Polymerization kinetics of a mixture of Lipiodol and Glubran 2 cyanoacrylate glue upon contact with a proteinaceous solution.

The Glubran 2 cyanoacrylate glue is a liquid embolic agent used to block blood vessels endovascularly. Typically mixed with an iodized oil (Lipiodol) for visualization under X-ray, it polymerizes when in contact with blood and tissues owing to the presence of ions and proteins. The objective of the study is to determine the influence of plasma proteins in the polymerization reaction. A triggering solution containing bovine serum albumin (BSA) and the main blood ions is used as a model of plasma. The polymerization kinetics of Glubran 2-Lipiodol mixtures is measured upon aspiration in a capillary tube and contact with the proteinaceous solution. Having varied the glue and protein concentrations, we show that glue-Lipiodol mixtures with concentrations larger or equal to 25% polymerize when put in contact with an ionic solution containing at least 4% of BSA. The reaction is decomposed into two phases: a fast zwitterionic polymerization induced by the BSA molecules followed by a slower polymerization phase. The reaction speed and extent of the solidification region mostly depend on the glue concentration. The time for the glue solution to polymerize over a 1mm thickness varies from 5s for pure glue to about 1min for a 50% glue concentration, and 10min for a 25% glue mixture. It is the first time that the kinetics of the two polymerization reactions is quantified for Glubran 2, which will provide the information needed by interventional radiologists to optimize the planning of endovascular glue injection.

Polymerization kinetics of n-butyl cyanoacrylate glues used for vascular embolization.

Vascular embolization is a minimally invasive treatment used for the management of vascular malformations and tumors. It is carried out under X-ray by navigating a microcatheter into the targeted blood vessel, through which embolic agents are delivered to occlude the vessels. Cyanoacrylate liquid glues have been widely used for vascular embolization owing to their low viscosity, rapid polymerization/solidification rate, good penetration ability and low tissue toxicity. The objective of this study is to quantitatively investigate the physical properties of two n-butyl cyanoacrylate (nBCA) glues (Glubran 2 and Histoacryl) mixed with an iodized oil (Lipiodol) at various concentrations. We show that an homogeneous solution results from the mixing of the glue and Lipiodol, and that the viscosity, density and interfacial tension of the mixture increase with the proportion in Lipiodol. We have designed a new experimental setup to systemically characterize the polymerization kinetics of a glue mixture upon contact with an ionic solution. We observe that the whole polymerization process includes two phases: an interfacial polymerization that takes place at the interface as soon as the two liquids are in contact with a characteristic time scale of the order of the minute; a volumetric polymerization during which a reaction front propagates within the mixture bulk with a characteristic time scale of the order of tens of minutes. The polymerization rate, front propagation speed and volume reduction increase with the glue concentrations. It is the first time that such comprehensive results are obtained on liquid embolic agents.

Characterizing the membrane properties of capsules flowing in a square-section microfluidic channel: effects of the membrane constitutive law.

A microfluidic method is presented to measure the elastic membrane properties of a population of microcapsules with diameter of order 60 µm. The technique consists of flowing a suspension of capsules enclosed by a polymerized ovalbumin membrane through a square-section microfluidic channel with cross dimension comparable with the capsule mean diameter. The deformed profile and the velocity of a given capsule are recorded. A full mechanical model of the motion and deformation of an initially spherical capsule flowing inside a square-section channel is designed for different flow strengths, confinement ratios, and membrane constitutive laws. The experimental deformed profiles are analyzed with the numerical model. This allows us to find the ratio between the viscous and elastic forces and thus the shear elastic modulus of the membrane. We show that the ovalbumin membrane tends to have a strain-softening behavior under the conditions studied here.

Tension of red blood cell membrane in simple shear flow.

When a red blood cell (RBC) is subjected to an external flow, it is deformed by the hydrodynamic forces acting on its membrane. The resulting elastic tensions in the membrane play a key role in mechanotransduction and govern its rupture in the case of hemolysis. In this study, we analyze the motion and deformation of an RBC in a simple shear flow and the resulting elastic tensions on the membrane. The large deformation of the red blood cell is modelled by coupling a finite element method to solve the membrane mechanics and a boundary element method to solve the flows of the internal and external liquids. Depending on the capillary number Ca, ratio of the viscous to elastic forces, we observe three kinds of RBC motion: tumbling at low Ca, swinging at larger Ca, and breathing at the transitions. In the swinging regime, the region of the high principal tensions periodically oscillates, whereas that of the high isotropic tensions is almost unchanged. Due to the strain-hardening property of the membrane, the deformation is limited but the membrane tension increases monotonically with the capillary number. We have quantitatively compared our numerical results with former experimental results. It indicates that a membrane isotropic tension O(10{-6} N/m) is high enough for molecular release from RBCs and that the typical maximum membrane principal tension for haemolysis would be O(10{-4} N/m). These findings are useful to clarify not only the membrane rupture but also the mechanotransduction of RBCs.

Comparison between spring network models and continuum constitutive laws: application to the large deformation of a capsule in shear flow.

A capsule is a liquid drop enclosed by a solid, deformable membrane. To analyze the deformation of a capsule accurately, both the fluid mechanics of the internal and external fluids and the solid mechanics of the membrane must be solved precisely. Recently, many researchers have used discrete spring network models to express the membrane mechanics of capsules and biological cells. However, it is unclear whether such modeling is sufficiently accurate to solve for capsule deformation. This study examines the correlations between the mechanical properties of the discrete spring network model and continuum constitutive laws. We first compare uniaxial and isotropic deformations of a two-dimensional (2D) sheet, both analytically and numerically. The 2D sheet is discretized with four kinds of mesh to analyze the effect of the spring network configuration. We derive the relationships between the spring constant and continuum properties, such as the Young modulus, Poisson ratio, area dilation modulus, and shear modulus. It is found that the mechanical properties of spring networks are strongly dependent on the mesh configuration. We then calculate the deformation of a capsule under inflation and in a simple shear flow in the Stokes flow regime, using various membrane models. To achieve high accuracy in the flow calculation, a boundary-element method is used. Comparing the results between the different membrane models, we find that it is hard to express the area incompressibility observed in biological membranes using a simple spring network model.

Comparison between measurements of elasticity and free amino group content of ovalbumin microcapsule membranes: discrimination of the cross-linking degree.

An inverse method is used to characterize the membrane mechanical behavior of liquid filled microcapsules. Cross-linked ovalbumin microcapsules are flowed and deformed into a cylindrical microchannel of comparable size. The deformed shape is compared to predictions obtained numerically when modeling a capsule under the same flow conditions. The unknown shear modulus value corresponds to the best fit. The degree of reticulation is estimated in parallel by determining the free amino groups remaining on the microcapsules after the cross-linking reaction. We characterize microcapsule populations fabricated at different reaction pH (5-8) and times (5-30 min) to study different cross-linking degrees. The capsule shear modulus and the amino groups are nearly constant with the reaction pH for the capsules fabricated after 5 min of reticulation. The shear modulus increases with the reaction time, while the NH(2) content decreases with it. A global increase in shear modulus with pH is also observed, together with an unexpected increase in NH(2) content. The study shows that the inverse method is capable of discriminating between various cross-linking degrees of microcapsules. Moreover, for this type of microcapsules, the mechanical method appears more reliable than the chemical one to obtain an estimation of their cross-linking degree.

Mechanical properties of alginate beads hosting hepatocytes in a fluidized bed bioreactor.

Fluidized bed bioartificial liver has been proposed as a temporary support to bridge patients suffering from acute liver failure to transplantation. In such a bioreactor, alginate beads hosting hepatocytes are in continuous motion during at least six hours. After having shown in vitro the functionality of such a device, the present study aims at analyzing the potential mechanical alterations of the beads in the bioreactor, perfused by different surrounding media. Compression experiments are performed and coupled for analysis with Hertz theory. They provide qualitative and quantitative data. The average value of the shear modulus, calculated for the different cases studied varied from 2.4 to 10.4 kPa, and could therefore be considered as a quantitative measure of the beads mechanical properties. From the compression experiments and the estimated values of the shear modulus, we could now evaluate the effect of different operating conditions (fluidization, presence of cells, surrounding medium) on the mechanical behavior of alginate beads. On the one hand, the motion during six hours in the bioreactor does not alter the beads significantly. On the other hand, the presence of different substances in the fluid phase might change their mechanical strength. These results can be considered as new encouragements to use such a device as a bioartificial organ.

Deformation and bursting of nonspherical polysiloxane microcapsules in a spinning-drop apparatus.

We analyze the deformation and bursting process of nonspherical organosiloxane capsules in centrifugal fields. Measurements were performed in a commercial spinning-drop tensiometer at different values of tube rotation. A theoretical analysis of the mechanics of initially ellipsoidal elastic shells subjected to centrifugal forces is developed where the deformation of the capsule is predicted as a function of the initial geometry and membrane elastic properties. For different types of organosiloxane membranes the Poisson number varies between 0 and 0.9. This phenomenon points to a considerable reduction of the membrane thickness at the onset of mechanical stress. Membrane-breaking processes always initiated at one of the pole ends of the capsules. Such rupture processes can be interpreted in terms of the derived theoretical model.

Swelling of hydrocolloid dressings.

Wound healing is promoted by dressings that maintain a moist environment. Specifically, hydrocolloid dressings allow excess fluid to escape without permitting wound desiccation. However, the fluid handling capacity of hydrocolloid dressings depends on many factors such as the physicochemical properties of the gel formulation, and the design of the dressing. We measured the moisture uptake kinetics of different hydrocolloid dressings by placing the gel side of a sample in contact with water. The time evolution of the thickness was measured by means of a video camera linked to a computer. The theory of Tanaka and Fillmore (1979) was used to predict the kinetics of uniaxial swelling of a cylindrical gel sample. The model allows to associate to an experimental curve a total thickness increase hf-h0 (where hf and h0 are respectively the final and initial thickness) and a characteristic time tau. The model also relates hf-h0 and tau to the physiochemical composition of the dressing, and to the initial thickness h0. The influence of h0 is discussed by means of experiments performed on dressings with different initial thickness.

Theoretical modelling of the motion and deformation of capsules in shear flows.

Mechanical models for capsules freely suspended in another liquid, are devised to predict the deformation, motion, breakup of one particle and also the rheological flow behaviour of a suspension. The capsule is filled with a newtonian liquid, and is surrounded by a thin deformable membrane having otherwise arbitrary mechanical properties. Initially spherical capsules in simple shear flow, are found to deform and orient with respect to streamlines, while their membrane is continuously rotating around the internal liquid. A dilute suspension of such capsules has a viscoelastic constitutive law which depends on the particle physical properties. It is then possible to use such models to interpret experiments in terms of the mean intrinsic properties of a capsule population.

Viscous filtration of red blood cell suspensions.

Filtration experiments on red blood cell suspensions are usually conducted in a saline buffer solution. As a result, the flow of a particle in a pore is largely dominated by viscous effects, and it is not possible to distinguish between normal and membrane altered cells. A new approach to red cell filtration is proposed here, whereby the cells are suspended in a Dextran solution that has roughly the same viscosity as the internal hemoglobin solution. It is thus aimed to detect alterations of the membrane properties. In order to prove this point, filtration measurements are conducted with a hemorheometer on dilute (hematocrit 8%) suspensions of normal and membrane hardened (diamide treatment) cells, suspended either in a 8 mPa.s Dextran solution or in a 1 mPa.s buffer solution. As expected when the cells are suspended in buffer, there is no detectable difference in the filtration index for normal and treated cells. However, when they are suspended in the 8 mPa.s solution, the filtration index is significantly larger for treated than for normal cells. This shows that filtration in a viscous liquid can be used to measure changes in cell deformability due to membrane modifications.

Determination of the red blood cell apparent membrane elastic modulus from viscometric measurements.

Rhelogical measurements on a dilute suspension of red blood cells (RBCs) are interpreted by means of a microheological model that relates the shear evolution of the apparent viscosity to the intrinsic properties of the suspended particles. It is then possible to quantify the average deformability of a RBC population in terms of a mean value of the membrane shear elastic modulus, Es. Dilute suspensions of erthrocytes exhibit shear-thinning behavior with a constant high shear viscosity. This behavior is identical to the one predicted for a suspension of spherical capsules where the same phenomena of deformation and orientation prevail. A comparison between theoretical and experimental curves yields a mean value of Es, assuming all other cell properties--internal viscosity, geometry--to be otherwise equal. In Dextran, the values of Es for normal RBCs are found to be of order 3.10(-6) N/m. For erythrocytes hardened by heat exposure for 15 minutes at 48 degrees C, the increase in Es reaches 45 percent. This procedure of shear elastic modulus determination is easy to perform and seems to give a good discrimination between normal and altered erythrocytes.