Electrospun vascular adventitia–derived ECM/PCL fiber-co-hydrogel scaffold: A novel approach to vascular regeneration with enhanced cell affinity and tunable biomechanical properties

Despite advancements in small-diameter vascular grafts (SDVGs), they continue to face significant clinical challenges, including thrombosis, insufficient endothelialization, and incompatible mechanical properties. To address these limitations, this study developed a heparin-incorporated vascular adventitia extracellular matrix (vaECM)/PCL fiber-co-hydrogel vascular scaffold using electrospinning-co-electrospray technology combined with vaECM self-assembly gelation. This scaffold combines the mechanical strength of PCL fibers with the bioactivity of vaECM hydrogel, while the incorporated heparin enhances its antithrombotic properties. Material characterization reveals that the fiber-co-hydrogel scaffold possesses a biomimetic layered structure, tunable mechanical properties, self-healing ability, low swelling ratio, and hierarchical degradation. Co-culture experiments with endothelial cells and smooth muscle cells demonstrate that this scaffold significantly promotes endothelial cell adhesion, proliferation, and migration, as well as the maturation of smooth muscle cells. Blood compatibility tests confirm its superior anticoagulant and antiplatelet properties. In a rat abdominal aorta replacement model, the scaffold showed significantly enhanced endothelial coverage by week 4, and by week 16, it supported the regeneration of mature vascular smooth muscle and orderly remodeling of the extracellular matrix. These results highlight the remarkable vascular regenerative potential of this fiber-co-hydrogel scaffold, driven by its bioactive vaECM hydrogel and bio-matched material stiffness, offering a promising avenue for the clinical application of small-diameter vascular grafts.