Blood Analog Research Articles

Ghost cells as a two-phase blood analog fluid-high-volume and high-concentration production.

Hemolysis in mechanical circulatory support systems is currently determined quantitatively. To also locally resolve hemolysis, we are developing a fluorescent hemolysis detection method. This requires a translucent two-phase blood analog fluid combined with particle image velocimetry, an optical flow field measurement. The blood analog fluid is composed of red blood cell surrogates. However, producing surrogates in sufficient volume is a challenge. We therefore present a high-volume and high-concentration production for our surrogates: ghost cells, hemoglobin-depleted erythrocytes. In the ghost cell production, the hemoglobin is removed by a repeated controlled osmolar lysis. We have varied the solution mixture, centrifugation time, and centrifugation force in order to increase production efficiency. The production is characterized by measurements of output volume, hematocrit, transparency, and rheology of the blood analog fluid. The volume of produced ghost cells was significantly increased, and reproducibility was improved. An average production of 389 mL of ghost cells were achieved per day. Those ghost cells diluted in plasma have a rheology similar to blood while being permeable to light. The volume of ghost cells produced is sufficient for optical measurements as particle image velocimetry in mechanical circulatory support systems. This makes further work on experimental measurements for a locally resolved hemolysis detection possible.

AN EXPERIMENTAL RIGHT ATRIUM PLATFORM TO ASSESS RECIRCULATION IN HEMODIALYSIS CATHETERS

Hemodialysis (HD) is a treatment supporting decreased kidney function, via a catheter inserted into the heart’s Right Atrium (RA). Recirculation is a source of inefficiency for treatment, where blood is dialyzed again due to poor catheter design. Lab-testing is still relatively unexplored, hence, a mechanical testing system was designed with the intention of providing a consistent and repeatable environment for testing HD catheters. System geometry was composed using a Computer-Aided Design (CAD) model of a heart, with the RA scaled to appropriate dimensions, and a PolyDiMethylSiloxane (PDMS) model produced through 3D printing and negative wax casting. Pulsatile blood flow was mimicked by peristaltic pumps driving a blood analogue (BA). Recirculation was induced by adding dyed BA to the system via the catheter and measured using a colorimeter. The developed platform was initially evaluated using two catheters, demonstrating the capability to accurately replicate atrial hemodynamic conditions. Two step-tipped catheters, A and B, were tested at 350 ml/min, producing recirculation values of 13.11% and 18.58%, respectively. The results exhibit the ability of the system developed to evaluate HD catheter performance, with the potential to explore a wider range of tip geometries relevant to clinical preference. Furthermore, this advancement towards an anatomically accurate lab-based test system could be paired with computational methods to progress the evaluation of such medical devices and enhance their development.

Application of 3D printing to create an in vitro aneurysm rupture model.

Currently available benchtop (in vitro) aneurysm models are inadequate for testing the efficacy of endovascular device treatments. Specifically, current models do not represent the mechanical instability of giant aneurysms (defined as aneurysms with 25 mm in height or width) and do not predictably rupture under simulated physiological conditions. Hence, in vitro aneurysm models with biomechanically relevant material properties and a predictable rupture timeframe are needed to accurately assess the efficacy of new medical device treatment options. Understanding the material properties of an aneurysm (e.g., shear and compression modulus) as it approaches rupture is a crucial step toward creating a pathologically relevant and sophisticated in vitro aneurysm rupture model. We investigated the change in material properties of a blood vessel, via enzymatic treatment, to simulate the degradation of an aneurysm wall and used this information to create a sophisticated aneurysm rupture model using the latest in additive manufacturing technologies (3D printing) with tissue-like materials. Mechanical properties (shear and compression modulus) of swine carotid vessels were evaluated before and after incubation with collagenase D enzyme (30 min at 37°C) to simulate the effect of biochemical activity on aneurysm wall approaching rupture compared to control vessels (untreated). Mechanical strength of a soft and flexible 3D-printed material (VCA-A30: 30 shore A hardness) was tested for comparison to these arterial vessels. This material was then used to create spherical shaped, giant-sized (25-mm diameter) aneurysm phantoms and were run under neurovascular pressures (120/80 ± 5 mmHg), beats per minute (BPM = 70) and flows representing the middle cerebral artery [MCA: 142.67 (±20.13) mL/min] using a blood analog [3.6 (±0.4) cP viscosity] with non-Newtonian shear-thinning properties. The shear modulus of swine carotid vessel before treatment was 12.2 (±2.7) KPa and compression modulus was 663.5 (±111.6) KPa. After enzymatic treatment by collagenase D, shear modulus of animal tissues reduced by 33% (p-value = .039) while compression modulus remained statistically unchanged (p-value = .615). Control group (untreated vessels) showed minimal reduction (13%, p-value = .226) in shear modulus and 78% increase (p-value = .034) in compression modulus. The shear modulus of the 3D-printed material was 228.59 (±24.82) KPa while its compression modulus was 668.90 (±13.16) KPa. This material was used to prototype a sophisticated in vitro giant aneurysm rupture model. When subjected to physiological pressures and flow rates, the untreated models consistently ruptured at ~12 min. These results indicate that aneurysm rupture can be recreated consistently in a benchtop in vitro model, utilizing the latest 3D-printed materials, connected to a physiologically relevant programmable pump. Further studies will investigate the optimization of various aneurysm dome thickness regions within the aneurysm, with tunable rupture times for comparison of aneurysm device deployment and benchtop controls based on the measurable effects of pressure and flow changes within the aneurysm models. These optimized in vitro rupture models could ultimately be used to test the efficacy of device treatment options and rupture risk by quantifying specific device rupture times and aneurysm rupture position.

An In-Vitro Study On The Carotid Bifurcation And Its Influence On Arterial Haemodynamics With Newtonian And Non-Newtonian Blood Analogs

The carotid artery bifurcation is a region susceptible to atherosclerosis and cardiovascular diseases. The geometry of the bifurcation is individually unique and significant differences have been correlated to both age and gender. Identifying geometric features that produce adverse flow patterns could enable clinicians to make early assessment of an individual’s risk of developing the disease enabling proactive management. Consequently, this study aims to evaluate the influence of the carotid bifurcation angle on arterial haemodynamics using stereoscopic particle image velocimetry. Pulsatile flow conditions were applied to a Newtonian and non-Newtonian blood analog in three compliant, physiologically realistic carotid artery bifurcation phantoms with different bifurcation angles. Results indicate large bifurcation angles can produce adverse flow conditions, increasing size of stagnation regions and promoting plaque development. Additionally, an optimal bifurcation angle could exist that could be considered atheroprotective. Comparison of Newtonian and non-Newtonian blood analogs in one of the geometries show subtle yet significant differences between flow fields, suggesting the shear-thinning behaviour of blood should be carefully considered prior to adopting a Newtonian assumption, even in large vessels.

Experiments and numerical modelling of secondary flows of blood and shear-thinning blood analogue fluids in rotating domains

The transition from concentric primary flow to non-tangential secondary flow of blood was investigated using experimental steady shear rheometry and numerical modelling. The aims were to: assess the difference in secondary flow in a Newtonian versus shear-thinning blood analogue; and measure the secondary flow in the blood. Both experiments and numerical modelling showed that the transition from primary to secondary flow was the same in a Newtonian fluid and a shear-thinning blood analogue. Experiments showed whole blood transitioned to secondary flow at lower modified Reynolds numbers than the Newtonian fluid; and transition was haematocrit dependent with higher RBC concentrations transitioning at lower modified Reynolds numbers. These results indicate that modelling blood as a purely shear-thinning fluid does not predict the correct secondary flow fields in whole blood; non-Newtonian effects beyond shear-thinning behaviour are influential, and incorporating effects such as multiphase contributions and viscoelasticity, yield stress and thixotropy is necessary.

Production and characterization of a blood analogue based on alginate microparticles

This work addresses the need for a universal blood substitute by focusing on developing alginate-based microparticles engineered to replicate the mechanical properties of red blood cells (RBCs). Alginate, known for its biocompatibility and tunable mechanical properties, is used to create microparticles that closely resemble RBCs in size and shape. These alginate microparticles are produced through premix membrane emulsification (PME), ensuring a uniform size distribution. The viscosity ratio and the size of the filter pores influence the final size of the microparticles. Filters with pores of 20 µm were used to produce 5 wt% alginate microparticles with a diameter of 7.81 µm ± 0.77, and filters with pores of 30 µm were used to produce 0.5 wt% alginate microparticles with a diameter of 8.69 µm ± 3.30. The Deformability Index (DI) of the alginate microparticles follows the correlation that microparticles with higher elastic modulus exhibit lower DI values. The DI found for 0.5 wt% alginate microparticles solution is higher than the DI found for 5 wt% alginate microparticles. The DI of RBCs is higher than the ones found for the alginate microparticles, however the value is in the range of the experimental error. Rheological studies reveal that suspensions of 25–30 wt% alginate microparticles exhibit a shear-thinning behavior similar to human blood. The DI of the alginate microparticles shows little influence on the rheology of the suspensions. Furthermore, the Cell-Free Layer (CFL) of alginate microparticles is close to that of RBCs, reinforcing the potential of alginate as a suitable material for blood substitute development. The alginate microparticles produced in this work show a great potential to contribute to creating a blood-mimicking fluid for applications in medical treatments and research.

Open-Source Image-Based Tool to Experimentally Evaluate Blood Residence Time in Clinical Devices.

This article introduces an open-source tool to experimentally compare blood residence time in biomedical devices using an image-based method. The experimental setup and the postprocessing workflow are comprehensively elucidated in a detailed report that conducts a thorough comparison of the residence times of a blood analog within three distinct blood oxygenator prototypes. To enable widespread accessibility and ease of use, the user-friendly MATLAB App developed for the analysis is available on the Mathworks repository: https://www.mathworks.com/matlabcentral/fileexchange/135156 .

Investigating the Hydrodynamics of Intravenous Drug Infusions

One of the most common reported adverse events for intravenous (IV) infusions are infusion site reactions, ranging from redness and pain at the site of infusion to thrombophlebitis. The connection between drug infusion and what drives these adverse events is not well understood. To aid in understanding these phenomena, it is crucial to accurately characterize the evolving hemodynamic environment of the infusion site when developing new intravenous formulations, as too rapid dilution may cause precipitation in the vein, while too little dilution might contribute to phlebitis. In this study, a Large-Eddy Simulation (LES) turbulence modeling inside a Computational Fluid Dynamics (CFD) framework has been used to simulate the flow and mixing characteristics of an infusion entering the bloodstream. This work represents the first such study reporting transient flow fields for intravenous infusions using LES CFD simulations with a realistic non-Newtonian blood model. The output of the CFD model closely resembled the flow and mixing patterns generated in benchtop tests for infusions into a blood analogue and water as the venous fluid across a wide range of flow rates. These models were then investigated further to compare how changes to the fluid rheology model, needle orientation and needle position within the vein resulted in altered mixing regimes at different flow rates.

Numerical evaluation and experimental validation of fluid flow behavior within an organ-on-a-chip model

Background and ObjectiveBy combining biomaterials, cell culture, and microfluidic technology, organ-on-a-chip (OoC) platforms have the ability to reproduce the physiological microenvironment of human organs. For this reason, these advanced microfluidic devices have been used to resemble various diseases and investigate novel treatments. In addition to the experimental assessment, numerical studies of biodevices have been performed aiming at their improvement and optimization. Despite considerable progress in numerical modeling of biodevices, the validation of these computational models through comparison with experimental assays remains a significant gap in the current literature. This step is critical to ensure the accuracy and reliability of numerical models, and consequently enhance confidence in their predictive results. The aim of the present work is to develop a numerical model capable of reproducing the fluid flow behavior within an OoC, for future investigations, encompassing the geometry optimization. MethodsIn this study, the validation of a numerical model for an OoC microfluidic device was undertaken. This comprised both quantitative and qualitative assessments of trace microparticles flowing through a physical OoC model. High-speed microscopy images of the flow, using a blood analog fluid, were analyzed and compared with the numerical simulations run using the Ansys Fluent software. For a qualitative analysis, the particles’ paths through the inlet and bifurcations were observed whereas, for a quantitative analysis, the particle velocities were measured. Furthermore, oxygen transport was simulated and evaluated for different Reynolds numbers. ResultsIn both qualitative and quantitative analyses, the results predicted by the numerical model and the ones outputted by the experimental model were in good agreement. These findings underscore the capability and potential of the developed numerical model. The examination of oxygen transport at various vertical positions within the organoid has revealed that for lower positions, oxygen transport predominantly occurs through diffusion, leading to a symmetric distribution of oxygen. Contrastingly, the convection phenomenon becomes more evident in the upper region of the organoid. ConclusionsThe successful validation of the numerical model against experimental data shows its accuracy and reliability in simulating the fluid flow within the OoC, which consequently can expedite the OoC design process by reducing the need for prototypes’ fabrication and costly laboratory experiments.

Effect of Hematocrit and Elevated Beat Rate on the 12cc Penn State Pediatric Ventricular Assist Device.

Congenital heart disease affects approximately 40,000 infants annually in the United States with 25% requiring invasive treatment. Due to limited number of donor hearts and treatment options available for children, pediatric ventricular assist devices (PVADs) are used as a bridge to transplant. The 12cc pneumatic Penn State PVAD is optimized to prevent platelet adhesion and thrombus formation at patient nominal conditions; however, children demonstrate variable blood hematocrit and elevated heart rates. Therefore, with pediatric patients exhibiting greater variability, particle image velocimetry is used to evaluate the PVAD with three non-Newtonian hematocrit blood analogs (20%, 40%, and 60%) and at two beat rates (75 and 120 bpm) to understand the device's performance. The flow fields demonstrate a strong inlet jet that transitions to a solid body rotation during diastole. During systole, the rotation dissipates and reorganizes into an outlet jet. This flow field is consistent across all hematocrits and beat rates but at a higher velocity magnitude during 120 bpm. There are also minor differences in flow field timing and surface washing due to hematocrit. Therefore, despite patient differences in hematocrit or required pumping output, thorough surface washing can be achieved in the PVAD by altering operating conditions, thus reducing platelet adhesion potential.

Intravenous Fluid Resuscitation Capabilities in Simulated Reduced Gravity.

BACKGROUND: Critical care for exploration space missions may require intravenous (IV) fluid resuscitation therapy. Resource constraints may limit availability of standard, Earth-based infusion technologies. The effect of variable acceleration on infusion flow rates using simple fluid resuscitation supplies was investigated.METHODS: Infusions of water or blood analog (40% glycerol) from a 1 L IV bag were performed using pressure bag augmentation at 0, 150, or 300 mmHg. The solution bag rested on an adjustable mount, configured to different heights to simulate relevant gravitational accelerations (1 G, Martian G, lunar G, and 0 G). The bag emptied through an IV line with a 14- or 20-gauge angiocath into a 3-mmHg venous pressure reservoir. Flow rates were measured using an in-line flow probe. Three determinations were made for each test condition.RESULTS: Temporal flow rate data for all test conditions displayed one-phase exponential decay. At 300 mmHg pressurization, maximum infusion rates ranged from 92-222 mL ⋅ min-1 for water and from 21-49 mL ⋅ min-1 for blood analog. All reduced gravity conditions had significantly longer infusion times in comparison to 1 G for both test solutions.DISCUSSION: Reduced acceleration significantly altered flow rates and infusion times for fluid resuscitation. Fluid resuscitation protocols specify a desired volume to infuse for a target time (e.g., 20-30 mL ⋅ min-1 for a 75-kg adult). This data demonstrates that this protocol parameter can be achieved with infusion pressure bag augmentation alone and provides information for the refinement of fluid resuscitation protocols for exploration space missions.Pantalos GM, Heidel JS, Jain IM, Warner SE, Barefoot TL, Baker RO, Hailey M. Intravenous fluid resuscitation capabilities in simulated reduced gravity. Aerosp Med Hum Perform. 2023; 94(8):596-603.

Effect of Particle Migration on the Stress Field in Microfluidic Flows of Blood Analog Fluids at High Reynolds Numbers.

In the present paper, we investigate how the reductions in shear stresses and pressure losses in microfluidic gaps are directly linked to the local characteristics of cell-free layers (CFLs) at channel Reynolds numbers relevant to ventricular assist device (VAD) applications. For this, detailed studies of local particle distributions of a particulate blood analog fluid are combined with wall shear stress and pressure loss measurements in two complementary set-ups with identical flow geometry, bulk Reynolds numbers and particle Reynolds numbers. For all investigated particle volume fractions of up to 5%, reductions in the stress and pressure loss were measured in comparison to a flow of an equivalent homogeneous fluid (without particles). We could explain this due to the formation of a CFL ranging from 10 to 20 μm. Variations in the channel Reynolds number between Re = 50 and 150 did not lead to measurable changes in CFL heights or stress reductions for all investigated particle volume fractions. These measurements were used to describe the complete chain of how CFL formation leads to a stress reduction, which reduces the apparent viscosity of the suspension and results in the Fåhræus-Lindqvist effect. This chain of causes was investigated for the first time for flows with high Reynolds numbers (Re∼100), representing a flow regime which can be found in the narrow gaps of a VAD.

Effect of flow rate ratio and positioning on a lighthouse tip ECMO return cannula.

Extracorporeal membrane oxygenation is a life-saving support therapy in the case of cardiopulmonary refractory failure. Its use is associated to complications due to the presence of artificial surfaces and supraphysiological stress conditions. Thus, knowledge of the fluid structures associated to each component can give insight into sources of blood damage. In this study, an experimentally validated numerical study of a conventional lighthouse tip cannula in return configuration was carried out to characterize the flow structures using water or a Newtonian blood analog with different flow rate ratios and cannula positioning and their influence on hemolysis. The results showed that strong shear layers developed where the jets from the side holes met the co-flow. Stationary backflow regions at the vessel wall were also present downstream of the cannula. In the tilted case, the recirculation was much more pronounced on the wide side and almost absent on the narrow side. Small vortical backflow structures developed at the side holes which behaved like obstacles to the co-flow, creating pairs of counter-rotating vortices, which induced locally higher risk of hemolysis. However, global hemolysis index did not show significant deviations. Across the examined flow rate ratios, the holes on the narrow side consistently reinfused a larger fraction of fluid. A radial force developed in the tilted case in a direction so as to recenter the cannula in the vessel.

MarioHeart: Novel In-Vitro Flow Model for Testing Heart Valve Prostheses and Anticoagulant Therapies.

Mechanical heart valve (MHV) prostheses present a risk of thromboembolic complications despite antithrombotic therapy. Further steps in the development of more hemocompatible MHVs and new anticoagulants are impeded due to the lack of adequate in-vitro models. With the development of a novel in-vitro model (MarioHeart), a pulsatile flow similar to the arterial circulation is emulated. The MarioHeart design owns unique features as 1) a single MHV within a torus with low surface/volume ratio, 2) a closed loop system, and 3) a dedicated external control system driving the oscillating rotational motion of the torus. For verification purposes, a blood analog fluid seeded with particles was used to assess fluid velocity and flow rate using a speckle tracking method on high-speed video recordings of the rotating model. The flow rate resembled the physiological flow rate in the aortic root, in both shape and amplitude. Additional in-vitro runs with porcine blood showed thrombi on the MHV associated with the suture ring, which is similar to the in-vivo situation. MarioHeart is a simple design which induces well-defined fluid dynamics resulting in physiologically nonturbulent flow without stasis of the blood. MarioHeart seems suitable for testing the thrombogenicity of MHVs and the potential of new anticoagulants.

Channel impeller design for centrifugal blood pump in hybrid pediatric total artificial heart: Modeling, magnet integration, and hydraulic experiments.

The purpose of this research is to address ongoing device shortfalls for pediatric patients by developing a novel pediatric hybrid total artificial heart (TAH). The valveless magnetically-levitated MCS device (Dragon Heart) has only two moving parts, integrates an axial and centrifugal blood pump into a single device, and will occupy a compact footprint within the chest for the pediatric patient population. Prior work on the Dragon Heart focused on the development of pump designs to achieve hemodynamic requirements. The impeller of these pumps was shaft-driven and thus could not be integrated for testing. The presented research leverages an existing magnetically levitated axial flow pump and focuses on centrifugal pump development. Using the axial pump diameter as a geometric constraint, a shaftless, magnetically supported centrifugal pump was designed for placement circumferentially around the axial pump domain. The new design process included the computational analysis of more than 50 potential centrifugal impeller geometries. The resulting centrifugal pump designs were prototyped and tested for levitation and no-load rotation, followed by in vitro testing using a blood analog. To meet physiologic demands, target performance goals were pressure rises exceeding 90 mm Hg for flow rates of 1-5L/min with operating speeds of less than 5000 RPM. Three puck-shaped, channel impellers for the centrifugal blood pump were selected based on achieving performance and space requirements for magnetic integration. A quasi-steady flow analysis revealed that the impeller rotational position led to a pulsatile component in the pressure generation. After prototyping, the centrifugal prototypes (3, 4, and 5 channeled designs) demonstrated levitation and no-load rotation. Hydraulic experiments established pressure generation capabilities beyond target requirements. The pressure-flow performance of the prototypes followed expected trends with a dependence on rotational speed. Pulsatile blood flow was observed without pump-speed modulation due to rotating channel passage frequency. The results are promising in the advancement of this pediatric TAH. The channeled impeller design creates pressure-flow curves that are decoupled from the flow rate, a benefit that could reduce the required controller inputs and improve treatment of hypertensive patients.

Experimental Characterization of a Microfluidic Device Based on Passive Crossflow Filters for Blood Fractionation

The separation of red blood cells (RBCs) from blood plasma and the analysis of individual RBCs are of great importance, as they provide valuable information regarding the health of their donor. Recent developments in microfluidics and microfabrication have contributed to the fabrication of microsystems with complex features to promote the separation and analysis of RBCs. In this work, the separation capacity of a multi-step crossflow microfluidic device was evaluated by using a blood analogue fluid made by Brij L4 micelles and human RBCs separated from whole blood, suspended in a solution with hematocrits (Ht) of 0.5 and 1%. All the samples collected at the outlets of the device were experimentally analyzed and compared. The absorbance spectrum was also measured for the prepared blood samples. The results indicate that the tested blood analogue fluid has exhibited a flow behavior similar to that of blood. In addition, the optical absorbance spectrophotometry revealed that it was possible to evaluate the separation efficiency of the microfluidic device, concluding that the concentration of cells was lower at the most lateral outside outlets of the microchannel due to the cumulative effect of the multiple cross-flow filters.

Determination of tryptamine analogs in whole blood by 96-well electromembrane extraction and UHPLC-MS/MS

Tryptamines are a class of new psychoactive substances relevant for analysis in forensic laboratories. Tryptamine analogs are diverse in structure and chemical properties, and prone to display instability. This puts high demands on sample preparation, especially from complex matrices such as whole blood. In the present paper, a prototype 96-well electromembrane extraction (EME) device was employed for the simultaneous extraction of 20 tryptamines from whole blood prior to UHPLC-MS/MS analysis. For the EME procedure, spiked whole blood diluted 3-fold with 1% ascorbic acid in 25 mM formic acid was extracted for 60 min across a supported liquid membrane (SLM) containing 5% bis(2-ethylhexyl) ether (DEHP) in 2-nitrophenyloctylether (NPOE) into an acceptor solution containing 1% ascorbic acid in 25 mM formic acid. The method was validated for 16 of the tryptamines in the range 5-500 nM according to SWGTOX guidelines and the analytes displayed limits of detection from >0.15 nM to 0.75 nM. An AGREEprep analysis was performed to evaluate method greenness with a final greenness score of 0.76. 96-well EME offered fast, efficient and green extraction of tryptamines from whole blood, demonstrating good potential for implementation in forensic laboratories when commercial devices will become available.

Hemodynamic characteristics in a cerebral aneurysm model using non-Newtonian blood analogues.

This study aims to develop an experimentally validated computational fluid dynamics (CFD) model to estimate hemodynamic characteristics in cerebral aneurysms (CAs) using non-Newtonian blood analogues. Blood viscosities varying with shear rates were measured under four temperatures first, which serves as the reference for the generation of blood analogues. Using the blood analogue, particle image velocimetry (PIV) measurements were conducted to quantify flow characteristics in a CA model. Then, using the identical blood properties in the experiment, CFD simulations were executed to quantify the flow patterns, which were used to compare with the PIV counterpart. Additionally, hemodynamic characteristics in the simplified Newtonian and non-Newtonian models were quantified and compared using the experimentally validated CFD model. Results showed the proposed non-Newtonian viscosity model can predict blood shear-thinning properties accurately under varying temperatures and shear rates. Another developed viscosity model based on the blood analogue can well represent blood rheological properties. The comparisons in flow characteristics show good agreements between PIV and CFD, demonstrating the developed CFD model is qualified to investigate hemodynamic factors within CAs. Furthermore, results show the differences of absolute values were insignificant between Newtonian and non-Newtonian fluids in the distributions of wall shear stress (WSS) and oscillatory shear index (OSI) on arterial walls. However, not only does the simplified Newtonian model underestimate WSS and OSI in most regions of the aneurysmal sac, but it also makes mistakes in identifying the high OSI regions on the sac surface, which may mislead the hemodynamic assessment on the pathophysiology of CAs.

Targeting Magnetic Nanoparticles in Physiologically Mimicking Tissue Microenvironment.

Magnetic nanoparticles as drug carriers, despite showing immense promises in preclinical trials, have remained to be only of limited use in real therapeutic practice primarily due to unresolved anomalies concerning their grossly contrasting controllability and variability in performance in artificial test benches as compared to human tissues. To circumvent the deficits of reported in vitro drug testing platforms that deviate significantly from the physiological features of the living systems and result in this puzzling contrast, here, we fabricate a biomimetic microvasculature in a flexible tissue phantom and demonstrate distinctive mechanisms of magnetic-field-assisted controllable penetration of biocompatible iron oxide nanoparticles across the same, exclusively modulated by tissue deformability, which has by far remained unraveled. Our experiments deciphering the transport of magnetic nanoparticles in a blood analogue medium unveil a decisive interplay of the flexibility of the microvascular pathways, magnetic pull, and viscous friction toward orchestrating the optimal vascular penetration and targeting efficacy of the nanoparticles in colorectal tissue-mimicking bioengineered media. Subsequent studies with biological cells confirm the viability of using localized magnetic forces for aiding nanoparticle penetration within cancerous lesions. We establish nontrivially favorable conditions to induce a threshold force for vascular rupture and eventual target of the nanoparticles toward the desired extracellular site. These findings appear to be critical in converging the success of in vitro trials toward patient-specific targeted therapies depending on personalized vascular properties obtained from medical imaging data.

CARD2: Demonstrating the Combined Effects Of Shear And Surface Roughness On Thrombosis On Titanium Alloy

Study: Titanium alloys used as blood contacting materials in a variety of artificial organs are often roughened on the nano- to micrometer scale during manufacture, requiring extensive and sometimes tedious polishing. However, there is no consensus of the tolerable limits of roughness. This study investigated the combined effects of supraphysiological shear and surface roughness on platelet deposition to provide guidelines for manufacturing. Methods: Microfluidic devices with roughened Ti6Al4V surfaces were used to create shear-controlled, clinically relevant micro-scale environments to quantify platelet deposition and aggregation. Ti6Al4V surfaces were roughened using diamond and glass abrasive techniques. A fresh human blood analog comprised of hemoglobin-depleted red blood cells, for optical clarity, and platelet-rich plasma with mepacrine-labeled platelets was perfused through the microdevices at three shear rates: 1000 s-1, 2000 s-1 and 5500 s-1. Four surface roughness levels were used: mirror finish, Ra 0.3 µm (data not shown here), Ra 0.8 µm and Ra 2.1 µm. Platelet deposition was visualized using fluorescent microscopy. Adherent platelet properties such as mean fluorescence intensity, aggregate area and number were quantified from processed microscopy images. Results: For all three roughnesses < 2.1 µm Ra, platelet adhesion demonstrated sustained growth in confluent monolayers at 1000 s-1 (figs 1a, 2a), formed stable, growing platelet aggregates at 2000 s-1 (fig 1b, 2b); and formed round, fibrous platelet aggregates at 5500 s-1 with increasing intensity and density with time (figs 1c, 2c). Embolization was observed with all surfaces after an initial increase in aggregate intensity (yellow shading, fig 2c). On the Ra 2.1 µm surface, platelet aggregates formed at all three shear rates, indicative of higher shear rates and gradients as a result of the roughness. Conclusions: These findings demonstrate that surface roughness and supraphysiologic shear act synergistically to promote platelet adhesion and thromboembolism. These results suggest a threshold of surface roughness, for the shear rates studied, between 0.8 and 2.1 µm Ra that provokes development of fibrous aggregates that are unstable and embolize. Ongoing work is investigating a wider combination of roughness textures, shear rate, and material chemistry. Figure 1. Platelet adhesion on Ti6Al4V (a) monolayer at 1000s-1, mirror finish), (b) aggregates 2000s-1, Ra 0.8 µm, and (c) fibrous aggregates at 5500s-1. (Scale bar length is 100 µm) Figure 2. Mean fluorescence intensity of aggregates versus time (900 seconds). Error bars represent standard error of the mean at each timepoint.