Development of 3D-printed vascular graft with compliance matching to reduce wall shear stress

다국어 초록 (Multilingual Abstract)

ABSTRACT

Atherosclerosis is a chronic arterial disease characterized by the accumulation of cholesterol and inflammatory cells within the vessel wall, leading to luminal narrowing and vascular stiffening, and is a major underlying cause of life‑threatening cardiovascular complications such as angina, myocardial infarction, stroke, and peripheral arterial disease. Coronary artery bypass grafting (CABG), in which the occluded vessel is surgically bypassed, is widely performed as a definitive treatment for advanced atherosclerotic disease, and autologous vascular conduits are regarded as the clinical gold standard. However, in many patients, comorbidities or a history of previous surgery limit the availability of suitable autologous vessels, thereby creating a persistent clinical need for small‑diameter artificial vascular grafts.
Commercial synthetic polymer vascular grafts such as expanded polytetrafluoroethylene (ePTFE) and Dacron have achieved satisfactory outcomes in large‑diameter vessels, but their use in small‑diameter arteries (< 6 mm) is severely limited by early thrombosis and restenosis driven by intimal hyperplasia (IH). The principal cause of these failures is the mechanical mismatch in compliance between the rigid synthetic graft and the native artery. Owing to their high stiffness and limited elastic response under pulsatile flow, conventional vascular grafts induce hemodynamic disturbances and abnormal wall shear stress at the anastomotic sites, which in turn trigger phenotypic switching and pathological proliferation of vascular smooth muscle cells (VSMCs), ultimately promoting neointimal thickening.
In this study, an auxetic architecture with a negative Poisson’s ratio was implemented in a polycaprolactone (PCL)‑based small‑diameter vascular graft to optimize graft–artery compliance and thereby mitigate hemodynamic disturbances associated with intimal hyperplasia. A three‑layered tubular graft was constructed by precisely 3D printing an auxetic PCL supporting scaffold and subsequently coating it with an electrospun layer that mimics the fibrous architecture of the extracellular matrix (ECM).
The performance of the auxetic vascular graft was systematically evaluated through stepwise assessment of compliance, hemodynamic behavior, and biological responses. Physiological pressure conditions were replicated using a balloon catheter expansion system, and graft compliance was quantified by measuring diameter changes between systolic and diastolic pressures. In addition, three‑dimensional computational fluid dynamics (CFD) analysis was performed to characterize blood flow patterns within the graft, including velocity fields and wall shear stress distributions. Finally, a biomimetic perfusion bioreactor system was employed to culture vascular smooth muscle cells under flow, enabling detailed assessment of cell adhesion, proliferation, and phenotype switching under physiologically relevant hemodynamic conditions.
Under uniaxial tensile testing, the auxetic cut‑missing rib pattern exhibited a negative Poisson’s ratio behavior, showing lateral expansion rather than contraction, and thereby achieved substantially enhanced compliance and flexibility compared with the positive Poisson’s ratio rhombus design, closely approximating the deformation characteristics of native arteries. CFD analysis further revealed that the cut‑missing rib graft minimized intraluminal flow disturbance and prevented abrupt local acceleration, resulting in a significant reduction in wall shear stress, a key hemodynamic driver of intimal hyperplasia. In a biomimetic pulsatile flow bioreactor, this mechanically and hemodynamically favorable environment suppressed excessive proliferation of vascular smooth muscle cells and prevented their transition to a synthetic phenotype, thereby maintaining a contractile phenotype profile as confirmed by Western blot analysis.
​These findings indicate that an auxetic structural design can serve as an effective structural strategy to address the long‑standing problem of compliance mismatch in synthetic vascular grafts. The 3D‑printed auxetic PCL graft, with its favorable hemodynamic performance and biocompatibility, is therefore expected to effectively suppress intimal hyperplasia and provide a promising small‑diameter graft platform with the potential to improve long‑term patency.