Synaptic-Like Structured Hierarchically Oriented Fibrous Scaffolds Guide Integrin Mechanotransduction for Myocardial Repair

Abstract

Myocardial infarction (MI) remains a severe threat to global health. The loss of cardiomyocytes and structural damage to the ventricles following MI lead to cardiac dysfunction. Current myocardial repair scaffolds promote tissue regeneration by mimicking the natural structure of myocardial tissue, yet suffer from the limitation of focusing on a single dimension of repair, failing to address the complex pathological microenvironment after MI characterized by ischemia, inflammation, and stress mismatch. To overcome this, our study has developed a multiscale bionic fibrous scaffold. The scaffold combines directional freezing with electrospinning technology. While constructing oriented channels that mimic natural myocardial tissue, it embeds nanofibers into the channel walls to form synapse-like microstructures. In vivo and in vitro experiments demonstrate that this scaffold synergistically promotes myocardial repair through multiple mechanisms: providing mechanical support, promoting angiogenesis, and regulating macrophage polarization. It significantly improves cardiac ejection function and inhibits ventricular remodeling. This repair mechanism results from the nanofiber synapse structure activating downstream intracellular signaling networks through its integrin binding sites, thereby regulating cellular behavior. In summary, this study provides a novel strategy for developing myocardial repair materials that synergistically regulate multicellular tissues and match complex pathological microenvironments.

Graphical Abstract