Heparin-grafted aligned chitosan/silk fibroin scaffolds with multifunctional bioactivities for cardiovascular applications.

Implantable cardiovascular biomaterials face critical clinical challenges, such as thrombosis, bacterial infection, and insufficient endothelial regeneration. In this study, aligned chitosan/silk fibroin (CS/SF) electrospun scaffolds were fabricated by heparin functionalization via parameter optimization, polydopamine-mediated surface modification, and controlled heparin grafting. A comprehensive characterization confirmed that the optimized scaffolds possessed well-aligned uniform nanofibers, desirable mechanical performance, adjustable hydrophilicity, and programmable degradation behavior. Immobilized heparin displayed a typical release profile consisting of an initial burst phase followed by sustained long-term delivery. In vitro biological evaluations demonstrated that the heparin-modified scaffolds inhibited platelet adhesion and activation and prolonged activated partial thromboplastin time (APTT), yielding favorable anticoagulant efficacy. Benefiting from the synergistic interaction between cationic CS and anionic heparin, the scaffolds exhibited prominent bactericidal effects against Escherichia coli and Staphylococcus aureus. Furthermore, the scaffolds suppressed the expression of pro-inflammatory Interleukin-6 (IL-6) to mitigate inflammatory reactions, facilitated the proliferation, migration and oriented arrangement of endothelial cells, and activated the Hypoxia-Inducible Factor 1-alpha/Vascular Endothelial Growth Factor‌‌ (HIF-1α/VEGF) signaling cascade. The elevated Platelet Endothelial Cell Adhesion Molecule-1 (CD31) expression further validated the endothelial maturation and angiogenic capacity of the scaffolds. Collectively, these multifunctional heparin-grafted CS/SF composite scaffolds integrated anticoagulant, antibacterial, anti-inflammatory, and pro-endothelial bioactivities, making them promising candidates for cardiovascular interventional implants. This study offers a facile and versatile strategy for designing multifunctional bioactive biomaterials for vascular tissue engineering applications.