Micropatterned surfaces as biointerface to reduce platelet adhesion in cardiovascular devices Marta Bonora, Veronica Viola, Stjepan Perak, Markus Lunzer, Sonja Kopp, Michael Mühlberger, Viktorija Jonaityte, Christian Grasl, Barbara Messner, Michael B. Fischer, Francesco Moscato Colloids and Interface Science Communications, 2026 The success of cardiovascular devices is hindered by non-physiological flow conditions and surface materials, which can trigger platelet activation and lead to thrombus formation with severe consequences for patients. While anticoagulation treatments help prevent thrombus formation, they can compromise hemostasis and thereby increase the risk of bleeding. In this study, physical surface modifications through specific micropatterning, cones, riblets, grids, and hemispheres were investigated as a non-pharmacological strategy to reduce platelet adhesion on blood-contacting devices. Fabrication methods based on two-photon polymerization (2PP) 3D printing combined with nanoimprinting lithography were employed to achieve high micro-scale resolution. Platelet adhesion was investigated under low-WSS conditions, and adhering platelets were reduced by 45%, 29%, 25%, and 41%, respectively, for cones, riblets, grids, and hemispheres compared to the flat reference control. Our findings demonstrate that surface micropatterning at the blood–material interface represents a promising approach to modulate thrombus formation risk in cardiovascular devices. • Micropatterned surfaces reduce platelet adhesion on blood-contacting surfaces. • Cone and hemisphere geometries show the highest antithrombogenic potential. • Two-photon polymerization with nanoimprinting enables precise micropattern fabrication. • Superhydrophobicity, surface topography, and local wall shear stress correlate with lower platelet adhesion. • Findings support the development of safer blood-contacting devices with reduced thrombosis and bleeding risks.
The Influence of Micropatterned Surfaces on Platelet Adhesion to Reduce the Risk of Thrombus Formation in Left Ventricular Assist Devices Marta Bonora, Stjepan Perak, Sonja Kopp, Josu Garcia Morales, Richard Benauer, Markus Lunzer, Michael Mühlberger, Teresa Ruthmeier, Barbara Messner, Michael Bernhard Fischer, Francesco Moscato Annals of Biomedical Engineering, 2026 Purpose Surface micropatterning is being explored as a strategy to mitigate thrombus formation and reduce long-term anticoagulation requirements in left ventricular assist devices (LVADs). This study investigated whether specific micro-topographies can modulate platelet deposition under LVAD supraphysiological wall shear stress (WSS) conditions. Materials and Methods A custom microfluidic platform was developed to generate a linear WSS gradient from 16 to 130 Pa. Microchannels were patterned with reverse cones and hemispheres in small (1–3 µ m) and large (3–9 µ m) sizes using two-photon polymerization and nanoimprinting. Human blood was perfused through the microchannels, and platelet deposition was quantified over time as the area coverage ratio ( A ₚₗₜ/ A ₜₒₜ) and area under the curve (AUC). Platelet detachment events were counted as an indicator of thrombus stability, and computational simulations supported the interpretation of local shear conditions. Results Consistent trends emerged, although no statistical differences were observed relative to flat controls. A ₚₗₜ/ A ₜₒₜ increased with WSS for all surfaces. At 16 Pa, small and large cones reduced platelet adhesion by approximately 84 and 98%, respectively, compared to flat controls. At 49 Pa, the reduction was about 95% for small cones and 80% for large cones. Conical geometries also promoted platelet washout at higher WSS. Small hemispherical features showed more than 50% lower platelet adhesion than flat surfaces for WSS > 16 Pa, with limited thrombus growth. Conclusion Conical micropatterns may be most effective at limiting platelet adhesion at lower WSS, while small hemispheres may perform better at higher WSS. These trends suggest a surface–shear interaction that warrants further investigation for LVAD surface optimization.
In-Vitro Hemocompatibility Evaluation of the HeartMate 3 under Realistic Operating Conditions Xiangyu He, Krishnaraj Narayanaswamy, Michael B. Fischer, Leonie Schmitt, Teresa Ruthmeier, Barbara Messner, Stefan Jakubek, Daniel Zimpfer, Marcus Granegger IEEE Transactions on Biomedical Engineering, 2025 OBJECTIVE Operating conditions significantly influence hemolysis generation in rotodynamic blood pumps (RBPs). Previous experiments conducted under constant operating conditions have demonstrated that lower flow rates are associated with a higher normalized index of hemolysis (NIH). However, in clinical scenarios, the pump flow rate fluctuates in response to the residual cardiac function. This study aims to investigate the effects of various pulsatile operating conditions on hemolysis generation and von Willebrand Factor (vWF) degradation of RBP. METHODS To investigate these conditions, pulsatile flow experiments were conducted for 12 hours using HeartMate 3 (HM3, Abbott Inc, USA) in a hybrid mock circulatory loop with citrated human blood from hemochromatosis patients. Three operating conditions (high, low, and no residual cardiac function) were examined under two pump speed settings: normal (5400rpm, 4.3L/min) and low (4800rpm, 2.5L/min). Hemolysis was assessed by measuring delta free hemoglobin every 30 minutes (dfHb30min) and calculating NIH. High molecular weight (HMW) vWF multimer degradation was assessed using immunoblotting. RESULTS There was no significant difference in dfHb30min (p>0.388), NIH (p>0.382), and HMW vWF multimers degradation (p>0.364) between the three operating conditions, but differences in these parameters were observed between the normal and low speed settings. Meanwhile, a consistent trend in the hemolysis outcomes was observed with slightly elevated hemolysis in no and high pulsatility conditions of both speed settings. CONCLUSION Hemocompatibility of the HM3 is not significantly affected by periodic high/low flow or backflows through the pump in in-vitro evaluation but rather by the pump operating condition: flow rate and pump speed.
Assessment of Platelet Response to Aspirin Therapy and Hemocompatibility-Related Adverse Events in HeartMate 3 Left Ventricular Assist Device Recipients Hebe Al Asadi, Theodor Abart, Caroline Schwarz, Roxana Moayedifar, Anne-Kristin Schaefer, Christiane Marko, Barbara Messner, Daniel Zimpfer, Julia Riebandt, Thomas Schlöglhofer Journal of Clinical Medicine, 2024 Background: Patients with a HeartMate 3 (HM3) left ventricular assist device (LVAD) typically receive anticoagulation and antiplatelet therapy. The HM3 has shown a marked reduction in hemocompatibility-related adverse events (HRAEs) like stroke, bleeding, and pump thrombosis. This study evaluated whether aspirin (ASA) response influences HRAE incidence and if ASA sensitivity changes over time in HM3 recipients. Methods: This single-center, cross-sectional study included 32 HM3 patients (age: 59.0 ± 10.0 years, 15.6% female). ASA sensitivity was assessed twice using the VerifyNow assay, with ASA resistance defined by ASA reactivity units (ARU) > 550. The primary endpoint was HRAE incidence in ASA responders vs. non-responders over two consecutive follow-ups; the secondary endpoint was temporal changes in ASA resistance. Results: At the first follow-up, 13 (40.6%) patients were ASA-resistant, and 8 (28.6%) were resistant at the second follow-up, without significant change (p = 0.22). ASA non-responders and responders had similar ASA doses and baseline characteristics. No significant difference in HRAE incidence was found between ASA non-responders and responders (0.0% vs. 15.8%, p = 0.14), and no additional HRAEs occurred during follow-up. Conclusions: ASA resistance varied considerably among HM3 patients without significant temporal changes, and the demonstrated excellent hemocompatibility supports recent evidence that ASA may have a limited role in the antithrombotic regimen for HM3 recipients.
Aluminum, a colorful gamechanger: Uptake of an aluminum-containing food color in human cells and its implications for human health Clara Ganhör, Marlene Rezk, Christian Doppler, Teresa Ruthmeier, Christian Wechselberger, Marina Müller, Michaela Kotnik, Špela Puh, Barbara Messner, David Bernhard Food Chemistry, 2024 Aluminum is added to many food colors to change their solubility. This study compares the aluminum-containing food color carmine with its aluminum-free version carminic acid (both E 120), hypothesizing that the addition of aluminum does not only change the color's solubility, but also its effects on human cells. We could show that carmine, but not carminic acid, is taken up by gastrointestinal Caco-2 and umbilical vein endothelial cells (HUVEC). Clear differences between gene expression profiles of Caco-2 cells exposed to carmine, carminic acid or control were shown. KEGG analysis revealed that carmine-specific genes suppress oxidative phosphorylation, and showed that this suppression is associated with neurodegenerative diseases such as Alzheimer and Parkinson disease. Furthermore, carmine, but not carminic acid, increased proliferation of Caco-2 cells. Our findings show that a food color containing aluminum induces different cellular effects compared to its aluminum-free form, which is currently not considered in EU legislation.
An Atraumatic Mock Loop for Realistic Hemocompatibility Assessment of Blood Pumps Moritz Bender, Andreas Escher, Barbara Messner, Michael Röhrich, Michael Bernhard Fischer, Christoph Hametner, Günther Laufer, Ulrich Kertzscher, Daniel Zimpfer, Stefan Jakubek, Marcus Granegger IEEE Transactions on Biomedical Engineering, 2024 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 <inline-formula><tex-math notation="LaTeX">$\\pm$</tex-math></inline-formula> 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 <inline-formula><tex-math notation="LaTeX">$\\pm$</tex-math></inline-formula> 1.37 mmHg while the fluid level remained within <inline-formula><tex-math notation="LaTeX">$\\pm$</tex-math></inline-formula>4% of its target value. The normalized indices of hemolysis (NIH) for the inactive H-MCL showed no significant differences to conventional loops (<inline-formula><tex-math notation="LaTeX">$\\Delta$</tex-math></inline-formula>NIH = −1.6 mg/100 L). Further, no significant difference was evident between the active and inactive mode in the H-MCL (<inline-formula><tex-math notation="LaTeX">$\\Delta$</tex-math></inline-formula>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.
Altered B-Cell Expansion and Maturation in Draining Mesenteric Lymph Nodes of Inflamed Gut in Crohn's Disease Sonja Kappel-Latif, Prasanti Kotagiri, Lukas Schlager, Gabor Schuld, Natalie Walterskirchen, Vanessa Schimek, Gavin Sewell, Carina Binder, Johanna Jobst, Supriya Murthy, Barbara Messner, Stefanie Dabsch, Arthur Kaser, Paul A. Lyons, Michael Bergmann, Anton Stift, Rudolf Oehler, Lukas W. Unger Cellular and Molecular Gastroenterology and Hepatology, 2024
The Role of Trace Elements in Cardiovascular Diseases Christian Wechselberger, Barbara Messner, David Bernhard Toxics, 2023 Essential trace elements play an important role in human physiology and are associated with various functions regulating cellular metabolism. Non-essential trace elements, on the other hand, often have well-documented toxicities that are dangerous for the initiation and development of diseases due to their widespread occurrence in the environment and their accumulation in living organisms. Non-essential trace elements are therefore regarded as serious environmental hazards that are harmful to health even in low concentrations. Many representatives of these elements are present as pollutants in our environment, and many people may be exposed to significant amounts of these substances over the course of their lives. Among the most common non-essential trace elements are heavy metals, which are also associated with acute poisoning in humans. When these elements accumulate in the body over years of chronic exposure, they often cause severe health damage in a variety of tissues and organs. In this review article, the role of selected essential and non-essential trace elements and their role in the development of exemplary pathophysiological processes in the cardiovascular system will be examined in more detail.
Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors Victoria Brandel, Vanessa Schimek, Samantha Göber, Thomas Hammond, Laura Brunnthaler, Waltraud Cornelia Schrottmaier, Marion Mussbacher, Monika Sachet, Ying Yu Liang, Siegfried Reipert, Gregor Ortmayr, David Pereyra, Jonas Santol, Marlene Rainer, Natalie Walterskirchen, Cristiano Ramos, Vasileios Gerakopoulos, Carina Rainer, Andreas Spittler, Tamara Weiss, Renate Kain, Barbara Messner, Thomas Gruenberger, Alice Assinger, Rudolf Oehler, Patrick Starlinger Journal of Hepatology, 2022
Hemolytic Footprint of Rotodynamic Blood Pumps Andreas Escher, Henrike Gobel, Marcel Nicolai, Thomas Schloglhofer, Emanuel J. Hubmann, Gunther Laufer, Barbara Messner, Ulrich Kertzscher, Daniel Zimpfer, Marcus Granegger IEEE Transactions on Biomedical Engineering, 2022
The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm Thomas Aschacher, Olivia Aschacher, Katy Schmidt, Florian K. Enzmann, Eva Eichmair, Bernhard Winkler, Zsuzsanna Arnold, Felix Nagel, Bruno K. Podesser, Andreas Mitterbauer, Barbara Messner, Martin Grabenwöger, Günther Laufer, Marek P. Ehrlich, Michael Bergmann International Journal of Molecular Sciences, 2022
Chemical imaging and assessment of cadmium distribution in the human body Alexander E. Egger, Gerlinde Grabmann, Can Gollmann-Tepeköylü, Elisabeth J. Pechriggl, Christian Artner, Adrian Türkcan, Christian G. Hartinger, Helga Fritsch, Bernhard K. Keppler, Erich Brenner, Michael Grimm, Barbara Messner, David Bernhard Metallomics, 2019
Telomere biology and thoracic aortic aneurysm Thomas Aschacher, Olivia Salameh, Florian Enzmann, Barbara Messner, Michael Bergmann International Journal of Molecular Sciences, 2018
Biodegradable, thermoplastic polyurethane grafts for small diameter vascular replacements Helga Bergmeister, Nargiz Seyidova, Catharina Schreiber, Magdalena Strobl, Christian Grasl, Ingrid Walter, Barbara Messner, Stefan Baudis, Sophie Fröhlich, Martina Marchetti-Deschmann, Markus Griesser, Matt di Franco, Martin Krssak, Robert Liska, Heinrich Schima Acta Biomaterialia, 2015
Erratum: Expression of messenger RNA of the cardiac isoforms of troponin T and I in myopathic skeletal muscle (American Journal of Clinical Pathology (2000) 114 (544-549)) American Journal of Clinical Pathology, 2000
