Harnessing Physiological Shear Stress in a Perfusion Bioreactor for Enhanced Endothelialization of Small-Diameter Vascular Grafts

This study presents a versatile perfusion bioreactor system designed to evaluate endothelialization on electrospun polycaprolactone (PCL)–gelatin vascular grafts under controlled flow conditions that mimic physiological and pathological shear stress. The bioreactor enables direct assessment of endothelial cell behavior on 3D graft structures, providing a more physiologically relevant platform compared to traditional static cultures. Electrospun PCL–gelatin grafts demonstrate uniform endothelial cell coverage when exposed to physiological shear stress (>10 dyn cm⁻²), with cells displaying alignment in the direction of flow. Under these conditions, endothelial cells upregulate endothelial nitric oxide synthase and platelet endothelial cell adhesion molecule-1, markers associated with vascular homeostasis, anti-inflammatory activity, and enhanced endothelial migration. In contrast, grafts subjected to pathological shear stress (<5 dyn cm⁻²) exhibit increased expression of intercellular adhesion molecule-1, promoting monocyte adhesion and a proinflammatory response. These findings highlight the importance of physiological flow dynamics in regulating endothelial function and demonstrate the value of this bioreactor system as a platform prior to preclinical evaluation of vascular grafts. By providing a more accurate in vitro model, this system may accelerate the development of bioengineered vascular grafts with improved clinical outcomes.