An energy-dissipation-based power-law formulation for estimating hemolysis.

Hemolysis is a major concern in blood-circulating devices, which arises due to non-physiological stresses on red blood cells from ambient flow environment or moving mechanical structures. Computational fluid dynamics (CFD) and empirical hemolysis prediction models have been increasingly used for the design and optimization of blood-circulating devices. The commonly used power-law models for hemolysis prediction often use Reynolds stress to represent effective stress, tend to over-predict hemolysis and fail to capture trends of flow-related hemolysis. This study proposed a new power-law formulation for the numerical hemolysis prediction. The new formulation related hemolysis to the energy dissipation rate, which could be readily obtained from CFD simulations. The model constants were regressed from existing hemolysis data. The new formulation was tested for three benchmark cases and compared to conventional power-law models. The results showed that the new formulation improved prediction of hemolysis for a broad range of flow regimes. The deviations of the predicted hemolysis from experimental results were within one order, and better correlated with experimental results. This study confirmed that Reynolds stress is the main cause of over-prediction of hemolysis for conventional power-law models. Proportionally, the blood damage predicted with Reynolds stresses is more than one order higher than viscous stress, in terms of energy dissipation.

Crucial Aspects for Using Computational Fluid Dynamics as a Predictive Evaluation Tool for Blood Pumps.

The suitability of computational fluid dynamics (CFD) as a regulatory tool for safety assessment of medical devices is still limited: A lack of standardized validation and evaluation methods impairs the quantitative comparability and reliability of simulation studies, particularly regarding the assessment of hemocompatibility. This study investigated important aspects of validation and verification for three common turbulence modeling approaches (laminar, k-ω shear stress transport [SST] and stress-blended eddy simulation [SBES]) and three different mesh refinements. Simulation results for pressure head, characteristic velocity, and shear stress for the benchmark blood pump model of the Food and Drug Administration critical path initiative were compared with its published experimental results. For the highest mesh resolution, all three models predicted the hydraulic pump characteristics with a relative deviation averaged over six operating conditions below 6.1%. In addition, the SBES model showed an accurate agreement of the characteristic velocity field in the pump's diffusor region (relative error <2.9%), while the laminar and SST model calculated significantly elevated and deviating velocity amplitudes (>43.6%). The ability to quantify shear stress is fundamental for the prediction of blood damage. In this respect, this study demonstrated that: 1) a close agreement and validation of both pressure head and characteristic velocity was feasible and 2) the shear stress quantification demanded higher near-wall mesh resolutions, although such high resolutions were not required for the validation of only pressure heads or velocity. Hence, a mesh verification analysis for shear stresses may prove significant for the development of credible CFD blood damage predictions in the future.

Mesh Sensitivity Analysis for Quantitative Shear Stress Assessment in Blood Pumps Using Computational Fluid Dynamics.

The reduction of excessive, nonphysiologic shear stresses leading to blood trauma can be the key to overcome many of the associated complications in blood recirculating devices. In that regard, computational fluid dynamics (CFD) are gaining in importance for the hydraulic and hemocompatibility assessment. Still, direct hemolysis assessments with CFD remain inaccurate and limited to qualitative comparisons rather than quantitative predictions. An underestimated quantity for improved blood damage prediction accuracy is the influence of near-wall mesh resolution on shear stress quantification in regions of complex flows. This study investigated the necessary mesh refinement to quantify shear stress for two selected, meshing sensitive hotspots within a rotary centrifugal blood pump (the blade leading edge and tip clearance gap). The shear stress in these regions is elevated due to presence of stagnation points and the flow around a sharp edge. The nondimensional mesh characteristic number y+, which is known in the context of turbulence modeling, underestimated the maximum wall shear stress by 60% on average with the recommended value of 1, but was found to be exact below 0.1. To evaluate the meshing related error on the numerical hemolysis prediction, three-dimensional simulations of a generic centrifugal pump were performed with mesh sizes from 3 × 106 to 30 × 106 elements. The respective hemolysis was calculated using an Eulerian scalar transport model. Mesh insensitivity was found below a maximum y+ of 0.2 necessitating 18 × 106 mesh elements. A meshing related error of up to 25% was found for the coarser meshes. Further investigations need to address: (1) the transferability to other geometries and (2) potential adaptions on blood damage estimation models to allow better quantitative predictions.

On the Accuracy of Hemolysis Models in Couette-Type Blood Shearing Devices.

Hemolysis is one of the most challenging issues faced by blood contacting devices. Empirical hemolysis models often relate hemolysis to shear stress and exposure time. These models were generally derived from the experimental results of Couette-type blood shearing devices, with assumption of uniform exposure time and shear stress. This assumption is not strictly valid since neither exposure time nor shear stress is uniform. Hence, this study evaluated the influence of the nonuniform exposure time and rotor eccentricity or run-out on the accuracy of power-law hemolysis models, using both theoretical and CFD analysis. This work first provided a systematic analysis of the flow regime in a typical Couette shearing device, and showed the axial flow component can be regarded as fully developed laminar plane Poiseuille flow. It was found that the influence of nonuniform exposure time is within 4% for several widely used power-law models, which were validated by steady CFD simulations. A theoretical relationship was then built between the rotor run-out and hemolysis. We noticed that the influence of rotor run-out on hemolysis is within 5% for a moderate rotor run-out ratio of 0.2. Next, transient CFD simulations were performed to investigate the influence of rotor run-out on hemolysis with run-out ratios of 0.1 and 0.2. The results showed negligible effects for a moderate run-out ratio of 0.1. However, a run-out ratio of 0.2 led to a significant increase of hemolysis, resulting from back flows induced by the run-out of the rotor. These findings will be of great importance for the improvement of the hemolysis estimation and blood compatibility design.

In-Series Versus In-Parallel Mechanical Circulatory Support for the Right Heart: A Simulation Study.

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end-stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long-term valve complications. We are developing an in-series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in-series (sRVAD) and in-parallel (pRVAD) (right atrium-pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in-series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in-parallel support.

Hydraulic and hemodynamic performance of a minimally invasive intra-arterial right ventricular assist device.

Right ventricular assistance is still in the early phase of development compared to left ventricular assist device (LVAD) technology. In order to provide flexible pulmonary support and potentially reduce the known complications, we propose a minimally invasive right ventricular assist device (MIRVAD), located in the pulmonary artery (PA) and operating in series with the right ventricle (RV). The MIRVAD is an intra-arterial rotary blood pump containing a single axial impeller, which is not enclosed by a rigid housing but stent-fixed within the vessel. The impeller geometry has been designed with the assistance of analytical methods and computational fluid dynamics (CFD). The hydraulic performance of the impeller was evaluated experimentally with a customized test setup using blood synthetic medium (HES). The blade-tip clearance (BTC) was varied between 0.25-4.25 mm to evaluate the effect of different PA sizes on impeller performance. Furthermore, the Langrangian particle-tracking method was used to estimate the level of hemolysis and generate numerical blood damage indexes.The impeller design generated 25.6 mmHg for flow rates of 5 lpm at a speed of 6,000 rpm at the baseline condition, capable of providing sufficient support for the RV. The BTC presented a significant effect on the static pressure generation and the efficiency, but the operational range is suitable for most vessel sizes. The numerical results demonstrated a low risk of blood damage at the design point (mean Lagrangian damage index 2.6*10(-7)). The preliminary results have encouraged further impeller optimization and development of the MIRVAD.

Hemolysis in a laminar flow-through Couette shearing device: an experimental study.

Reducing hemolysis has been one of the major goals of rotary blood pump development and in the investigational phase, the capability of hemolysis estimation for areas of elevated shear stresses is valuable. The degree of hemolysis is determined by the amplitude of shear stress and the exposure time, but to date, the exact hemolytic behavior at elevated shear stresses and potential thresholds for subcritical shear exposure remain vague. This study provides experimental hemolysis data for a set of shear stresses and exposure times to allow better estimations of hemolysis for blood exposed to elevated shearing. Heparinized porcine blood with a hematocrit of 40% was mechanically damaged in a flow-through laminar Couette shear flow at a temperature of 23°C. Four levels of shear stress, 24, 592, 702, and 842 Pa, were replicated at two exposure times, 54 and 873 ms. For the calculation of the shear stresses, an apparent viscosity of 5 mPas was used, which was verified in an additional measurement of the blood viscosity. The hemolysis measurements were repeated four times, whereby all conditions were measured once within the same day and with blood from the same source. Samples were taken at the inlet and outlet of the shear region and an increase in plasma-free hemoglobin was measured. An index of hemolysis (IH) was thereby calculated giving the ratio of free to total hemoglobin. The results are compared with data from previously published studies using a similar shearing device. Hemolysis was found to increase exponentially with shear stress, but high standard deviations existed at measurements with elevated IH. At short exposure times, the IH remained low at under 0.5% for all shear stress levels. For high exposure times, the IH increased from 0.84% at 592 Pa up to 3.57% at the highest shear stress level. Hemolysis was significant for shear stresses above ∼600 Pa at the high exposure time of 873 ms.

Experimental and analytical performance evaluation of short circular hydrodynamic journal bearings used in rotary blood pumps.

Rotary blood pumps (RBPs) have demonstrated considerable promise while treating heart failure patients, such that they are being placed at an earlier stage of the disease. These devices may therefore be required to operate for prolonged durations which yields the need for RBPs exhibiting high durability, reliability, and blood compatibility. Noncontacting bearings, utilizing magnetic and/or hydrodynamic suspension techniques, appear to provide a suitable solution to these challenges. Hydrodynamic suspension has the advantage that it does not need feedback control systems. Among various hydrodynamic bearing types, the circular journal bearing has the particular benefit of easy manufacturing. This study presents methods to evaluate the performance of short (length to diameter ratio <1) circular hydrodynamic journal bearings (HJBs) for RBPs. Analytical calculations with specific boundary conditions are presented to predict the rotor's eccentricity under equilibrium states and thus the related performance parameters such as load capacity, power loss, and shear rates. These results and boundary conditions were confirmed experimentally in a specially designed test set-up. The bearing performance was found to correlate to analytical solutions using the full Sommerfeld boundary condition instead of the half Sommerfeld condition conventionally used for such applications. Geometrical and operational parameter variations showed that HJB designs with a short Sommerfeld Number SS >0.02 can provide sufficient fluid film thicknesses and low shear rates. The measurements were further used to evaluate the bearings' stability. The estimation of the stability threshold drawn in relation to a modified stability index and the equilibrium eccentricity of the rotor allows the prediction of stability for short circular HJB designs under full Sommerfeld condition.

Evaluation of hydraulic radial forces on the impeller by the volute in a centrifugal rotary blood pump.

In many state-of-the-art rotary blood pumps for long-term ventricular assistance, the impeller is suspended within the casing by magnetic or hydrodynamic means. For the design of such suspension systems, profound knowledge of the acting forces on the impeller is crucial. Hydrodynamic bearings running at low clearance gaps can yield increased blood damage and magnetic bearings counteracting high forces consume excessive power. Most current rotary blood pump devices with contactless bearings are centrifugal pumps that incorporate a radial diffuser volute where hydraulic forces on the impeller develop. The yielding radial forces are highly dependent on impeller design, operating point and volute design. There are three basic types of volute design--singular, circular, and double volute. In this study, the hydraulic radial forces on the impeller created by the volute in an investigational centrifugal blood pump are evaluated and discussed with regard to the choice of contactless suspension systems. Each volute type was tested experimentally in a centrifugal pump test setup at various rotational speeds and flow rates. For the pump's design point at 5 L/min and 2500 rpm, the single volute had the lowest radial force (∼0 N), the circular volute yielded the highest force (∼2 N), and the double volute possessed a force of approx. 0.5 N. Results of radial force magnitude and direction were obtained and compared with a previously performed computational fluid dynamics (CFD) study.

Tuning adhesion failure strength for tissue-specific applications.

Soft tissue adhesives are employed to repair and seal many different organs, which range in both tissue surface chemistry and mechanical challenges during organ function. This complexity motivates the development of tunable adhesive materials with high resistance to uniaxial or multiaxial loads dictated by a specific organ environment. Co-polymeric hydrogels comprising aminated star polyethylene glycol and dextran aldehyde (PEG:dextran) are materials exhibiting physico-chemical properties that can be modified to achieve this organ- and tissue-specific adhesion performance. Here we report that resistance to failure under specific loading conditions, as well as tissue response at the adhesive material-tissue interface, can be modulated through regulation of the number and density of adhesive aldehyde groups. We find that atomic force microscopy (AFM) can characterize the material aldehyde density available for tissue interaction, and in this way enable rapid, informed material choice. Further, the correlation between AFM quantification of nanoscale unbinding forces with macroscale measurements of adhesion strength by uniaxial tension or multiaxial burst pressure allows the design of materials with specific cohesion and adhesion strengths. However, failure strength alone does not predict optimal in vivo reactivity. Thus, we demonstrate that the development of adhesive materials is significantly enabled when experiments are integrated along length scales to consider organ chemistry and mechanical loading states concurrently with adhesive material properties and tissue response.

Viscoelastic adhesive mechanics of aldehyde-mediated soft tissue sealants.

Soft tissue sealants generally sacrifice adhesive strength for biocompatibility, motivating the development of materials which interact with tissue to a predictable and controllable extent. Crosslinked hydrogels comprising aminated star polyethylene glycol and high molecular weight dextran aldehyde polymers (PEG:dextran) display aldehyde-mediated adhesion and readily tunable reactivity with soft tissue ex-vivo. Evaluation of PEG:dextran compositional variants revealed that the burst pressure of repaired intestinal wounds and the extent of material-induced tissue deformation both increase nonlinearly with formulation aldehyde content and are consistently within the desired range established by traditional sealants. Adhesive test elements featuring PEG:dextran and intestinal tissue exhibited considerable viscoelasticity, prompting use of a standard linear solid (SLS) model to describe adhesive mechanics. Model elements were accurately represented as continuous functions of PEG:dextran chemistry, facilitating prediction of adhesive mechanics across the examined range of compositional formulations. SLS models of traditional sealants were also constructed to allow general correlative analyses between viscoelastic adhesive mechanics and metrics of sealant performance. Linear correlation of equilibrium SLS stiffness to sealant-induced tissue deformation indicates that dense adhesive crosslinking restricts tissue expansion, while correlation of instantaneous SLS stiffness to burst pressure suggests that the adhesive stress relaxation capacity of PEG:dextran enhances their overall performance relative to traditional sealants.