Enhanced solute transport and steady mechanical stimulation in a novel dynamic perifusion bioreactor increase the efficiency of the in vitro culture of ovarian cortical tissue strips.

Introduction: We report the development and preliminary evaluation of a novel dynamic bioreactor to culture ovarian cortical tissue strips that leverages tissue response to enhanced oxygen transport and adequate mechanical stimulation. In vitro multistep ovarian tissue static culture followed by mature oocyte generation, fertilization, and embryo transfer promises to use the reserve of dormant follicles. Unfortunately, static in vitro culture of ovarian tissue does not promote development of primordial to secondary follicles or sustain follicle viability and thereby limits the number of obtainable mature oocytes. Enhancing oxygen transport to and exerting mechanical stimulation on ovarian tissue in a dynamic bioreactor may more closely mimic the physiological microenvironment and thus promote follicle activation, development, and viability. Materials and Methods: The most transport-effective dynamic bioreactor design was modified using 3D models of medium and oxygen transport to maximize strip perifusion and apply tissue fluid dynamic shear stresses and direct compressive strains to elicit tissue response. Prototypes of the final bioreactor design were manufactured with materials of varying cytocompatibility and assessed by testing the effect of leachables on sperm motility. Effectiveness of the bioreactor culture was characterized against static controls by culturing fresh bovine ovarian tissue strips for 7 days at 4.8 × 10-5 m/s medium filtration flux in air at -15% maximal total compressive strain and by assessing follicle development, health, and viability. Results and Conclusions: Culture in dynamic bioreactors promoted effective oxygen transport to tissues and stimulated tissues with strains and fluid dynamic shear stresses that, although non-uniform, significantly influenced tissue metabolism. Tissue strip culture in bioreactors made of cytocompatible polypropylene preserved follicle viability and promoted follicle development better than static culture, less so in bioreactors made of cytotoxic ABS-like resin.

Reconstruction of Trauma Dynamics Due to Ligature Strangulation by Using a Dynamometer: A Technical Report.

Asphyxiation caused by violence, particularly through ligature strangulation, necessitates the application of a force that is characterized by a point of application, direction, and intensity. These properties can be quantified through the use of a dynamometer, which is composed of a graduated scale and a spring. In this particular study, an experimental model utilizing a dynamometer was employed to aid in the diagnosis and analysis of the dynamics of violent trauma resulting from homicidal ligature strangulation. The experimental model was applied to an attempted murder case involving strangulation. The primary challenge in this case was to establish the attempted murder scientifically, as the offender claimed that there had been no intent to kill, but instead an attempt to frighten the victim. To prove his assertion, the assailant emphasized the absence of strangulation injuries on the victim's neck. To investigate, a crane scale dynamometer was fixed on a cable and placed on a manikin's neck. The potential measurable combinations with the dynamometer were then compared to witness accounts and the injuries found on the victim. The utilization of a dynamometer in our case permitted the diagnosis and verification of a trauma that was undoubtedly caused by violent asphyxiation via strangulation. The information yielded by the dynamometer was subsequently submitted as scientific evidence in Court, serving to substantiate the intent to commit homicide and substantiate the credibility of the victim's testimony.

Dynamic in vitro culture of bovine and human ovarian tissue enhances follicle progression and health.

In vitro ovarian cortical tissue culture, followed by culture of isolated secondary follicles, is a promising future option for production of mature oocytes. Although efforts have been made to improve the culture outcome by changing the medium composition, so far, most studies used static culture systems. Here we describe the outcome of 7 days cultures of bovine and human ovarian cortical tissue in a dynamic system using a novel perifusion bioreactor in comparison to static culture in conventional and/or gas permeable dishes. Findings show that dynamic culture significantly improves follicle quality and viability, percentage and health of secondary follicles, overall tissue health, and steroid secretion in both species. Model predictions suggest that such amelioration can be mediated by an enhanced oxygen availability and/or by fluid-mechanical shear stresses and solid compressive strains exerted on the tissue.

Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors.

Liver cells cultured in 3D bioreactors is an interesting option for temporary extracorporeal liver support in the treatment of acute liver failure and for animal models for preclinical drug screening. Bioreactor capacity to eliminate drugs is generally used for assessing cell metabolic competence in different bioreactors or to scale-up bioreactor design and performance for clinical or preclinical applications. However, drug adsorption and physical transport often disguise the intrinsic drug biotransformation kinetics and cell metabolic state. In this study, we characterized the intrinsic kinetics of lidocaine elimination and adsorption by porcine liver cells cultured in 3D four-compartment hollow fiber membrane network perfusion bioreactors. Models of lidocaine transport and biotransformation were used to extract intrinsic kinetic information from response to lidocaine bolus of bioreactor versus adhesion cultures. Different from 2D adhesion cultures, cells in the bioreactors are organized in liver-like aggregates. Adsorption on bioreactor constituents significantly affected lidocaine elimination and was effectively accounted for in kinetic analysis. Lidocaine elimination and cellular monoethylglicinexylidide biotransformation featured first-order kinetics with near-to-in vivo cell-specific capacity that was retained for times suitable for clinical assist and drug screening. Different from 2D cultures, cells in the 3D bioreactors challenged with lidocaine were exposed to close-to-physiological lidocaine and monoethylglicinexylidide concentration profiles. Kinetic analysis suggests bioreactor technology feasibility for preclinical drug screening and patient assist and that drug adsorption should be accounted for to assess cell state in different cultures and when laboratory bioreactor design and performance is scaled-up to clinical use or toxicological drug screening.

Dynamic Characterization of the Biomechanical Behaviour of Bovine Ovarian Cortical Tissue and Its Short-Term Effect on Ovarian Tissue and Follicles.

The ovary is a dynamic mechanoresponsive organ. In vitro, tissue biomechanics was reported to affect follicle activation mainly through the Hippo pathway. Only recently, ovary responsiveness to mechanical signals was exploited for reproductive purposes. Unfortunately, poor characterization of ovarian cortex biomechanics and of the mechanical challenge hampers reproducible and effective treatments, and prevention of tissue damages. In this study the biomechanical response of ovarian cortical tissue from abattoir bovines was characterized for the first time. Ovarian cortical tissue fragments were subjected to uniaxial dynamic testing at frequencies up to 30 Hz, and at increasing average stresses. Tissue structure prior to and after testing was characterized by histology, with established fixation and staining protocols, to assess follicle quality and stage. Tissue properties largely varied with the donor. Bovine ovarian cortical tissue consistently exhibited a nonlinear viscoelastic behavior, with dominant elastic characteristics, in the low range of other reproductive tissues, and significant creep. Strain rate was independent of the applied stress. Histological analysis prior to and after mechanical tests showed that the short-term dynamic mechanical test used for the study did not cause significant tissue tear, nor follicle expulsion or cell damage.

Computational fluid dynamics of a novel perfusion strategy during hybrid thoracic aortic repair.

BACKGROUND AND AIM: To mitigate the risk of perioperative neurological complications during frozen elephant trunk procedures, we aimed to computationally evaluate the effects of direct cerebral perfusion strategy through a left carotid-subclavian bypass on hemodynamics in a patient-specific thoracic aorta model. METHODS: Between July 2016 and March 2019, 11 consecutive patients underwent frozen elephant trunk operation using the left carotid-subclavian bypass with a side graft anastomosis and right-axillary cannulation for systemic and brain perfusion. A multiscale model realized coupling three-dimensional computational fluid dynamics was developed and validated with in vivo data. Model comparison with direct antegrade cannulation of all epiaortic vessels was performed. Wall shear stress, wall shear stress spatial gradient, and localized normalized helicity were selected as hemodynamic indicators. Four cerebral perfusion flows were tested (6 to 15 mL/kg/min). RESULTS: Direct cerebral perfusion of the left subclavian bypass resulted in higher flow rates with augmented speeds in all epiaortic vessels in comparison with traditional perfusion model. At the level of the left vertebral artery (LVA), a speed of 22.5 vs 21 mL/min and mean velocity of 3.07 vs 2.93 cm/s were registered, respectively. With a cerebral perfusion flow of 15 mL/kg, lower LVA wall shear stress (1.596 vs 2.030 N/m2 ), and wall shear stress gradient (1445 vs 5882 N/m3 ) were observed. A less disturbed flow considering the localized normalized helicity was documented. No patients experienced neurological/spinal cord damages. CONCLUSIONS: Direct perfusion of a left carotid bypass proved to be cerebroprotective, resulting in a more physiological and stable anterior and posterior cerebral perfusion.

Model and Application to Support the Coronary Artery Diseases (CAD): Development and Testing.

Cardiovascular diseases are among the main causes of morbidity, disability, and mortality. Most of them occur because of an atherosclerotic plaque developing within a coronary artery, which can cause a narrowing of the vessel lumen (coronary stenosis) or even break it. It is, therefore, useful to evaluate the role of the stress state of the endothelial layer of the arterial tissue, both for the maintenance of the blood circulation and for the implications in presence of a pathology that can lead to thromboembolic complications. The aim of the following study was to develop and test an application that is able to evaluate specific hemodynamic shear stress indicators in coronary arteries at different percentages of stenosis and in different patients' specific conditions. The application, based on Java, allows users to view the results of simulations performed on a coronary anatomy that can be customized with a stenosis of different degrees and positions. Being in possession of a predictive tool for disturbed flow factors may be important for the location and development of atherosclerotic plaque. Moreover, the application can be a valid tool to help in the evaluation of the condition and in the follow-up of the coronary affected by pathology.

Validation of a novel 3D flow model for the optimization of construct perfusion in radial-flow packed-bed bioreactors (rPBBs) for long-bone tissue engineering.

Osteogenic cell culture in three-dimensional (3D) hollow cylindrical porous scaffolds in radial-flow packed-bed bioreactors (rPBBs) may overcome the transport limitations of static and axial perfusion bioreactors in the engineering of long-bone substitutes. Flow models of rPBBs help optimize radial flux distribution of medium and tissue maturation in vitro. Only a 2D model is available for steady flow transport in rPBBs with axisymmetric inlet and outlet accounting for the fluid dynamics of void spaces, assessed against literature information. Here, a novel 3D model is proposed for steady flow transport in the three compartments of rPBBs with a more practical lateral outlet. A 3D model of transient tracer transport was developed based on the flow model to predict bioreactor residence time distribution (RTD). Model-predicted flow patterns were validated in terms of RTD against tracer experiments performed with bioreactor prototypes equipped with commercial scaffolds for bone tissue engineering. Bioreactors were challenged with a step change in entering tracer concentration in an optimized set-up under conditions promoting uniform radial flux distribution and typical shunt flows. Model-predicted RTDs agreed well with those experimentally determined. In conclusion, tracer experiments validate the use of the 3D flow model for optimizing construct perfusion in rPBBs to engineer long-bone substitutes.

On the reliability of measurements for a stent positioning simulation system.

BACKGROUND AND OBJECTIVE: Computer aided simulations are useful to support the physician in many steps of the surgical activity, but also in pre-surgical patient classification and in post-surgical diagnosis and treatment decisions. At a broader level, computerized technologies and infrastructures permeate every aspect of the medical activity, from patient management to surgery and patients' follow up with outcomes analyses. Radiography assisted surgery is often used in hemodynamic surgery to study and support cardio-circulatory stents positioning with the use of radioscopy coupled with contrast liquid injected into the vessels. Computer based surgery instruments (both software and hardware) are used to support clinicians during interventions, e.g., to reduce radioscopy time exposure, to minimize errors and to estimate tissues and organs dimension. In this paper we present the use of a newly developed system which supports physicians during transcatheter percutaneous coronary interventions. METHODS: This paper presents a Java-based tool which acquires images from angiographic equipment during surgery procedures. An high performance image acquisition module has been used and a stent simulation environment module is available to simulate stent positioning and to measure vessels. Operators may acquire images, perform measurements and simulations on DICOM images. We performed tests off-line on images to validate the reliability of the tool. Real cases and on line tests have been performed by operators showing the robustness of the system to be used in surgery room. The system has been integrated in the surgery room control panel and allows (i) vascular images acquisition, (ii) vessels and coronary measurement and (iii) stent positioning simulations. The tool is an aid for the physician for both measuring tissues or lesions and for defining the stent's geometry and position before its deployment in the patient's vessels. RESULTS: Experiments have been performed on lesions and vessels by different operators using the system and an available commercial system, on both real patient cases and synthetic images designed with a CAD. It has been tested on 76 images extracted from real angiography cases and on 11 synthetic images created by using CAD. Five different operators performed 2128 measurements for the real cases images (for both Cartesio and CAAS tools) and 112 for the synthetic dataset. Results show the efficacy of the system compared with the commercial one by means of several statistical tests. CONCLUSIONS: The proposed system is a reliable tool for hemodynamic surgery and can be used both for decision support in stent positioning procedures and for didactic training of new physicians.

The Maximal Pore Size of Hydrophobic Microporous Membranes Does Not Fully Characterize the Resistance to Plasma Breakthrough of Membrane Devices for Extracorporeal Blood Oxygenation.

Extracorporeal membrane oxygenation (ECMO) in blood-outside devices equipped with hydrophobic membranes has become routine treatment of respiratory or cardiac failure. In spite of membrane hydrophobicity, significant amounts of plasma water may form in the gas compartment during treatment, an event termed plasma water breakthrough. When this occurs, plasma water occludes some gas pathways and ultimately cripples the oxygenator gas exchange capacity requiring its substitution. This causes patient hemodilution and increases the activation of the patient's immune system. On these grounds, the resistance to plasma water breakthrough is regarded as an important feature of ECMO devices. Many possible events may explain the occurrence of plasma breakthrough. In spite of this, the resistance to plasma breakthrough of ECMO devices is commercially characterized only with respect to the membrane maximal pore size, evaluated by the bubble pressure method or by SEM analysis of membrane surfaces. The discrepancy between the complexity of the events causing plasma breakthrough in ECMO devices (hence determining their resistance to plasma breakthrough), and that claimed commercially has caused legal suits on the occasion of the purchase of large stocks of ECMO devices by large hospitals or regional institutions. The main aim of this study was to identify some factors that contribute to determining the resistance to plasma breakthrough of ECMO devices, as a means to minimize litigations triggered by an improper definition of the requirements of a clinically efficient ECMO device. The results obtained show that: membrane resistance to breakthrough should be related to the size of the pores inside the membrane wall rather than at its surface; membranes with similar nominal maximal pore size may exhibit pores with significantly different size distribution; membrane pore size distribution rather than the maximal pore size determines membrane resistance to breakthrough; the presence of surfactants in the patient's blood (e.g., lipids, alcohol, etc.) may significantly modify the intrinsic membrane resistance to breakthrough, more so the higher the surfactant concentration. We conclude that the requirements of ECMO devices in terms of resistance to plasma breakthrough ought to account for all these factors and not rely only on membrane maximal pore size.

An Innovative Framework for Bioimage Annotation and Studies.

The collection and analysis of clinical data are needed to investigate diseases and to define medical protocols and treatments. Bioimages, medical annotations and patient history are clinical data acquired and studied to perform a correct diagnosis and to propose an appropriate therapy. Currently, hospital departments manage these data using legacy systems which do not often allow data integration among different departments or health structures. Thus, in many cases clinical information sharing and exchange are difficult to implement. This is also the case for biomedical images for which data integration or data overlapping is usually not available. Image annotations and comparison can be crucial for physicians in many case studies. In this paper, a general purpose framework for bioimage management and annotations is proposed. Moreover, a simple-to-use information system has been developed to integrate clinical and diagnosis codes. The framework allows physicians (1) to integrate DICOM images from different platforms and (2) to report notes and highlights directly on images, thus offering, among the others, to query and compare similar clinical cases. This contribution is the result of a framework aimed to support oncologists in managing DICOM images and clinical data from different departments. Data integration is performed using a here-proposed XML-based module also utilized to trace temporal changes in image annotations.

Influence of IABP-Induced Abdominal Occlusions on Aortic Hemodynamics: A Patient-Specific Computational Evaluation.

Intraaortic balloon pump (IABP) is used as temporary mechanical assistance in case of cardiovascular diseases, even if different hemodynamic problems and, thus, clinical complications may happen, such as the decrease of visceral perfusion. A computational fluid dynamic (CFD) study was carried out to investigate the effects of different IABP-induced abdominal occlusions on patient-specific aortic flow. Two possible sizes (25 and 34 cm) and two locations (2 and 3 cm) of the balloon were compared, modeling four abdominal occlusions and numerically reproducing IAB inflation/deflation behavior. The results highlighted that the perfusion in renal, mesenteric, and iliac arteries decreases when the abdominal occlusion increases with balloon inflation. The study illustrates also how the balloon size affects the flow in aorta vessels in both locations, and that the positioning is of little relevance for the 34 cm balloon, whereas it influences the aortic flow very much in case of 25 cm IAB. This analysis demonstrates how the IAB-induced occlusion may vary the abdominal circulation; therefore, the correct size and positioning are emphasized for patient's outcome.

Computational analysis of aortic hemodynamics during total and partial extracorporeal membrane oxygenation and intra-aortic balloon pump support.

PURPOSE: The extracorporeal membrane oxygenation (ECMO) is a temporary, but prolonged circulatory support for cardiopulmonary failure. Clinical evidence suggests that pulsed flow is healthier than non pulsatile perfusion. The aim of this study was to computationally evaluate the effects of total and partial ECMO assistance and pulsed flow on hemodynamics in a patient-specific aorta model. METHODS: The pulsatility was obtained by means of the intra-aortic balloon pump (IABP), and two different cases were investigated, considering a cardiac output (CO) of 5 L/min: Case A - total assistance - the whole flow delivered through the ECMO arterial cannula; Case B - partial assistance - flow delivered half through the cannula and half through the aorta. Computational fluid dynamic (CFD) analysis was carried out using the multiscale approach to couple the 3D aorta model with the lumped parameter model (resistance boundary condition). RESULTS: In case A pulsatility followed the balloon radius change, while in case B it was mostly influenced by the cardiac one. Furthermore, during total assistance, a blood stagnation occurred in the ascending aorta; in the case of partial assistance, the flow was orderly when the IABP was on and was chaotic when the balloon was off. Moreover, the mean arterial pressure (MAP) was higher in case B. The wall shear stress was worse in ascending aorta in case A. CONCLUSIONS: Partial support is hemodynamically advisable.

Percutaneous Double Lumen Cannula for Right Ventricle Assist Device System: A Computational Fluid Dynamics Study.

OBJECTIVES: Our goal is to develop a double lumen cannula (DLC) for a percutaneous right ventricular assist device (pRVAD) in order to eliminate two open chest surgeries for RVAD installation and removal. The objective of this study was to evaluate the performance, flow pattern, blood hemolysis, and thrombosis potential of the pRVAD DLC. METHODS: Computational fluid dynamics (CFD), using the finite volume method, was performed on the pRVAD DLC. For Reynolds numbers <4000, the laminar model was used to describe the blood flow behavior, while shear-stress transport k-ω model was used for Reynolds numbers >4000. Bench testing with a 27 Fr prototype was performed to validate the CFD calculations. RESULTS: There was <1.3% difference between the CFD and experimental pressure drop results. The Lagrangian approach revealed a low index of hemolysis (0.012% in drainage lumen and 0.0073% in infusion lumen) at 5 l/min flow rate. Blood stagnancy and recirculation regions were found in the CFD analysis, indicating a potential risk for thrombosis. CONCLUSIONS: The pRVAD DLC can handle up to 5 l/min flow with limited potential hemolysis. Further modification of the pRVAD DLC is needed to address blood stagnancy and recirculation.

Computational analysis of stenosis geometry effects on right coronary hemodynamics.

Coronary artery disease (CAD) is one of the most frequent causes of death in western countries. It is characterized by the presence of coronary artery stenosis that can be flow-limiting or susceptible to rupture, triggering intracoronary thrombosis and -consequently- an acute myocardial infarction. For these reasons, hemodynamic alterations associated to the presence of coronary stenosis are of large relevance. Aim of this study was to numerically investigate the effect of stenosis geometry on hemodynamics, comparing three different shapes with an equivalent stenotic lumen. A right coronary artery (RCA) was reconstructed from the angiogram of a patient. Flow pattern analyses were performed using the computational fluid dynamic (CFD) approach, showing that the worst stenosis geometry is the elliptical one, characterized by areas with stasis, multidirectional velocity and high wall shear stress (WSS). On the other hand, the least dangerous stenosis is the parabolic one. However, the strongest predictor of pressure drop is not geometry but the minimal lumen area. In conclusion, while the minimal lumen area is associated to the trans-stenotic pressure drop, stenosis geometry has a significant impact on translesional flow pattern and WSS.

A computational fluid dynamics comparison between different outflow graft anastomosis locations of Left Ventricular Assist Device (LVAD) in a patient-specific aortic model.

Left ventricular assist devices (LVADs) are mechanical supports used in case of heart failure. Little is known as the height of the anastomosis in aorta might influence the hemodynamic. The aim of the study was to evaluate the fluid dynamic behavior due to the outflow graft placement of a continuous flow LVAD in ascending aorta and to identify the insertion site with the best hemodynamic profile. Computational fluid dynamic studies were carried out to analyze 4 different anastomosis locations in a patient-specific aorta 3D model coupled with a lumped parameters model: 1 cm (case 1), 2 cm (case 2), 3 cm (case 3) and 4 cm (case 4) above the ST junction. In cases 1 and 2, epiaortic vessels presented a steady flow, while in cases 3 and 4 the flow was whirling. Moreover, maximum velocity occurred before: brachiocephalic trunk (case 1), brachiocephalic and left carotid arteries (case 2), left carotid and left subclavian artery (case 3) and left subclavian vessel and upper wall of aortic arch (case 4). Maximum time averaged wall shear stress (TAWSS) was located in: the ascending aorta (cases 1 and 2), the inferior curvature of the arch (case 3); at the origin of epiaortic vessels (case 4). Furthermore, a flow recirculation (cases 1 and 2), a blood stagnation and chaotic flow (cases 3 and 4) occurred above the aortic valve. The results suggested that the placement of the outflow graft at 2 cm above the ST junction gave the most favorable hemodynamic profile.

Apicoaortic conduit and cerebral perfusion in mixed aortic valve disease: a computational analysis.

OBJECTIVES: The revival of the apicoaortic conduit has attracted new interest in this alternative treatment for severe aortic stenosis unsuitable for conventional valve replacement. However, doubts still exist about the perfusion of the epiaortic vessels after apicoaortic conduit implantation, especially when severe aortic stenosis is associated with aortic valve insufficiency. The aim of the study was to evaluate the perfusion of the epiaortic vessels (innominate artery, left carotid artery and left subclavian artery) in cases of mixed aortic valve disease before and after apicoaortic conduit implantation. METHODS: Starting from the data of a real patient with severe aortic stenosis and mild aortic insufficiency who underwent apicoaortic conduit implantation, we created a computational model where severe aortic valve stenosis was associated with different grades of aortic insufficiency (mild, medium and moderate). RESULTS: A total of six combinations were analysed. In all simulations, the more severe the concomitant aortic insufficiency, the more the flow through the epiaortic vessels was diminished. After apicoaortic conduit implantation, there was an absolute augmentation of the median output in each epiaortic vessel compared with the same combination of mixed aortic valve disease before implantation. Interestingly, retrograde flow from the conduit in the descending aorta was minimal and did not contribute to the improved output of the epiaortic vessels. CONCLUSIONS: The computational analysis suggested a protective effect, rather than steal phenomenon, of the apicoaortic conduit towards the cerebral perfusion, even in cases of mixed aortic valve disease.

Numerical and experimental flow analysis of the Wang-Zwische double-lumen cannula.

An experimental and numerical analysis was performed for the Wang-Zwische double-lumen cannula (DLC) (Avalon Elite). The aim of this work was to provide insight for future improvement by characterizing the fluid dynamic behavior of the novel catheter with metrics often associated with blood trauma. Pressure and flow distributions were measured on a steady-flow rig using a 50% glycerol-water mixture by imposing a 2 L/min flow rate across the drainage and infusion lumens. The fluid was modeled as Newtonian with density of 1050 kg/m³ and dynamic viscosity of 0.0035 kg/m·s. Reynolds numbers typical for transitional flow (Re = 2000-2500) were computed within the lumens because of the changing cross-sections of the cannula geometry. Numerical computations were performed using the steady three-dimensional Reynolds-averaged Navier-Stokes (RANS) equations and the low-Reynolds k-ω turbulence model. Discretization of governing equations was based on a cell-centered finite volume method. Numerical results correlated well with global performance of the cannula, allowing evaluation of the geometry toward potential blood trauma. Peak wall shear stress (WSS) in the drainage lumen was higher than that of infusion lumen, mainly due to the presence of side holes. Furthermore, recirculation regions were predicted in transition tubing to connectors of both the drainage and the infusion lumens because of adverse pressure gradients caused by the sudden enlargement of the cannula geometry. In this three-dimensional computational fluid dynamics (CFD) study, we observed higher peak WSS values for the drainage lumen, which may potentially cause blood trauma. Furthermore, recirculation regions were predicted in the proximity of the exit sections of both the infusion and drainage lumens, which may contribute to thrombosis formation. This study provides insight for future DLC modifications in minimizing cannula-induced blood trauma and thrombogenicity in long-term applications.