Introduction Femoropopliteal artery (FPA) mechanics play a paramount role in pathophysiology and the artery’s response to therapeutic interventions, but data on FPA mechanical properties are scarce. Our goal was to characterize human FPAs over a wide population to derive a constitutive description of FPA ageing to be used for computational modeling. Methods Fresh human FPA specimens (n=579) were obtained from n=351 predominantly male (80%) donors 54±15 years old (range 13–82 years). Morphometric characteristics including radius, wall thickness, opening angle, and longitudinal pre-stretch were recorded. Arteries were subjected to multi-ratio planar biaxial extension to determine constitutive parameters for an invariant-based model accounting for the passive contributions of ground substance, elastin, collagen and smooth muscle. Nonparametric bootstrapping was used to determine unique sets of material parameters that were used to derive age-group-specific characteristics. Physiologic stress-stretch state was calculated to capture changes with ageing. Results Morphometric and constitutive parameters were derived for seven age groups. Vessel radius, wall thickness, and circumferential opening angle increased with ageing, while longitudinal pre-stretch decreased (p<0.01). Age-group-specific constitutive parameters portrayed orthotropic FPA stiffening, especially in the longitudinal direction. Structural changes in artery wall elastin were associated with reduction of physiologic longitudinal and circumferential stretches and stresses with age. Conclusions These data and the constitutive description of FPA ageing shed new light on our understanding of peripheral arterial disease pathophysiology and arterial ageing. Application of this knowledge might improve patient selection for specific treatment modalities in personalized, precision medicine algorithms and could assist in device development for treatment of peripheral artery disease.

Endovascular stenting has matured into a commonly used treatment for peripheral arterial disease (PAD) due to its minimally invasive nature and associated reductions in short-termmorbidity and mortality. The mechanical properties of the superelastic Nitinol alloy have played a major role in the explosion of peripheral artery stenting, with modern stents demonstrating reasonable resilience and durability. Yet in the superficial femoral and popliteal arteries, even the newest generation Nitinol stents continue to demonstrate clinical outcomes that leave significant room for improvement. Restenosis and progression of native arterial disease often lead to recurrence of symptoms and reinterventions that increase morbidity and health care expenditures. One of the main factors thought to be associated with stent failure in the femoropopliteal artery (FPA) is the unique and highly dynamic mechanical environment of the lower limb. Clinical and experimental data demonstrate that the FPA undergoes significant deformations with limb flexion. It is hypothesized that the inability of many existing stent designs to conform to these deformations likely plays a role in reconstruction failure, as repetitive movements of the leg and thigh combine with mechanical mismatch between the artery and the stent and result in mechanical damage to both the artery and the stent. In this review we will identify challenges and provide a mechanical perspective of FPA stenting, and then discuss current research directions with promise to provide a better understanding of Nitinol, specific features of stent design, and improved characterization of the biomechanical environment of the FPA to facilitate development of better stents for patients with PAD.

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and prestretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13-78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8kPa and from 18 to 5kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72kPa and from 90 to 17kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of *

Endovascular treatment of Peripheral Arterial Disease (PAD) is notorious for high failure rates, and interaction between the arterial wall and the repair devices plays a significant role. Computational modeling can help improve clinical outcomes of these interventions, but it requires accurate inputs of elastic and damage characteristics of the femoropopliteal artery (FPA) which are currently not available. Fresh human FPAs from n=104 tissue donors 14-80 years old were tested using planar biaxial extension to capture elastic and damage characteristics. Damage initiation stretches and stresses were determined for both longitudinal and circumferential directions, and their correlations with age and risk factors were assessed. Two and four-fiber-family invariantbased constitutive models augmented with damage functions were used to describe stress softening with accumulating damage. In FPAs younger than 50 years, damage began accumulating after 1.51±0.13 and 1.49±0.11 stretch, or 196±110 kPa and 239±79 kPa Cauchy stress in the longitudinal and circumferential directions, respectively. In FPAs older than 50 years, damage initiation stretches and stresses decreased to 1.27±0.09 (106±52 kPa) and 1.26±0.09 (104±59 kPa), respectively. Damage manifested primarily as tears at the internal and external elastic laminae and within the tunica media layer. Higher body mass index and presence of diabetes were associated with lower damage initiation stretches and higher stresses. The selected constitutive models were able to accurately portray the FPA behavior in both elastic and inelastic domains, and properties were derived for six age groups. Presented data can help improve fidelity of computational models simulating endovascular PAD repairs that involve arterial damage.

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