SIPA in 10 milliseconds: VWF tentacles agglomerate and capture platelets under high shear

Shear-Induced Platelet Aggregation (SIPA) occurs under elevated shear rates (~10000 s-1) found in stenotic coronary and carotid arteries. The pathologically high-shear environment can lead to occlusive thrombosis by SIPA from the interaction of nonactivated platelets and von Willebrand factor (VWF) via glycoprotein Ib (GPIb)-A1 binding. This process under high shear rates is difficult to visualize experimentally with concurrent molecular- and cellular-resolutions. To understand this fast bonding, we employ a validated multiscale in-silico model incorporating measured molecular kinetics and a thrombosis-on-a-chip device to delineate the flow-mediated biophysics of VWF and platelets assembly into mural micro-thrombi. We show that SIPA begins with VWF elongation, followed by agglomeration of platelets in the flow by soluble VWF entanglement before mural capture of the agglomerate by immobilized VWF. The entire SIPA process occurs on the order of 10 ms with the agglomerate travelling a lag distance of a few hundred microns before capture, matching in vitro results. Increasing soluble VWF concentration by ~20x in silico leads to a 2~3x increase in SIPA rates, matching the increase in occlusion rates found in vitro. The morphology of mural aggregates is primarily controlled by VWF molecular weight (length), where normal-length VWF leads to cluster or elongated aggregates and ultra-long VWF leads to loose aggregates seen by others' experiments. Finally, we present phase diagrams of SIPA which provides biomechanistic rationales for a variety of thrombotic and hemostatic events in terms of platelet agglomeration and capture.

Macroscopic rheology of non-Brownian suspensions at high shear rates: the influence of solid volume fraction and non-Newtonian behaviour of the liquid phase

Modelling the macroscopic rheology of non-Brownian suspensions is complicated by the non-linear behaviour that originates from the interaction between solid particles and the liquid phase. In this contribution, a model is presented that describes suspension rheology as a function of solid volume fraction and shear rate dependency of both the liquid phase, as well as the suspension as a whole. It is experimentally validated using rotational rheometry ($$\varphi$$ φ ≤ 0.40) and capillary rheometry (0.55 ≤ $$\varphi$$ φ ≤ 0.60) at shear rates > 50 s−1. A modified Krieger-Dougherty relation was used to describe the influence of solid volume fraction on the consistency coefficient, $$K$$ K , and was fitted to suspensions with a shear thinning liquid phase, i.e. having a flow index, $$n$$ n , of 0.50. With the calculated fit parameters, it was possible to predict the consistency coefficients of suspensions with a large variation in the shear rate dependency of the liquid phase ($$n$$ n = 0.20–1.00). With increasing solid volume fraction, the flow indices of the suspensions were found to decrease for Newtonian and mildly shear thinning liquid phases ($$n$$ n ≥0.50), whereas they were found to increase for strongly shear thinning liquid phases ($$n$$ n ≤0.27). It is hypothesized that this is related to interparticle friction and the relative contribution of friction forces to the viscosity of the suspension. The proposed model is a step towards the prediction of the flow curves of concentrated suspensions with non-Newtonian liquid phases at high shear rates.

Investigation of the Strength of Plastic Parts Improved with Selective Induction Heating

The use of selective induction heating of molding surfaces allows for better filling of molding cavities and has a positive effect on the properties of molded products. This is particularly important in the production of parts that include flexible hinges, which are thin plastic layers connecting two or more parts of the product. By using hinges, it is possible to expand the use of injection molding products and their capabilities. They are widely used in the production of parts for the electrical engineering industry and for packaging Fast Moving Consumer Goods (FMCG). The use of hinges also entails specific reductions in wall thickness. Increases in the shear rate can be expected, which can lead to the degradation of polymers and deterioration of mechanical properties of materials. This paper investigates injection molded flexible hinge parts manufactured with selective induction heating to improve their properties. To verify the efficiency of reduction of material degradation due to high shear rates, open/close tests of elastic hinges were performed. The linear relation between the number of cycles the hinges can withstand, mold temperature and injection time was identified, where mold temperature was the more significant factor.

The von Willebrand Factor A-1 domain binding aptamer BT200 elevates plasma levels of VWF and Factor VIII: a first-in-human trial

Von Willebrand Factor (VWF) and Factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary haemostasis and clotting respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomised, placebo-controlled, double-blind trial tested the hypothesis that BT200 is well tolerated and has favourable pharmacokinetic and pharmacodynamic effects in 112 volunteers. Participants received one of the following: Single ascending dose of BT200 (0.18-48mg) subcutaneously, an intravenous dose, BT200 with concomitant desmopressin or multiple doses. Pharmacokinetics were characterised, and the pharmacodynamic effects were measured by VWF levels, FVIII clotting activity, ristocetin induced aggregation, platelet function under high shear rates, and thrombin generation. Mean half-lives ranged from 7-12 days and subcutaneous bioavailability increased dosedependently exceeding 55% for doses of 6-48 mg. By blocking free A1 domains, BT200 dose-dependently decreased ristocetin-induced aggregation, and prolonged collagenadenosine diphosphate and shear-induced platelet plug formation times. However, BT200 also increased VWF antigen and FVIII levels 4-fold (p

METHOD OF RESEARCH ON THE DYNAMIC VISCOSITY OF MAGNETIC FLUIDS AT HIGH SHEAR RATE

Magnetic fluids have an important position in the design of technical systems due to their unique properties. They are used primarily in mechanical energy dissipation systems, i.e. brakes and vibration dampers, as well as in the design of seals. In many applications, the magnetic fluid operates at high flow velocities through narrow slots. Therefore, there is a need to determine the rheological properties of this type of substance at high shear rates. Due to the high density of magnetic fluids and the associated occurrence of mass forces, as well as the requirements regarding the distribution of the magnetic field, the measurement of the viscosity of magnetic fluids at high shear rates is extremely difficult when conventional measuring systems are used. The paper presents a proposal for a new measuring system and a method to determine the viscosity of magnetic fluids at high shear rates, as well as the results of research on the possibility of using the presented structure in the case of ferrofluids.

Extrusion rheometry of collagen dough

Although collagen is widely used (for example, in the food industry, in the pharmaceutical industry and in biomedicine), the rheological properties of the material are not well known for high concentrations (8% collagen, 90% water). Rheological properties were measured using a capillary-slit rheometer (an extrusion process), where the tested sample of collagen matter was pushed by a hydraulically driven piston through a narrow rectangular slit at very high shear rates of 50–6 000 s^–1. The Herschel-Bulkley (HB) constitutive equation and a new correlation taking into account the finite gap width was used to evaluate the rheological properties (n = 0.2, K = 879 Pa sⁿ, τ₀ = 2 380 Pa). Use was made of a new yield stress measurement method evaluating τ₀ 'post mortem' after extrusion stops. The effects of wall slip and of air bubbles, which caused apparent compressibility of the 'silly putty' collagen material, were also studied. Corrections of the wall slip effect were implemented using sliding layer thickness δ.