Anatomical compatibility of a novel total artificial heart-An in-silico study.

BACKGROUND: ShuttlePump is a novel total artificial heart (TAH) recently introduced to potentially overcome the limitations associated with the current state-of-the-art mechanical circulatory support devices intended for adults. In this study, we adapted the outflow cannulation of the previously established ShuttlePump TAH and evaluated the anatomical compatibility using the virtual implantation technique. METHODS: We retrospectively assessed the anatomical compatibility of the ShuttlePump using virtual implantation techniques within 3D-reconstructed anatomies of adult heart failure patients. Additionally, we examined the impact of outflow cannula modification on the hemocompatibility of the ShuttlePump through computational fluid dynamic simulations. RESULTS: A successful virtual implantation in 9/11 patients was achieved. However, in 2 patients, pump interaction with the thoracic cage was observed and considered unsuccessful virtual implantation. A strong correlation (r <-0.78) observed between the measured anatomical parameters and the ShuttlePump volume exceeding pericardium highlights the importance of these measurements apart from body surface area. The numerical simulation revealed that the angled outflow cannulation resulted in a maximum pressure drop of 1.8 mmHg higher than that of the straight outflow cannulation. With comparable hemolysis index, the shear stress thresholds of angled outflow differ marginally (<5%) from the established pump model. Similar washout behavior between the pump models indicate that the curvature did not introduce stagnation zone. CONCLUSION: This study demonstrates the anatomic compatibility of the ShuttlePump in patients with biventricular failure, which was achieved by optimizing the outflow cannulation without compromising hemocompatibility. Nevertheless, clinical validation is critical to ensure the clinical applicability of these findings.

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.

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.

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.

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.

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.

Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity.

BACKGROUND: Since autologous veins are unavailable when needed in more than 20% of cases in vascular surgery, the production of personalized biological vascular grafts for implantation has become crucial. Surface modification of decellularized xenogeneic grafts with vascular cells to achieve physiological luminal coverage and eventually thromboresistance is an important prerequisite for implantation. However, ex vivo thrombogenicity testing remains a neglected area in the field of tissue engineering of vascular grafts due to a multifold of reasons. METHODS: After seeding decellularized bovine carotid arteries with human endothelial progenitor cells and umbilical cord-derived mesenchymal stem cells, luminal endothelial cell coverage (LECC) was correlated with glucose and lactate levels on the cell supernatant. Then a closed loop whole blood perfusion system was designed. Recellularized grafts with a LECC > 50% and decellularized vascular grafts were perfused with human whole blood for 2 h. Hemolysis and complete blood count evaluation was performed on an hourly basis, followed by histological and immunohistochemical analysis. RESULTS: While whole blood perfusion of decellularized grafts significantly reduced platelet counts, platelet depletion from blood resulting from binding to re-endothelialized grafts was insignificant (p = 0.7284). Moreover, macroscopic evaluation revealed thrombus formation only in the lumen of unseeded grafts and histological characterization revealed lack of CD41 positive platelets in recellularized grafts, thus confirming their thromboresistance. CONCLUSION: In the present study we were able to demonstrate the effect of surface modification of vascular grafts in their thromboresistance in an ex vivo whole blood perfusion system. To our knowledge, this is the first study to expose engineered vascular grafts to human whole blood, recirculating at high flow rates, immediately after seeding.

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.

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.

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.

A Valveless Pulsatile Pump for Heart Failure with Preserved Ejection Fraction: Hemo- and Fluid Dynamic Feasibility.

Treatment of heart failure with preserved ejection fraction (HFpEF) remains a major unmet medical need. An implantable valveless pulsatile pump with a single cannula-the CoPulse pump-may provide beneficial hemodynamic support for select HFpEF patients when connected to the failing ventricle. We aimed to demonstrate hemodynamic efficacy and hemocompatible design feasibility for this novel assist device. The hemodynamic effect of the pump was investigated with an in vitro circulatory mock loop and an ex vivo isolated porcine heart model. The hydraulic design was optimized using computational fluid dynamics (CFD), and validated by 4D-flow magnetic resonance imaging (MRI). The pump reduced left atrial pressure (> 27%) and increased cardiac output (> 14%) in vitro. Ex vivo experiments revealed elevated total stroke volume at increased end-systolic volume during pump support. Asymmetric cannula positioning indicated superior washout, decreased stagnation (8.06 mm2 vs. 31.42 mm2), and marginal blood trauma potential with moderate shear stresses (< 24 Pa) in silico. Good agreement in flow velocities was evident among CFD and 4D-flow MRI data (r > 0.76). The CoPulse pump proved hemodynamically effective. Hemocompatibility metrics were comparable to those of a previously reported, typical pulsatile pump with two cannulae. The encouraging in vitro, ex vivo, and hemocompatibility results substantiate further development of the CoPulse pump.

User-dependent variability in mitral valve segmentation and its impact on CFD-computed hemodynamic parameters.

PURPOSE: While novel tools for segmentation of the mitral valve are often based on automatic image processing, they mostly require manual interaction by a proficient user. Those segmentations are essential for numerical support of mitral valve treatment using computational fluid dynamics, where the reconstructed geometry is incorporated into a simulation domain. To quantify the uncertainty and reliability of hemodynamic simulations, it is crucial to examine the influence of user-dependent variability in valve segmentation. METHODS: Previously, the inter-user variability of landmarks in mitral valve segmentation was investigated. Here, the inter-user variability of geometric parameters of the mitral valve, projected orifice area (OA) and projected annulus area (AA), is investigated for 10 mitral valve geometries, each segmented by three users. Furthermore, the propagation of those variations into numerically calculated hemodynamics, i.e., the blood flow velocity, was investigated. RESULTS: Among the three geometric valve parameters, AA was least user-dependent. Almost all deviations to the mean were below 10%. Larger variations were observed for OA. Variations observed for the numerically calculated hemodynamics were in the same order of magnitude as those of geometric parameters. No correlation between variation of geometric parameters and variation of calculated hemodynamic parameters was found. CONCLUSION: Errors introduced due to the user-dependency were of the same size as the variations of calculated hemodynamics. The variation was thereby of the same scale as deviations in clinical measurements of blood flow velocity using Doppler echocardiography. Since no correlation between geometric and hemodynamic uncertainty was found, further investigation of the complex relationship between anatomy, leaflet shape and flow is necessary.

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.

Noninvasive assessment of blood pressure in rotary blood pump recipients using a novel ultrasonic Doppler method.

In rotary blood pump recipients with low blood pressure pulsatility, current oscillometric methods to measure blood pressure are not applicable. The aim of this study was to use ultrasonic Doppler flow measurements to determine blood pressure in this patient population noninvasively. In 28 rotary blood pump recipients, blood pressure was measured three times with the developed Doppler method and compared to the invasive arterial line (n = 15) or to the oscillometric Terumo Elemano BP monitor (n = 13). Blood velocities in the radial artery were recorded by the new Doppler sensor during cuff deflation. A sigmoid curve was fitted to a preprocessed velocity signal and the systolic and mean arterial pressures were determined. A total of 84 measurements were performed, and 17 recordings were visually excluded from further analysis due to obvious artifacts. Both the systolic and mean pressures derived by the Doppler method were in good accordance with the invasively measured pressure (3.7 ± 6.6 mmHg for the systolic and -2.1 ± 7.3 mmHg for the mean pressure). A good agreement between the oscillometric monitor and the Doppler method for the systolic (0.0 ± 6.0 mmHg) and mean (1.0 ± 5.9 mmHg) pressures was observed. In this study, a new Doppler blood pressure measurement system was developed and clinically validated. The novel sensor allows easier placement above the radial artery compared to commercial probes. An algorithm was developed which processes the Doppler signal robustly and is able to determine the systolic as well as the mean arterial blood pressure.