A Bilayer Vascular Graft With Functionally Separated Structural Support and Bioactive Remodeling for Stable...

Cardiovascular diseases remain a leading cause of mortality worldwide, and the lack of effective small-diameter vascular grafts (SDVGs, < 6 mm) continues to limit clinical treatment options. A major challenge in the development of tissue-engineered vascular grafts (TEVGs) is the mismatch between material degradation and tissue regeneration rates, which is driven by individual variability and leads to failure in mechanical support transition, subsequent graft failure, and impeded clinical translation. Here, we report a functionally separated bilayer SDVG that decouples long-term structural support from early bioactive remodeling. The graft consists of a slowly degradable knitted polylactic acid (PLA) framework that preserves mechanical integrity, and a rapidly remodelable chitosan/gelatin (CS/GE) porous phase that promotes cell infiltration and tissue regeneration. By tuning the CS/GE composition, we identified a balanced remodeling window, in which the 1% CS/GE-PLA graft achieved favorable permeability, cytocompatibility, hemocompatibility, and mechanical performance. In a rabbit carotid interposition model, this optimized graft maintained 100% patency for 3 months and progressively remodeled into a native vessel-like trilaminar structure with endothelial coverage, smooth muscle organization, and extracellular matrix maturation. This bilayer design provides a strategy to coordinate scaffold degradation with tissue regeneration, enabling stable mechanical support and functional vascular remodeling in small-diameter grafts.