Mechanical damage characterization in human femoropopliteal arteries of different ages.

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 invariant-based 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 ±â€¯0.13 and 1.49 ±â€¯0.11 stretch, or 196 ±â€¯110 kPa and 239 ±â€¯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 ±â€¯0.09 (106 ±â€¯52 kPa) and 1.26 ±â€¯0.09 (104 ±â€¯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. STATEMENT OF SIGNIFICANCE: This manuscript describes inelastic, i.e. damage, behavior of human femoropopliteal arteries, and provides values for three constitutive models simulating this behavior computationally. Using a set of 104 human FPAs 14-80 years old, we have investigated stress and stretch levels corresponding to damage initiation, and have studied how these damage characteristics change across different age groups. Presented inelastic arterial characteristics are important for computational simulations modeling balloon angioplasty and stenting of peripheral arterial disease lesions.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. STATEMENT OF SIGNIFICANCE: Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic differentiation and maturation of human adipose progenitor cells and adipose derived mesenchymal stromal cells. Moreover, the cryogels also supported 3D bioprinting on top, forming vascularized adipose constructs. This study demonstrates the potential of the implementation of cryogels for generating volume-stable adipose tissue constructs and provides a strategy to fabricate vascularized flap-like constructs for complex soft tissue regeneration.

Limb flexion-induced axial compression and bending in human femoropopliteal artery segments.

BACKGROUND: High failure rates of femoropopliteal artery (FPA) interventions are often attributed in part to severe mechanical deformations that occur with limb movement. Axial compression and bending of the FPA likely play significant roles in FPA disease development and reconstruction failure, but these deformations are poorly characterized. The goal of this study was to quantify axial compression and bending of human FPAs that are placed in positions commonly assumed during the normal course of daily activities. METHODS: Retrievable nitinol markers were deployed using a custom-made catheter system into 28 in situ FPAs of 14 human cadavers. Contrast-enhanced, thin-section computed tomography images were acquired with each limb in the standing (180 degrees), walking (110 degrees), sitting (90 degrees), and gardening (60 degrees) postures. Image segmentation and analysis allowed relative comparison of spatial locations of each intra-arterial marker to determine axial compression and bending using the arterial centerlines. RESULTS: Axial compression in the popliteal artery (PA) was greater than in the proximal superficial femoral artery (SFA) or the adductor hiatus (AH) segments in all postures (P = .02). Average compression in the SFA, AH, and PA ranged from 9% to 15%, 11% to 19%, and 13% to 25%, respectively. The FPA experienced significantly more acute bending in the AH and PA segments compared with the proximal SFA (P < .05) in all postures. In the walking, sitting, and gardening postures, average sphere radii in the SFA, AH, and PA ranged from 21 to 27 mm, 10 to 18 mm, and 8 to 19 mm, whereas bending angles ranged from 150 to 157 degrees, 136 to 147 degrees, and 137 to 148 degrees, respectively. CONCLUSIONS: The FPA experiences significant axial compression and bending during limb flexion that occur at even modest limb angles. Moreover, different segments of the FPA appear to undergo significantly different degrees of deformation. Understanding the effects of limb flexion on axial compression and bending might assist with reconstructive device selection for patients requiring peripheral arterial disease intervention and may also help guide the development of devices with improved characteristics that can better adapt to the dynamic environment of the lower extremity vasculature.

Comparison of femoropopliteal artery stents under axial and radial compression, axial tension, bending, and torsion deformations.

High failure rates of Peripheral Arterial Disease (PAD) stenting appear to be associated with the inability of certain stent designs to accommodate severe biomechanical environment of the femoropopliteal artery (FPA) that bends, twists, and axially compresses during limb flexion. Twelve Nitinol stents (Absolute Pro, Supera, Lifestent, Innova, Zilver, Smart Control, Smart Flex, EverFlex, Viabahn, Tigris, Misago, and Complete SE) were quasi-statically tested under bench-top axial and radial compression, axial tension, bending, and torsional deformations. Stents were compared in terms of force-strain behavior, stiffness, and geometrical shape under each deformation mode. Tigris was the least stiff stent under axial compression (6.6N/m axial stiffness) and bending (0.1N/m) deformations, while Smart Control was the stiffest (575.3N/m and 105.4N/m, respectively). Under radial compression Complete SE was the stiffest (892.8N/m), while Smart Control had the lowest radial stiffness (211.0N/m). Viabahn and Supera had the lowest and highest torsional stiffness (2.2µNm/° and 959.2µNm/°), respectively. None of the 12 PAD stents demonstrated superior characteristics under all deformation modes and many experienced global buckling and diameter pinching. Though it is yet to be determined which of these deformation modes might have greater clinical impact, results of the current analysis may help guide development of new stents with improved mechanical characteristics.

Limb flexion-induced twist and associated intramural stresses in the human femoropopliteal artery.

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb movement. Torsion of the FPA likely plays a significant role, but is poorly characterized and the associated intramural stresses are currently unknown. FPA torsion in the walking, sitting and gardening postures was characterized in n = 28 in situ FPAs using intra-arterial markers. Principal mechanical stresses and strains were quantified in the superficial femoral artery (SFA), adductor hiatus segment (AH) and the popliteal artery (PA) using analytical modelling. The FPA experienced significant torsion during limb flexion that was most severe in the gardening posture. The associated mechanical stresses were non-uniformly distributed along the length of the artery, increasing distally and achieving maximum values in the PA. Maximum twist in the SFA ranged 10-13° cm-1, at the AH 8-16° cm-1, and in the PA 14-26° cm-1 in the walking, sitting and gardening postures. Maximum principal stresses were 30-35 kPa in the SFA, 27-37 kPa at the AH and 39-43 kPa in the PA. Understanding torsional deformations and intramural stresses in the FPA can assist with device selection for peripheral arterial disease interventions and may help guide the development of devices with improved characteristics.

The choice of a constitutive formulation for modeling limb flexion-induced deformations and stresses in the human femoropopliteal arteries of different ages.

Open and endovascular treatments for peripheral arterial disease are notorious for high failure rates. Severe mechanical deformations experienced by the femoropopliteal artery (FPA) during limb flexion and interactions between the artery and repair materials play important roles and may contribute to poor clinical outcomes. Computational modeling can help optimize FPA repair, but these simulations heavily depend on the choice of constitutive model describing the arterial behavior. In this study finite element model of the FPA in the standing (straight) and gardening (acutely bent) postures was built using computed tomography data, longitudinal pre-stretch and biaxially determined mechanical properties. Springs and dashpots were used to represent surrounding tissue forces associated with limb flexion-induced deformations. These forces were then used with age-specific longitudinal pre-stretch and mechanical properties to obtain deformed FPA configurations for seven age groups. Four commonly used invariant-based constitutive models were compared to determine the accuracy of capturing deformations and stresses in each age group. The four-fiber FPA model most accurately portrayed arterial behavior in all ages, but in subjects younger than 40 years, the performance of all constitutive formulations was similar. In older subjects, Demiray (Delfino) and classic two-fiber Holzapfel-Gasser-Ogden formulations were better than the Neo-Hookean model for predicting deformations due to limb flexion, but both significantly overestimated principal stresses compared to the FPA or Neo-Hookean models.

Constitutive description of human femoropopliteal artery aging.

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 aging to be used for computational modeling. Fresh human FPA specimens ([Formula: see text]) were obtained from [Formula: see text] 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 aging. Morphometric and constitutive parameters were derived for seven age groups. Vessel radius, wall thickness, and circumferential opening angle increased with aging, while longitudinal pre-stretch decreased ([Formula: see text]). 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. These data and the constitutive description of FPA aging shed new light on our understanding of peripheral arterial disease pathophysiology and arterial aging. 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.

In situ longitudinal pre-stretch in the human femoropopliteal artery.

In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14-80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=-0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r=-0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users. STATEMENT OF SIGNIFICANCE: This work studies in situ longitudinal pre-stretch (LPS) in the human femoropopliteal artery. LPS has a fundamental role in arterial mechanics, but is rather poorly studied due to lack of direct in vivo measurement method. We have investigated LPS in the n=148 human femoropopliteal arteries in the context of subject demographics and risk factors, and structural and physiologic characteristics of the artery. Our results demonstrate that LPS reduces with age due to degradation and fragmentation of intramural elastin. LPS may serve as an energy reserve for adaptive remodeling, and reduction of LPS can be accelerated in tobacco users.

Community-acquired pneumonia: doctors do not follow national guidelines.

OBJECTIVES: Appropriate assessment of community-acquired pneumonia (CAP) allows accurate severity scoring and hence optimal management, leading to reduced morbidity and mortality. British Thoracic Society (BTS) guidelines provide an appropriate score. Adherence to BTS guidelines was assessed in our medical assessment unit (MAU) in 2001/2 and again in 2005/6, 3 years after introducing an educational programme. METHODS: A retrospective case-note study, comparing diagnosis, documentation of severity, management and outcome of CAP during admission to MAU during 3 months of each winter in 2001/2 and 2005/6. RESULTS: In 2001/2, 65/165 patients were wrongly coded as CAP and 100 were included in the study. In 2005/6 43/130 were excluded and 87 enrolled. In 2005/6, 87% did not receive a severity score, a significant increase from 48% in 2001/2 (p<0.0001). Parenteral antibiotics were given to 79% of patients in 2001/2 and 77% in 2005/6, and third generation cephalosporins were given to 63% in 2001/2 and 54% in 2005/6 (p = NS). In 2001, 15 different antibiotic regimens were prescribed, increasing to 19 in 2005/6. CONCLUSIONS: Coding remains poor. Adherence to CAP management guidelines was poor and has significantly worsened. Educational programmes, alone, do not improve adherence. Restriction of antibiotic prescribing should be considered.