Hierarchically structured nanocomposite cardiac patch for localized therapeutic delivery of bFGF for myocardial repair

The cardiac lymphatic network plays a vital role in maintaining tissue homeostasis and fluid balance. Myocardial infarction (MI) severely disrupts the lymphatic vasculature, resulting in edema and inflammation, impeding cardiac repair. There is currently limited research on therapies targeting cardiac lymphatics for cardiac repair. Therefore, in the current study, we have developed a bioengineered cardiac patch to load and deliver bioactive lymphangiocrine (bFGF) to the infarcted cardiac tissue. The fabricated cardiac patch consisted of electrospun core–shell nanofibers (PCL-Gelatin), functionalized with “Donut-like” mesoporous polydopamine nanoparticles to load bFGF (DGF-CP). The DGF-CP demonstrated sustained release behavior of bFGF for more than 7 days and maintained its bioactivity. When tested in vivo on a rodent MI model, a significant improvement in cardiac function (EF% & FS%) was observed. The improved cardiac function may be attributed to the synergistic effect of bFGF delivery and patch-mediated structural support, which effectively attenuated cardiac fibrosis and pathological left ventricular remodeling. Furthermore, DGFP-CP treatment resulted in enhanced angiogenesis (VWF + , α-SMA + ), lymphangiogenesis (LYVE1 + ), and reduced accumulation of CD68 + macrophages, supporting cardiac repair. The transcriptomic changes at the cellular level were assessed by single-nuclei RNA sequencing post-MI. Additionally, exploratory analysis suggests that DGF-CP augments cardiac repair by promoting lymphangiogenesis through the VEGFC axis, which is pivotal in resolving chronic inflammation after myocardial infarction. This study highlights the importance of cardiac patch for localized drug delivery and providing structural support for cardiac repair.