A Systematic Review of the Design, Method of Implantation and Early Clinical Outcomes of Transcatheter Tricuspid Prostheses.

Background: Intervention for tricuspid regurgitation (TR) tends to happen concurrently with and is addressed during mitral valve surgery. Isolated TR interventions, however, are not unusual and are becoming more common. The purpose of this study was to provide a general overview of the transcatheter tricuspid valve implantation (TTVI) devices, taking into account the several design variations, and to unify the implantation technique, existing clinical results, and potential future directions for TR replacement therapy. Methods: The major databases, namely Pubmed via Medline, Embase, and Cochrane library, were systematically searched from the date of conception until 10 February 2023, in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Results: Eleven studies were isolated from a total cohort of 5842 publications. All the transcatheter tricuspid prostheses were circular in design yet categorized into annular tricuspid valve implantation (ATVI) and caval valve implantation (CAVI) groups. Bleeding (25.2%), severe access site and vascular issues requiring intervention (5.8%), device migration or embolization (3.6%), and paravalvular leak (38%) are among the early TTVI-related complications that have been observed. The CAVI group experienced 3 of 28 bleeding cases and 2 of 4 device migration cases. Conclusions: Following the intervention with a transcatheter tricuspid prosthesis, this review discovered an early favorable outcome and a general improvement in heart failure symptoms. However, there was a lot of variation in their design, implantation technique, and early clinical outcomes. Understanding the design variations, difficulty of implantation and learning from this review's key findings could help with the future development of catheter-based tricuspid valves. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022312142.

A model-driven approach towards rational microbial bioprocess optimization.

Due to sustainability concerns, bio-based production capitalizing on microbes as cell factories is in demand to synthesize valuable products. Nevertheless, the nonhomogenous variations of the extracellular environment in bioprocesses often challenge the biomass growth and the bioproduction yield. To enable a more rational bioprocess optimization, we have established a model-driven approach that systematically integrates experiments with modeling, executed from flask to bioreactor scale, and using ferulic acid to vanillin bioconversion as a case study. The impacts of mass transfer and aeration on the biomass growth and bioproduction performances were examined using minimal small-scale experiments. An integrated model coupling the cell factory kinetics with the three-dimensional computational hydrodynamics of bioreactor was developed to better capture the spatiotemporal distributions of bioproduction. Full-factorial predictions were then performed to identify the desired operating conditions. A bioconversion yield of 94% was achieved, which is one of the highest for recombinant Escherichia coli using ferulic acid as the precursor.

An in vitro investigation into the hemodynamic effects of orifice geometry and position on left ventricular vortex formation and turbulence intensity.

In a healthy human cardiac system, a large asymmetric clockwise vortex present in the left ventricle (LV) efficiently diverts the filling jet from the mitral annulus to the left ventricular outflow track. However, prior clinical studies have shown that artificial mitral valve replacement can affect the formation of physiological vortex, resulting in overall flow instability in the LV. Lately, the findings from several recent hemodynamic studies seem to suggest that the native D-shaped mitral annulus might be a crucial factor in the development of this physiological flow pattern, with its inherent flow stability and formation of coherent structures within the LV. This study aims to investigate the effect of orifice shape and its position with respect to the posterior wall of the ventricle on vortical formation and turbulence intensity in the LV, by utilizing four separate orifice configurations within an in vitro left heart simulator. Stereo particle image velocimetry experiments were then carried out to characterize the downstream flow field of each configuration. Our findings demonstrate that the generation of the physiological left ventricular vortical flow was not solely dependent upon the orifice shape but rather the subsequent jet-wall interaction. The distance of the orifice geometric center from the left ventricular posterior wall plays a significant role in this jet-wall interaction, and thus, vortical flow dynamics.

Computational Fluid Dynamics Modeling of Hemodynamic Parameters in the Human Diseased Aorta: A Systematic Review.

BACKGROUND: The analysis of the correlation between blood flow and aortic pathology through computational fluid dynamics (CFD) shows promise in predicting disease progression, the effect of operative intervention, and guiding patient treatment. However, to date, there has not been a comprehensive systematic review of the published literature describing CFD in aortic diseases and their treatment. METHODS: This review includes 136 published articles which have investigated the application of CFD in all types of aortic disease (aneurysms, dissections, and coarctation). We took into account case studies of both, treated or untreated pathology, investigated with CFD. We also graded all studies using an author-defined Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach based on the validation method used for the CFD results. RESULTS: There are no randomized controlled trials assessing the efficacy of CFD as applied to aortic pathology, treated or untreated. Although a large number of observational studies are available, those using clinical imaging tools as independent validation of the calculated CFD results exist in far smaller numbers. Only 21% of all studies used clinical imaging as a tool to validate the CFD results and these were graded as high-quality studies. CONCLUSIONS: Contemporary evidence shows that CFD can provide additional hemodynamic parameters such as wall shear stress, vorticity, disturbed laminar flow, and recirculation regions in untreated and treated aortic disease. These have the potential to predict the progression of aortic disease, the effect of operative intervention, and ultimately help guide the choice and timing of treatment to the benefit of patients and clinicians alike.

Bioresorbable Polymeric Scaffold in Cardiovascular Applications.

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6-8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript.

Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.

The deteriorating nature of severe functional tricuspid regurgitation (FTR) has led to the heightened interest in this pathology. However, therapies are heterogeneous and an ideal technique is uncertain. The hemodynamic impact on the cardiac chamber following therapeutic repairs has not been well studied, while its analysis could be used to predict the treatment success. In this study, the hemodynamics of the right ventricle (RV) after 1) clover edge-to-edge tricuspid repair, and 2) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in a more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Postrepair RV domain was mostly occupied with irregular vortical features and isolated vortex residuals. Moreover, vortical features varied among repair samples, indicating enhanced sensitivity of RV flow to postrepair TV morphology. Compared with clover repair, double orifice subjected the RV to enhanced swirling motions and exposed more regions to vortical motions, potentially indicating better rinsing and lower risk of mural thrombus formation. Double orifice repair increased the levels of RV mean kinetic energy and viscous energy loss than those observed in clover repair, although the impact of these on the cardiac efficiency remains unclear. These preliminary insights could be used to improve future treatment design and planning.NEW & NOTEWORTHY While clover and double orifice tricuspid repairs markedly improved leaflet coaptation, they substantially reduced diastolic tricuspid opening area. Postrepair right ventricle (RV) exhibited specific hemodynamic traits, including the loss of ring-shaped vortical structure and the enhanced sensitivity of RV flow to postrepair tricuspid valve morphology. Compared with clover technique, double orifice repair led to higher swirling motions in the RV domain, which could indicate lower risk of mural thrombus formation.

Human fetal hearts with tetralogy of Fallot have altered fluid dynamics and forces.

Studies have suggested the effect of blood flow forces in pathogenesis and progression of some congenital heart malformations. It is therefore of interest to study the fluid mechanic environment of the malformed prenatal heart, such as the tetralogy of Fallot (TOF), especially when little is known about fetal TOF. In this study, we performed patient-specific ultrasound-based flow simulations of three TOF and seven normal human fetal hearts. TOF right ventricles (RVs) had smaller end-diastolic volumes (EDVs) but similar stroke volumes (SVs), whereas TOF left ventricles (LVs) had similar EDVs but slightly increased SVs compared with normal ventricles. Simulations showed that TOF ventricles had elevated systolic intraventricular pressure gradient (IVPG) and required additional energy for ejection but IVPG elevations were considered to be mild relative to arterial pressure. TOF RVs and LVs had similar pressures because of equalization via ventricular septal defect (VSD). Furthermore, relative to normal, TOF RVs had increased diastolic wall shear stresses (WSS) but TOF LVs were not. This was caused by high tricuspid inflow that exceeded RV SV, leading to right-to-left shunting and chaotic flow with enhanced vorticity interaction with the wall to elevate WSS. Two of the three TOF RVs but none of the LVs had increased thickness. As pressure elevations were mild, we hypothesized that pressure and WSS elevation could play a role in the RV thickening, among other causative factors. Finally, the endocardium surrounding the VSD consistently experienced high WSS because of RV-to-LV flow shunt and high flow rate through the over-riding aorta. NEW & NOTEWORTHY Blood flow forces are thought to cause congenital heart malformations and influence disease progression. We performed novel investigations of intracardiac fluid mechanics of tetralogy of Fallot (TOF) human fetal hearts and found essential differences from normal hearts. The TOF right ventricle (RV) and left ventricle had similar and elevated pressure but only the TOF RV had elevated wall shear stress because of elevated tricuspid inflow, and this may contribute to the observed RV thickening. TOF hearts also expended more energy for ejection.

Is Multiple Overlapping Uncovered Stents Technique Suitable for Aortic Aneurysm Repair?

A computational fluid dynamic model to assess the impact of flow-diverter device on intra-aneurysmal flow in complex aortic aneurysm from the viewpoint of hemodynamics is presented. The aim of this study is to investigate the hemodynamic effects of an endovascular flow-diverter technique using multiple overlapping uncovered stents (MOUS) in the treatment of complex aortic aneurysm involving side branch. The placement of porous barrier such as MOUS across the aneurysm alters the blood flow pattern in the aneurysm sac. Subsequently, flow diversion effect creates a natural hemodynamic environment to promote aneurysm thrombosis, thus stabilizing the aneurysm. The study revealed that intra-aneurysmal flow was reduced and low time average wall shear stress (TAWSS), high relative residence time (RRT), and high oscillatory shear index (OSI) regions were observed in the aneurysm sac. Three to four MOUS stents produced the best hemodynamic environment for the formation of thrombus, with saccular aneurysm performing better than fusiform aneurysm from the viewpoint of hemodynamics. A result also revealed that flow in the branch vessel was not compromised suggesting the capacity of preserving patency of branch vessels while at the same time stabilizing the aneurysm. Based on the hemodynamic performance of this study coupled with existing reported clinical studies, deploying three to four MOUS stents is a feasible solution to treat aneurysm with side branch, favorably for saccular shape aneurysm.

Design and Development of Novel Transcatheter Bicaval Valves in the Interventional Treatment of Tricuspid Regurgitation.

The concept of heterotopic implantation of transcatheter tricuspid valve is new and has shown promising results thus far. While the Reynolds shear stress values measured in the vicinity of this valve are relatively low, the values at some time points are higher than the threshold of platelet activation. Hence, in this study, we aim to reduce these values with an innovative stent design. It was shown that the Reynolds shear stress values measured were lower than those of valves made of generic stent design and the maximum Reynolds shear stress values in the vicinity of the valves was very low (∼10 dynes/cm2 ). The results also depicted the interesting flow phenomenon of this non-physiological treatment approach. Thus, this study has shown that bicaval valves could potentially be considered as a minimally invasive option to treat tricuspid regurgitation and valve design improvements could reduce the flow disturbances that were observed.

A pump-free microfluidic 3D perfusion platform for the efficient differentiation of human hepatocyte-like cells.

The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs). The device contains a micropillar array to immobilize cells three-dimensionally in a central cell culture compartment flanked by two side perfusion channels. Constant pump-free medium perfusion is accomplished by controlling the differential heights of horizontally orientated inlet and outlet media reservoirs. Computational fluid dynamic simulation is used to estimate the hydrostatic pressure heads required to achieve different perfusion flow rates, which are experimentally validated by micro-particle image velocimetry, as well as viability and functional assessments in a primary rat hepatocyte model. We perform on-chip differentiation of HepaRG, a human bipotent progenitor cell, and discover that 3D microperfusion greatly enhances the hepatocyte differentiation efficiency over static 2D and 3D cultures. However, HepaRG progenitor cells are highly sensitive to the time-point at which microperfusion is applied. Isolated HepaRG cells that are primed as static 3D spheroids before being subjected to microperfusion yield a significantly higher proportion of HLCs (92%) than direct microperfusion of isolated HepaRG cells (62%). This platform potentially offers a simple and efficient means to develop highly functional microfluidic liver models incorporating human stem cell-derived HLCs. Biotechnol. Bioeng. 2017;114: 2360-2370. © 2017 Wiley Periodicals, Inc.

Simulated Bench Testing to Evaluate the Mechanical Performance of New Carotid Stents.

Our group recently developed a novel covered carotid stent that can prevent emboli while preserving the external carotid artery (ECA) branch blood flow. However, our recent in vitro side-branch ECA flow preservation tests on the covered stents revealed the need for further stent frame design improvements, including the consideration to crimp the stent to a low profile for the delivery of the stent system and having bigger cells. Hence, the current work aims to design new bare metal stents with bigger cell size to improve the crimpability and to accommodate more slits so that the side-branch flow could be further increased. Three new stent designs were analyzed using finite element analysis and benchmarked against two commercially available carotid stents in terms of their mechanical performances such as crimpability, radial strength, and flexibility. Results indicated that the new bare metal stent designs matched well against the commercial stents. Hence our new generation covered stents based on these designs can be expected to perform better in side-branch flow preservation without compromising on their mechanical performances.

Symmetry recovery of cell-free layer after bifurcations of small arterioles in reduced flow conditions: effect of RBC aggregation.

Heterogeneous distribution of red blood cells (RBCs) in downstream vessels of arteriolar bifurcations can be promoted by an asymmetric formation of cell-free layer (CFL) in upstream vessels. Consequently, the CFL widths in subsequent downstream vessels become an important determinant for tissue oxygenation (O2) and vascular tone change by varying nitric oxide (NO) availability. To extend our previous understanding on the formation of CFL in arteriolar bifurcations, this study investigated the formation of CFL widths from 2 to 6 vessel-diameter (2D-6D) downstream of arteriolar bifurcations in the rat cremaster muscle (D = 51.5 ± 1.3 µm). As the CFL widths are highly influenced by RBC aggregation, the degree of aggregation was adjusted to simulate levels seen during physiological and pathological states. Our in vivo experimental results showed that the asymmetry of CFL widths persists along downstream vessels up to 6D from the bifurcating point. Moreover, elevated levels of RBC aggregation appeared to retard the recovery of CFL width symmetry. The required length of complete symmetry recovery was estimated to be greater than 11D under reduced flow conditions, which is relatively longer than interbifurcation distances of arterioles for vessel diameter of ∼50 µm. In addition, our numerical prediction showed that the persistent asymmetry of CFL widths could potentially result in a heterogeneous vasoactivity over the entire arteriolar network in such abnormal flow conditions.

Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans.

There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts.

Effects of Microporous Stent Graft on the Descending Aortic Aneurysm: A Patient-Specific Computational Fluid Dynamics Study.

Thoracic endovascular aortic repair (TEVAR) method is an alternative treatment for thoracic aortic aneurysm (TAA) compared to open surgery. It is believed that stent graft implantation can potentially reduce the risk of aneurysm rupture by altering the associated blood flow disturbances within an aneurysm. To investigate the hemodynamics changes of TEVAR intervention to the TAA, three models, namely healthy, aneurysm before treatment, and aneurysm after stent graft implantation models were built. These three models were presented and compared in terms of their flow patterns, time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and relative residence time (RRT). Reduced TAWSS and OSI with altered flow pattern were found on the aneurysm wall after the deployment of the microporous stent graft. Elevated RRT on the aneurysm sac indicated that red blood cells and platelets tended to stay longer in the aneurysm sac after implantation of the microporous stent graft. The alteration of flow patterns caused by the microporous stent graft revealed its potential to create a beneficial hemodynamic environment, which promotes platelet activation within the aneurysm and elicits localization of thrombus formation that ultimately lead to the recovery of an aortic aneurysm.

Covered Stent Membrane Design for Treatment of Atheroembolic Disease at Carotid Artery Bifurcation and Prevention of Thromboembolic Stroke: An In Vitro Experimental Study.

In this study, a polymeric membrane has been designed and developed for carotid stents to prevent detachment of emboli from the arterial wall and subsequent stroke, while maintaining side-branch flow. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition in a life-size silicone anastomotic model of carotid artery bifurcation. These evaluations include both quantitative and qualitative experimental (in vitro) assessments of emboli prevention capability, side-branch flow preservation, and flow visualization. The covered stents with the novel membrane demonstrated significantly higher emboli prevention capability than the corresponding bare nitinol stent as well as some earlier related designs, while preserving more than 93% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation or retrograde flow that might predispose the vessel wall to intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis and prevention of late embolic stroke. However, further in vivo investigations of biological effects and mechanical performance of this covered stent design (e.g., its thrombogenicity potential and biocompatibility) are warranted.

Biomimetic Precapillary Flow Patterns for Enhancing Blood Plasma Separation: A Preliminary Study.

In this study, a biomimetic microfluidic plasma separation device is discussed. The design of the device drew inspiration from in vivo observations of enhanced cell-free layer (CFL) formation downstream of vascular bifurcations. The working principle for the plasma separation was based on the plasma skimming effect in an arteriolar bifurcation, which is modulated by CFL formation. The enhancement of the CFL width was achieved by a local hematocrit reduction near the collection channel by creating an uneven hematocrit distribution at the bifurcation of the channel. The device demonstrated a high purity of separation (~99.9%) at physiological levels of hematocrit (~40%).

Computational Hemodynamic Investigation of Bileaflet and Trileaflet Mechanical Heart Valves.

BACKGROUND AND AIM OF THE STUDY: The trileaflet heart valve is a more desirable mechanical heart valve due to its similarity to native heart valves, which produce a central blood flow with decreased blood flow disturbance. There are, however, many challenges and difficulties in designing a trileaflet valve, mainly due to a greater number of moving mechanical parts. METHODS: The flow profiles through a bileaflet mechanical heart valve (BMHV) and a trileaflet mechanical heart valve (TMHV) were compared at downstream regions. Geometric models of a 29 mm St. Jude Medical BMHV and a TMHV were used and positioned at the anatomic position in a curved aortic downstream geometry. Three-dimensional numerical simulations for both types of mechanical heart valve were performed under normal physiological pulsatile flow conditions. Flow profiles were studied under three different implantation locations at Z = 1D (D = 29 mm inlet diameter), 2D and 4D along the aorta centerline during peak systole. RESULTS: The simulation results showed different flow fields at the downstream positions at Z = 1D and 2D. The leaflets of the BMHV obstructed the flow, while the TMHV allowed a central orifice flow which resulted in a more physiological flow profile. Further downstream, at Z = 4D, the flow fields shared similarities in terms of the flow profile and velocity magnitude. CONCLUSION: The findings of this study may help to further improve the development of the TMHV.

In Vitro Investigation of the Hemodynamics of Transcatheter Heterotopic Valves Implantation in the Cavo-Atrial Junction.

Severe tricuspid regurgitation (TR) is life-threatening but is often undertreated. Many patients with severe TR are denied heart valve replacement surgery because their old age or comorbidities predispose them to a higher risk of surgical complications associated with open-heart surgery. With the advent of transcatheter technology, it is now possible to deliver the valve to the desired location without the need for open-heart surgery. However, presently, there is no commercially available transcatheter tricuspid valve. This may be due to the complex tricuspid valve anatomy, which lacks an anchorage zone for the percutaneous valves. In view of this drawback, we have recently developed and tested two percutaneous caval heart valves that are designed to deploy at the vena cava and atrium junction. The hemodynamic characteristics of these valves are tested in a mock circulatory system with patient-specific silicone atrium and vena cava, which emulates the physiological pressure and flow conditions at the right side of the human heart. Particle imaging velocimetry results showed that flow velocity and the associated Reynolds shear stress (RSS) and the turbulent kinetic energy (TKE) downstream of the valves increased after the implantation of the valves. A maximum flow velocity of 0.94 m/s was observed at the region downstream of the percutaneous valve at the superior vena cava (SVC). Maximum RSS value of 2076.1 dynes/cm(2) was observed downstream of the valve at the inferior vena cava during the deceleration phase while maximum TKE measured was 572.6 J/m(3) at the upstream of the valve in the SVC during the peak flow phase. While these values appear high, they are significantly lower than those reported in prosthetic mitral and aortic valves. Hence, caval stented valves can be potentially considered as a minimally invasive option to treat TR.

Computational fluid model incorporating liver metabolic activities in perfusion bioreactor.

The importance of in vitro hepatotoxicity testing during early stages of drug development in the pharmaceutical industry demands effective bioreactor models with optimized conditions. While perfusion bioreactors have been proven to enhance mass transfer and liver specific functions over a long period of culture, the flow-induced shear stress has less desirable effects on the hepatocytes liver-specific functions. In this paper, a two-dimensional human liver hepatocellular carcinoma (HepG2) cell culture flow model, under a specified flow rate of 0.03 mL/min, was investigated. Besides computing the distribution of shear stresses acting on the surface of the cell culture, our numerical model also investigated the cell culture metabolic functions such as the oxygen consumption, glucose consumption, glutamine consumption, and ammonia production to provide a fuller analysis of the interaction among the various metabolites within the cell culture. The computed albumin production of our 2D flow model was verified by the experimental HepG2 culture results obtained over 3 days of culture. The results showed good agreement between our experimental data and numerical predictions with corresponding cumulative albumin production of 2.9 × 10(-5) and 3.0 × 10(-5) mol/m(3) , respectively. The results are of importance in making rational design choices for development of future bioreactors with more complex geometries.

Two-dimensional strain-hardening membrane model for large deformation behavior of multiple red blood cells in high shear conditions.

BACKGROUND: Computational modeling of Red Blood Cell (RBC) flow contributes to the fundamental understanding of microhemodynamics and microcirculation. In order to construct theoretical RBC models, experimental studies on single RBC mechanics have presented a material description for RBC membranes based on their membrane shear, bending and area moduli. These properties have been directly employed in 3D continuum models of RBCs but practical flow analysis with 3D models have been limited by their computationally expensive nature. As such, various researchers have employed 2D models to efficiently and qualitatively study microvessel flows. Currently, the representation of RBC dynamics using 2D models is a limited methodology that breaks down at high shear rates due to excessive and unrealistic stretching. METHODS: We propose a localized scaling of the 2D elastic moduli such that it increases with RBC local membrane strain, thereby accounting for effects such as the Poisson effect and membrane local area incompressibility lost in the 2D simplification. Validation of our 2D Large Deformation (2D-LD) RBC model was achieved by comparing the predicted RBC deformation against the 3D model from literature for the case of a single RBC in simple shear flow under various shear rates (dimensionless shear rate G = 0.05, 0.1, 0.2, 0.5). The multi-cell flow of RBCs (38% Hematocrit) in a 20 µm width microchannel under varying shear rates (50, 150, 150 s-1) was then simulated with our proposed model and the popularly-employed 2D neo-Hookean model in order to evaluate the efficacy of our proposed 2D-LD model. RESULTS: The validation set indicated similar RBC deformation for both the 2D-LD and the 3D models across the studied shear rates, highlighting the robustness of our model. The multi-cell simulation indicated that the 2D neo-Hookean model predicts noodle-like RBC shapes at high shear rates (G = 0.5) whereas our 2D-LD model maintains sensible RBC deformations. CONCLUSION: The ability of the 2D-LD model to limit RBC strain even at high shear rates enables this proposed model to be employed in practical simulations of high shear rate microfluidic flows such as blood separation channels.