Hierarchical Biomimetic Electrospun Vascular Grafts for Improved Patency and Regeneration

Abstract Small‐diameter vascular grafts (SDVGs) are essential for cardiovascular disease treatment, particularly in arterial replacement and bypass surgeries. Despite their importance, SDVGs often fail due to thrombosis, inflammation, and intimal hyperplasia, limiting their clinical application. This study develops a hierarchical biomimetic SDVG with a bilayered structure, comprising a dense inner layer and a loose outer layer with larger pores, integrated with a multifunctional coating containing polydopamine (PDA), copper ions (Cu2⁺), and REDV peptides. The PDA‐based hydrophilic coating mimics the endothelial glycocalyx, reducing platelet adhesion, suppressing macrophage activation, and promoting M2 macrophage polarization. These effects, along with Cu‐catalyzed nitric oxide (NO) release, regulate thrombosis and inflammation, establishing a favorable microenvironment for vascular healing and regeneration. REDV peptides synergize with NO to selectively enhance endothelial cell (EC) adhesion, proliferation, and migration, enabling rapid endothelialization. The porous outer layer facilitates smooth muscle cell (SMC) infiltration, while NO inhibit excessive SMC proliferation, preventing restenosis. In vitro and in vivo studies, including implantation in Beagle dog iliac arteries, demonstrate that the graft achieves long‐term patency, superior hemocompatibility, and balanced tissue regeneration. This work offers a promising strategy to overcome current limitations in SDVGs, paving the way for advanced vascular repair and regeneration.