Increased Flexibility and Hemocompatibility of NO-Releasing Small Diameter Vascular Grafts in an Ex Vivo Sheep Model

Addressing global cardiovascular morbidity, the high thrombogenicity, occlusion, and failure risk in small-diameter vascular grafts (SDVGs, <6 mm) necessitate regenerative SDVGs with antithrombotic properties. In this study, a previously developed nanoengineered controlled release system of nitric oxide (NO) was now preclinically investigated in a 3D printed polylactic acid SDVG using an ex vivo arteriovenous shunt model in sheep. Thrombogenicity of the NO releasing SDVGs was evaluated by short-term (30 min) and long-term (2 h) clot formation. To facilitate future long-term implantation, the flexibility of the cast SDVGs was customized by tailoring Young's modulus of polycaprolactone to closely mimic the native vascular tissue. Ex vivo assessments demonstrated that NO releasing grafts significantly reduced thrombus formation with significantly lower clot weights (0 to 4 mg) compared with control grafts (16.42 ± 4.65 mg, P <0.0001), showing their antithrombogenicity. Flow rate reduction was minimal (0% vs 7.54 ± 3.92%, P = 0.0022) compared to control grafts. Tailored adjustment of the mechanical properties demonstrated plasticized casted PCL SDVGs at 40 wt % plasticizer, an essential balance for surgical handling and future in vivo implantation. These results indicate reduced thrombogenic response under ex vivo conditions, a basic requirement for future preclinical evaluation of NO releasing SDVGs and mechanically tailored scaffolds. The findings contribute to advancements in translational vascular graft development and hold potential for broader tissue engineering applications, making an important impact in the field of regenerative implants.