Physiological Flow Research Articles

Mathematical modeling of electroosmotically driven peristaltic propulsion due to transverse deflections of two periodically deformable curved tubes of unequal wavelengths

The present study aims to investigate the viscid fluid propulsion due to the electroosmosis and transverse deflections of the sinusoidally deformable tubes of unequal wavelengths in the presence of electro-kinetic forces. This situation is estimated from the physical model of physiological fluid flow through a tubular structure in which an artificial flexible tube is being inserted. In this model, both peristaltically deforming tubes are taken in a curved configuration. The flow-governing momentum equations are simplified by the approximation of the long wavelength as compared to the outer tube's radius, whereas the Debye–Hückel approximation is used to simplify the equations that govern the electric potential distribution. Here, the authors have used the DSolve command in the scientific computing software MATHEMATICA 14 to obtain the expressions for electric potential and axial velocity of viscid fluid. In this work, the authors have analyzed the impact of various controlling parameters, such as the electro-physical parameters, curvature parameter, radius ratio, wavelength ratio, and amplitude ratios, on the various flow quantities graphically during the transport of viscid fluid through a curved endoscope. Here, contour plots are also drawn to visualize the streamlines and to observe the impacts of the control parameters on fluid trapping. During the analysis of the results, a noteworthy outcome extracted from the present model is that an increment in electro-physical parameters, such as Helmholtz–Smoluchowski velocity and the Debye–Hückel parameter, are responsible for enhancement in the shear stress at the inner tube's wall and the axial velocity under the influence of electro-kinetic forces. This is because of the electric double layer (EDL) thickness, which gets reduced on strengthening the Debye–Hückel parameter. This reduced EDL thickness is responsible for the enhancement in the axial velocity of the transporting viscid fluid. The present model also suggests that the axial velocity of viscid fluid can be reduced by enhancing the ratio of wavelengths of waves that travel down the walls of the outer curved tube and the inner curved tube. The above-mentioned results can play a significant role in developing and advancing the endoscopes that will be useful in many biomedical processes, such as gastroscopy, colonoscopy, and laparoscopy.

A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows

BackgroundNormothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers.MethodsHuman livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion.ResultsPerfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120–184 h), with preserved viability throughout.ConclusionsLivers can be reproducibly perfused in excess of 120 (range 121–184) hours with evidence of preserved hepatocyte and cholangiocyte function.

Human Anterior Segment Perfusion Organ Culture.

The human anterior segment perfusion organ culture is an ex vivo model system for studying the human conventional outflow pathway with reference to pressure regulation. In this model, anterior segments dissected from human donor eyes can be fixed to a modified petri dish and perfused with media along with various study agents at the physiological flow rate of 2.5μL/min. The model mimics the one-way flow of aqueous humor in human eyes and can be used to evaluate the effects of various drugs on eye pressure in real time. Using this model, cells and tissues of the anterior segment can be maintained for up to 28days, enabling histological and molecular evaluations.

Numerical Methods in Modelling of Red Blood Cellflow Behaviour Through a Specific Stacking Pattern

Abstract: The dynamics of red blood cells (RBCs) is one of the major aspects of the cardiovascular system that has been studied intensively in the past few decades. Using computational fluid dynamics, complex nonlinear fluid flows have been modeled. The dynamics of biconcave RBCs are thought to have major influences in cardiovascular diseases and other problems associated with cardiovascular flow behaviour, and the determination of blood rheology and properties. Most reported computational models have been confined to the behaviour of a single RBC in 2-dimensional domains, under physiological flow conditions. This work investigates a particular stacking pattern in analyzing the RBC flow behavior under physiological flow conditions, using the D2Q9 lattice Boltzmann numerical method created using Matlab. Prior to the analysis the Matlab script was benchmarked using the Poiseuille flow and the flow around the cross-section of a cylinder, after which the accuracy of the method used was determined. The benchmarks showed that the lattice Boltzmann code had minimal error. The accuracy was determined using the data obtained from Matlab and a created excel program. It also showed that the lattice Boltzmann method was of the first order, which corresponds with results existing in literatures. The analysis of the stacking pattern showed how RBC flows through the chosen stacking pattern, and the results are shown.

Spatial patterns of high-risk biomechanical metrics in plaques with abnormal vs. normal physiological flow indices

BackgroundPlaques associated with abnormally low physiological flow reserve indices are appropriate for percutaneous coronary intervention (PCI). However, recent trials demonstrate that PCI of ischemia-producing lesions does not reduce major adverse cardiac events (MACE). Low endothelial shear stress (ESS) or high ESS gradient (ESSG) are associated with MACE wherever they occur along the plaque. This study aims to determine the presence of high-risk ESS metrics in obstructive coronary plaques with high-risk (<0.80) vs. borderline-risk (0.80–0.89) vs. normal Instantaneous Wave-free Ratio (iFR) (>0.89). MethodsWe included 50 coronary arteries (50 patients) with variable iFR values who underwent coronary angiography and optical coherence tomography (OCT), followed by 3D reconstruction and computational fluid dynamics calculations of ESS/ESSG. The cohort was divided into 3 groups: iFR < 0.80, iFR 0.80–0.89, and iFR > 0.89. Spatial distribution of ESS metrics was reported along the course of each plaque, and high-risk ESS metrics and their location were compared among the 3 iFR subgroups. ResultsHigh-risk ESS features (Minimal ESS, Maximum ESSG) were similarly distributed along the course of the atherosclerotic plaque in the three iFR subgroups, both in absolute value and in location: Min ESS: 0.5 ± 0.3 vs. 0.4 ± 0.2 vs. 0.4 ± 0.2 Pa respectively (p = 0.60); Max ESSG any direction: 13.7 ± 9.4 vs. 10.4 ± 10.6 vs. 10.0 ± 7.8 Pa/mm respectively (p = 0.30). ESS metrics were spatially located up to ≥18 mm from the plaque minimal luminal area (MLA) in both directions. ConclusionHigh-risk ESS metrics are similarly observed in plaques with normal or abnormal iFR, both in absolute value and spatial location in reference to the MLA. Utilizing iFR to identify plaques likely to cause MACE would miss the majority of plaques mechanistically at high-risk to destabilize and cause future adverse cardiac events.

Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts.

Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production. A novel perfusion bioreactor was designed, capable of accurately controlling fluid flow rate and pressure waveforms for preconditioning of small-diameter vascular grafts. A closed-loop system controlled pressure waveforms, mimicking physiological values of 50-120mmHg at a frequency of 8.75Hz for fluid flow reaching 5mL/min. Plant-based vascular grafts were recellularized with endothelial and vascular smooth muscle cells and cultured for up to 3weeks in this bioreactor. Cell density, scaffold structure and mechanics, thrombogenicity, and immunogenicity of grafts were evaluated. Bioreactor treatment with fluid flow significantly increased luminal endothelial cell density, while pressure waveforms reduced thrombus formation and maintained viable vascular smooth muscle cells within inner layers of grafts compared to static controls. Suture retention of grafts met transplantation standards and white cell viability was suitable for vascular remodeling. Low thrombogenicity of endothelialized leatherleaf viburnum holds great potential for vascular repair. This study provides insight into benefits of conditioning plant-based materials with hemodynamic forces at higher frequencies that have not previously been investigated.

Dynamic conformational response of von Willebrand factor to varying shear stress: A hybrid computational approach

This computational study examines the mechanobiological responses of von Willebrand Factor (vWF) to different shear stress levels, emphasizing the unique structural dynamics of its various domains. We introduce a novel coarse-grained model, representing each cluster of six amino acids as a bead, to synthesize the Lattice Boltzmann method with Brownian dynamics. This approach captures the vWF molecule’s conformational adaptability across a spectrum of shear rates, ranging from 5 to 5e + 7s−1, encompassing normal physiological flows to those resembling the high-shear environment of arterial stenosis.Our results reveal domain-specific responses of vWF, particularly in the A2 and A3 domains, which demonstrate significant elongation under elevated shear—reflecting their pivotal roles in clotting processes. Moreover, the study underscores the critical influence of random thermal forces on the molecule’s conformation, with simulations including these forces showing substantially greater conformational variability compared to those without.As shear rates increase, we observe a notable reorganization in the spatial arrangement of vWF domains. This reconfiguration is most evident in the increased separation between the A1 and D’D3 domains under high shear conditions, potentially enhancing the accessibility of platelets to key binding sites on vWF. These findings are paramount for a deeper understanding of vWF’s mechanical behavior in blood clotting and thrombosis, particularly the delicate balance between facilitating platelet adhesion and avoiding excessive stretching that could lead to thrombosis.Our work provides a foundation for future studies investigating vWF behavior in complex flow geometries and its interactions with other blood components. Such insights pave the way for more informed therapeutic strategies targeting vWF function in vascular health and disease, potentially leading to improved treatments for thrombotic disorders.

Influence of Intraocular Pressure on the Expression and Activity of Sodium-Potassium Pumps in the Corneal Endothelium.

The corneal endothelium is responsible for pumping fluid out of the stroma in order to maintain corneal transparency, which depends in part on the expression and activity of sodium-potassium pumps. In this study, we evaluated how physiologic pressure and flow influence transcription, protein expression, and activity of Na+/K+-ATPase. Native and engineered corneal endothelia were cultured in a bioreactor in the presence of pressure and flow (hydrodynamic culture condition) or in a Petri dish (static culture condition). Transcription of ATP1A1 was assessed using qPCR, the expression of the α1 subunit of Na+/K+-ATPase was measured using Western blots and ELISA assays, and Na+/K+-ATPase activity was evaluated using an ATPase assay in the presence of ouabain. Results show that physiologic pressure and flow increase the transcription and the protein expression of Na+/K+-ATPase α1 in engineered corneal endothelia, while they remain stable in native corneal endothelia. Interestingly, the activity of Na+/K+-ATPase was increased in the presence of physiologic pressure and flow in both native and engineered corneal endothelia. These findings highlight the role of the in vivo environment on the functionality of the corneal endothelium.

How predictive are isolated perfused liver data of in vivo hepatic clearance? A meta-analysis of isolated perfused rat liver data

Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (CLH ). However, to date, IPRL data has not been evaluated for in vivo CLH prediction accuracy. In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in CLH prediction. While the entire dataset poorly predicted CLH (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat CLH (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis. Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current in vitro-in vivo disconnects of hepatic metabolic clearance and improve our methodology for CLH predictions.

MR Lymphangiography: Congenital Lymphatic Flow Disorders.

Congenital lymphatic flow disorders collectively refer to a heterogeneous group of diseases that manifest as chylothorax, chylous ascites, intestinal lymphangiectasia, protein-losing enteropathy, and peripheral extremity or genital lymphedema, all in the absence of identifiable injury to the lymphatic system. We have only recently begun to understand congenital lymphatic flow disorders through the ability to image lymph flow dynamically. Intranodal dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) is a crucial technique for imaging lymphatic flow in pediatric patients with congenital lymphatic flow disorders. However, as lymphatic imaging is still a nascent discipline with many uncertainties regarding optimal imaging and treatment, effective patient management requires a comprehensive understanding of imaging techniques, disease pathophysiology, and multidisciplinary treatment approaches. Above all, a fundamental understanding of the physiological lymphatic flow of the central conducting lymphatics is essential for the correct interpretation of DCMRL images. This knowledge helps to avoid unnecessary examinations, erroneous diagnoses, and potentially harmful treatment approaches. This review provides an overview of the methods, advantages, and precautions for interpreting the DCMRL examination, a state-of-the-art lymphatic system imaging technique, and shares various case studies.

Unified framework for laser-induced transient bubble dynamics within microchannels

Oscillatory flow in confined spaces is central to understanding physiological flows and rational design of synthetic periodic-actuation based micromachines. Using theory and experiments on oscillating flows generated through a laser-induced cavitation bubble, we associate the dynamic bubble size (fluid velocity) and bubble lifetime to the laser energy supplied—a control parameter in experiments. Employing different channel cross-section shapes, sizes and lengths, we demonstrate the characteristic scales for velocity, time and energy to depend solely on the channel geometry. Contrary to the generally assumed absence of instability in low Reynolds number flows (<1000\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$<1000$$\\end{document}), we report a momentary flow distortion that originates due to the boundary layer separation near channel walls during flow deceleration. The emergence of distorted laminar states is characterized using two stages. First the conditions for the onset of instabilities is analyzed using the Reynolds number and Womersley number for oscillating flows. Second the growth and the ability of an instability to prevail is analyzed using the convective time scale of the flow. Our findings inform rational design of microsystems leveraging pulsatile flows via cavitation-powered microactuation.

Image-Based Computational Fluid Dynamics to Compare Two Repair Techniques for Mitral Valve Prolapse.

OBJECTIVE: The treatment of mitral valve prolapse involves two distinct repair techniques: chordal replacement (Neochordae technique) and leaflet resection (Resection technique). However, there is still a debate in the literature about which is the optimal one. In this context, we performed an image-based computational fluid dynamic study to evaluate blood dynamics in the two surgical techniques. METHODS: We considered a healthy subject (H) and two patients (N and R) who underwent surgery for prolapse of the posterior leaflet and were operated with the Neochordae and Resection technique, respectively. Computational Fluid Dynamics (CFD) was employed with prescribed motion of the entire left heart coming from cine-MRI images, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method for managing valve dynamics. We created three different virtual scenarios where the operated mitral valves were inserted in the same left heart geometry of the healthy subject to study the differences attributed only to the two techniques. RESULTS: We compared the three scenarios by quantitatively analyzing ventricular velocity patterns and pressures, transition to turbulence, and the ventricle ability to prevent thrombi formation. From these results, we found that the operative techniques affected the ventricular blood dynamics in different ways, with variations attributed to the reduced mobility of the Resection posterior leaflet. Specifically, the Resection technique resulted in turbulent forces, related with the risk of hemolysis formation, up to 640 Pa, while the other two scenarios exhibited a maximum of 240 Pa. Moreover, in correspondence of the ventricular apex, the Resection technique reduced the areas with low velocity to 15%, whereas the healthy case and the Neochordae case maintained these areas at 30 and 48%, respectively. Our findings suggest that the Neochordae technique developed a more physiological flow with respect to the Resection technique. CONCLUSION: Resection technique gives rise to a different direction of the mitral jet during diastole increasing the ability to washout the ventricular apex preventing from thrombi formation, but at the same time it promotes turbulence formation that is associated with ventricular effort and risk of hemolysis.

Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI

Background and objectiveThe evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. MethodsA complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. ResultsThe analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. ConclusionsThe findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Muticomponent Melt‐Electrowritten Vascular Graft to Mimic and Guide Regeneration of Small Diameter Blood Vessels

AbstractCardiovascular disease is a leading cause of morbidity. Current treatments include vessel substitution using autologous/synthetic vascular grafts, but these commonly fail in small diameter applications, largely due to compliance mismatch and clot formation. In this study, a multicomponent vascular graft, that takes inspiration from native vessel architecture, is developed to overcome these limitations. Melt electrowriting (MEW) is used to produce tubular scaffolds with vascular‐mimetic fiber architecture and mechanics, which is combined with a lyophilized fibrinogen matrix with tailored degradation kinetics to generate a hybrid graft. The MEW framework not only contributes to graft mechanics, but also provides contact guidance to direct cell/neotissue orientation and mimic the native tunica media. This construct is further functionalized with heparin, which in combination with the smooth extracellular matrix (ECM) surface, reduced platelet adhesion and clot formation providing a substrate for endothelization, thereby mimicking the function of the intima. Lastly, an outer electrospun layer representing the adventitia is added to improve elasticity and reduce permeability. This graft satisfies ISO implantability requirements, matches the compliance of native vessels, and reestablishes physiological flow with minimal clot formation in a preclinical model. Therefore, this graft represents an innovative off‐the‐shelf alternative to address the unmet clinical need for small‐diameter vascular grafts.

Beyond the Rex: an innovative meso-intrahepatic portal vein bypass for late-onset extrahepatic portal vein occlusion after living donor liver transplantation.

The Meso-Rex bypass (MRB) is recognized as an effective treatment for portal hypertension secondary to extrahepatic portal vein occlusion (EHPVO) both in the pediatric and adult population, within or outside the context of liver transplantation. It is the preferred surgical treatment in most centers because not only does it addresses the portal hypertension, but also restores physiologic portal hepatopetal flow. However, the Rex recess, the landmark for this technique, may not be safely accessible in some patients. We present a 22-year-old male who underwent living donor liver transplant (LDLT) for neonatal hepatitis. He presented with variceal bleeding due to EHPVO at 13 years after transplant. Various endoscopic, radiologic, and surgical interventions were employed to address the recurrent gastrointestinal bleeding, but results have been unsatisfactory. We performed a meso-intrahepatic portal vein bypass (MIPVB), an innovative alternative to the MRB, for this patient with extensive post-operative adhesions, perihilar collaterals, and cavernous transformation. MIPVB creation in patients where the Rex recess is inaccessible is technically challenging. But with a multidisciplinary team approach, meticulous preoperative planning, and close follow-up, the authors have demonstrated that it is a safe and feasible option for patients with late-onset EHPVO after liver transplantation.

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.

Stored platelet hemostatic phenotype and function is not altered when donors are on testosterone replacement therapy.

Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.

Clot Accumulation in 3D Microfluidic Bifurcating Microvasculature Network.

The microvasculature, which makes up the majority of the cardiovascular system, plays a crucial role in the process of thrombosis, with the pathological formation of blood clots inside blood vessels. Since blood microflow conditions significantly influence platelet activation and thrombosis, accurately mimicking the structure of bifurcating microvascular networks and emulating local physiological blood flow conditions are valuable for understanding blood clot formation. In this work, we present an in vitro model for blood clotting in microvessels, focusing on 3D bifurcations that align with Murray's law, which guides vascular networks by maintaining a constant wall shear rate throughout. Using these models, we demonstrate that microvascular bifurcations act as sites facilitating thrombus formation compared to straight models. Additionally, by culturing endothelial cells on the luminal surfaces of the models, we show the potential of using our in vitro platforms to recapitulate the initial clotting in diseases involving endothelial dysfunction, such as Thrombotic Thrombocytopenic Purpura.

Engineering a biopolymer for vascular embolization based on fundamental polymer principals

Here we describe the engineering of a potential polymer substitute to metal coils for achieving vascular embolization. Our system is based on a methacrylate end-functionalized polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymer which displays thermal-reversible gelation properties and FCC ordering of the original copolymer while also being able to chemically crosslink. This system shows injectability, two-step gelation, chemical crosslinking with a five-fold increase in modulus and is highly resistant to washout under physiological flow conditions. Furthermore, we show that exposure to aqueous flow imparts resistance to swelling where less than 10 % swelling was observed under physiological flow as opposed to more than 60 % under static conditions after 30 days. Auxiliary experiments with PEO-PPO-PEO copolymers of various molecular weights indicate that this phenomenon may possibly be attributed to entanglements known to occur between adjacent micelles, where the reptation time, the time for polymer disentanglement, is long compared to the flow rate.

Influence of the Presence of Different Signatures on the Heat Transfer Profile of Laminar Flow Inside a Microchannel

Abstract The process of transferring heat and mass involves a high-pressure decline. Hence microchannels are utilized in extremely efficient heat and mass transfer processes, such as in the systems of the lungs and kidneys. Due to their high surface-to-volume ratio and compact volume, microchannels have demonstrated superior thermal performance. In this work, micro-fins of different topologies and arrangements were used inside microchannels for modulating heat transfer from the surface of the fins, in the presence of flowing media. The influx of media was simulated in sinusoidal form, reproducing simplified form of physiological circulatory blood flow. The study was conducted in numerical domain, while heat transfer and mass transfer equations were solved using pardiso solver. Temperature modulation at the fin surfaces was conducted to examine the transient profile of heat transfer, as function of both variable fluid velocity as well as variable feeding heat sources. In case of different input boundary conditions, the effect of heat distributions on fluid flow with respect to spatial distribution of micro-fins within a microchannel was evaluated. Results revealed the difference in heat transfer profiles in microchannels in presence of different sets of fin configurations. It was found that rectangular fins have the highest heat transfer in fluid at all its spatial configurations; while semi-ellipsoidal-shaped fins had shown the least heat transfer profile at same surface area. At the same time, it was also observed that the rate of heat dissipation was faster and limited in semi-ellipsoidal-shaped fins configuration; while the heat transfer rate was found symmetrical and low in presence of rectangular fins. Hence, this article emphasizes the modulation of temperature and velocity variations within the working fluid by emphasizing the thermo-fluid coupling effects in microchannels.