Effect of the anisotropic permeability in the frequency dependent properties of the superficial layer of articular cartilage.

Articular cartilage is a tissue of fundamental importance for the mechanics of joints, since it provides a smooth and lubricated surface for the proper transfer of loads. From a mechanical point of view, this tissue is an anisotropic poroviscoelastic material: its characteristics at the macroscopic level depend on the complex microscopic architecture. With the ability to probe the local microscopic features, dynamic nanoindentation test is a powerful tool to investigate cartilage mechanics. In this work we focus on a length scale where the time dependent behaviour is regulated by poroelasticity more than viscoelasticity and we aim to understand the effect of the anisotropic permeability on the mechanics of the superficial layer of the articular cartilage. In a previous work, a finite element model for the dynamic nanoindentation test has been presented. In this work, we improve the model by considering the presence of an anisotropic permeability tensor that depends on the collagen fibers distribution. Our sensitivity analysis highlights that the permeability decreases with increasing indentation, thus making the tissue stiffer than the case of isotropic permeability, when solicited at the same frequency. With this improved model, a revised identification of the mechanical and physical parameters for articular cartilage is provided. To this purpose the model was used to simulate experimental data from tests performed on bovine tissue, giving a better estimation of the anisotropy in the elastic properties. A relation between the identified macroscopic anisotropic permeability properties and the microscopic rearrangement of the fiber/matrix structure during indentation is also provided.

Radiation endurance in Al2O3 nanoceramics.

The lack of suitable materials solutions stands as a major challenge for the development of advanced nuclear systems. Most issues are related to the simultaneous action of high temperatures, corrosive environments and radiation damage. Oxide nanoceramics are a promising class of materials which may benefit from the radiation tolerance of nanomaterials and the chemical compatibility of ceramics with many highly corrosive environments. Here, using thin films as a model system, we provide new insights into the radiation tolerance of oxide nanoceramics exposed to increasing damage levels at 600 °C -namely 20, 40 and 150 displacements per atom. Specifically, we investigate the evolution of the structural features, the mechanical properties, and the response to impact loading of Al2O3 thin films. Initially, the thin films contain a homogeneous dispersion of nanocrystals in an amorphous matrix. Irradiation induces crystallization of the amorphous phase, followed by grain growth. Crystallization brings along an enhancement of hardness, while grain growth induces softening according to the Hall-Petch effect. During grain growth, the excess mechanical energy is dissipated by twinning. The main energy dissipation mechanisms available upon impact loading are lattice plasticity and localized amorphization. These mechanisms are available in the irradiated material, but not in the as-deposited films.

Poroelastic response of articular cartilage by nanoindentation creep tests at different characteristic lengths.

Nanoindentation is an experimental technique which is attracting increasing interests for the mechanical characterization of articular cartilage. In particular, time dependent mechanical responses due to fluid flow through the porous matrix can be quantitatively investigated by nanoindentation experiments at different penetration depths and/or by using different probe sizes. The aim of this paper is to provide a framework for the quantitative interpretation of the poroelastic response of articular cartilage subjected to creep nanoindentation tests. To this purpose, multiload creep tests using spherical indenters have been carried out on saturated samples of mature bovine articular cartilage achieving two main quantitative results. First, the dependence of indentation modulus in the drained state (at equilibrium) on the tip radius: a value of 500 kPa has been found using the large tip (400 µm radius) and of 1.7 MPa using the smaller one (25 µm). Secon, the permeability at microscopic scale was estimated at values ranging from 4.5×10(-16) m(4)/N s to 0.1×10(-16) m(4)/N s, from low to high equivalent deformation. Consistently with a poroelastic behavior, the size-dependent response of the indenter displacement disappears when characteristic size and permeability are accounted for. For comparison purposes, the same protocol was applied to intrinsically viscoelastic homogeneous samples of polydimethylsiloxane (PDMS): both indentation modulus and time response have been found size-independent.

Poroviscoelastic finite element model including continuous fiber distribution for the simulation of nanoindentation tests on articular cartilage.

Articular cartilage is a soft hydrated tissue that facilitates proper load transfer in diarthroidal joints. The mechanical properties of articular cartilage derive from its structural and hierarchical organization that, at the micrometric length scale, encompasses three main components: a network of insoluble collagen fibrils, negatively charged macromolecules and a porous extracellular matrix. In this work, a constituent-based constitutive model for the simulation of nanoindentation tests on articular cartilage is presented: it accounts for the multi-constituent, non-linear, porous, and viscous aspects of articular cartilage mechanics. In order to reproduce the articular cartilage response under different loading conditions, the model considers a continuous distribution of collagen fibril orientation, swelling, and depth-dependent mechanical properties. The model's parameters are obtained by fitting published experimental data for the time-dependent response in a stress relaxation unconfined compression test on adult bovine articular cartilage. Then, model validation is obtained by simulating three independent experimental tests: (i) the time-dependent response in a stress relaxation confined compression test, (ii) the drained response of a flat punch indentation test and (iii) the depth-dependence of effective Poisson's ratio in a unconfined compression test. Finally, the validated constitutive model has been used to simulate multiload spherical nanoindentation creep tests. Upon accounting for strain-dependent tissue permeability and intrinsic viscoelastic properties of the collagen network, the model accurately fits the drained and undrained curves and time-dependent creep response. The results show that depth-dependent tissue properties and glycosaminoglycan-induced tissue swelling should be accounted for when simulating indentation experiments.

A novel flow chamber for biodegradable alloy assessment in physiologically realistic environments.

In order to better understand the in vivo corrosion of biodegradable alloys, it is necessary to replicate the physiological environment as closely as possible. In this study, a novel flow chamber system is developed that allows the investigation of biodegradable alloy corrosion in a simulated physiological environment. The system is designed to reproduce flow conditions encountered in coronary arteries using a parallel plate setup and to allow the culturing of cells. Computational fluid dynamics and analytical methods are used as part of the design process to ensure that suitable flow conditions are maintained in the test region. The system is used to investigate the corrosion behavior of AZ31 alloy foils of different thickness, in test media with and without proteins and in static and dynamic solutions. It is observed that pulsatile flows, similar to those in the coronary arteries, significantly increase corrosion rates and lead to a different corrosion surface morphologies relative to static immersion tests.

Continuum damage model for bioresorbable magnesium alloy devices - Application to coronary stents.

The main drawback of a conventional stenting procedure is the high risk of restenosis. The idea of a stent that "disappears" after having fulfilled its mission is very intriguing and fascinating, since it can be expected that the stent mass decreases in time to allow the gradual transmission of the mechanical load to the surrounding tissues owing to controlled dissolution by corrosion. Magnesium and its alloys are appealing materials for designing biodegradable stents. The objective of this work is to develop, in a finite element framework, a model of magnesium degradation that is able to predict the corrosion rate, thus providing a valuable tool for the design of bioresorbable stents. Continuum damage mechanics is suitable for modeling several damage mechanisms, including different types of corrosion. In this study, the damage is assumed to be the superposition of stress corrosion and uniform microgalvanic corrosion processes. The former describes the stress-mediated localization of the corrosion attack through a stress-dependent evolution law, while the latter affects the free surface of the material exposed to an aggressive environment. Comparisons with experimental tests show that the developed model can reproduce the behavior of different magnesium alloys subjected to static corrosion tests. The study shows that parameter identification for a correct calibration of the model response on the results of uniform and stress corrosion experimental tests is reachable. Moreover, three-dimensional stenting procedures accounting for interaction with the arterial vessel are simulated, and it is shown how the proposed modeling approach gives the possibility of accounting for the combined effects of an aggressive environment and mechanical loading.

A finite element model for direction-dependent mechanical response to nanoindentation of cortical bone allowing for anisotropic post-yield behavior of the tissue.

A finite element model was developed for numerical simulations of nanoindentation tests on cortical bone. The model allows for anisotropic elastic and post-yield behavior of the tissue. The material model for the post-yield behavior was obtained through a suitable linear transformation of the stress tensor components to define the properties of the real anisotropic material in terms of a fictitious isotropic solid. A tension-compression yield stress mismatch and a direction-dependent yield stress are allowed for. The constitutive parameters are determined on the basis of literature experimental data. Indentation experiments along the axial (the longitudinal direction of long bones) and transverse directions have been simulated with the purpose to calculate the indentation moduli and the tissue hardness in both the indentation directions. The results have shown that the transverse to axial mismatch of indentation moduli was correctly simulated regardless of the constitutive parameters used to describe the post-yield behavior. The axial to transverse hardness mismatch observed in experimental studies (see, for example, Rho et al. [1999, "Elastic Properties of Microstructural Components of Human Bone Tissue as Measured by Nanoindentation," J. Biomed. Mater. Res., 45, pp. 48-54] for results on human tibial cortical bone) can be correctly simulated through an anisotropic yield constitutive model. Furthermore, previous experimental results have shown that cortical bone tissue subject to nanoindentation does not exhibit piling-up. The numerical model presented in this paper shows that the probe tip-tissue friction and the post-yield deformation modes play a relevant role in this respect; in particular, a small dilatation angle, ruling the volumetric inelastic strain, is required to approach the experimental findings.

Finite element shape optimization for biodegradable magnesium alloy stents.

Biodegradable magnesium alloy stents (MAS) are a promising solution for long-term adverse events caused by interactions between vessels and permanent stent platforms of drug eluting stents. However, the existing MAS showed severe lumen loss after a few months: too short degradation time may be the main reason for this drawback. In this study, a new design concept of MAS was proposed and a shape optimization method with finite element analysis was applied on two-dimensional (2D) stent models considering four different magnesium alloys: AZ80, AZ31, ZM21, and WE43. A morphing procedure was utilized to facilitate the optimization. Two experiments were carried out for a preliminary validation of the 2D models with good results. The optimized designs were compared to an existing MAS by means of three-dimensional finite element analysis. The results showed that the final optimized design with alloy WE43, compared to the existing MAS, has an increased strut width by approximately 48%, improved safety properties (decreased the maximum principal stress after recoil with tissue by 29%, and decreased the maximum principal strain during expansion by 14%) and improved scaffolding ability (increased by 24%). Accordingly, the degradation time can be expected to extend. The used methodology provides a convenient and practical way to develop novel MAS designs.

Calibration issues for nanoindentation experiments: direct atomic force microscopy measurements and indirect methods.

This article discusses calibration issues for shallow depth nanoindentation experiments with Berkovich tips with respect to the accurate measurement of the diamond area function (DAF). For this purpose, two different calibration procedures are compared: (i) the direct measurement of the DAF through atomic force microscopy (AFM) imaging of the Berkovich tip at shallow depth and (ii) a novel indirect calibration method based on an iterative robust and converging scheme in which both reduced modulus and indentation hardness are simultaneously used. These results are obtained by indentation measurements on a standard specimen of fused silica, performed in the 0.5-200 mN load range with a Berkovich indenter. Direct tip shape measurements were carried out through different AFM methods. Comparisons with the standard indirect calibration procedure are also reported. For both the indirect calibration procedures a sensitivity and convergence study is presented.

Clonal differences in survival capacity, copper and zinc accumulation, and correlation with leaf polyamine levels in poplar: a large-scale field trial on heavily polluted soil.

Three ex situ collections of poplar clones from natural populations of Populus alba and P. nigra growing in northern Italy were assessed for their genetic dissimilarity (GD) by means of amplified fragment length polymorphism (AFLP). The high GD evidenced within populations was exploited for screening 168 clones in a field trial on heavy metal-polluted soil. After one growth season, clonal differences in plant survival and growth were observed. On the basis of performance, six clones were singled out, and used to evaluate copper and zinc accumulation in different organs. Clonal differences in metal concentrations were most evident for leaves and stems; one clone of P. alba (AL35) had a distinctly higher concentration of both metals in the roots. Leaf polyamine (putrescine, spermidine, spermine) profiles correlated with tissue metal concentrations, depending on the clone, plant organ and metal. In particular, the high metal-accumulating clone AL35 exhibited a dramatically higher concentration of free and conjugated putrescine. Overall, the results indicate that, given the high GD of Populus even within populations, it is possible to identify genotypes best suited for soil clean-up, and useful also for investigating physiological markers associated with high metal accumulation/tolerance.

Finite element analysis of cancellous bone failure in the vertebral body of healthy and osteoporotic subjects.

The aim of this work is to assess the fracture risk prediction of the cancellous bone in the body of a lumbar vertebra when the mechanical parameters of the bone, i.e. stiffness, porosity, and strength anisotropy, of elderly and osteoporotic subjects are considered. For this purpose, a non-linear three-dimensional continuum-based finite element model of the lumbar functional spinal unit L4-L5 was created and strength analyses of the spongy tissue of the vertebral body were carried out. A fabric-dependent strength criterion, which accounts for the micro-architecture of the cancellous bone, based on histomorphometric analyses was used. The strength analyses have shown that the cancellous bone of none of the subject types undergoes failure under loading applied during normal daily life like axial compression; however, bone failure occurs for the osteoporotic segment, subjected to a combination of the compression preloading and moments in the sagittal or in the frontal plane, which are conditions that may not be considered to occur 'daily'. In particular, critical stress conditions are met because of the high porosity values in the horizontal direction within the cancellous bone. The computational approach presented in the paper can potentially predict the material fracture risk of the cancellous bone in the vertebral body and it may be usefully employed to draw failure maps representing, for a given micro-architecture of the spongy tissue, the critical loading conditions (forces and moments) that may lead to such a risk. This approach could be further developed in order to assess the effectiveness of biomedical devices within an engineering approach to the clinical problem of the spinal diseases.

Modeling and mechanobiology of cerebral aneurysms.

The purpose of this work is to review the computational models of the adaptive behavior of the cerebral vascular wall aimed at simulating aneurysm formation and enlargement. Cerebral aneurysms are localized abnormal enlargements of the intracranial arterial vessels. The origin of this pathology is still unclear: however, aneurysm formation is thought to be the result of interplay between biomechanical properties of the vessel wall and their possible changes, such as adaptive response to mechanical stimuli. Recently, different computational approaches were suggested in the literature aiming to describe the mechanobiology of the cerebral vascular wall. Most of the computational adaptive models showed a common approach for the geometrically non-linear kinematic description of the phenomenon, whilst the constitutive laws defining the rates of growth variables may differ considerably according to the specific phenomenon considered. These studies allowed the reproduction of some peculiar aspects of aneurysm mechanobiology; however, continued interdisciplinary research is mandatory for a better understanding of the mechanisms involved in the evolution of cerebral aneurysms.

Mass spectrometry analysis of IgA1 hinge region in patients with IgA nephropathy.

BACKGROUND: Physicochemical alterations of the IgA molecule are supposed to play a pathogenetic role in IgA nephropathy (IgAN). The present study was carried out to analyze the structural variety of O-glycans on the IgA1 hinge region in IgAN. Sera from 9 IgAN patients and 9 healthy controls were individually examined to evaluate the IgA1 content and binding lectins (jacalin and Helix aspersa), using enzyme-linked immunosorbent assay (ELISA) techniques. The IgA1 from pooled sera were separated by affinity chromatography (jacalin), and the fragment containing the hinge region was prepared by pyridylethylation and trypsin treatment. The IgA fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated by jacalin affinity chromatography. Because we used jacalin, we only analyzed the Gal-3GalNAc residue containing IgA. The molecular weight (MW) of the IgA1 fragments was estimated using an ion trap mass spectrometer equipped with an electrospray ion source (ESI/MS). RESULTS: IgA1 concentration in pathological sera was higher than in the control serum (p<0.01). Compared with controls, serum IgA1 from IgAN patients showed significantly greater binding to the 2 lectins, jacalin (p<0.01) and Helix aspersa (HA, p<0.001), which are specific for O-linked Gal-beta1,3-GalNAc and GalNAc, respectively. Analyses of pooled sera showed that the number of O-glycosidic chains was comparable in IgAN and normal sera. With regards to the individual residues, we found that IgAN sera contained less sugar and galactose and sialic acid moieties than sera from control subjects, was reduced in IgAN sera, while terminal N-acetylgalactosamine levels were higher when compared with normal serum. CONCLUSIONS: Abnormalities of hinge region O-linked glycans were confirmed using advanced spectrometry technology. The pathogenetic implications for aggregation and defective removal of IgA1 are discussed.

A constituent-based model for the nonlinear viscoelastic behavior of ligaments.

This paper presents a constitutive model for predicting the nonlinear viscoelastic behavior of soft biological tissues and in particular of ligaments. The constitutive law is a generalization of the well-known quasi-linear viscoelastic theory (QLV) in which the elastic response of the tissue and the time-dependent properties are independently modeled and combined into a convolution time integral. The elastic behavior, based on the definition of anisotropic strain energy function, is extended to the time-dependent regime by means of a suitably developed time discretization scheme. The time-dependent constitutive law is based on the postulate that a constituent-based relaxation behavior may be defined through two different stress relaxation functions: one for the isotropic matrix and one for the reinforcing (collagen) fibers. The constitutive parameters of the viscoelastic model have been estimated by curve fitting the stress relaxation experiments conducted on medial collateral ligaments (MCLs) taken from the literature, whereas the predictive capability of the model was assessed by simulating experimental tests different from those used for the parameter estimation. In particular, creep tests at different maximum stresses have been successfully simulated. The proposed nonlinear viscoelastic model is able to predict the time-dependent response of ligaments described in experimental works (Bonifasi-Lista et al., 2005, J. Orthopaed. Res., 23, pp. 67-76; Hingorani et al., 2004, Ann. Biomed. Eng., 32, pp. 306-312; Provenzano et al., 2001, Ann. Biomed. Eng., 29, pp. 908-214; Weiss et al., 2002, J. Biomech., 35, pp. 943-950). In particular, the nonlinear viscoelastic response which implies different relaxation rates for different applied strains, as well as different creep rates for different applied stresses and direction-dependent relaxation behavior, can be described.

[Myocardial revascularization in patients with severely depressed left ventricular function]. / La rivascolarizzazione miocardica nei pazienti con funzione ventricolare sinistra severamente depressa.

BACKGROUND: Improvements in anesthetic and surgical management of patients with left ventricular dysfunction have resulted in a decline in perioperative mortality and morbidity. Nevertheless, coronary artery bypass grafting (CABG) in patients with left ventricular ejection fraction < or = 0.30 remains a surgical challenge. METHODS: Fifty-one patients with end-stage coronary artery disease and left ventricular ejection fraction between 16 and 30% underwent CABG. Mean age at operation was 66.1 +/- 7.85 years. Selection criteria included the clinical diagnosis of ischemic heart disease with angiographic demonstration of critical coronary artery obstructive lesions. Mean number of grafts per patient was 2.94 (range 1-5). Average duration of cardiopulmonary bypass was 74.5 +/- 22.4 min and mean aortic cross clamp time was 47.6 +/- 17 min. RESULTS: No operative and in-hospital deaths occurred. Eight patients (15.7%) had postoperative low cardiac output syndrome, requiring intraaortic balloon counterpulsation. There were two major neurological complications (3.9%). There were four late deaths (7.8%), due to recurrence of untreatable congestive heart failure. Left ventricular ejection fraction increased from a mean of 25.51 +/- 4.75% preoperatively to 31.35 +/- 9.9% postoperatively (p < 0.001). Improvement in NYHA functional class (preoperatively 2.98 +/- 0.79 vs 2.35 +/- 0.6 postoperatively, p < 0.001) was found in this group at follow-up. CONCLUSIONS: CABG leads to an excellent prognosis in high risk patients with ischemic heart disease and low left ventricular ejection fraction, improving their functional and clinical outcome and consequently their life expectancy.

Single-step purification of immunotoxins containing a high ionic charge ribosome inactivating protein clavin by carboxymethyl high-performance membrane chromatography.

High-performance membrane chromatography (HPMC) and HPLC hydroxyapatite chromatography were compared for their efficiency in purifying immunotoxins (ITs) containing the ribosome-inactivating protein clavin, which is characterized by a high anionic charge and a low molecular mass. Both methods efficiently removed unreacted clavin from the conjugate crude mixture, but only the cation-exchange HPMC allowed efficient single-step separation of the unreacted monoclonal antibody (mAb) from ITs obtained by different coupling procedures.