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Development of the Next-Generation Biomimetic Lower Extremity Bypass Graft for the Treatment of Peripheral Artery Disease

Courtney K Keiser, University of Nebraska - Lincoln

Abstract

Peripheral artery disease (PAD) often refers to a blockage of the femoropopliteal artery (FPA) due to atherosclerosis that limits blood flow to the lower extremities. Vascular bypass grafts are surgically implanted conduits used to redirect blood flow around the diseased segment of an artery. Synthetic grafts, particularly when used below the knee, have high failure rates, and recent studies attribute failure to the hostile biomechanical environment of the flexing limb that subjects the grafts to complex deformations producing excessive tortuosity, kinking, and slow disturbed flow. The objective of this dissertation was to develop a reinforced vascular bypass graft with mechanical properties similar to native human FPA and capable of longitudinal pre-stretch to minimize graft kinking and tortuosity in the flexed lower limb. Mechanical testing of human FPAs was used to guide the development of the grafts using electrospinning. Nitinol stents and polymers were explored as reinforcement structures. The nitinol reinforcement demonstrated that stents were abrasive under deformations typically experienced with limb movement, but the work resulted in a novel method of assessing abrasive damage of self-expanding peripheral stents that correlated with 12-month primary patency rates of analyzed stents. The use of polymer reinforcement led to the development of a deposition method that generated cohesive kink-resistant grafts capable of physiologic longitudinal pre-stretch. Benchtop testing methods were used to characterize polymer-reinforced grafts in terms of their longitudinal stiffness, burst pressure (689 ± 7 mmHg), suture retention (2.6 ± 0.62 N), cytotoxicity (not cytotoxic), water permeability (71 ± 5 mL*min-1*cm-2), thrombogenicity (negligible platelet activation), and circumferential compliance (1.03 ± 0.04 stretch) under pulsatile flow (120/80 mmHg). Grafts were evaluated in a perfused human cadaver model, which demonstrated 35% reduced graft tortuosity under limb flexion compared to a reinforced commercial polytetrafluoroethylene graft. The results of this dissertation provide new knowledge of manufacturing reinforced nanofibrillar bypass grafts capable of accommodating physiologic longitudinal pre-stretch and describe a new testing methodology for quantifying the abrasiveness of peripheral nitinol stents.

Subject Area

Materials science|Biomedical engineering

Recommended Citation

Keiser, Courtney K, "Development of the Next-Generation Biomimetic Lower Extremity Bypass Graft for the Treatment of Peripheral Artery Disease" (2022). ETD collection for University of Nebraska - Lincoln. AAI29257241.
https://digitalcommons.unl.edu/dissertations/AAI29257241

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