Angioplasty and stenting for Peripheral Arterial Disease (PAD) of the femoropopliteal artery (FPA) carries one of the highest rates of reconstruction failure because the FPA experiences low blood flow and large deformations during flexion of the limbs. Our results using perfused human cadaver models and PAD patients demonstrate that these deformations are significantly more severe than assumed previously, and that none of the existing PAD stents are able to adequately accommodate them, resulting in adverse stent-artery interactions that contribute to treatment failure. Informed by the mechanical and structural characteristics of human FPAs determined by studying >900 human arteries of different ages with different risk factors, and utilizing knowledge gained from studying 12 different commercial PAD stents, we propose to focus the current project on translating the results we obtained using human cadaver models to patients, and testing the hypothesis that a new optimized stent design capable of withstanding the severe biomechanical environment of the flexing limbs improves arterial healing. We will accomplish this through three Specific Aims.
In Aim 1 we will validate cadaveric limb flexion-induced deformations using bent-limb patient CTAs at baseline and at 9 and 18 months after stenting. These data will allow us to translate results previously obtained using human cadavers to PAD patients, and to validate the ability of our computational models to predict location and severity of restenosis as a function of patient, lesion, and stent characteristics.
In Aim 2 we will develop and manufacture optimized and generic stents for the FPA that would be able to accommodate limb flexion induced deformations while maintaining low intramural stresses and optimal hemodynamics. These stents will then be manufactured and evaluated in silico and in vitro in comparison with existing commercial devices. Finally, in Aim 3 we will compare optimal, generic, and commercial stents in a preclinical swine model of limb flexion, where performance of our optimized stent design will be compared to the generic design, and to one of the most commonly used commercial stents (Zilver) implanted in the popliteal artery. Validation of cadaveric FPA deformations in live PAD patients, and design of an optimized lower extremity stent may facilitate more durable reconstructions benefiting PAD patients with claudication and critical limb ischemia. Our extensive knowledge of FPA biomechanics and mechanobiology combined with deep understanding of commercial stent designs and computational models of limb flexion-induced deformations, will ensure successful completion of the new Aims, and will promote cost-effective in silico comparative effectiveness studies of current and future cardiovascular devices, helping advance the paradigm of patient-specific modeling and personalized medicine.
Blockages of arteries in the legs are often treated with metal mesh tubes called stents to keep the arteries propped open. These stents often fail resulting in return of symptoms, repeat surgery, or amputation. We propose to develop and test an optimally-designed stent that bends and twists with the artery during walking, and we hypothesize that it will help arteries stay open longer by improving arterial healing.
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|Kamenskiy, Alexey; Poulson, William; Sim, Sylvie et al. (2018) Prevalence of Calcification in Human Femoropopliteal Arteries and its Association with Demographics, Risk Factors, and Arterial Stiffness. Arterioscler Thromb Vasc Biol 38:e48-e57|
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|MacTaggart, Jason; Poulson, William; Seas, Andreas et al. (2018) Stent Design Affects Femoropopliteal Artery Deformation. Ann Surg :|
|Desyatova, Anastasia; MacTaggart, Jason; Romarowski, Rodrigo et al. (2018) Effect of aging on mechanical stresses, deformations, and hemodynamics in human femoropopliteal artery due to limb flexion. Biomech Model Mechanobiol 17:181-189|
|Kamenskiy, Alexey; Seas, Andreas; Deegan, Paul et al. (2017) Constitutive description of human femoropopliteal artery aging. Biomech Model Mechanobiol 16:681-692|
|Desyatova, Anastasia; MacTaggart, Jason; Poulson, William et al. (2017) The choice of a constitutive formulation for modeling limb flexion-induced deformations and stresses in the human femoropopliteal arteries of different ages. Biomech Model Mechanobiol 16:775-785|
|Desyatova, Anastasia; MacTaggart, Jason; Kamenskiy, Alexey (2017) Constitutive modeling of human femoropopliteal artery biaxial stiffening due to aging and diabetes. Acta Biomater 64:50-58|
|Maleckis, Kaspars; Deegan, Paul; Poulson, William et al. (2017) Comparison of femoropopliteal artery stents under axial and radial compression, axial tension, bending, and torsion deformations. J Mech Behav Biomed Mater 75:160-168|
|Desyatova, Anastasia; Poulson, William; Deegan, Paul et al. (2017) Limb flexion-induced twist and associated intramural stresses in the human femoropopliteal artery. J R Soc Interface 14:|
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