Mechanically tuned vascular graft demonstrates rapid endothelialization and integration into the porcine iliac artery wall.

Mechanical properties of vascular grafts likely play important roles in healing and tissue regeneration. Healthy arteries are compliant at low pressures but stiffen rapidly with increasing load, ensuring sufficient volumetric expansion without overstretching the vessel. Commercial synthetic vascular grafts are stiff and unable to expand under physiologic loads, which may result in altered hemodynamics, deleterious cellular responses, and compromised clinical performance. The goal of this study was to develop an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned nonlinear compliance and compare its healing responses to conventional expanded polytetrafluoroethylene (ePTFE) grafts in a porcine iliac artery model. Human and porcine iliac arteries were mechanically characterized, and an ENG with similar properties was created by utilizing residual strains within electrospun nanofibers. The ENG was tested for implantation suitability and implanted onto n = 5 domestic swine iliac arteries, with control ePTFE grafts implanted onto the contralateral iliac arteries. After two weeks in vivo, all iliac arteries and grafts remained patent with no signs of thrombosis or dilation. The mechanically tuned ENG implants exhibited a more confluent CD31-positive cell monolayer (1.53 ± 0.73 µm2/mm vs 0.52 ± 0.55 µm2/mm, p = 0.042) on the graft lumenal surface and a higher fraction of αSMA-positive cells (16.2 ± 8.6% vs 1.4 ± 0.7%, p = 0.018) within the graft wall than the ePTFE controls. Despite heavy cellular infiltration, the ENG retained its artery-like mechanical characteristics after two weeks in vivo. These short-term results demonstrate potential advantages of mechanically tuned biomimetic vascular grafts over standard ePTFE grafts. STATEMENT OF SIGNIFICANCE: Off-the-shelf synthetic vascular grafts are often the only option available for treating advanced stages of vascular disease. Despite significant efforts devoted to improving their biochemical characteristics, synthetic peripheral arterial grafts continue to demonstrate poor clinical outcomes leading to costly reinterventions. Here, we hypothesized that a synthetic vascular graft with elastomeric mechanical properties tuned to a healthy peripheral artery promotes better healing responses than a synthetic stiff graft. To test this hypothesis, we developed an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned mechanical properties and compared its performance to a commercial ePTFE graft in a preclinical porcine iliac artery model. Our results suggest that mechanically tuned ENGs can offer better healing responses, potentially leading to better clinical outcomes for peripheral arterial repairs.

Hierarchical Mechanisms of Lateral Interactions in High-Performance Fibers.

The processing conditions used in the production of advanced polymer fibers facilitate the formation of an oriented fibrillar network that consists of structures spanning multiple length scales. The irregular nature of fiber tensile fracture surfaces suggests that their structural integrity is defined by the degree of lateral (interfacial) interactions that exist within the fiber microstructure. To date, experimental studies have quantified interfacial adhesion between nanoscale fibrils measuring 10-50 nm in width, and the global fracture energy through applying peel loads to fiber halves. However, a more in-depth evaluation of tensile fracture indicates that fiber failure typically occurs at an intermediate length scale, involving fibrillation along interfaces between fibril bundles of a few 100s of nanometers in width. Interaction mechanisms at this length scale have not yet been studied, due in part to a lack of established experimental techniques. Here, a new focused ion beam-based sample preparation protocol is combined with nanoindentation to probe interfaces at the intermediate length scale in two high-performance fibers, a rigid-rod poly(p-phenylene terephthalamide) and a flexible chain ultrahigh molecular weight polyethylene fiber. Higher interfacial separation energy recorded in the rigid-rod fiber correlated with less intensive fibrillation during failure and is discussed in the context of fiber chemistry and processing. Power law scaling of the total absorbed interfacial separation energy at three different scales in the polyethylene fiber is observed and analyzed, and distinct energy absorption mechanisms, featuring a degree of self-similarity, are identified. The contribution of these mechanisms to the overall integrity of the fiber is discussed, and the importance of the intermediate scale is elucidated. Results from this study provide new insights into the mechanical implications of hierarchical lateral interactions and will aid in the development of novel fibers with further improved mechanical performance.

Quantifying Polymer Chain Orientation in Strong and Tough Nanofibers with Low Crystallinity: Toward Next Generation Nanostructured Superfibers.

Advanced fibers revolutionized structural materials in the second half of the 20th century. However, all high-strength fibers developed to date are brittle. Recently, pioneering simultaneous ultrahigh strength and toughness were discovered in fine (<250 nm) individual electrospun polymer nanofibers (NFs). This highly desirable combination of properties was attributed to high macromolecular chain alignment coupled with low crystallinity. Quantitative analysis of the degree of preferred chain orientation will be crucial for control of NF mechanical properties. However, quantification of supramolecular nanoarchitecture in NFs with low crystallinity in the ultrafine diameter range is highly challenging. Here, we discuss the applicability of traditional as well as emerging methods for quantification of polymer chain orientation in nanoscale one-dimensional samples. Advantages and limitations of different techniques are critically evaluated on experimental examples. It is shown that straightforward application of some of the techniques to sub-wavelength-diameter NFs can lead to severe quantitative and even qualitative artifacts. Sources of such size-related artifacts, stemming from instrumental, materials, and geometric phenomena at the nanoscale, are analyzed on the example of polarized Raman method but are relevant to other spectroscopic techniques. A proposed modified, artifact-free method is demonstrated. Outstanding issues and their proposed solutions are discussed. The results provide guidance for accurate nanofiber characterization to improve fundamental understanding and accelerate development of nanofibers and related nanostructured materials produced by electrospinning or other methods. We expect that the discussion in this review will also be useful to studies of many biological systems that exhibit nanofilamentary architectures and combinations of high strength and toughness.

Biomimetic substrate control of cellular mechanotransduction.

Extracellular mechanophysical signals from both static substrate cue and dynamic mechanical loading have strong potential to regulate cell functions. Most of the studies have adopted either static or dynamic cue and shown that each cue can regulate cell adhesion, spreading, migration, proliferation, lineage commitment, and differentiation. However, there is limited information on the integrative control of cell functions by the static and dynamic mechanophysical signals. For example, a majority of dynamic loading studies have tested mechanical stimulation of cells utilizing cultures on flat surfaces without any surface modification. While these approaches have provided significant information on cell mechanotransduction, obtained outcomes may not correctly recapitulate complex cellular mechanosensing milieus in vivo. Several pioneering studies documented cellular response to mechanical stimulations upon cultures with biomimetic substrate modifications. In this min-review, we will highlight key findings on the integrative role of substrate cue (topographic, geometric, etc.) and mechanical stimulation (stretch, fluid shear) in modulating cell function and fate. The integrative approaches, though not fully established yet, will help properly understand cell mechanotransduction under biomimetic mechanophysical environments. This may further lead to advanced functional tissue engineering and regenerative medicine protocols.

Focal adhesion kinase regulation in stem cell alignment and spreading on nanofibers.

While electrospun nanofibers have demonstrated the potential for novel tissue engineering scaffolds, very little is known about the molecular mechanism of how cells sense and adapt to nanofibers. Here, we revealed the role of focal adhesion kinase (FAK), one of the key molecular sensors in the focal adhesion complex, in regulating mesenchymal stem cell (MSC) shaping on nanofibers. We produced uniaxially aligned and randomly distributed nanofibers from poly(l-lactic acid) to have the same diameters (about 130 nm) and evaluated MSC behavior on these nanofibers comparing with that on flat PLLA control. C3H10T1/2 murine MSCs exhibited upregulations in FAK expression and phosphorylation (pY397) on nanofibrous cultures as assessed by immunoblotting, and this trend was even greater on aligned nanofibers. MSCs showed significantly elongated and well-spread morphologies on aligned and random nanofibers, respectively. In the presence of FAK silencing via small hairpin RNA (shRNA), cell elongation length in the aligned nanofiber direction (cell major axis length) was significantly decreased, while cells still showed preferred orientation along the aligned nanofibers. On random nanofibers, MSCs with FAK-shRNA showed impaired cell spreading resulting in smaller cell area and higher circularity. Our study provides new data on how MSCs shape their morphologies on aligned and random nanofibrous cultures potentially via FAK-mediated mechanism.

Role of Mechanical Factors in Applications of Stimuli-Responsive Polymer Gels - Status and Prospects.

Due to their unique characteristics such as multifold change of volume in response to minute change in the environment, resemblance of soft biological tissues, ability to operate in wet environments, and chemical tailorability, stimuli responsive gels represent a versatile and very promising class of materials for sensors, muscle-type actuators, biomedical applications, and autonomous intelligent structures. Success of these materials in practical applications largely depends on their ability to fulfill application-specific mechanical requirements. This article provides an overview of recent application-driven development of covalent polymer gels with special emphasis on the relevant mechanical factors and properties. A short account of mechanisms of gel swelling and mechanical characteristics of importance to stimuli-responsive gels is presented. The review highlights major barriers for wider application of these materials and discusses latest advances and potential future directions toward overcoming these barriers, including interpenetrating networks, homogeneous networks, nanocomposites, and nanofilamentary gels.

Effects of age on the physiological and mechanical characteristics of human femoropopliteal arteries.

Surgical and interventional therapies for peripheral artery disease (PAD) are notorious for high rates of failure. Interactions between the artery and repair materials play an important role, but comprehensive data describing the physiological and mechanical characteristics of human femoropopliteal arteries are not available. Fresh femoropopliteal arteries were obtained from 70 human subjects (13-79 years old), and in situ vs. excised arterial lengths were measured. Circumferential and longitudinal opening angles were determined for proximal superficial femoral, proximal popliteal and distal popliteal arteries. Mechanical properties were assessed by multi-ratio planar biaxial extension, and experimental data were used to calculate physiological stresses and stretches, in situ axial force and anisotropy. Verhoeff-Van Gieson-stained axial and transverse arterial sections were used for histological analysis. Most specimens demonstrated nonlinear deformations and were more compliant longitudinally than circumferentially. In situ axial pre-stretch decreased 0.088 per decade of life. In situ axial force and axial stress also decreased with age, but circumferential physiological stress remained constant. Physiological circumferential stretch decreased 55-75% after 45 years of age. Histology demonstrated a thickened external elastic lamina with longitudinally oriented elastin that was denser in smaller, younger arteries. Axial elastin likely regulates axial pre-stretch to help accommodate the complex deformations required of the artery wall during locomotion. Degradation and fragmentation of elastin as a consequence of age, cyclic mechanical stress and atherosclerotic arterial disease may contribute to decreased in situ axial pre-stretch, predisposing to more severe kinking of the artery during limb flexion and loss of energy-efficient arterial function.

Three-dimensional bending, torsion and axial compression of the femoropopliteal artery during limb flexion.

High failure rates of femoropopliteal artery reconstruction are commonly attributed to complex 3D arterial deformations that occur with limb movement. The purpose of this study was to develop a method for accurate assessment of these deformations. Custom-made stainless-steel markers were deployed into 5 in situ cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were acquired with each limb in the straight and acutely bent states. Image segmentation and 3D reconstruction allowed comparison of the relative locations of each intra-arterial marker position for determination of the artery's bending, torsion and axial compression. After imaging, each artery was excised for histological analysis using Verhoeff-Van Gieson staining. Femoropopliteal arteries deformed non-uniformly with highly localized deformations in the proximal superficial femoral artery, and between the adductor hiatus and distal popliteal artery. The largest bending (11±3-6±1 mm radius of curvature), twisting (28±9-77±27°/cm) and axial compression (19±10-30±8%) were registered at the adductor hiatus and the below knee popliteal artery. These deformations were 3.7, 19 and 2.5 fold more severe than values currently reported in the literature. Histology demonstrated a distinct sub-adventitial layer of longitudinally oriented elastin fibers with intimal thickening in the segments with the largest deformations. This endovascular intra-arterial marker technique can quantify the non-uniform 3D deformations of the femoropopliteal artery during knee flexion without disturbing surrounding structures. We demonstrate that 3D arterial bending, torsion and compression in the flexed lower limb are highly localized and are substantially more severe than previously reported.

Biaxial mechanical properties of the human thoracic and abdominal aorta, common carotid, subclavian, renal and common iliac arteries.

The biomechanics of large- and medium-sized arteries influence the pathophysiology of arterial disease and the response to therapeutic interventions. However, a comprehensive comparative analysis of human arterial biaxial mechanical properties has not yet been reported. Planar biaxial extension was used to establish the passive mechanical properties of human thoracic (TA, [Formula: see text]) and abdominal (AA, [Formula: see text]) aorta, common carotid (CCA, [Formula: see text]), subclavian (SA, [Formula: see text]), renal (RA, [Formula: see text]) and common iliac (CIA, [Formula: see text]) arteries from 11 deceased subjects ([Formula: see text] years old). Histological evaluation determined the structure of each specimen. Experimental data were used to determine constitutive parameters for a structurally motivated nonlinear anisotropic constitutive model. All arteries demonstrated appreciable anisotropy and large nonlinear deformations. Most CCA, SA, TA, AA and CIA specimens were stiffer longitudinally, while most RAs were stiffer circumferentially. A switch in anisotropy was occasionally demonstrated for all arteries. The CCA was the most compliant, least anisotropic and least frequently diseased of all arteries, while the CIA and AA were the stiffest and the most diseased. The severity of atherosclerosis correlated with age, but was not affected by laterality. Elastin fibers in the aorta, SA and CCA were uniformly and mostly circumferentially distributed throughout the media, while in the RA and CIA, elastin was primarily axially aligned and concentrated in the external elastic lamina. Constitutive modeling provided good fits to the experimental data for most arteries. Biomechanical and architectural features of major arteries differ depending on location and functional environment. A better understanding of localized arterial mechanical properties may support the development of site-specific treatment modalities for arterial disease.

Passive biaxial mechanical properties and in vivo axial pre-stretch of the diseased human femoropopliteal and tibial arteries.

Surgical and interventional therapies for atherosclerotic lesions of the infrainguinal arteries are notorious for high rates of failure. Frequently, this leads to expensive reinterventions, return of disabling symptoms or limb loss. Interaction between the artery and repair material likely plays an important role in reconstruction failure, but data describing the mechanical properties and functional characteristics of human femoropopliteal and tibial arteries are currently not available. Diseased superficial femoral (SFA, n = 10), popliteal (PA, n = 8) and tibial arteries (TA, n = 3) from 10 patients with critical limb ischemia were tested to determine passive mechanical properties using planar biaxial extension. All specimens exhibited large nonlinear deformations and anisotropy. Under equibiaxial loading, all arteries were stiffer in the circumferential direction than in the longitudinal direction. Anisotropy and longitudinal compliance decreased distally, but circumferential compliance increased, possibly to maintain a homeostatic multiaxial stress state. Constitutive parameters for a four-fiber family invariant-based model were determined for all tissues to calculate in vivo axial pre-stretch that allows the artery to function in the most energy efficient manner while also preventing buckling during extremity flexion. Calculated axial pre-stretch was found to decrease with age, disease severity and more distal arterial location. Histological analysis of the femoropopliteal artery demonstrated a distinct sub-adventitial layer of longitudinal elastin fibers that appeared thicker in healthier arteries. The femoropopliteal artery characteristics and properties determined in this study may assist in devising better diagnostic and treatment modalities for patients with peripheral arterial disease.

A mathematical evaluation of hemodynamic parameters after carotid eversion and conventional patch angioplasty.

Carotid endarterectomy has a long history in stroke prevention, yet controversy remains concerning optimal techniques. Two methods frequently used are endarterectomy with patch angioplasty (CEAP) and eversion endarterectomy (CEE). The objective of this study was to compare hemodynamics-related stress and strain distributions between arteries repaired using CEAP and CEE. Mathematical models were based on in vivo three-dimensional arterial geometry, pulsatile velocity profiles, and intraluminal pressure inputs obtained from 16 patients with carotid artery disease. These data were combined with experimentally derived nonlinear, anisotropic carotid artery mechanical properties to create fluid-structure interaction models of CEAP and CEE. These models were then used to calculate hemodynamic parameters thought to promote recurrent disease and restenosis. Combining calculations of stress and strain into a composite risk index, called the integral abnormality factor, allowed for an overall comparison between CEAP and CEE. CEE demonstrated lower mechanical stresses in the arterial wall, whereas CEAP straightened the artery and caused high stress and strain concentrations at the suture-artery interface. CEAP produced a larger continuous region of oscillatory, low-shear, vortical flow in the carotid bulb. There was a more than two-fold difference in the integral abnormality factor, favoring CEE. In conclusion, in a realistically simulated carotid artery, fluid-structure interaction modeling demonstrated CEE to produce less mechanical wall stress and improved flow patterns compared with CEAP. Clinical validation with larger numbers of individual patients will ultimately be required to support modeling approaches to help predict arterial disease progression and comparative effectiveness of reconstruction methods and devices.

Effects of carotid artery stenting on arterial geometry.

BACKGROUND: The role of carotid artery stenting (CAS) for the treatment of carotid artery disease continues to evolve, despite higher stroke and restenosis risks for CAS compared with conventional open endarterectomy. Understanding the effects of CAS on arterial geometry, which strongly influence hemodynamics and wall mechanics, can assist in better stratifying the inherent risk of CAS to individual patients. STUDY DESIGN: Fifteen consecutive patients undergoing CAS had pre- and post-stenting CT angiograms. These images were used to reconstruct the 3-dimensional geometries of the bilateral carotid arteries from their origin to the skull base. Quantitative assessment of the carotid bifurcation angle, cross-sectional area, tortuosity and artery length, were compared pre- and post-stenting. Plaque volume and calcification were also measured. Mathematical models were devised to determine the mechanisms of CAS-induced geometric changes, and their mechanical and hemodynamic significances. RESULTS: Major and moderate changes in arterial tortuosity and elongation were seen in 5 (33%) patients. Characteristics most associated with the development of CAS-induced geometric changes were stenoses located in the internal carotid artery distal to the carotid bulb, circumferential distribution of plaque, and plaque calcification. Modeling did not demonstrate substantial alterations in wall shear stress due to geometric changes, but did show considerable increases in arterial wall axial stress. CONCLUSIONS: Carotid artery stenting can produce geometric changes to the artery that promote favorable conditions for complications and recurrent disease. Patients with circumferential, highly calcified plaques that are located relatively distal in the internal carotid artery are most likely to have post-stenting geometric changes.

The role of RhoA kinase (ROCK) in cell alignment on nanofibers.

While the potential of nanofibers as tissue engineering scaffolds has been demonstrated, very little has been revealed as regards the molecular mechanism by which cells sense and respond to nanofibers. It was hypothesized that RhoA kinase (ROCK), one of the vital cell tension signaling cascades, plays a role in regulating cell alignment on nanofibers. To test this, unidirectionally aligned and randomly distributed nanofibers, both with an average diameter of ∼130nm, were fabricated with poly(l-lactic acid) (PLLA). A flat PLLA film was used as the control. Mesenchymal stem cells (MSCs, C3H10T1/2) displayed high fidelity in cell orientation along aligned nanofibers, and showed an increased cell spreading area on random nanofibers. Interestingly, cells cultured on aligned nanofibers displayed significantly greater ROCK expression relative to cells on a flat surface, as assessed by immunoblotting. To further test the role of ROCK, MSCs with ROCK small hairpin RNA (shRNA) were established. It is notable that, even when ROCK was stably knocked down via shRNA, cells could still display preferred orientation along aligned nanofibers. However, MSCs with shRNA-ROCK displayed a significantly decreased cell major axis length following aligned nanofibers compared with shRNA vector control, suggesting that ROCK may be involved in cell elongation on aligned nanofibers. Along with the reduction in cell length, cell area was decreased with ROCK silencing. These cell morphological changes induced by shRNA-ROCK were generally maintained on a flat surface and random nanofibers. A pharmacological ROCK inhibitor, Y-27632, produced results similar to those of shRNA-ROCK. The data on the role of ROCK in regulating cell alignment on nanofibers may provide a new mechanistic insight into nanofiber control of cells.

Simultaneously strong and tough ultrafine continuous nanofibers.

Strength of structural materials and fibers is usually increased at the expense of strain at failure and toughness. Recent experimental studies have demonstrated improvements in modulus and strength of electrospun polymer nanofibers with reduction of their diameter. Nanofiber toughness has not been analyzed; however, from the classical materials property trade-off, one can expect it to decrease. Here, on the basis of a comprehensive analysis of long (5-10 mm) individual polyacrylonitrile nanofibers, we show that nanofiber toughness also dramatically improves. Reduction of fiber diameter from 2.8 µm to ∼100 nm resulted in simultaneous increases in elastic modulus from 0.36 to 48 GPa, true strength from 15 to 1750 MPa, and toughness from 0.25 to 605 MPa with the largest increases recorded for the ultrafine nanofibers smaller than 250 nm. The observed size effects showed no sign of saturation. Structural investigations and comparisons with mechanical behavior of annealed nanofibers allowed us to attribute ultrahigh ductility (average failure strain stayed over 50%) and toughness to low nanofiber crystallinity resulting from rapid solidification of ultrafine electrospun jets. Demonstrated superior mechanical performance coupled with the unique macro-nano nature of continuous nanofibers makes them readily available for macroscopic materials and composites that can be used in safety-critical applications. The proposed mechanism of simultaneously high strength, modulus, and toughness challenges the prevailing 50 year old paradigm of high-performance polymer fiber development calling for high polymer crystallinity and may have broad implications in fiber science and technology.

Hemodynamically motivated choice of patch angioplasty for the performance of carotid endarterectomy.

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of materials are available, but little is known to aid the surgeon in choosing a patch while caring for a patient with carotid disease. The objective of this study was to investigate biomechanics of the carotid artery (CA) repaired with patch angioplasty, study the influence of patch width and location of closure on hemodynamics, and to select the optimal patch material from those commonly used. For this purpose, a mathematical model was built that accounts for fluid-structure interaction, three-dimensional arterial geometry, non-linear anisotropic mechanical properties, non-Newtonian flow and in vivo boundary conditions. This model was used to study disease-related mechanical factors in the arterial wall and blood flow for different types of patch angioplasty. Analysis indicated that patch closures performed with autologous vein and bovine pericardium were hemodynamically superior to carotid endarterectomy with synthetic patch angioplasty (polytetrafluoroethylene, Dacron) in terms of restenosis potential. Width of the patch and location of arteriotomy were found to be of paramount importance, with narrow patches being superior to wide patches, and anterior arteriotomy being superior to the lateral arteriotomy. These data can aid vascular surgeons in their selection of patch angioplasty technique and material for the care of patients undergoing open CA repair.

Extraordinary improvement of the graphitic structure of continuous carbon nanofibers templated with double wall carbon nanotubes.

Carbon nanotubes are being widely studied as a reinforcing element in high-performance composites and fibers at high volume fractions. However, problems with nanotube processing, alignment, and non-optimal stress transfer between the nanotubes and surrounding matrix have so far prevented full utilization of their superb mechanical properties in composites. Here, we present an alternative use of carbon nanotubes, at a very small concentration, as a templating agent for the formation of graphitic structure in fibers. Continuous carbon nanofibers (CNF) were manufactured by electrospinning from polyacrylonitrile (PAN) with 1.2% of double wall nanotubes (DWNT). Nanofibers were oxidized and carbonized at temperatures from 600 °C to 1850 °C. Structural analyses revealed significant improvements in graphitic structure and crystal orientation in the templated CNFs, with the largest improvements observed at lower carbonization temperatures. In situ pull-out experiments showed good interfacial bonding between the DWNT bundles and the surrounding templated carbon matrix. Molecular Dynamics (MD) simulations of templated carbonization confirmed oriented graphitic growth and provided insight into mechanisms of carbonization initiation. The obtained results indicate that global templating of the graphitic structure in fine CNFs can be achieved at very small concentrations of well-dispersed DWNTs. The outcomes reveal a simple and inexpensive route to manufacture continuous CNFs with improved structure and properties for a variety of mechanical and functional applications. The demonstrated improvement of graphitic order at low carbonization temperatures in the absence of stretch shows potential as a promising new manufacturing technology for next generation carbon fibers.

Three-dimensional geometry of the human carotid artery.

Accurate characterization of carotid artery geometry is vital to our understanding of the pathogenesis of atherosclerosis. Three-dimensional computer reconstructions based on medical imaging are now ubiquitous; however, mean carotid artery geometry has not yet been comprehensively characterized. The goal of this work was to build and study such geometry based on data from 16 male patients with severe carotid artery disease. Results of computerized tomography angiography were used to analyze the cross-sectional images implementing a semiautomated segmentation algorithm. Extracted data were used to reconstruct the mean three-dimensional geometry and to determine average values and variability of bifurcation and planarity angles, diameters and cross-sectional areas. Contrary to simplified carotid geometry typically depicted and used, our mean artery was tortuous exhibiting nonplanarity and complex curvature and torsion variations. The bifurcation angle was 36 deg ± 11 deg if measured using arterial centerlines and 15 deg ± 14 deg if measured between the walls of the carotid bifurcation branches. The average planarity angle was 11 deg ± 10 deg. Both bifurcation and planarity angles were substantially smaller than values reported in most studies. Cross sections were elliptical, with an average ratio of semimajor to semiminor axes of 1.2. The cross-sectional area increased twofold in the bulb compared to the proximal common, but then decreased 1.5-fold for the combined area of distal internal and external carotid artery. Inter-patient variability was substantial, especially in the bulb region; however, some common geometrical features were observed in most patients. Obtained quantitative data on the mean carotid artery geometry and its variability among patients with severe carotid artery disease can be used by biomedical engineers and biomechanics vascular modelers in their studies of carotid pathophysiology, and by endovascular device and materials manufacturers interested in the mean geometrical features of the artery to target the broad patient population.

Nonlinear mechanical behavior of the human common, external, and internal carotid arteries in vivo.

BACKGROUND: The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA), and internal (ICA) carotid arteries over the cardiac cycle in vivo. METHODS: Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA, and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semiautomatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and strain-induced stiffness of the arterial wall (stiffening in response to the increase of intraluminal blood pressure) for each patient. RESULTS: The diameter and wall thickness of the segments (CCA, ECA, and ICA) of the carotid bifurcation were found to decrease and strain-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25 ± 7 to 63 ± 23 kPa (CCA), from 22 ± 7 to 57 ± 19 kPa (ECA), and from 28 ± 8 to 67 ± 23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40 ± 0.25 to 1.50 ± 2.05 MPa (CCA), from 0.49 ± 0.34 to 1.14 ± 0.52 MPa (ECA), and from 0.68 ± 0.31 to 1.51 ± 0.69 MPa (ICA). The strain-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared with end-diastole. CONCLUSIONS: The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries--CCA, ECA and ICA--exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.

Comparative analysis of the biaxial mechanical behavior of carotid wall tissue and biological and synthetic materials used for carotid patch angioplasty.

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n = 1), Dacron (n = 2), bovine pericardium (n = 10), autogenous greater saphenous vein (n = 10), and autogenous external jugular vein (n = 9) with the wall of the common carotid artery (n = 18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy.

Highly efficient rapid ethanol sensing based on Co-doped In2O3 nanowires.

Pristine and Co-doped In(2)O(3) nanowires were synthesized via electrospinning with subsequent calcination. Scanning electron microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were used to characterize nanowire morphology and structure. Ethanol sensing performance analyzed in the range of temperatures and concentrations showed that Co-doped In(2)O(3) nanowires exhibited significantly enhanced sensitivity and rate of performance with the response and recovery times of 2s and 3s, respectively. Combined with excellent selectivity and linearity, these properties make the fabricated nanowires a good candidate for practical ethanol sensing. Further performance improvements are possible with utilization of nanofiber continuity intrinsic of the used top-down nanowire nanomanufacturing process.