A stabilized finite element method for finite-strain three-field poroelasticity

We construct a stabilized finite-element method to compute flow and finitestrain deformations in an incompressible poroelastic medium. We employ a three- field mixed formulation to calculate displacement, fluid flux and pressure directly and introduce a Lagrange multiplier to enforce flux boundary conditions. We use a low order approximation, namely, continuous piecewise-linear approximation for the displacements and fluid flux, and piecewise-constant approximation for the pressure. This results in a simple matrix structure with low bandwidth. The method is stable in both the limiting cases of small and large permeability. Moreover, the discontinuous pressure space enables efficient approximation of steep gradients such as those occurring due to rapidly changing material coefficients or boundary conditions, both of which are commonly seen in physical and biological applications

Neural responses to others’ pain vary with psychopathic traits in healthy adult males

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid- and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affective-interpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population

As Far as the Eye Can See: Relationship between Psychopathic Traits and Pupil Response to Affective Stimuli

Psychopathic individuals show a range of affective processing deficits, typically associated with the interpersonal/affective component of psychopathy. However, previous research has been inconsistent as to whether psychopathy, within both offender and community populations, is associated with deficient autonomic responses to the simple presentation of affective stimuli. Changes in pupil diameter occur in response to emotionally arousing stimuli and can be used as an objective indicator of physiological reactivity to emotion. This study used pupillometry to explore whether psychopathic traits within a community sample were associated with hypo-responsivity to the affective content of stimuli. Pupil activity was recorded for 102 adult (52 female) community participants in response to affective (both negative and positive affect) and affectively neutral stimuli, that included images of scenes, static facial expressions, dynamic facial expressions and sound-clips. Psychopathic traits were measured using the Triarchic Psychopathy Measure. Pupil diameter was larger in response to negative stimuli, but comparable pupil size was demonstrated across pleasant and neutral stimuli. A linear relationship between subjective arousal and pupil diameter was found in response to sound-clips, but was not evident in response to scenes. Contrary to predictions, psychopathy was unrelated to emotional modulation of pupil diameter across all stimuli. The findings were the same when participant gender was considered. This suggests that psychopathy within a community sample is not associated with autonomic hypo-responsivity to affective stimuli, and this effect is discussed in relation to later defensive/appetitive mobilisation deficits

Discrimination of meniscal cell phenotypes using gene expression profiles

The lack of quantitative and objective metrics to assess cartilage and meniscus cell phenotypes contributes to the challenges in fibrocartilage tissue engineering. Although functional assessment of the final resulting tissue is essential, initial characterization of cell sources and quantitative description of their progression towards the natural, desired cell phenotype would provide an effective tool in optimizing cell-based tissue engineering strategies. The purpose of this study was to identify quantifiable characteristics of meniscal cells and thereby find phenotypical markers that could effectively categorize cells based on their tissue of origin (cartilage, inner, middle, and outer meniscus). The combination of gene expression ratios collagen VI/collagen II, ADAMTS-5/collagen II, and collagen I/collagen II was the most effective indicator of variation among different tissue regions. We additionally demonstrate a possible application of these quantifiable metrics in evaluating the use of serially passaged chondrocytes as a possible cell source in fibrocartilage engineering. Comparing the ratios of the passaged chondrocytes and the native meniscal cells may provide direction to optimize towards the desired cell phenotype. We have thus shown that measurable markers defining the characteristics of the native meniscus can establish a standard by which different tissue engineering strategies can be objectively assessed. Such metrics could additionally be useful in exploring the different stages of meniscal degradation in osteoarthritis and provide some insight in the disease progression

Cyclic Tensile Culture Promotes Fibroblastic Differentiation of Marrow Stromal Cells Encapsulated in Poly(Ethylene Glycol)-Based Hydrogels

To inform future efforts in tendon/ligament tissue engineering, our laboratory has developed a well-controlled model system with the ability to alter both external tensile loading parameters and local biochemical cues to better understand marrow stromal cell differentiation in response to both stimuli concurrently. In particular, the synthetic, poly(ethylene glycol)-based hydrogel material oligo(poly(ethylene glycol) fumarate) (OPF) has been explored as a cell carrier for this system. This biomaterial can be tailored to present covalently incorporated bioactive moieties and can be loaded in our custom cyclic tensile bioreactor for up to 28 days with no loss of material integrity. Human marrow stromal cells encapsulated in these OPF hydrogels were cultured (21 days) under cyclic tensile strain (10%, 1 Hz, 3 h of strain followed by 3 h without) or at 0% strain. No difference was observed in cell number due to mechanical stimulation or across time (n = 4), with cells remaining viable (n = 4) through 21 days. Cyclic strain significantly upregulated all tendon/ligament fibroblastic genes examined (collagen I, collagen III, and tenascin-C) by day 21 (n ≥ 6), whereas genes for other pathways (osteogenic, chondrogenic, and adipogenic) did not increase. After 21 days, the presence of collagen I and tenascin-C was observed via immunostaining (n = 2). This study demonstrates the utility of this hydrogel/bioreactor system as a versatile, yet well-controlled, model environment to study marrow stromal cell differentiation toward the tendon/ligament phenotype under a variety of conditions

Validating MRI-Derived Myocardial Stiffness Estimates Using In Vitro Synthetic Heart Models

Impaired cardiac filling in response to increased passive myocardial stiffness contributes to the pathophysiology of heart failure. By leveraging cardiac MRI data and ventricular pressure measurements, we can estimate in vivo passive myocardial stiffness using personalized inverse finite element models. While it is well-known that this approach is subject to uncertainties, only few studies quantify the accuracy of these stiffness estimates. This lack of validation is, at least in part, due to the absence of ground truth in vivo passive myocardial stiffness values. Here, using 3D printing, we created soft, homogenous, isotropic, hyperelastic heart phantoms of varying geometry and stiffness and simulate diastolic filling by incorporating the phantoms into an MRI-compatible left ventricular inflation system. We estimate phantom stiffness from MRI and pressure data using inverse finite element analyses based on a Neo-Hookean model. We demonstrate that our identified softest and stiffest values of 215.7 and 512.3 kPa agree well with the ground truth of 226.2 and 526.4 kPa. Overall, our estimated stiffnesses revealed a good agreement with the ground truth (< 5.8 % error) across all models. Our results suggest that MRI-driven computational constitutive modeling can accurately estimate synthetic heart material stiffnesses in the range of 200–500 kPa.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Medical Instruments & Bio-Inspired Technolog

Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

Small animal models of osteoarthritis are often used for evaluating the efficacy of pharmacologic treatments and cartilage repair strategies, but noninvasive techniques capable of monitoring matrix-level changes are limited by the joint size and the low radiopacity of soft tissues. Here we present a technique for the noninvasive imaging of cartilage at micrometer-level resolution based on detecting the equilibrium partitioning of an ionic contrast agent via microcomputed tomography. The approach exploits electrochemical interactions between the molecular charges present in the cartilage matrix and an ionic contrast agent, resulting in a nonuniform equilibrium partitioning of the ionic contrast agent reflecting the proteoglycan distribution. In an in vitro model of cartilage degeneration we observed changes in x-ray attenuation magnitude and distribution consistent with biochemical and histological analyses of sulfated glycosaminoglycans, and x-ray attenuation was found to be a strong predictor of sulfated glycosaminoglycan density. Equilibration with the contrast agent also permits direct in situ visualization and quantification of cartilage surface morphology. Equilibrium partitioning of an ionic contrast agent via microcomputed tomography thus provides a powerful approach to quantitatively assess 3D cartilage composition and morphology for studies of cartilage degradation and repair