关键词: 气流辅助电纺, 聚四氟乙烯血管支架覆膜, 功能化改性, 抗凝血, 促内皮化

Abstract:

Objective Cardiovascular diseases (CVDs) are a class of clinical syndromes characterized by dysfunction of the heart and vascular system, and have become the leading cause of death globally. In clinical practice, stent grafts are widely used for interventional treatment, where the graft membrane serves as a physical barrier and plays a critical role in cases such as aneurysm occlusion, vascular perforation repair, and arterial stenosis management. Currently, expanded polytetrafluoroethylene (ePTFE) has become one of the commonly used membrane materials in clinical practice by virtue of its excellent biocompatibility, stable mechanical properties, and chemical inertness. However, commercial ePTFE grafts often suffer from poor long-term patency due to their chemical inertness, which hinders endothelialization and triggers thrombogenic responses. While electrospinning offers a promising alternative for mimicking the natural extracellular matrix (ECM), conventional electrospinning is severely limited by low production efficiency and jet instability, hindering industrial-scale manufacturing. Therefore, this study aims to address these dual challenges by developing a high-throughput airflow-assisted electrospinning strategy to fabricate PTFE vascular stent membranes. Furthermore, to overcome the bio-inert nature of PTFE, a surface functionalization strategy is proposed to simultaneously endow the grafts with potent anticoagulant properties and the capacity to promote rapid endothelialization, thereby enhancing their clinical translation potential.

Method A novel airflow-assisted electrospinning system utilized a high-velocity air stream to manipulate the polymer jet trajectory and enhance solvent evaporation. The influences of key processing parameters, particularly extrusion rate, on fiber morphology and deposition efficiency were systematically optimized. In order to functionalize the chemically inert PTFE surface, a multi-step modification protocol was employed. First, the membranes underwent air plasma activation to introduce initial reactive groups. Subsequently, a bio-adhesive intermediate layer was constructed by co-depositing dopamine (DA) and polyethyleneimine (PEI) under mild alkaline conditions (Tris-HCl, pH=8.5). Finally, heparin (HEP) was covalently immobilized onto the amine-rich DA/PEI layer by EDC/NHS activation chemistry. Physicochemical properties were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy(FT-IR), energy dispersive spectroscopy(EDS), and contact angle measurements. Biological performance was evaluated through in vitro heparin release profiles, hemolysis assays, blood clotting index (B_BCI) tests, platelet adhesion studies, and endothelial cell (ECs) proliferation assays using CCK-8 and fluorescence imaging.

Results Airflow assisting significantly suppressed the whipping instability of the electrospinning jet, resulting in more uniform and finer fibers compared to the conventional method. The airflow-assisted process achieved a unit time production of 0.012 8 g/min, a 4.13 time increase over the 0.003 1 g/min rate of conventional electrospinning. This denser packing improved mechanical performance, with the tensile strength of the PTFE stent membrane increasing significantly to 13.38 MPa. Surface analysis confirmed the successful deposition of the functional coating, with the water contact angle dropping drastically to near 0°, indicating a transition from superhydrophobicity to superhydrophilicity. The DA/PEI intermediate layer is proved highly effective for drug loading; the functionalized PTFE-DA/PEI-HEP surface achieved a heparin density of 32.914 μg/cm², a 4.7 time increase compared to direct adsorption (P<0.01), and demonstrated a sustained release profile over 7 d. Regarding hemocompatibility, the modified membranes exhibited an extremely low hemolysis ratio of 0.72%, far below the 5% international standard. The B_BCI value was improved by 24.97% compared to unmodified PTFE, reaching 74.23%. Furthermore, SEM revealed that platelet adhesion density decreased by 44.19% (to 480 platelets/mm²), with minimal platelet activation observed. Cytocompatibility assays demonstrated that the coating created a favorable microenvironment for endothelial cells; by 5 d, the relative proliferation rate of endothelial cells on the modified surface reached 104.13%, representing a 3.1% enhancement over the unmodified control, with fluorescence imaging confirming a dense, healthy cell monolayer.

Conclusion This study establishes a scalable airflow-assisted electrospinning protocol that overcomes the production efficiency bottleneck of PTFE nanofiber membranes while significantly reducing costs compared to thermal stretching methods. The combination of plasma treatment and DA/PEI-mediated heparin grafting transforms the bio-inert PTFE surface into a bioactive interface. The resulting vascular stent membranes possess excellent mechanical strength, superior hemocompatibility, and the ability to promote endothelialization. These findings suggest that the developed PTFE-DA/PEI-HEP membranes offer a robust solution for replacing ePTFE stent membranes, which is promising for future clinical applications.

Key words: airflow-assisted electrospinning, polytetrafluoroethylene vascular stent membrane, functional modification, anticoagulation, endothelialization promotion