Development of an efficient, ready to use, blood platelet-release device based on two new flow regime parameters: The periodic hydrodynamic loading and the shear stress accumulation.

In vitro production of blood platelets for transfusion purposes is gaining interest. While platelet production is now possible on a laboratory scale, the challenge is to move towards industrial production. Attaining this goal calls for the development of platelet release devices capable of producing large quantities of platelets. To this end, we have developed a continuous-flow platelet release device composed of five spherical chambers each containing two calibrated cones placed in a staggered configuration. Following perfusion of proplatelet-bearing cultured megakaryocytes, the device achieves a high yield of about 100 bona-fide platelets/megakaryocyte, at a flow rate of ∼80 mL/min. Performances and operating conditions comply with the requirements of large-scale platelet production. Moreover, this device enabled an in-depth analysis of the flow regimes through Computational Fluid Dynamics (CFD). This revealed two new universal parameters to be taken into account for an optimal platelet release: i.e. a periodic hydrodynamic load and a sufficient accumulation of shear stress. An efficient 16 Pa.s shear stress accumulation is obtained in our system at a flow rate of 80 mL/min.

Biomechanical consequences of the intervertebral disc centre of rotation kinematics during lateral bending and axial rotation.

The location of the instantaneous centre of rotation (ICR) of a lumbar unit has a considerable clinical importance as a spinal health estimator. Consequently, many studies have been conducted to measure or estimate the ICR during rotations in the three anatomical planes; however the results reported are widely scattered. Even if some inter-subjects variability is to be expected, such inconsistencies are likely explained by the differences in methods and experiments. Therefore, in this paper we seek to model three behaviours of the ICR during lateral bending and axial rotation based on results published in the literature. In order to assess the metabolic and mechanical sensibility to the assumption made on the ICR kinematics, we used a previously validated three dimensional non-linear poroelastic model of a porcine intervertebral disc to simulate physiological lateral and axial rotations. The impact of the geometry was also briefly investigated by considering a 11[Formula: see text] wedge angle. From our simulations, it appears that the hypothesis made on the ICR location does not significantly affect the critical nutrients concentrations but gives disparate predictions of the intradiscal pressure at the centre of the disc (variation up to 0.7 MPa) and of the displacement fields (variation up to 0.4 mm). On the contrary, the wedge angle does not influence the estimated intradiscal pressure but leads to minimal oxygen concentration decreased up to 33% and increased maximal lactate concentration up to 13%. While we can not settle on which definition of the ICR is more accurate, this work suggests that patient-specific modeling of the ICR is required and brings new insights that can be useful for the development of new tools or the design of surgical material such as total lumbar disc prostheses.

Assessment of intervertebral disc degeneration-related properties using finite element models based on [Formula: see text]-weighted MRI data.

Quantitative magnetic resonance imaging (MRI) provides useful information about intervertebral disc (IVD) biomechanical properties, especially those in relation to the fluid phase. These properties may improve IVD finite element (FE) models using data closer to physiological reality. The aim of this study is to investigate IVD degeneration-related properties using a coupling between MRI and FE modeling. To this end, proton density ([Formula: see text])-weighted MRI sequences of a porcine lumbar IVD were carried out to develop two biphasic swelling models with hyperelastic extracellular matrix behavior. The first model is isotropic, and the second one is anisotropic and takes into account the role of collagen fibers in the mechanical behavior of the IVD. MRI sequences permitted to determine the geometry and the real porosity mapping within the disc. The differentiation between disc components (nucleus pulposus, annulus fibrosus and cartilaginous end plates) was taken into account using spatial continuous distributions of the mechanical properties. The validation of the FE models was performed through two steps: the identification of the model's mechanical properties using relaxation compressive test and the comparison between the MRI after load porosity distributions and those numerically obtained using the set of identified properties. The results confirmed that the two developed FE models were able to predict the mechanical response of uniaxial time-dependent compressive test and the redistribution of porosity after load. A slight difference between the measured and the numerical local bulges of the disc was found. This study suggests that from the coupling between MRI imaging in different state of load and finite element modeling we can deduce relevant information that can be used in the assessment of the early intervertebral disc degeneration changes.

Biaxial tensile tests of the porcine ascending aorta.

One of the aims of this work is to develop an original custom built biaxial set-up to assess mechanical behavior of soft tissues. Stretch controlled biaxial tensile tests are performed and stereoscopic digital image correlation (SDIC) is implemented to measure the 3D components of the generated displacements. Using this experimental device, the main goal is to investigate the mechanical behavior of porcine ascending aorta in the more general context of human ascending aorta pathologies. The results highlight that (i) SDIC arrangement allows accurate assessment of displacements and so stress strain curves, (ii) porcine ascending aorta has a nearly linear and anisotropic mechanical behavior until 30% of strain, (iii) porcine ascending aorta is stiffer in the circumferential direction than in the longitudinal one, (iv) the material coefficient representing the interaction between the two loading directions is thickness dependent, (v) taking into account the variability of the samples the stress values are independent of the stretch rate in the range of values from 10(-3) to 10(-1)s(-1) and finally, (vi) unlike other segments of the aorta, 4-month-old pigs ascending aorta is definitely not a relevant model to investigate the mechanical behavior of the human ascending aorta.

Realistic glottal motion and airflow rate during human breathing.

The glottal geometry is a key factor in the aerosol delivery efficiency for treatment of lung diseases. However, while glottal vibrations were extensively studied during human phonation, the realistic glottal motion during breathing is poorly understood. Therefore, most current studies assume an idealized steady glottis in the context of respiratory dynamics, and thus neglect the flow unsteadiness related to this motion. This is particularly important to assess the aerosol transport mechanisms in upper airways. This article presents a clinical study conducted on 20 volunteers, to examine the realistic glottal motion during several breathing tasks. Nasofibroscopy was used to investigate the glottal geometrical variations simultaneously with accurate airflow rate measurements. In total, 144 breathing sequences of 30s were recorded. Regarding the whole database, two cases of glottal time-variations were found: "static" or "dynamic" ones. Typically, the peak value of glottal area during slow breathing narrowed from 217 ± 54 mm(2) (mean ± STD) during inspiration, to 178 ± 35 mm(2) during expiration. Considering flow unsteadiness, it is shown that the harmonic approximation of the airflow rate underevaluates the inertial effects as compared to realistic patterns, especially at the onset of the breathing cycle. These measurements provide input data to conduct realistic numerical simulations of laryngeal airflow and particle deposition.

Stereoscopically observed deformations of a compliant abdominal aortic aneurysm model.

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07 mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120 mm Hg. These strains are 1-2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.

Nutrient distribution and metabolism in the intervertebral disc in the unloaded state: a parametric study.

A 2-D finite element model for the intervertebral disc in which quadriphasic theory is coupled to the transport of solutes involved in cellular nutrition was developed for investigating the main factors contributing to disc degeneration. Degeneration is generally considered to result from chronic disc cell nutrition insufficiency, which prevents the cells from renewing the extracellular matrix and thus leads to the loss of proteoglycans. Hence, the osmotic power of the disc is decreased, causing osmomechanical impairments. Cellular metabolism depends strongly on the oxygen, lactate and glucose concentrations and on pH in the disc. To study the diffusion of these solutes in a mechanically or osmotically loaded disc, the osmomechanical and diffusive effects have to be coupled. The intervertebral disc is modeled here using a plane strain formulation at the equilibrium state under physiological conditions after a long rest period (called unloaded state). The correlations between solute distribution and various properties of healthy and degenerated discs are investigated. The numerical simulation shows that solute distribution in the disc depends very little on the elastic modulus or the proteoglycan concentration but greatly on the porosity, diffusion coefficient and endplate diffusion area. This coupled model therefore opens new perspectives for investigating intervertebral disc degeneration mechanisms.