cardiac remodeling and function after MI. Here, we engineered a biocompatible microneedle (MN) patch using gelatin methacryloyl and loaded it with galunisertib, a transforming growth factor-beta (TGF-β)-specific inhibitor, to treat excessive cardiac fibrosis after MI. The MN patch could sustainably release galunisertib for more than 2 weeks and provide mechanical support for the fragile ventricular wall. After being applied to a rat model of MI, the galunisertib-loaded MN patch improved long-term cardiac function and reduced cardiac fibrosis by effectively inhibiting TGF-β depending on fibroblast activation. This strategy shows the potential of the MN patch as an advanced platform to locally deliver direct antifibrotic drugs to prevent myocardial fibrosis for the treatment of MI and the promotion of cardiac repair.
心肌梗死后（MI）梗死周边区不受控制和过度的纤维化会导致左心室重构和心功能恶化。在心脏修复的成熟阶段抑制成纤维细胞激活可改善 MI 后的心脏重构和功能。在这里，我们使用明胶甲基丙烯酰基构建了一种生物相容性的微针（MN）贴片，并将其装载成纤维细胞生长因子-β（TGF-β）特异性抑制剂 galunisertib，以治疗 MI 后过度的心脏纤维化。MN 贴片可以持续释放 galunisertib 超过 2 周，并为脆弱的心室壁提供机械支撑。在应用于 MI 大鼠模型后，载有 galunisertib 的 MN 贴片通过有效抑制 TGF-β依赖的成纤维细胞激活，改善了长期的心脏功能并减少了心脏纤维化。该策略显示了 MN 贴片作为一种先进平台的潜力，可局部递送直接抗纤维化药物，以预防 MI 心肌纤维化并促进心脏修复。
