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, <6mm) necessitate regenerative SDVGs with antithrombotic properties. In this study, a recently developed 3D printed regenerative SDVG with a nanoengineered controlled release system of nitric oxide (NO) was pre-clinically investigated in a sheep model aiming to tackle this unmet clinical need. Thrombogenicity of the NO releasing SDVGs was evaluated in an ex vivo shunt model in sheep, investigating short-term (30 minutes) and long-term (2 hours) clot formation. Moreover, to facilitate long-term implantability, the flexibility and suturability of the SDVGs were customized closely mimicking the native vascular tissue. Ex vivo assessments demonstrated that NO releasing grafts prevented thrombus formation with significantly (P < 0.0001) lower clot weights (0 to 4 mg) comparing with control grafts (16.42 ± 4.65 mg), showing their anti-thrombogenicity. Flow rate was minimal reduced (0% vs. 7.54 ± 3.92%, P=0.0022) compared to control grafts. Tailored adjustment of tensile moduli exhibited promising flexibility and suturability of SDVGs to the sheep carotid artery ex vivo, which is crucial for future in vivo implantation. In conclusion, this study represents a potential breakthrough of implanting NO releasing grafts in vivo, thereby addressing clinical challenges associated with current options. The findings contribute to advancements in cardiovascular applications and hold a potential for broader tissue engineering applications, making an important impact in the field of regenerative implants.