Compliant bilayer vascular grafts with in situ heparin functionalization for small diameter vascular regeneration

Given the scarcity of autologous graft donors, a substantial and pressing demand exists for small-diameter (<6 mm) vascular grafts (SDVGs) as viable alternatives in bypass and reconstructive surgeries for the treatment of cardiovascular diseases, including coronary artery disease and peripheral artery disease. However, the challenges of compliance mismatch, inadequate endothelialization, and insufficient anticoagulation of SDVGs generally lead to side effects like thrombosis, inflammation and intimal hyperplasia. To address these issues, this study proposes a biomimetic bilayer SDVG with heparin modification fabricated through dry-jet wet spinning. This comprises a reinforced outer layer for sufficient mechanical strength and a flexible inner layer for high compliance, effectively mimicking the mechanical properties of natural vessels. The one-step in-situ heparin coating strategy represents a significant simplification for fabrication, ensuring uniform heparin distribution to prevent platelet aggregation and thrombus formation, and enhancing endothelial cell (EC) adhesion, spreading, and proliferation. The in vivo evaluation of rabbit carotid artery demonstrates that the vascular graft achieves excellent long-term patency without apparent obstruction or thrombosis. Five months post-implantation, compositions similar to native blood vessels are formed, and immunofluorescence staining shows positive expression for ECs and smooth muscle cells and the persistent infiltration of M2-polarized macrophages on the inner surface. The proposed fabrication strategy provides a novel solution for vascular replacement and has potential applications in vascular bypass and reconstruction.