The reduction of blood damage is still a big challenge in blood-carrying medical devices. In vitro experiments are performed to investigate the damage-causing effects, but due to the opaqueness of ...blood cells, only near-wall flows can be observed. Thus, several transparent blood models to visualize the rheologic behavior of blood have been proposed and examined. Nevertheless, two-phase blood models with added particles still represent the properties of blood inadequately or are very expensive and complex to produce. In this in vitro study, the viscosity, the flow behavior and the cell deformation of human red blood cells have been compared to a novel, easy-to-produce, two-phase blood model fluid with deformable alginate microspheres. The comparison has been performed in a cone-plate rheometer, a straight and a hyperbolic converging microchannel. The viscosity of the blood model fluid with a particle fraction of 30% showed a shear-thinning behavior, comparable to that of blood at room and human body temperature within shear rates from 7 to
2000
s
-
1
. The alginate microspheres were deformable in an extensional flow and formed a cell free layer comparable to that of blood in a straight microchannel. The experiments showed a good optical accessibility of the two-phase flow with traceable movements of individual microspheres in the center of the microchannel. It could be shown that our proposed blood model fluid is a promising tool for the analysis of two-phase flows in complex flow geometries.
Graphical Abstract
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.
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 mm
2
vs. 31.42 mm
2
), 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.
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 × 10
4
CFU/mL and 1.5 × 10
5
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.
Graphic abstract
OBJECTIVES:To analyze alveolar dynamics in healthy and acid-injured lungs of ventilated mice. Protective ventilation is potentially lifesaving in patients with acute lung injury. However, ...optimization of ventilation strategies is hampered by an incomplete understanding of the effects of mechanical ventilation at the alveolar level.
DESIGN:In anesthetized and ventilated Balb/c mice, subpleural alveoli were visualized by darkfield intravital microscopy and optical coherence tomography.
SETTING:Animal research laboratory.
SUBJECTS:Male Balb/c mice.
INTERVENTIONS:Lung injury was induced by intratracheal instillation of hydrochloric acid. In control animals and mice with lung injury, ventilation pressures were varied between 0 and 24 cm H2O at baseline, 60 mins, and 120 mins, and alveolar distension and cyclic opening and collapse of alveolar clusters were analyzed.
MEASUREMENTS AND MAIN RESULTS:In normal lungs, alveolar clusters distend with increasing ventilation pressure in a sigmoid relationship. Although an increase in ventilation pressure from 0 to 24 cm H2O increases alveolar size by 41.5 ± 2.3% in normal lungs, alveolar distension is reduced to 20.6 ± 2.2% 120 mins after induction of lung injury by acid aspiration. Cyclic opening and collapse of alveolar clusters are neither observed in normal nor acid-injured lungs. Alveolar compliance is highest in small and distensible alveolar clusters, which are also most prone to acid-induced injury.
CONCLUSIONS:Over the applied pressure range, volume changes in control and acid-injured mouse lungs result predominantly from alveolar distension rather than cyclic opening and collapse of alveolar clusters. Preferential loss of compliance in small alveolar clusters redistributes tidal volume to larger alveoli, which increases spatial heterogeneity in alveolar inflation and may promote alveolar overdistension.
The formation of thrombi is still a challenge when it comes to ventricular assist devices (VADs). This can be caused by the subsequent deposition of proteins and platelets on foreign surfaces. In ...VADs, the blood contacting components are mainly made of titanium alloys due to hemocompatible properties and corrosion resistance. However, surfaces where mechanical contact of the rotor and the stator occur like bearing areas of axial VADs require high wear resistance due to the greater potential of scratches. Therefore, an in vitro test bench to optically investigate the deposition of fluorescent labelled platelets on the protein layer of different surfaces is hereby presented, aiming to investigate the potential for thrombi formation of five different inorganic hard material coatings on titanium. The coating materials included Titanium Nitride (TiN), Titanium Niobium Nitride (TiNbN), Diamond-Like Carbon (Ionbond-Medthin-43 (DLCI) and Oerlikon Balimed A (DLCO)) and Wolfram Carbid Oerlikon Balimed C (WC). Uncoated titanium (Ti) was investigated as reference. Heparinized human whole blood was incubated with Mepacrine (fluorescent dye) and then pumped through a flow chamber with defined shear rate conditions over the samples. The adhered platelets were visualized via inverted fluorescence microscopy. The analyzation of the green values and the binary image of the generated fluorescent picture offers conclusions about the platelet accumulation and the percentage of the covered surface area, respectively. Statistical analysis showed a significant lower potential for platelet deposition for TiN compared to Ti and no significant differences for the rest. It can be concluded that none of these coatings have a higher potential for platelet deposition than Ti and therefore point towards suitability for blood contacting components.
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.
Hypotensive periods during surgery lead to an increase in postoperative complications. To further avoid the adverse events associated with the invasive measurement of the blood pressure, a ...perioperative, continuous, non-invasive blood pressure measurement method was developed. The precision of the method was tested for different mean pressure values and different thicknesses of the tissue model using a specifically designed and validated simulator that has the characteristics of the lower arm. The mean pressure difference between the pressure determined by the proposed method and simulated blood pressure from the simulator was 3.93 mmHg (±4.75 mmHg) for the systole and 4.89 mmHg (±6.10 mmHg) for the diastole. The results showed that the method can be a promising alternative to invasive blood pressure measurement methods.
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. 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. 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. 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.
Continuous‐flow ventricular assist devices (VADs) have established themselves as a lifesaving therapy option in patients with severe cardiovascular disease. Unfortunately, complications with VADs ...resulting from the shear‐induced formation of surface blood clots are common. In the current work, an antifouling coating based on the combination of mussel‐inspired dendritic polyglycerol (MI‐dPG) and linear polyglycerol (lPG) is tested for its cell‐repelling properties, biocompatibility, and complement activating properties. Furthermore, the adhesion and activation of blood platelets are tested under static and flow conditions. The adhesion and proliferation of two cell types are studied by means of LIVE/DEAD cell staining, and it is clearly observed that the lPG‐functionalized MI‐dPG coating prevents cell adhesion. Additionally, no cell mortality is observed on all substrates, indicating the biocompatibility of the tested coatings. All coatings show lower (or equal) complement‐activating properties than bare titanium, which is considered a highly biocompatible material. Most importantly, the lPG‐functionalized system prevents the adhesion and activation of blood platelets under static and flow conditions. Finally, a prototype VAD is successfully coated with MI‐dPG under flow conditions. In the current study, the efficient lPG‐functionalization of the MI‐dPG coating is proved to obtain cell‐ and platelet‐repelling surfaces.
The current work investigates the biocompatibility and the cell‐ and platelet‐repelling properties of an antifouling coating based on the combination of mussel‐inspired dendritic polyglycerol and linear polyglycerol. The results are compared to a similar mussel‐inspired poly(ethylene glycol)‐functionalized coating. The platelet repelling properties of the coatings are shown under static and medically relevant flow conditions.
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