Experimental validation of the power law hemolysis model using a Couette shearing device.

BACKGROUND: The study of blood trauma, such as hemolysis in blood-carrying devices, is crucial due to the high incidence of adverse events like alteration of blood function, bleeding, and multi-organ failure. The extent of flow-induced hemolysis, predominantly influenced by stress duration and intensity, is described by established model parameters based on the power law approach. In recent years, various parameters were determined using different Couette shearing devices and donor species. However, they have not been validated due to limited experimental data. METHODS: This study provides hemolysis measurements in a Couette shearing device and evaluates the suitability of different power law parameters. The revised Couette shearing device generates well-defined dynamic stress loads that are repeatedly applied to blood samples at a defined temperature. Human blood samples with an adjusted hematocrit of 30%, were tested with varying repetitions (20 to 80 times). The half-sinusoidal stress loads had amplitudes of 73 to 140 Pa and exposure times of 24 msec per repetition. The parameters of five common power law hemolysis approaches were then compared with the experimental data. RESULTS: The prediction with the power law model parameters C = 3.458 × 10-6, α = 0.2777 and ß = 2.0639 showed a good agreement with the experimental results. CONCLUSION: The effect of multiple short-time stresses on hemolysis was investigated to validate the power law hemolysis model with the Couette shearing device of this study.

Novel measurement system for respiratory aerosols and droplets in indoor environments.

The SARS-CoV-2 pandemic has created a great demand for a better understanding of the spread of viruses in indoor environments. A novel measurement system consisting of one portable aerosol-emitting mannequin (emitter) and a number of portable aerosol-absorbing mannequins (recipients) was developed that can measure the spread of aerosols and droplets that potentially contain infectious viruses. The emission of the virus from a human is simulated by using tracer particles solved in water. The recipients inhale the aerosols and droplets and quantify the level of solved tracer particles in their artificial lungs simultaneously over time. The mobile system can be arranged in a large variety of spreading scenarios in indoor environments and allows for quantification of the infection probability due to airborne virus spreading. This study shows the accuracy of the new measurement system and its ability to compare aerosol reduction measures such as regular ventilation or the use of a room air purifier.

Teburu-Open source 3D printable bioreactor for tissue slices as dynamic three-dimensional cell culture models.

Three-dimensional tissue cultures are important models for the study of cell-cell and cell-matrix interactions, as well as, to investigate tissue repair and reconstruction pathways. Therefore, we designed a reproducible and easy to handle printable bioreactor system (Teburu), that is applicable for different approaches of pathway investigation and targeted tissue repair using human tissue slices as a three-dimensional cell culture model. Here, we definitively describe Teburu as a controlled environment to reseed a 500-µm thick decellularized human liver slice using human mesenchymal stroma cells. During a cultivation period of eight days, Teburu, as a semi-open and low consumption system, was capable to maintain steady pH and oxygenation levels. Its combination with additional modules delivers an applicability for a wide range of tissue engineering approaches under optimal culture conditions.

Experimental and Numerical Investigation of an Axial Rotary Blood Pump.

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near-wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds-averaged Navier-Stokes simulations-computational fluid dynamics (URANS-CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall-particle image velocimetry technique, and the visualization of near-wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS-CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.

MRI-based computational fluid dynamics for diagnosis and treatment prediction: clinical validation study in patients with coarctation of aorta.

PURPOSE: To reduce the need for diagnostic catheterization and optimize treatment in a variety of congenital heart diseases, magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) is proposed. However, data about the accuracy of CFD in a clinical context are still sparse. To fill this gap, this study compares MRI-based CFD to catheterization in the coarctation of aorta (CoA) setting. MATERIALS AND METHODS: Thirteen patients with CoA were investigated by routine MRI prior to catheterization. 3D whole-heart MRI was used to reconstruct geometries and 4D flow-sensitive phase-contrast MRI was used to acquire flows. Peak systolic flows were simulated using the program FLUENT. RESULTS: Peak systolic pressure drops in CoA measured by catheterization and CFD correlated significantly for both pre- and posttreatment measurements (pre: r = 0.98, p = 0.00; post: r = 0.87, p = 0.00). The pretreatment bias was -0.5 ± 3.33 mmHg (95% confidence interval -2.55 to 1.47 mmHg). CFD predicted a reduction of the peak systolic pressure drop after treatment that ranged from 17.6 ± 5.56 mmHg to 6.7 ± 5.58 mmHg. The posttreatment bias was 3.0 ± 2.91 mmHg (95% CI -1.74 to 5.43 mmHg). CONCLUSION: Peak systolic pressure drops can be reliably calculated using MRI-based CFD in a clinical setting. Therefore, CFD might be an attractive noninvasive alternative to diagnostic catheterization.

Numerical Analysis of Blood Damage Potential of the HeartMate II and HeartWare HVAD Rotary Blood Pumps.

Implantable left ventricular assist devices (LVADs) became the therapy of choice in treating end-stage heart failure. Although survival improved substantially and is similar in currently clinically implanted LVADs HeartMate II (HM II) and HeartWare HVAD, complications related to blood trauma are frequently observed. The aim of this study was to compare these two pumps regarding their potential blood trauma employing computational fluid dynamics. High-resolution structured grids were generated for the pumps. Newtonian flow was calculated, solving Reynolds-averaged Navier-Stokes equations with a sliding mesh approach and a k-ω shear stress transport turbulence model for the operating point of 4.5 L/min and 80 mm Hg. The pumps were compared in terms of volumes subjected to certain viscous shear stress thresholds, below which no trauma was assumed (von Willebrand factor cleavage: 9 Pa, platelet activation: 50 Pa, and hemolysis: 150 Pa), and associated residence times. Additionally, a hemolysis index was calculated based on a Eulerian transport approach. Twenty-two percent of larger volumes above 9 Pa were observed in the HVAD; above 50 Pa and 150 Pa the differences between the two pumps were marginal. Residence times were higher in the HVAD for all thresholds. The hemolysis index was almost equal for the HM II and HVAD. Besides the gap regions in both pumps, the inlet regions of the rotor and diffuser blades have a high hemolysis production in the HM II, whereas in the HVAD, the volute tongue is an additional site for hemolysis production. Thus, in this study, the comparison of the HM II and the HVAD using numerical methods indicated an overall similar tendency to blood trauma in both pumps. However, influences of turbulent shear stresses were not considered and effects of the pivot bearing in the HM II were not taken into account. Further in vitro investigations are required.

Influence of titanium surface roughness on a nanoscale on the zeta potential and platelet adhesion.

Thromboembolic complications still arise on blood contacting surfaces. Surface charge and topography influence the subsequent deposition of proteins and platelets, potentially leading to thrombi. Research showed a correlation of surface charge and nanoscale roughness, and a negative surface charge as well as a smooth surface finish are associated with lower thrombogenicity. The aim of this study was to compare the platelet adhesion on titanium with different nanoscale roughnesses and to examine if those roughness variations caused a change in surface charge. Titanium samples were polished and roughened to four different nanoscale roughness levels. Platelet adhesion (covered surface area (CSA), N = 8) was tested in flow chambers with human whole blood using fluorescence imaging. ζ-potential was measured over a broad range of pH-values and interpolated to obtain the ζ-potential for pHBlood (7.4). Platelet adhesion tests were evaluated in terms of p-values and the Wilcoxon test effect size and the trend of the ζ-potential at pHBlood and the CSA was compared. Ra-values ranged between 35 (polished) and 156 nm. Regarding platelet adhesion, the polished sample showed the lowest mean CSA with a medium or strong effect size compared to the roughened samples. The interpolated ζ-potentials for pHBlood follow a similar trend as the CSA, with the lowest ζ-potential measured for the polished surface. These findings suggest that the decreasing ζ-potential due to lower nanoscale roughness might be an additional explanation for the improved hemocompatibility besides the smoother topography.

A Novel Pumping Principle for a Total Artificial Heart.

OBJECTIVE: Total artificial hearts (TAH) serve as a temporary treatment for severe biventricular heart failure. The limited durability and complication rates of current devices hamper long-term cardiac replacement. The aim of this study was to assess the feasibility of a novel valveless pumping principle for a durable pulsatile TAH (ShuttlePump). METHODS: The pump features a rotating and linearly shuttling piston within a cylindrical housing with two in- and outlets. With a single moving piston, the ShuttlePump delivers pulsatile flow to both systemic and pulmonary circulation. The pump and actuation system were designed iteratively based on analytical and in silico methods, utilizing finite element methods (FEM) and computational fluid dynamics (CFD). Pump characteristics were evaluated experimentally in a mock circulation loop mimicking the cardiovascular system, while hemocompatibility-related parameters were calculated numerically. RESULTS: Pump characteristics cover the entire required operating range for a TAH, providing 2.5-9 L/min of flow rate against 50-160 mmHg arterial pressures at stroke frequencies of 1.5-5 Hz while balancing left and right atrial pressures. FEM analysis showed mean overall copper losses of 8.84 W, resulting in a local maximum blood temperature rise of <2 K. The CFD results of the normalized index of hemolysis were 3.57 mg/100 L, and 95% of the pump's blood volume was exchanged after 1.42 s. CONCLUSION AND SIGNIFICANCE: This study indicates the feasibility of a novel pumping system for a TAH with numerical and experimental results substantiating further development of the ShuttlePump.

An Atraumatic Mock Loop for Realistic Hemocompatibility Assessment of Blood Pumps.

OBJECTIVE: Conventional mock circulatory loops (MCLs) cannot replicate realistic hemodynamic conditions without inducing blood trauma. This constrains in-vitro hemocompatibility examinations of blood pumps to static test loops that do not mimic clinical scenarios. This study aimed at developing an atraumatic MCL based on a hardware-in-the-loop concept (H-MCL) for realistic hemocompatibility assessment. METHODS: The H-MCL was designed for 450 ± 50 ml of blood with the polycarbonate reservoirs, the silicone/polyvinyl-chloride tubing, and the blood pump under investigation as the sole blood-contacting components. To account for inherent coupling effects a decoupling pressure control was derived by feedback linearization, whereas the level control was addressed by an optimization task to overcome periodic loss of controllability. The HeartMate 3 was showcased to evaluate the H-MCL's accuracy at typical hemodynamic conditions. To verify the atraumatic properties of the H-MCL, hemolysis (bovine blood, n = 6) was evaluated using the H-MCL in both inactive (static) and active (minor pulsatility) mode, and compared to results achieved in conventional loops. RESULTS: Typical hemodynamic scenarios were replicated with marginal coupling effects and root mean square error (RMSE) below 1.74 ± 1.37 mmHg while the fluid level remained within ±4% of its target value. The normalized indices of hemolysis (NIH) for the inactive H-MCL showed no significant differences to conventional loops ( ∆NIH = -1.6 mg/100 L). Further, no significant difference was evident between the active and inactive mode in the H-MCL ( ∆NIH = +0.3 mg/100 L). CONCLUSION AND SIGNIFICANCE: Collectively, these findings indicated the H-MCL's potential for in-vitro hemocompatibility assessment of blood pumps within realistic hemodynamic conditions, eliminating inherent setup-related risks for blood trauma.

The concept of rhinorespiratory homeostasis--a new approach to nasal breathing.

The suggested concept of rhinorespiratory homeostasis is a new theoretical model for the discussion of physiologic and physical principles of nasal breathing. This model is based on a comprehensive view of nasal functions that takes comparative animal physiology into account. Consequently, it has a universal cross-species character and emphasizes the central role of nasal secretion. In contrast to the established view, the focus is transferred from the inspired air to the nasal wall. This concept considers the parietal effect of airflow represented by wall shear stress with special regard to the epithelial lining fluid. It delivers one possible mechanism of an inherent triggering of the nasal cycle. Furthermore, the issue of biological fluid-structure interaction is introduced. This article presents a rethinking of nasal breathing that was inspired by clinical experience and results of flow field investigations through computational fluid dynamics.

In-Vitro Flow Validation of Third-Generation Ventricular Assist Devices: Feasibility and Challenges.

Computational fluid dynamics (CFD) is a powerful tool for the in-silico evaluation of rotodynamic blood pumps (RBPs). Corresponding validation, however, is typically restricted to easily accessible, global flow quantities. This study showcased the HeartMate 3 (HM3) to identify feasibility and challenges of enhanced in-vitro validation in third-generation RBPs. To enable high-precision acquisition of impeller torques and grant access for optical flow measurements, the HM3 testbench geometry was geometrically modified. These modifications were reproduced in silico , and global flow computations validated along 15 operating conditions. The globally validated flow in the testbench geometry was compared with CFD-simulated flows in the original geometry to assess the impact of the necessary modifications on global and local hydraulic properties. Global hydraulic properties in the testbench geometry were successfully validated (pressure head: r = 0.999, root mean square error [RMSE] = 2.92 mmHg; torque: r = 0.996, RMSE = 0.134 mNm). In-silico comparison with the original geometry demonstrated good agreement ( r > 0.999, relative errors < 11.97%) of global hydraulic properties. Local hydraulic properties (errors up to 81.78%) and hemocopatibility predictions (deviations up to 21.03%), however, were substantially affected by the geometric modifications. Transferability of local flow measures derived on advanced in-vitro testbenches toward original pump designs is challenged by significant local effects associated with the necessary geometrical modifications.

Feasibility of an Animal Model for Cavopulmonary Support With a Double-Outflow Pump.

Both single- and double-outflow cavopulmonary assist devices (CPADs) were recently proposed for the Fontan population, whereas single-outflow configurations were evaluated in large animal trials and double-outflow concepts are lacking an equivalent in vivo assessment. The aim of this study was to test the hemodynamic properties of a double-outflow CPAD device in an acute sheep model. The two inflow cannulae of a CPAD were anastomosed to the caval veins. Outflow graft connection was performed via end-to-side anastomosis to the right (RPA) and main pulmonary artery (MPA). Speed ramp protocols were conducted, and hemodynamic effects were monitored in terms of caval flows, cardiac output (CO), central venous pressure (CVP), pulmonary artery pressure (PAP), and left atrial pressure (LAP). Six experiments were conducted (53.35 ± 5.1 kg). In three experiments, the animal model was established, the CPAD was examined, and restoration of biventricular equivalency in terms of venous return was achieved. Venous pressures (CVP) declined linearly with increasing pump speed (r > 0.879), whereas caval flow (r > 0.973), CO (r > 0.993), PAP (r > 0.973), and LAP (r > 0.408) increased. Despite the considerable complexity of the sheep model caused by the sheep pulmonary arterial anatomy that requires substantial graft bending, the CPAD was evaluated in three acute experiments and showed the potential to completely substitute a subpulmonary ventricle.

Eight-channel SiNx microring-resonator based photonic biosensor for label-free fluid analysis in the optical C-band.

A lab-on-a-chip multichannel sensing platform for biomedical analysis based on optical silicon nitride (SiNx) microring-resonators (MRR) was established. The resonators were surface functionalized and finally combined with a microfluidic chamber for validation using an avidin-biotin ligand-binding assay. The results with a limit of detection (LOD) of 2.3∙10-5 and a mean intra-assay coefficient of variation (CV) of ±10.0 %, also under consideration of FDA guidelines, show promising future applicability for a wide variety of targets in the field of outpatient medical diagnostics and life science.Clinical Relevance- Biomarkers play a crucial role in physiological processes of the human body. To enable instantaneous and decentralized analysis of these markers, systems are needed that can be used in a laboratory-independent environment with minimal amounts of biofluid. An example is the utilization of such systems for neonates or infants.

Tri-leaflet valve design with a purge flow for heart-assist devices: an in vitro optimization study.

The objective of this study is to assess the effect of a purge flow on valves of pulsatile heart-assist devices. Clinical applications of these devices are still limited because of frequent thromboembolic complications. These complications often originate at the valves and the unavoidable flow separation regions that are found behind the leaflets. The flow separations cause a long residence time of blood that is considered particularly detrimental. To solve this problem, a valve with a purge flow is proposed. A purge flow is a jet, which is separated from the main blood flow and directed behind the leaflets into the sinus to flush it. Even though the purge flow does not prevent a flow separation, it shortens the residence time of the blood in the sinus. Thus, the purge flow improves the periodic washout of the blood in the region of flow separation. The complex purge flow was investigated in a tri-leaflet valve. The geometrical parameters of the valve were varied systematically. A statistical technique--the Taguchi method--was used to reduce the number of investigated models to 12. The flows through the resulting valve models were numerically simulated and analyzed. The evaluated models with the best results were subsequently investigated experimentally using different methods: hemodynamic tests in a valve tester and flow visualization using the dye washout method. It was shown that the purge flow can effectively wash out the sinus. Therefore, the purge flow valve reduces the potential of a thrombus formation normally associated with the valve.

Verification of a Novel Minimally Invasive Device for the Isolation of Rare Circulating Tumor Cells (CTC) in Cancer Patients' Blood.

Circulating tumor cells (CTCs) exist in low quantities in the bloodstream in the early stages of cancers. It, therefore, remains a technical challenge to isolate them in large enough quantities for a precise diagnosis and downstream analysis. We introduce the BMProbe™, a minimally invasive device that isolates CTCs during a 30-minute incubation in the median cubital vein. The optimized geometry of the device creates flow conditions for improved cell deposition. The CTCs are isolated using antibodies that are bound to the surface of the BMProbe™. In this study, flow experiments using cell culture cells were conducted. They indicate a 31 times greater cell binding efficiency of the BMProbe™ compared to a flat geometry. Further, the functionality of isolating CTCs from patient blood was verified in a small ex vivo study that compared the cell count from seven non-small-cell lung carcinoma (NSCLC) patients compared to nine healthy controls with 10 mL blood samples. The median cell count was 1 in NSCLC patients and 0 in healthy controls. In conclusion, the BMProbe™ is a promising method to isolate CTCs in large quantities directly from the venous bloodstream without removing blood from a patient. The future step is to verify the functionality in vivo.

Hemolytic Footprint of Rotodynamic Blood Pumps.

OBJECTIVE: In preclinical examinations, rotodynamic blood pumps (RBPs) are predominantly evaluated at design-point conditions. In clinical practice, however, they run at diversified modes of operation. This study aimed at extending current preclinical evaluation of hemolytic profiles in RBPs toward broader, clinically relevant ranges of operation. METHODS: Two implantable RBPs - the HeartMate 3 (HM3) and the HeartWare Ventricular Assist Device (HVAD) - were analyzed at three pump speeds (HM3: 4300, 5600, 7000 rpm; HVAD: 1800, 2760, 3600 rpm) with three flow rates (1-9L/min) per speed setting. Hemolysis measurements were performed in heparinized bovine blood. The delta free hemoglobin (dfHb) and the normalized index of hemolysis (NIH) served as hemolytic measures. Statistical analysis was performed by multiple comparison of the 9 operating conditions. Moreover, computational fluid dynamics (CFD) was applied to provide mechanistic insights into the interrelation between hydraulics and hemolysis by correlating numerically computed hydraulic losses with in-vitro hemolytic measures. RESULTS: In both devices, dfHb increased toward increasing speeds, particularly during low but also during high flow condition. By contrast, in both RBPs magnitudes of NIH were significantly elevated during low flow operation compared to high flow conditions (p<0.0036). Maps of hemolytic metrics revealed morphologically similar trends to in-silico hydraulic losses (r>0.793). CONCLUSIONS: While off-design operation is associated with increased hemolytic profiles, the setting of different operating conditions render a preclinical prediction of clinical impact with current hemolysis metrics difficult. SIGNIFICANCE: The identified increase in hemolytic measures during episodes of off-design operation is highlighting the need to consider worst-case operation during preclinical examinations.

A Cavopulmonary Assist Device for Long-Term Therapy of Fontan Patients.

Treatment of univentricular hearts remains restricted to palliative surgical corrections (Fontan pathway). The established Fontan circulation lacks a subpulmonary pressure source and is commonly accompanied by progressively declining hemodynamics. A novel cavopulmonary assist device (CPAD) may hold the potential for improved therapeutic management of Fontan patients by chronic restoration of biventricular equivalency. This study aimed at translating clinical objectives toward a functional CPAD with preclinical proof regarding hydraulic performance, hemocompatibility and electric power consumption. A prototype composed of hemocompatible titanium components, ceramic bearings, electric motors, and corresponding drive unit was manufactured for preclinical benchtop analysis: hydraulic performance in general and hemocompatibility characteristics in particular were analyzed in-silico (computational fluid dynamics) and validated in-vitro. The CPAD's power consumption was recorded across the entire operational range. The CPAD delivered pressure step-ups across a comprehensive operational range (0-10 L/min, 0-50 mm Hg) with electric power consumption below 1.5 W within the main operating range. In-vitro hemolysis experiments (N = 3) indicated a normalized index of hemolysis of 3.8 ± 1.6 mg/100 L during design point operation (2500 rpm, 4 L/min). Preclinical investigations revealed the CPAD's potential for low traumatic and thrombogenic support of a heterogeneous Fontan population (pediatric and adult) with potentially accompanying secondary disorders (e.g., elevated pulmonary vascular resistance or systemic ventricular insufficiency) at distinct physical activities. The low power consumption implied adequate settings for a small, fully implantable system with transcutaneous energy transfer. The successful preclinical proof provides the rationale for acute and chronic in-vivo trials aiming at the confirmation of laboratory findings and verification of hemodynamic benefit.

How can we achieve infection-resistant percutaneous energy transfer?

Clinical records show ever increasing functional times of rotary blood pumps implanted in patients. With longer functional time, the problem of driveline infection is becoming more urgent. No material or scaffold has been found, which allows a permanent and stable ingrowth of skin cells that would prevent (pathogenic) germs entering the body. Usually, the epithelial cells die at the exit site and new cells form a sulcus around the driveline, which grows deeper and finally becomes infected. The purpose of this project is to present a solution to this problem by elaborating a new mechanism, the active skin-penetrating device. The device is composed of a tube with a 5-mm diameter, a protective sleeve that surrounds the catheter exit site, and an active traction device. The protective sleeve is made of thin polyurethane covered with polyethylenterephtalat (PET, i.e. Dacron) fibers to permit the attachment of keratinocytes, similar to the standard driveline. The active traction device exerts a constant pull on the protective sleeve. The ingrown keratinocytes slowly give way and the protective sleeve gradually moves out of the body at a rate of a few millimeters per week. Meanwhile, the keratinocytes transform into horny cells and are then shed as in natural skin. Therefore, the formation of a sulcus is avoided, and the protective sleeve remains infection-free. In a first proof of the concept, four of the new devices and 10 control devices were implanted in goats. The devices remained infection-free for a period of 420 days, whereas four of the 10 control devices became infected. On the basis of these experiments, the active skin-penetrating device has been further developed and is being tested again in goats in a refined version. The results so far indicate that with the active-skin penetrating device an infection-resistant percutaneous energy transfer can be achieved for a prolonged period of time.

Validation of Numerically Predicted Shear Stress-dependent Dissipative Losses Within a Rotary Blood Pump.

Computational fluid dynamics find widespread application in the development of rotary blood pumps (RBPs). Yet, corresponding simulations rely on shear stress computations that are afflicted with limited resolution while lacking validation. This study aimed at the experimental validation of integral hydraulic properties to analyze global shear stress resolution across the operational range of a novel RBP. Pressure head and impeller torque were numerically predicted based on Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations and validated on a testbench with integrated sensor modalities (flow, pressure, and torque). Validation was performed by linear regression and Bland-Altman analysis across nine operating conditions. In power loss analysis (PLA), in silico hydraulic power losses were derived based on the validated hydraulic quantities and balanced with in silico shear-dependent dissipative power losses. Discrepancies among both terms provided a measure of in silico shear stress resolution. In silico and in vitro data correlated with low discordance in pressure (r = 0.992, RMSE = 1.02 mmHg), torque (r = 0.999, RMSE = 0.034 mNm), and hydraulic power losses (r = 0.990, RMSE = 0.015W). PLA revealed numerically predicted dissipative losses to be up to 34.4% smaller than validated computations of hydraulic losses. This study confirmed the suitability of URANS settings to predict integral hydraulic properties. However, numerical credibility was hampered by lacking resolution of shear-dependent dissipative losses.

Bacterial biofilms in infective endocarditis: an in vitro model to investigate emerging technologies of antimicrobial cardiovascular device coatings.

OBJECTIVE: In spite of the progress in antimicrobial and surgical therapy, infective endocarditis (IE) is still associated with a high morbidity and mortality. IE is characterized by bacterial biofilms of the endocardium, especially of the aortic and mitral valve leading to their destruction. About one quarter of patients with formal surgery indication cannot undergo surgery. This group of patients needs further options of therapy, but due to a lack of models for IE prospects of research are low. Therefore, the purpose of this project was to establish an in vitro model of infective endocarditis to allow growth of bacterial biofilms on porcine aortic valves, serving as baseline for further research. METHODS AND RESULTS: A pulsatile two-chamber circulation model was constructed that kept native porcine aortic valves under sterile, physiologic hemodynamic and temperature conditions. To create biofilms on porcine aortic valves the system was inoculated with Staphylococcus epidermidis PIA 8400. Aortic roots were incubated in the model for increasing periods of time (24 h and 40 h) and bacterial titration (1.5 × 104 CFU/mL and 1.5 × 105 CFU/mL) with 5 L cardiac output per minute. After incubation, tissue sections were analysed by fluorescence in situ hybridization (FISH) for direct visualization of the biofilms. Pilot tests for biofilm growth showed monospecies colonization consisting of cocci with time- and inocula-dependent increase after 24 h and 40 h (n = 4). In n = 3 experiments for 24 h, with the same inocula, FISH visualized biofilms with ribosome-containing, and thus metabolic active cocci, tissue infiltration and similar colonization pattern as observed by the FISH in human IE heart valves infected by S. epidermidis. CONCLUSION: These results demonstrate the establishment of a novel in vitro model for bacterial biofilm growth on porcine aortic roots mimicking IE. The model will allow to identify predilection sites of valves for bacterial adhesion and biofilm growth and it may serve as baseline for further research on IE therapy and prevention, e.g. the development of antimicrobial transcatheter approaches to IE.