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Purpose: To develop a mathematical model for predicting shear-induced von Willebrand factor (vWF) function modification which can be used to guide ventricular assist devices (VADs) design, and evaluate the damage of high molecular weight multimers (HMWM)-vWF in VAD patients for reducing clinical complications., Methods: Mathematical models were constructed based on three morphological variations (globular vWF, unfolded vWF and degraded vWF) of vWF under shear stress conditions, in which parameters were obtained from previous studies or fitted by experimental data. Different clinical support modes (pediatric vs. adult mode), different VAD operating states (pulsation vs. constant mode) and different clinical VADs (HeartMate II, HeartWare and CentriMag) were utilized to analyze shear-induced damage of HMWM-vWF based on our vWF model. The accuracy and feasibility of the models were evaluated using various experimental and clinical cases, and the biomechanical mechanisms of HMWM-vWF degradation induced by VADs were further explained., Results: The mathematical model developed in this study predicted VAD-induced HMWM-vWF degradation with high accuracy (correlation with experimental data r 2  > 0.99). The numerical results showed that VAD in the pediatric mode resulted in more HMWM-vWF degradation per unit time and per unit flow rate than in the adult mode. However, the total degradation of HMWM-vWF is less in the pediatric mode than in the adult mode because the pediatric mode has fewer times of blood circulation than the adult mode in the same amount of time. The ratio of HMWM-vWF degradation was lower in the pulsation mode than in the constant mode. This is due to the increased flushing of VADs in the pulsation mode, which avoids prolonged stagnation of blood in high shear regions. This study also found that the design feature, rotor size and volume of the VADs, and the superimposed regions of high shear stress and long residence time inside VADs affect the degradation of HMWM-vWF. The axial flow VADs (HeartMate II) showed higher degradation of HMWM-vWF compared to centrifugal VADs (HeartWare and CentriMag). Compared to fully magnetically suspended VADs (CentriMag), hydrodynamic suspended VADs (HeartWare) produced extremely high degradation of HWMW-vWF in its narrow hydrodynamic clearance. Finally, the study used a mathematical model of HMWM-vWF degradation to interpret the clinical statistics from a biomechanical perspective and found that minimizing the rotating speed of VADs within reasonable limits helps to reduce HWMW-vWF degradation. All predicted conclusions are supported by the experimental and clinical data., Conclusion: This study provides a validated mathematical model to assess the shear-induced degradation of HMWM-vWF, which can help to evaluate the damage of HMWM-vWF in patients implanted with VADs for reducing clinical complications, and to guide the optimization of VADs for improving hemocompatibility., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Atherosclerosis preferentially occurs at regions in arterial branching, curvature, and stenosis, which may be explained by the geometric predilection of low-density lipoprotein (LDL) concentration polarization that has been investigated in major arteries in previous studies. Whether this also happens in arterioles remains unknown., Methods: Herein, a radially non-uniform distribution of LDL particles and a heterogeneous endothelial glycocalyx layer in the mouse ear arterioles, as shown by fluorescein isothiocyanate labeled wheat germ agglutinin (WGA-FITC), were successfully observed by a non-invasive two-photon laser-scanning microscopy (TPLSM) technique. The stagnant film theory was applied as the fitting function to evaluate LDL concentration polarization in arterioles., Results: The concentration polarization rate (CPR, the ratio of the number of polarized cases to that of total cases) in the inner walls of curved and branched arterioles was 22% and 31% higher than the outer counterparts, respectively. Results from the binary logistic regression and multiple linear regression analysis showed that endothelial glycocalyx thickness increases CPR and the thickness of the concentration polarization layer (CPL). Flow field computation indicates no obvious disturbances or vortex in modeled arterioles with different geometries and the mean wall shear stress is about 7.7-9.0 Pa., Conclusions: These findings suggest a geometric predilection of LDL concentration polarization in arterioles for the first time, and the existence of an endothelial glycocalyx, acting together with a relatively high wall shear stress in arterioles, may explain to some extent why atherosclerosis rarely occurs in these regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The geometric structure of the membrane oxygenator can exert an impact on its hemodynamic features, which contribute to the development of thrombosis, thereby affecting the clinical efficacy of ECMO treatment. The purpose of this study is to investigate the impact of varying geometric structures on hemodynamic features and thrombosis risk of membrane oxygenators with different designs., Methods: Five oxygenator models with different structures, including different number and location of blood inlet and outlet, as well as variations in blood flow path, were established for investigation. These models are referred to as Model 1 (Quadrox-i Adult Oxygenator), Model 2 (HLS Module Advanced 7.0 Oxygenator), Model 3 (Nautilus ECMO Oxygenator), Model 4 (OxiaACF Oxygenator) and Model 5 (New design oxygenator). The hemodynamic features of these models were numerically analyzed using the Euler method combined with computational fluid dynamics (CFD). The accumulated residence time (ART) and coagulation factor concentrations (C[i], where i represents different coagulation factors) were calculated by solving the convection diffusion equation. The resulting relationships between these factors and the development of thrombosis in the oxygenator were then investigated., Results: Our results show that the geometric structure of the membrane oxygenator, including the location of the blood inlet and outlet as well as the design of the flow path, has a significant impact on the hemodynamic surroundings within the oxygenator. In comparison to Model 4, which had the inlet and outlet located in the center position, Model 1 and Model 3, which had the inlet and outlet at the edge of the blood flow field, exhibited a more uneven distribution of blood flow within the oxygenator, particularly in areas distant from the inlet and outlet, which was accompanied with lower flow velocity and higher values of ART and C[i], leading to the formation of flow dead zones and an elevated risk of thrombosis. The oxygenator of Model 5 is designed with a structure that features multiple inlets and outlets, which greatly improves the hemodynamic environment inside the oxygenator. This results in a more even distribution of blood flow within the oxygenator, reducing areas with high values of ART and C[i], and ultimately lowering the risk of thrombosis. The oxygenator of Model 3 with circular flow path section shows better hemodynamic performance compared to the oxygenator of Model 1 with square circular flow path. The overall ranking of hemodynamic performance for all five oxygenators is as follows: Model 5 > Model 4 > Model 2 > Model 3 > Model 1, indicating that Model 1 has the highest thrombosis risk while Model 5 has the lowest., Conclusion: The study reveals that the different structures can affect the hemodynamic characteristics inside membrane oxygenators. The design of multiple inlets and outlets can improve the hemodynamic performance and reduce the thrombosis risk in membrane oxygenators. These findings of this study can be used to guide the optimization design of membrane oxygenators for improving hemodynamic surroundings and reducing thrombosis risk., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Device-induced blood damage contributes the hemolysis, thrombosis and bleeding complications in patients supported with ventricular assist device (VAD). This study aims to use a multi-indicator method to understand how devices causes blood damage and identify the "hot spots" of blood trauma within VADs., Methods: Computational fluid dynamics (CFD) methods were chosen to investigate the hemodynamic features of five clinical VADs (Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II) under the same clinical support condition (flow rate of 4.5L/min, pressure head around 75 mmHg). A comprehensive multi-indicator evaluation method including hemodynamic parameters, hemolysis model, thrombotic potential model and bleeding probability model was used to analyze blood damage and assess the hemodynamic performance and hemocompatibility of these VADs., Results: Simulation results show that shear stress from 50 Pa to 100 Pa plays a major role in blood damage in Impella 5.0, UltraMag and CHVAD, while blood damage in HVAD and HeartMate II is mainly caused by shear stress greater than 100 Pa. Residence time was not the main factor for blood damage in Impella 5.0, and also makes a limited contribution to blood trauma in UltraMag and CHVAD, while it takes a critical role in elevating thrombotic potential in HVAD and HeartMate II. The distribution of regions of high hemolysis risk and high bleeding probability was similar for all these VADs and partially overlapped for high thrombotic potential regions. For Impella 5.0, regions with high hemolysis and bleeding risk were found mainly in the blade tip clearance and diffuser domains, high thrombotic potential regions were almost absent. For UltraMag, regions with high hemolysis, bleeding and thrombosis potential were found in two corners of the inlet pipe, the secondary flow passage, and the impeller eye. For CHVAD, the high-risk regions for hemolysis, bleeding and thrombosis are mainly in the inner side of the secondary flow passage and the middle region of the impeller passage. The narrow hydrodynamic clearance and impeller passage had a high risk of hemolysis and bleeding, and the clearance between the rotor and guide cone and the hydrodynamic clearance had high thrombotic potential. For HeartMate II, regions of high hemolysis risk and bleeding probability were found in the near-wall region of the straightener, the blade tip clearance and the diffuser domain. The corners of the inlet and outlet pipe and the straightener and diffuser regions had high thrombotic potential., Conclusion: The risk of hemolysis, bleeding and thrombosis for these five VADs, in increasing order, was Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II. Flow losses caused by the rotor mechanical movement, chaotic flow and narrow clearances increase the blood damage for all these VADs. The multi-indicator analysis can comprehensively evaluate the VAD performance with improved assessment accuracy of CFD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Most small diameter vascular grafts (inner diameter<6 mm) evaluation studies are performed in healthy animals that cannot represent the clinical situation. Herein, an hypercholesterolemia (HC) rat model with thickened intima and elevated expression of pro-inflammatory intercellular adhesion molecular-1 (ICAM-1) in the carotid branch is established. Electrospun polycaprolactone (PCL) vascular grafts (length: 1 cm; inner diameter: 2 mm) are implanted into the HC rat abdominal aortas in an end to end fashion and followed up to 43 days, showing a relative lower patency accompanied by significant neointima hyperplasia, abundant collagen deposition, and slower endothelialization than those implanted into healthy ones. Moreover, the proliferation, migration, and adhesion behavior of endothelial cells (ECs) isolated from the HC aortas are impaired as evaluated under both static and pulsatile flow conditions. DNA microarray studies of the HC aortic endothelium suggest genes involved in EC proliferation (Egr2), apoptosis (Zbtb16 and Mt1), and metabolism (Slc7a11 and Hamp) are down regulated. These results suggest the impaired proliferative, migratory, and adhesive abilities of ECs are associated with the bad performances of grafts in HC rat. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications. STATEMENT OF SIGNIFICANCE: During the development of small diameter vascular grafts (D<6 mm), young and healthy animal models from pigs, sheep, dogs, to rabbits and rats are preferred. However, it cannot represent the clinic situation, where most cardiovascular grafting procedures are performed in the elderly and age is the primary risk factor for disease development or death. Herein, the performance of electrospun polycaprolactone (PCL) vascular grafts implanted into hypercholesterolemia (HC) or healthy rats were evaluated. Results suggest the proliferative, migratory, and adhesive abilities of endothelial cells (ECs) are already impaired in HC rats, which contributes to the observed slower endothelialization of implanted PCL grafts. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Thoracic aortic aneurysm (TAA) is fatal diseases, which leads to aortic rupture and sudden death. Blood pressure-lowering drugs are ineffective for most of the patients. Our previous study demonstrated the inhibition of endothelial secreted miR-126-3p by rapamycin ameliorate the aneurysmal phenotype of smooth muscle cells (SMCs) in vitro. Hence, this study aimed to evaluate the modulation and mechanism of miR-126-3p in a murine model of TAA (Fbn1 C1039G/+ ). Our results showed that noticeable disturbed flow (DF) was observed in the aorta of Fbn1 C1039G/+ mice, and the expression of miR-126-3p was significantly increased under the DF in the cell chamber. This finding was also confirmed by tests in the corresponding DF area of the human aortic aneurysm tissue. Constant rapamycin administration significantly ameliorates the incidence and severity of Fbn1 C1039G/+ mice characterized by decreased aortic media degradation, macrophage infiltration and MMP2/9 expression in the aortic wall. Mechanistic studies showed that rapamycin attenuates TAA progression by inhibiting miR-126-3p through ERK1/2 inactivation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that the venous graft when implanted in an arterial bypass might endure a significantly elevated water filtration rate, leading to fast infiltration/accumulation of low-density lipoproteins (LDLs) within the graft wall and hence the accelerated atherogenesis., Methods: We measured filtration rates of the swine femoral artery and lateral saphenous vein under venous and arterial hemodynamic conditions in vitro. Based on the measured filtration rates, we numerically simulated LDL transport in an arterial bypass model with a venous graft. Moreover, in order to validate the theoretical prediction, we measured DiI-LDLs uptake by both arteries and veins under arterial condition., Results: The experimental results showed that when subjected to arterial hemodynamic condition, the filtration rate of the venous wall was increased sharply, and significantly higher than that of the artery. Moreover, different from the hydraulic conductivity of artery, the venous one would increase with increasing pressure. The numerical results showed that for the venous graft, both luminal surface LDL concentration and LDL accumulation within the vessel wall were significantly higher than those for the host artery. In addition, the experiment, which was used to confirm theoretical prediction, showed that the amount of DiI-LDLs uptake by the venous wall was much higher compared with arterial wall., Conclusion: The present study suggests that the accelerated atherogenesis of the venous graft is attributable to its elevated filtration rate that may lead to both aggravated concentration polarization of LDLs and enhanced convective transport of LDLs into the graft wall., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)