Engineering Next-Generation Vascular Grafts with Improved Endothelialization and Long-Term Patency

The rising global burden of cardiovascular diseases has intensified the demand for vascular grafts (VGs) that provide mechanical durability and hemocompatibility for replacing damaged or occluded vessels. While autologous conduits remain the clinical gold standard, their limited availability has accelerated the pursuit of dependable synthetic and tissue-engineered alternatives for both vascular reconstruction and regeneration. An ideal VG must function as a multifunctional conduit, offering anatomical conformity, mechanical robustness, long-term patency, thromboresistance, and active support for endothelialization. However, despite extensive progress, a comprehensive assessment evaluation integrating these diverse requirements remains limited. This review addresses this gap by presenting a comprehensive overview of the current landscape of VG development. It outlines fundamental design principles rooted in vascular anatomy and highlights persistent challenges in achieving seamless biological integration. Key fabrication strategies, such as electrospinning, 3D bioprinting, and decellularization, are discussed alongside surface modification approaches, including heparinization, peptide functionalization, and endothelial cell (EC) seeding. Hemocompatibility parameters such as platelet adhesion, thrombogenicity, and complement activation are summarized with reference to ISO 10993 and FDA regulatory standards. The review also evaluates material selection, recent clinical outcomes, commercial grafts, and regulatory-compliant testing protocols. By integrating these advances, this work offers a strategic framework to accelerate the development and clinical translation of physiologically relevant VGs.