Tissue-engineered Collagenous Fibrous Cap Models to Systematically Elucidate Atherosclerotic Plaque Rupture.

A significant amount of vascular thrombotic events is associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of an successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.

Second gradient substitution model for high contrast bi-phase structure

Lightweight structures with soft inclusion material, such as hollow core slabs, foam sandwich wall, pervious pavement ... are widely used in construction engineering for sustainable goals. Voids and soft inclusion can be modeled as a very soft material, while the main material is modeled with its original rigidity, which is so much higher than inclusion's one. In consequence, highly contrast bi-phase structure attracts the interests of scientists and engineers. One important demand is how to build a homogeneous equivalent model to replace the multi-phase structure which requires much resources and time to perform structure analysis. Various homogenization schemes have succeeded in establishing a homogeneous substitution model for composite materials which fulfill the scale separation condition (characteristic length of heterogeneity is very small in comparison to structure dimensions). Herein, elastic stiffness matrix of a homogeneous model which replaces a bi-phase material is computed by a higher-order homogenization scheme. A non-homogeneous boundary condition (a polynomial inspired from Taylor series expansion) is used in computation. Homogeneous substitution model constructed from this computation process, can give engineers a fast and effective tool to predict the behavior of bi-phase structure. Instead of a classical Cauchy continuum, second gradient model is selected as a potential candidate for substituting the composite material behavior because of the separation scale (volume ratio of inclusion to matrix phase reaches unit). Keywords: generalized continuum; second-gradient medium; higher-order homogenization; non-homogeneous boundary conditions; representative volume element.

Elastic geobarometry of multiphase inclusions

<p>Elastic geobarometry allows one to recover the PT entrapment conditions of a host-inclusion pair from measurements of the residual pressure of the inclusion which develops upon exhumation due to differences of its thermo-elastic properties from the host (Angel et al., 2015). At the present, calculations assume that the inclusion is a single phase. For a soft inclusion in a stiffer host, the volume change of a free inclusion crystal would be greater than that of the host, which leads to the inclusions being compressed into a smaller volume than expected and thus positive inclusion pressures. Conversely, an inclusion stiffer than the host should develop a negative pressure.</p><p>Rutile-in-garnet would be a good candidate for elastic geobarometry because of its common occurrence in high-pressure high-temperature (HP-HT) metamorphic rocks, its simple structure and chemistry and its broad PT stability field. However, recent work by Zaffiro et al. (2019) demonstrated that rutile trapped in garnet should always exhibit negative pressure upon exhumation because rutile is stiffer than garnet, making this pair unsuitable for elastic geobarometry.</p><p>Nevertheless, rutile inclusions in garnets from the Pohorje eclogite seem to challenge this thermodynamic prediction. Rutile inclusions show no Raman peak shifts relative to free crystals within the measurement error, despite there being strain birefringence in the garnet host around the rutile which indicates the relaxation of stressed inclusions. High resolution 3D Raman mapping on one of these rutile inclusions revealed the presence of tiny (2-3 µm thick) amphibole crystals located between the garnet and rutile, with the amphibole occupying about 25-30% of the volume of the inclusion. The presence of this amount of amphibole lowers the bulk modulus of the composite inclusion (rutile + amphibole) to less than the bulk modulus of the garnet, hence leading to pressurization of the inclusions upon exhumation. This study shows that careful characterization of host inclusion systems, linked to thermodynamic modelling, is thus necessary to interpret residual pressures (P<sub>inc</sub>) in terms of entrapment conditions.</p><p>This project has received funding from the European Research Council under the H2020 research and innovation program (N. 714936 TRUE DEPTHS to M. Alvaro).</p><p>References:</p><p>Angel R.J. et al. 2015. J. Metamorph. Geol., 33(8), 801-813.</p><p>Zaffiro G. et al. 2019.  Mineralogical Magazine, 83(3), 339-347.</p>

Theoretical analysis of a rolling-sliding elastohydrodynamic lubrication line contact with a subsurface inclusion

This work investigates the transient effects of a single subsurface inclusion over the pressure, film thickness, and von Mises stress in a line elastohydrodynamic lubrication contact. Results are obtained with a fully-coupled finite element model for either a stiff or a soft inclusion moving at the speed of the surface. Two cases analyzed consider the inclusion moving either at the same speed as the mean velocity of the lubricant or moving slower. Two additional cases investigate reducing either the size of the inclusion or its stiffness differential with respect to the matrix. It is shown that the well-known two-wave elastohydrodynamic lubrication mechanism induced by surface features is also applicable to the inclusions. Also, that the effects of the inclusion become weaker both when its size is reduced and when its stiffness approaches that of the matrix. A direct comparison with predictions by the semi-analytical model of Morales-Espejel et al. ( Proc IMechE, Part J: J Engineering Tribology 2017; 231) shows reasonable qualitative agreement. Quantitatively some differences are observed which, after accounting for the semi-analytical model's simplicity, physical agreement, and computational efficiency, may then be considered as reasonable for engineering applications.

Formation Mechanism of Voids around Hard Inclusion during Hot Rolling Processes

To investigate the mechanism by which voids form around hard inclusions, the deformations of a plastic slab with hard and soft inclusions that form inside it during the hot rolling process have been simulated with a finite element method. By comparing plastic strain distributions, the relative displacements of contact surfaces, and the deformations between hard and soft inclusions have preceded analysis of the formation mechanism of these voids. The variations of strain measurements between the matrix and hard inclusions cause relative displacement of their contact surfaces. Therefore, voids occur at the front and rear of the hard inclusions. Trials on the slab deformations using a titanium ball instead of the soft inclusion inside the slab during the hot rolling process are conducted. The simulated shapes of the soft inclusions with different reductions mostly agree with the experimental results.

Regularizing Biomechanical Maps for Partially Known Material Properties

We present the solution of the inverse problem for partially known elastic modulus values, e.g., the elastic modulus is known in some small region on the boundary of the domain from measurements. The inverse problem is posed as a constrained minimization problem and regularized with two different regularization types. In particular, the total variation diminishing (TVD) and the total contrast diminishing (TCD) regularizations are employed. We test both regularization strategies with theoretical diseased tissues, such as a stiff tumor surrounded by healthy background tissue and an atherosclerotic plaque having a soft inclusion surrounded by a stiff cap. In the present study, it is assumed that no traction data is available and the absolute elastic modulus distribution is calibrated from partially known elastic modulus values. We observe that this calibration fails with TVD regularization, while TCD regularization yields well-recovered absolute elastic modulus reconstructions in the presence of high noise levels in the displacement data. Finally, we investigate this problem analytically and provide an explanation for these observations. This work will advance efforts in parameter identification of heterogeneous materials as it provides a methodology to incorporate partially known parameters into the inverse problem formulation that will ultimately drive the inverse solution to an absolute and unique parameter distribution. This has great importance in classifying breast tumors based on their elastic modulus values and in planning surgical interventions of atherosclerotic plaques.