Engineering functional perfusion in vascularized cardiac grafts through bioactive biomaterials and biofabrication

Vascularized cardiac grafts are being developed to overcome the limited survival and incomplete integration of engineered myocardial tissues after implantation. Although many platforms can now generate endothelial networks, the central challenge is no longer the presence of vascular-like structures alone, but the establishment of networks that remain perfusable, mechanically stable, and functionally coupled to the host circulation. This review discusses cellular design, bioactive biomaterial selection, biofabrication strategies, flow-mediated endothelial maturation, and preclinical evaluation of vascularized cardiac grafts. We compare the roles of cardiomyocytes, endothelial and mural cells, and supportive stromal populations, and examine how bioactive matrix cues, bioprinting, perfusion culture, and hemodynamic conditioning influence vascular stability. Attention is given to the distinction between structural vascularization and functional perfusion, as this remains a major bottleneck in interpreting experimental outcomes and advancing translational studies. Finally, we highlight emerging challenges related to hiPSC-derived cell maturity, manufacturing reproducibility, long-term patency, electromechanical integration, and large-animal validation. Progress in this field will likely depend on treating vascularized grafts as integrated living systems rather than static tissue constructs.