Relevant Shear Rates Research Articles

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor). Given the proinflammatory function of dissociated CRP and the important role of inflammation in the pathogenesis of AS, we investigated whether shear stress can modify CRP conformation and induce inflammatory effects relevant to AS. To determine the effects of pathological shear rates on the function of human CRP, pCRP was subjected to pathophysiologically relevant shear rates and analyzed using biophysical and biochemical methods. To investigate the effect of shear on CRP conformation in vivo, we used a mouse model of arterial stenosis. Levels of mCRP and pCRP were measured in patients with severe AS pre- and post-transcatheter aortic valve implantation, and the presence of CRP was investigated on excised valves from patients undergoing aortic valve replacement surgery for severe AS. Microfluidic models of AS were then used to recapitulate the shear rates of patients with AS and to investigate this shear-dependent dissociation of pCRP and its inflammatory function. Exposed to high shear rates, pCRP dissociates into its proinflammatory monomers (mCRP) and aggregates into large particles. Our in vitro findings were further confirmed in a mouse carotid artery stenosis model, where the administration of human pCRP led to the deposition of mCRP poststenosis. Patients undergoing transcatheter aortic valve implantation demonstrated significantly higher mCRP bound to circulating microvesicles pre-transcatheter aortic valve implantation compared with post-transcatheter aortic valve implantation. Excised human stenotic aortic valves display mCRP deposition. pCRP dissociated in a microfluidic model of AS and induces endothelial cell activation as measured by increased ICAM-1 (intercellular adhesion molecule 1) and P-selectin expression. mCRP also induces platelet activation and TGF-β (transforming growth factor beta) expression on platelets. We identify a novel mechanism of shear-induced pCRP dissociation, which results in the activation of cells central to the development of AS. This novel mechanosensing mechanism of pCRP dissociation to mCRP is likely also relevant to other pathologies involving increased shear rates, such as in atherosclerotic and injured arteries.

Modeling of spatiotemporal dynamics of ligand-coated particle flow in targeted drug delivery processes

Nanoparticles tethered with vasculature-binding epitopes have been used to deliver the drug into injured or diseased tissues via the bloodstream. However, the extent that blood flow dynamics affects nanoparticle retention at the target site after adhesion needs to be better understood. This knowledge gap potentially underlies significantly different therapeutic efficacies between animal models and humans. An experimentally validated mathematical model that accurately simulates the effects of blood flow on nanoparticle adhesion and retention, thus circumventing the limitations of conventional trial-and-error-based drug design in animal models, is lacking. This paper addresses this technical bottleneck and presents an integrated mathematical method that derives heavily from a unique combination of a mechanics-based dispersion model for nanoparticle transport and diffusion in the boundary layers, an asperity model to account for surface roughness of endothelium, and an experimentally calibrated stochastic nanoparticle-cell adhesion model to describe nanoparticle adhesion and subsequent retention at the target site under external flow. PLGA-b-HA nanoparticles tethered with VHSPNKK peptides that specifically bind to vascular cell adhesion molecules on the inflamed vascular wall were investigated. The computational model revealed that larger particles perform better in adhesion and retention at the endothelium for the particle sizes suitable for drug delivery applications and within physiologically relevant shear rates. The computational model corresponded closely to the in vitro experiments which demonstrates the impact that model-based simulations can have on optimizing nanocarriers in vascular microenvironments, thereby substantially reducing in vivo experimentation as well as the development costs.

Peripheral Endothelial and Microvascular Function with Repeated Far-infrared Sauna in Adults with Obesity

Obesity can lead to vascular dysfunction and elevated cardiovascular risk. Repeated far-infrared sauna bathing has improved cardiovascular function in cardiac patients. It is unknown if repeated far-infrared sauna bathing improves vascular function in adults with obesity. Purpose: We hypothesized that brachial artery flow-mediated dilation (FMD) and post-occlusion reactive hyperemia would be improved after 30 far-infrared sauna sessions in adults with obesity. Methods: Five adults with obesity (4 men, 1 woman; age: 33 ± 11; BMI: 36.3 ± 4.2 kg/m2) were assigned to a heat therapy (n=3) or time-control group (n=2). The heat therapy group completed 30 sessions of far-infrared sauna bathing (43 ± 4 min at 54 ± 2°C) at 3-4 times/week for 9 weeks. Peripheral vascular function was assessed before (PRE) and after (POST) the intervention. Brachial artery diameter and blood velocity were recorded via Doppler ultrasound for 1 min of baseline, 5 min of forearm occlusion, and 3 min of post-occlusion. FMD was calculated as the percent change from baseline diameter to peak diameter during post-occlusion. Relevant shear rate was calculated as the area under the curve (AUC) to peak dilation. Peak post-occlusion reactive hyperemia was defined as the peak blood flow during post-occlusion. Total post-occlusion reactive hyperemia was calculated as the AUC for blood flow above baseline for 3 min. Results: Baseline diameter did not differ at PRE vs. POST or between Control (3.76 ± 0.08 vs. 3.78 ± 0.09 mm) and Heat (4.25 ± 0.03 vs. 4.25 ± 0.02 mm) (all p > 0.3977). FMD did not differ at PRE vs. POST and between Control (11.2 ± 5.2 vs. 10.6 ± 10.2%) or Heat (2.8 ± 2.4 vs. 6.2 ± 4.2%) (all p > 0.2684). Relevant shear rate AUC did not differ at PRE vs. POST or between Control (27,412 ± 7,506 vs. 31,251 ± 20,608 a.u.) and Heat (16,538 ± 11,617 vs. 24,952 ± 10,639 a.u.) (all p > 0.2577). Peak post-occlusion reactive hyperemia did not differ at PRE vs. POST or between Control (396 ± 42 vs. 387 ± 17 ml/min) and Heat (464 ± 40 vs. 441 ± 32 ml/min) (all p > 0.1049). Total post-occlusion reactive hyperemia AUC was lower in Heat (140 ± 7 ml) vs Control (262 ± 12 ml) at PRE but did not differ across time or between groups at POST for Heat (212 ± 35 ml) vs Control (246 ± 66 ml). Conclusions: These preliminary data suggest there is no effect of 30 sessions of far-infrared sauna bathing on peripheral endothelial and microvascular function in adults with obesity. This may be due to the duration, frequency, and intensity of the far-infrared sauna compared to other passive heating modalities that have generated beneficial vascular adaptations in other studies. AHA 19TPA34890033. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Extensive Characterization of Alginate, Chitosan and Microfibrillated Cellulose Cast Films to Assess their Suitability as Barrier Coating for Paper and Board.

The vast amount of synthetic polymers used in packaging is putting a strain on the environment and is depleting finite, non-renewable raw materials. Abundantly available biopolymers such as alginate, chitosan and microfibrillated cellulose (MFC) have frequently been suggested in the literature to replace synthetic polymers and their barrier properties have been investigated in detail. Many studies aim to improve the properties of standalone biopolymer films. Some studies apply these biopolymers as barrier coatings on paper, but the solids content in most of these studies is quite low, which in turn would result in a high energy demand in industrial drying processes. The aim of this study is to suggest a laboratory procedure to investigate the suitability of these biopolymers at higher and such more industrially relevant solids content as potential coating materials for paper and board in order to improve their barrier properties. First, biopolymer solutions are prepared at a high solids content at which the viscosity at industrially relevant higher shear rates of 50,000 s-1 (1000 s-1 for MFC) is in the same range as a synthetic reference material (in this case ethylene vinyl alcohol EVOH) at 10 wt%. These solutions are analyzed regarding properties such as rheology and surface tension that are relevant for their coatability in industrial coating processes. Then, free-standing films are cast, and the films are characterized regarding important properties for packaging applications such as different surface, mechanical and barrier properties. Based on these results suitable biopolymers for future coating trials can be easily identified.

Experimental and simulative determination and correction of the effective gap extension in structured coaxial measuring systems

The use of structured measuring systems to prevent wall slip is a common approach to obtain absolute rheological values. Typically, only the minimum distance between the measuring surfaces is used for further calculation, implying that no flow occurs between the structural elements. But this assumption is misleading, and a gap correction is necessary. To determine the radius correction Delta r for specific geometries, we conducted investigations on three Newtonian fluids (two silicon oils and one suspension considered to be Newtonian in the relevant shear rate range). The results show that Delta r is not only shear- and material-independent, but geometry-dependent, providing a Newtonian flow behaviour in a similar viscosity range. Therefore, a correction value can be determined with only minute deviations in different Newtonian fluids. As the conducted laboratory measurements are very time-consuming and expensive, a CFD-approach with only very small deviations was additionally developed and compared for validation purposes. Therefore, simulation is an effective and resource-efficient alternative to the presented laboratory measurements to determine Delta r for the correction of structured coaxial geometries even for non-Newtonian fluids in the future.

Enzyme Responsive Delivery of Anti-Retroviral Peptide via Smart Hydrogel.

In response to an urgent need for advanced formulations for the delivery of anti-retrovirals, a stimuli-sensitive hydrogel formulation that intravaginally delivers HIV-1 entry inhibitor upon being exposed to a specific protease was developed. The hydrogel formulation consists of PEG-azide and PEG-DBCO covalently linked to the entry inhibitor peptide, enfuvirtide, via substrate linker that is designed to undergo proteolysis by prostate specific antigen (PSA) present in seminal fluid and release innate enfuvirtide. Of the tested PSA substrate linkers (HSSKLQYY, GISSFYSSK, AYLMYY, and AYLMGRR), HSSKLQ was found to be an optimal candidate for PEG-based hydrogel with kcat/KM of 2.2M-1s-1. The PEG-based hydrogel displayed a pseudoplastic, thixotropic behavior with overall viscosity varying between 1516 and 2.2Pa.s, within the biologically relevant shear rates of 0.01-100s-1. It also exhibited viscoelastic properties appropriate for uniform spreading and being retained in vagina. PEG-based hydrogels were loaded with N3-HSSKLQ-enfuvirtide (HF42) that is customarily synthesized enfuvirtide prodrug with its N-terminus connected to HSSKLQ linker. The stimuli-sensitive PEG-based hydrogel formulations upon being exposed to PSA released 36.5 ± 4.8% of enfuvirtide over 24h in human ejaculate mimic of vaginal simulant fluid and seminal simulant fluid mixed in 1:3 ratio, which is significantly greater than its IC50. The PEG-based hydrogel was non-cytotoxic to both vaginal epithelial cells (VK2/E6E7) and murine macrophages (RAW 264.7) and did not significantly induce the production of nitric oxide, an inflammatory mediator. The PEG-based hydrogel is found to have suitable physicochemical properties for an intravaginal formulation of the PSA substrate-linked anti-retrovirals and is safe towards vaginal epithelium. It is capable of delivering enfuvirtide with effective concentrations to prevent women from HIV-1 infection.

Shear-Thinning and Temperature-Dependent Viscosity Relationships of Contemporary Ocular Lubricants.

PurposeTo evaluate the shear viscosity of contemporary, commercially available ocular lubricants at various shear rates and temperatures and to derive relevant mathematical viscosity models that are impactful for prescribing and developing eye drops to treat dry eye disease.MethodsThe shear viscosity of 12 ocular lubricants was measured using a rheometer and a temperature-controlled bath at clinically relevant temperatures at which users may experience exposure to the drops (out of the refrigerator [4.3°C]; room temperature [24.6°C]; ocular surface temperature [34.5°C]). Three replicates for each sample at each temperature were obtained using a standard volume (0.5 mL) of each sample. The viscosity of each ocular lubricant was measured over the full range of shear rates allowed by the rheometer.ResultsThe shear viscosity of the same ocular lubricant varied significantly among the three temperatures. In general, a higher temperature resulted in smaller viscosities than a lower temperature (an average of −48% relative change from 4.3°C to 24.6°C and −21% from 24.6°C to 34.5°C). At a constant temperature, the viscosity of an ocular lubricant over the studied shear rates can be well approximated by a power-law model.ConclusionsRheological analysis revealed that the ocular lubricants exhibited shear-thinning behavior at the measured temperatures. Differences in the ocular lubricants’ formulations and measured temperatures resulted in different viscosities.Translational RelevanceWhen prescribing eye drops, eye care professionals can select the optimal one for their patients by considering a variety of factors, including its rheological property at physiologically relevant shear rates and temperatures, which can improve residence time on the ocular surface, while ensuring appropriate comfort and vision. However, care must be taken when using the derived mathematical models in this study because the in vivo shear behavior of the ocular lubricants has not been examined and might show deviations from those reported when placed on the ocular surface.

Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model.

The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06–0.78 cm s−1 and backflows of −2.16–−0.21 cm s−1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05–10.12 s−1 and 5.11–20.34 s−1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.

Annular Frictional Pressure Losses for Drilling Fluids

Abstract In the paper, it is demonstrated how a Herschel–Bulkley fluid model, where the parameters are selected from relevant shear rate range of the flow and are parametrically independent, can be used for pressure loss calculations. The model is found to provide adequate pressure loss predictions for axial flow in an annulus where the inner cylinder does not rotate. It is described how one can simplify a slot model approximation of the annulus pressure loss using the Herschel–Bulkley fluid model (Founargiotakis model). This simplified model gives approximately the same accuracy as does the full Founargiotakis model. It is shown that the use of such a parallel plate model gives reasonably good fit to measured data on laminar flow of oil-based drilling fluids if the viscous data are measured at relevant shear rates for the flow. Laboratory measurements indicate that the use of the simplified pressure loss model is also valid for turbulent flow. However, the predictions should be adjusted for the surface roughness in the well.

Influence of Rheological Properties on the Starting Torque of Magnetic Fluid Seal

In this article, the experimental investigation and analysis of the effect of rheological properties on the starting torque of the magnetic fluid seal are reported. The change of the starting torque with a standing time for perfluoropolyether-based magnetic fluid seal and diester-based magnetic fluid seal, as well as the viscosity of magnetic fluids under the relevant magnetic field and shear rate, were measured. It was observed that the magnetic fluid with higher viscosity correspondingly exhibited higher starting torque. The starting torque of seals with two different magnetic fluids exhibited the same variation tendency. The starting torque was exponentially increased with the standing time and then tended to be a stable state with small scale fluctuation. The average maximum starting torque of PFPE-based ferrofluid seal after standing five days was ten times as large as the value of the initial standing, whereas that of diester-based ferrofluid seal was 3.5 times as large the value of the initial standing. The rheological behavior was the key factor influencing the starting torque of the magnetic fluid seal. Particle agglomeration and shear thinning were the main microscopic mechanisms leading to the change of starting torque with a standing time. The correlation between macroscopic rheological properties and starting torque was established based on the microstructure variation.

Viscosity Models for Drilling Fluids—Herschel-Bulkley Parameters and Their Use

An evaluation is presented of the practical usage of the Herschel-Bulkley viscosity model for drilling fluids. If data from automatic viscosity measurements exist, the parameters should be selected from relevant shear rate ranges to be applicable. To be able to be used properly, viscosity measurements must be measured with a sufficient accuracy. It is shown that a manual reading of standard viscometers may yield insufficient accuracy. It is also shown that the use of yield point/plastic viscosity (YP/PV) as measured using API or ISO standards normally provide inaccurate viscosity parameters. The use of the Herschel-Bulkley model using dimensionless shear rates is more suitable than the traditional way of writing this model when the scope is to compare different drilling fluids. This approach makes it also easier to make correlations with thermodynamic quantities like pressure and temperature or chemical or mineralogical compositions of the drilling fluid.

The Role of Grease Composition and Rheology in Elastohydrodynamic Lubrication

Grease lubrication is inherently complicated due to its non-Newtonian flow dynamics. The flow behavior of grease is difficult to determine under tribological shear rates as these shear rates are often extremely high, and therefore, are not accessible on a regular rheometer. In this work, we demonstrate the use of shear rate-concentration superposition method to extrapolate the data measured with a rheometer to tribologically relevant shear rates. This method is similar to the other superposition methods routinely employed by rheologists for predicting flow behavior beyond the measurement range of rheometer. In this method, a data master curve, which extends over a broad range of shear rates, is constructed by superposing individual flow curves for greases with different thickener concentrations. The master curve is utilized to determine infinite shear viscosity of grease which is then used for the film thickness estimation. Furthermore, the grease samples are tribologically tested using a four-ball tester to identify the individual and interactive roles of the thickener type, concentration and base oil in lubrication behavior. A change in thickener concentration or type influences frictional torque and wear scar size through modification in infinite shear viscosity and structural stability of grease. The SEM images show deposition of thickener particles on the contact surface, which also apparently affect friction and wear during the test. The lubrication performance is strongly influenced by base oil, which points towards the importance of its role in dictating flow resistance and film-forming behavior of grease inside elastohydrodynamic contact.

Gravity separation in the REFLUX™ Classifier in the presence of slimes

Significant levels of ultrafine particles remain in the feed after desliming via cyclones. These slimes represent a challenge for downstream processing due to the increased viscosity, moisture retention in the product including associated materials handling issues, and entrainment of contaminant with the product. This paper examines the influence of slimes on the recovery of high-grade iron ore fines across a size range of 0–0.3 mm using the REFLUX™ Classifier. Experiments were performed using closely spaced inclined plates (3 mm apart and 1000 mm long) over a range of solids throughputs of 3.5–28 t/(m2 h). Lower feed solids concentrations led to higher recoveries due to the reduction in the viscosity arising from the slimes. At the higher volumetric flowrates used to increase the solids throughput, the very high shear rates generated in the channels further reduced the viscous effects of the slimes. The results are supported by rheological data, based on the ultrafine solids collected from the overflow stream which show strong shear thinning at the relevant shear rates within the inclined channels.

Oscillatory and steady shear rheological properties of aqueous polyacrylamide solutions

Abstract Dynamic and steady shear data representing the flow behaviour of aqueous solutions of Polyacrylamide, in the concentration range of 0.25–0.6% wt./vol. and temperature range of 5–45 °C, have been reported. Maxwell model, Carreau model and power law model were used to represent the present experimental data. Rheological parameter such as fluid relaxation time (λ), representative of fluid elasticity, was evaluated by fitting the oscillatory shear data to the four element Maxwell model. Other rheological parameters such as flow behaviour index (n) and flow consistency index (K) were evaluated by fitting the steady shear data to the power law model in the relevant shear rate range. The shear dependent viscosity data are well represented by Carreau model. Predictive equations for λ, n and K are proposed by incorporating the combined effect of temperature and concentration. Presented data could be of great use in various engineering applications such as enhanced oil recovery.

Dynamical Analysis of the Inhibitory Effect of Aspirin and Clopidogrel on Platelet Adhesion and Aggregation for Healthy People under Physiological Flow Condition by Microfluidic Chip Technology

Objective To explore the inhibitory effect of aspirin and clopidogrel on platelet adhesion and aggregation behaviors under the physiological flow condition using microfluidic chip technology for health volunteers. Methods Peripheral venous blood samples collected from twelve randomly recruited health volunteers were treated with 20 μmol/L acetylsalicylic acid,50 μmol/L 2-methlthioadenosine-5'-monophosphate triethylammonium salt,and their combination,respectively,with untreated blood samples being control group. The blood samples were flowed through a microchannel modified with type I collagen protein at a physiological relevant shear rate of 1000 s-1 for 300 s,while the fluorescent images of platelet aggregations were dynamic captured using a microscope. Based on the images,the platelet coverage rates were calculated and used as quantitative parameters for evaluating platelet adhesion and aggregation behaviors. Results Under a flow condition of 1000 s-1 shear rate,an expected in vivo-like platelet adhesion and aggregation behaviors were observed at the surfaces of collagen proteins for control blood samples. Aspirin alone or clopidogrel alone suppressed platelet adhesion and aggregation at the later period of flow(200-300 s),while the combination of aspirin and clopidogrel reduced the adhesion numbers of platelets at the earlier stage of flow(≤150 s) and compromised the stability of platelet aggregation at the later period of flow(200-300 s). The combination showed synergistic effect in inhibiting platelet aggregation. Furthermore,such inhibitory effect was heterogeneous among 12 volunteers. Conclusion This simple microfluidic technology can offer a new technical platform for analyzing the inhibitory effect of antiplatelet drugs.

Flow Behavior of PP-Polymer Nanocomposites in Capillary and Injection Molding Dies

Abstract For simulation of thin-wall injection molding, accurate viscosity data measured at shear rates up to 800,000 s−1 and more are important, but not available in any commercial material database. Such data can be measured on conventional injection molding machines with the help of a rheological mold, which is constructed like a standard injection mold with interchangeable dies. It enables operators to measure viscosity in time on their own machines at practically relevant shear rates (from 102 s−1 to 2 × 106 s−1). A special feature allows measuring the pressure dependency of viscosity using closed-loop counter pressure control. Experimental data are evaluated taking into account the melt temperature rise due to dissipative heating. Using capillary dies having different diameters, D, and length-to-diameter L/D ratios, a full rheological characterization has been carried out for a polypropylene-filled nanocomposite, and the experimental data have been fitted both with a viscous model (Cross) and a viscoelastic one (the Kaye – Bernstein, Kearsley, Zapas/Papanastasiou, Scriven, Macosko or K-BKZ/PSM model). Four injection molding dies have been also used to reach apparent shear rates up to 800,000 s−1. Particular emphasis has been given on the pressure-dependence of viscosity. It was found that only the viscoelastic simulations were capable of reproducing the experimental data well, while any viscous modeling always underestimates the pressures, especially at the higher apparent shear rates and L/D ratios.

Enhanced microvascular function in the cutaneous circulation with platelet inhibition is not related to alterations in blood viscoelastic properties

Platelet inhibition with aspirin and/or clopidogrel are part of a comprehensive strategy for the primary and secondary prevention of cardiovascular disease, respectively. In the cutaneous microcirculation, treatment of clopidogrel (CLO) but not aspirin (ASA) increases cutaneous microvascular relaxation in response to reactive hyperemia. CLO is mechanistically distinct from ASA in that it works through inhibiting the platelet P2Y12 receptor and may change blood viscosity and thus the shear stimulus on the microcirculation. In this study, we sought to determine if platelet inhibition with CLO changes whole blood viscoelastic properties and is related to increased microvascular function. Nine middle‐aged healthy subjects (5 men, 4 women; 56 ± 1 yr) participated in a randomized, double blind, placebo‐controlled crossover experiment. Treatment phases included a sucrose placebo, CLO (75 mg; Bristol‐Myers Squibb), and ASA (81 mg; Bayer) for 7–10 days with a two week washout period between each treatment. On the final day of treatment, laser Doppler flux (LDF) was measured during a standardized 5 minutes reactive hyperemia protocol and area under the curve (AUC) and total hyperemic response (THR) were calculated and normalized to maximal cutaneous vascular conductance (%CVCmax: 43°C and 28 mM sodium nitroprusside). Blood viscoelasticity was measured using a Vilastic‐3 viscoelasticity analyzer at 2 Hz across a physiologically relevant shear rate range of 25 to 1000 s−1. Blood temperature was maintained at time of draw using a heat exchanger. CLO and ASA did not change hematocrit relative to the placebo control (41.6 ± 0.9, 41.9 ± 0.6, and 41.5 ± 0.7 % respectively). AUC and THR increased in the CLO trial (AUC = 3783 ± 342, THR = 2306 ± 266 %CVCmax * s; P<0.0001 vs. placebo) but there was no difference between ASA (AUC = 3101 ± 325, THR = 1695 ± 197 %CVCmax * s) and placebo (AUC = 3000 ± 283, THR = 1675 ± 170 %CVCmax * s, P>0.05) Apparent kinematic viscosity and elasticity was unchanged in either CLO or ASA treatment relative to placebo across the entire range measured when normalized to a hematocrit of 45 %. 7–10 days of CLO or ASA does not change hematocrit or blood viscoelastic properties in healthy humans and is not related to functional measures of microvascular function (p>0.05). Improvements in cutaneous microvascular function by CLO is not a result of shear‐stress induced vasodilation, further indicating that CLO may alter sensory nervous activity and/or endothelium‐derived hyperpolarizing factor mechanisms.Support or Funding InformationNIH R01 HL093238‐07

Collagen-binding nanoparticles for extracellular anti-inflammatory peptide delivery decrease platelet activation, promote endothelial migration, and suppress inflammation.

In this manuscript, we present our work on the development and characterization of a novel temperature sensitive collagen-binding nanoparticle system. We demonstrate that when bound to a collagenous matrix, the nanoparticles are able to promote endothelial migration while avoiding cellular uptake. We also show that the nanoparticles are able to reduce inflammation via the release of anti-inflammatory peptides which, when combined with its ability to inhibit platelet binding, could lead to reduced intimal hyperplasia following balloon angioplasty. The drug delivery platform presented represents a unique dual therapy biomaterial wherein the nanoparticle itself plays a crucial role in the system's overall therapeutic potential while simultaneously releasing anti-inflammatory peptides.

Dynamics of blood flow and thrombus formation in a multi-bypass microfluidic ladder network.

The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s-1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between microvascular geometry and thrombus formation dynamics under shear. This model holds potential for use as an integrative approach to identify regions susceptible to intravascular thrombus formation within the microvasculature as well as extravascular devices such as ECMO.

Rheotaxis facilitates upstream navigation of mammalian sperm cells.

A major puzzle in biology is how mammalian sperm maintain the correct swimming direction during various phases of the sexual reproduction process. Whilst chemotaxis may dominate near the ovum, it is unclear which cues guide spermatozoa on their long journey towards the egg. Hypothesized mechanisms range from peristaltic pumping to temperature sensing and response to fluid flow variations (rheotaxis), but little is known quantitatively about them. We report the first quantitative study of mammalian sperm rheotaxis, using microfluidic devices to investigate systematically swimming of human and bull sperm over a range of physiologically relevant shear rates and viscosities. Our measurements show that the interplay of fluid shear, steric surface-interactions, and chirality of the flagellar beat leads to stable upstream spiralling motion of sperm cells, thus providing a generic and robust rectification mechanism to support mammalian fertilisation. A minimal mathematical model is presented that accounts quantitatively for the experimental observations.DOI: http://dx.doi.org/10.7554/eLife.02403.001.