*Result*: Computational Fluid Dynamics Simulation of Endothelium-Modulated Thrombosis.
Title:
Computational Fluid Dynamics Simulation of Endothelium-Modulated Thrombosis.
Authors:
He W; Sibley School of Mechanical and Aerospace Engineering, Cornell University, 237 Tower Road, Ithaca, NY, 14850, USA., Karmakar A; Meinig School of Biomedical Engineering, Cornell University, 237 Tower Road, Ithaca, NY, 14850, USA., Antaki JF; Meinig School of Biomedical Engineering, Cornell University, 237 Tower Road, Ithaca, NY, 14850, USA. antaki@cornell.edu.
Source:
Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2026 Feb 18; Vol. 19 (1), pp. 25. Date of Electronic Publication: 2026 Feb 18.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Springer Country of Publication: United States NLM ID: 101468585 Publication Model: Electronic Cited Medium: Internet ISSN: 1937-5395 (Electronic) Linking ISSN: 19375387 NLM ISO Abbreviation: J Cardiovasc Transl Res Subsets: MEDLINE
Imprint Name(s):
Original Publication: New York, NY : Springer
MeSH Terms:
Thrombosis*/physiopathology , Thrombosis*/blood , Thrombosis*/pathology , Thrombosis*/metabolism , Thrombosis*/etiology , Endothelium, Vascular*/metabolism , Endothelium, Vascular*/physiopathology , Blood Platelets*/metabolism , Endothelial Cells*/metabolism , Computer Simulation* , Models, Cardiovascular*, Nitric Oxide/metabolism ; Humans ; Hydrodynamics ; Numerical Analysis, Computer-Assisted ; Blood Coagulation ; Regional Blood Flow ; Platelet Adhesiveness ; Stress, Mechanical
References:
Jayaraman A, Kang J, Jani P, Abbott NL, Antaki JF, Kirby BJ. Red blood cell entrapment in thrombi formed under pathological flow: Stiffness and binding antigens impact thrombus morphology and cell distribution. Acta Biomaterialia 201(December 2024), 2025;336–346. https://doi.org/10.1016/j.actbio.2025.05.055 .
He W, Butcher JT, Rowlands GW, Antaki JF. Biological response to sintered titanium in left ventricular assist devices: pseudoneointima, neointima, and pannus. ASAIO Journal Publish Ah. 2022. https://doi.org/10.1097/mat.0000000000001777 . (PMID: 10.1097/mat.0000000000001777)
Figueiredo C, Eicke D, Yuzefovych Y, Avsar M, Hanke JS, Pflaum M, et al. Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device. Sci Rep. 2019;9(1):1–13. https://doi.org/10.1038/s41598-019-47780-7 . (PMID: 10.1038/s41598-019-47780-7)
Gong X, Yao J, He H, Zhao X, Liu X, Zhao F, et al. Combination of flow and micropattern alignment affecting flow-resistant endothelial cell adhesion. J Mech Behav Biomed Mater. 2017;74(April):11–20. https://doi.org/10.1016/j.jmbbm.2017.04.028 . (PMID: 10.1016/j.jmbbm.2017.04.02828525819)
Neubauer K, Zieger B. Endothelial cells and coagulation. 2022. https://doi.org/10.1007/s00441-021-03471-2 . (PMID: 10.1007/s00441-021-03471-2)
Jin RC, Voetsch B, Loscalzo J. Endogenous mechanisms of inhibition of platelet function. Microcirculation. 2005;12(3):247–58. https://doi.org/10.1080/10739680590925493 . (PMID: 10.1080/1073968059092549315814434)
Ghosh DK, Salerno JC. Nitric oxide synthases domain structure and alignment in enzyme function and control. Front Biosci. 2003;8(4):959. https://doi.org/10.2741/959 . (PMID: 10.2741/959)
Wolfe JT, Shradhanjali A, Tefft BJ. Strategies for Improving Endothelial Cell Adhesion to Blood-Contacting Medical Devices. Tissue Engineering Part B: Reviews. 2022;28(5). https://doi.org/10.1089/ten.teb.2021.0148 .
Alabdullh HA, Pflaum M, Mälzer M, Kipp M, Naghilouy-Hidaji H, Adam D, Kühn C, Natanov R, Niehaus A, Haverich A, Wiegmann B. Biohybrid lung Development: Towards Complete Endothelialization of an Assembled Extracorporeal Membrane Oxygenator. Bioengineering 2023;10(1). https://doi.org/10.3390/bioengineering10010072 .
Haritz JL, Pflaum M, Güntner HJ, Katsirntaki K, Hegermann J, Hehnen F, Lommel M, Kertzscher U, Arens J, Haverich A, Ruhparwar A, Wiegmann B. Citrate-Coated Iron Oxide Nanoparticles Facilitate Endothelialization of Left Ventricular Assist Device Impeller for Improved Antithrombogenicity. Adv Sci. 2025;12(6). https://doi.org/10.1002/advs.202408976 .
Grande Gutiérrez N, Mukherjee D, Bark D. Decoding thrombosis through code a review of computational models. 2024. https://doi.org/10.1016/j.jtha.2023.08.021 . (PMID: 10.1016/j.jtha.2023.08.021)
Wu W-T, Jamiolkowski MA, Wagner WR, Aubry N, Massoudi M, Antaki JF. Multi-Constituent Simulation of Thrombus Deposition. Sci Rep. 2017;7(1):42720. https://doi.org/10.1038/srep42720 , arXiv:1601.06717.
Zhussupbekov M, Méndez Rojano R, Wu WT, Massoudi M, Antaki JF. A continuum model for the unfolding of von Willebrand Factor. Ann Biomed Eng. 2021;49(9):2646–58. https://doi.org/10.1007/s10439-021-02845-5 . (PMID: 10.1007/s10439-021-02845-5344019709847011)
He W, Ibrahim AM, Karmakar A, Tuli S, Butcher JT, Antaki JF. Computational Fluid Dynamic Optimization of Micropatterned Surfaces: Towards Biofunctionalization of Artificial Organs. Bioengineering 2024;11(11). https://doi.org/10.3390/bioengineering11111092 .
Andrews AM, Jaron D, Buerk DG, Kirby PL, Barbee KA. Direct, real-time measurement of shear stress-induced nitric oxide produced from endothelial cells in vitro. Nitric Oxide. 2010;23(4):335–42. https://doi.org/10.1016/j.niox.2010.08.003 . (PMID: 10.1016/j.niox.2010.08.003207192522965060)
Malinski T, Taha Z, Grunfeld S, Patton S, Kapturczak M, Tomboulian P. Diffusion of Nitric Oxide in the Aorta Wall Monitored in Situ by Porphyrinic Microsensors. Biochem Biophys Res Commun. 1993;193(3):1076–82. https://doi.org/10.1006/bbrc.1993.1735 . (PMID: 10.1006/bbrc.1993.17358323533)
Fadel AA, Barbee KA, Jaron D. A computational model of nitric oxide production and transport in a parallel plate flow chamber. Ann Biomed Eng. 2009;37(5):943–54. https://doi.org/10.1007/s10439-009-9658-5 . (PMID: 10.1007/s10439-009-9658-519242805)
Tsai M, Kita A, Leach J, Rounsevell R, Huang JN, Moake J, et al. In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J Clin Investig. 2012;122(1):408–18. https://doi.org/10.1172/JCI58753 . (PMID: 10.1172/JCI5875322156199)
Ramamurthi A, Lewis RS. Influence of Agonist, Shear Rate, and Perfusion Time on Nitric Oxide Inhibition of Platelet Deposition. Ann Biomed Eng. 2000;28(2):174–81. https://doi.org/10.1114/1.242 . (PMID: 10.1114/1.24210710189)
Ramamurthi A, Robson SC, Lewis RS. Effects of Nitric Oxide (NO) and Soluble Nucleoside Triphosphate Diphosphohydrolase (NTPDase) on Inhibition of Platelet Deposition In Vitro. Thromb Res. 2001;102(4):331–41. https://doi.org/10.1016/S0049-3848(01)00244-4 . (PMID: 10.1016/S0049-3848(01)00244-411369426)
Costa PF, Albers HJ, Linssen JEA, Middelkamp HHT, Hout LVD, Passier R, et al. Mimicking arterial thrombosis in a 3d-printed microfluidic: In vitro vascular model based on computed tomography angiography data. Lab Chip. 2017;17:2785–92. https://doi.org/10.1039/c7lc00202e . (PMID: 10.1039/c7lc00202e28717801)
Sorensen EN, Burgreen GW, Wagner WR, Antaki JF. Computational Simulation of Platelet Deposition and Activation: I. Model Development and Properties. Annals Biomed Eng. 1999;27(4):436–48. https://doi.org/10.1114/1.200 . (PMID: 10.1114/1.200)
Sorensen EN, Burgreen GW, Wagner WR, Antaki JF. Computational Simulation of Platelet Deposition and Activation: II. Results for Poiseuille Flow over Collagen. Annals Biomed Eng. 1999;27(4):449–58. https://doi.org/10.1114/1.201 . (PMID: 10.1114/1.201)
Li S, Yang S, Sun X, Ma T, Zheng Y, Liu X. Nitric oxide distribution correlates with intraluminal thrombus in abdominal aortic aneurysm: A computational study. Bioengineering 2025;12. https://doi.org/10.3390/bioengineering12020191 .
Brouns SL, Provenzale I, Geffen JP, Meijden PE, Heemskerk JW. Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study. J Thromb Haemost. 2020;18(4):931–41. (PMID: 10.1111/jth.14719318635487187151)
Lancaster JR. Simulation of the diffusion and reaction of endogenously produced nitric oxide. Proc Natl Acad Sci USA. 1994;91(17):8137–41. https://doi.org/10.1073/pnas.91.17.8137 . (PMID: 10.1073/pnas.91.17.8137805876944560)
Laurent M, Lepoivre M, Tenu JP. Kinetic modelling of the nitric oxide gradient generated in vitro by adherent cells expressing inducible nitric oxide synthase. Biochemical Journal. 1996;314(1):109–13. https://doi.org/10.1042/bj3140109 . (PMID: 10.1042/bj314010986602701217012)
Vaughn MW, Kuo L, Liao JC. Estimation of nitric oxide production and reactionrates in tissue by use of a mathematical model. American Journal of Physiology-Heart and Circulatory Physiology. 1998;274(6):2163–76. https://doi.org/10.1152/ajpheart.1998.274.6.H2163 .
He W, Butcher JT, Rowlands GW, Antaki JF. Biological response to sintered titanium in left ventricular assist devices: pseudoneointima, neointima, and pannus. ASAIO Journal Publish Ah. 2022. https://doi.org/10.1097/mat.0000000000001777 . (PMID: 10.1097/mat.0000000000001777)
Figueiredo C, Eicke D, Yuzefovych Y, Avsar M, Hanke JS, Pflaum M, et al. Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device. Sci Rep. 2019;9(1):1–13. https://doi.org/10.1038/s41598-019-47780-7 . (PMID: 10.1038/s41598-019-47780-7)
Gong X, Yao J, He H, Zhao X, Liu X, Zhao F, et al. Combination of flow and micropattern alignment affecting flow-resistant endothelial cell adhesion. J Mech Behav Biomed Mater. 2017;74(April):11–20. https://doi.org/10.1016/j.jmbbm.2017.04.028 . (PMID: 10.1016/j.jmbbm.2017.04.02828525819)
Neubauer K, Zieger B. Endothelial cells and coagulation. 2022. https://doi.org/10.1007/s00441-021-03471-2 . (PMID: 10.1007/s00441-021-03471-2)
Jin RC, Voetsch B, Loscalzo J. Endogenous mechanisms of inhibition of platelet function. Microcirculation. 2005;12(3):247–58. https://doi.org/10.1080/10739680590925493 . (PMID: 10.1080/1073968059092549315814434)
Ghosh DK, Salerno JC. Nitric oxide synthases domain structure and alignment in enzyme function and control. Front Biosci. 2003;8(4):959. https://doi.org/10.2741/959 . (PMID: 10.2741/959)
Wolfe JT, Shradhanjali A, Tefft BJ. Strategies for Improving Endothelial Cell Adhesion to Blood-Contacting Medical Devices. Tissue Engineering Part B: Reviews. 2022;28(5). https://doi.org/10.1089/ten.teb.2021.0148 .
Alabdullh HA, Pflaum M, Mälzer M, Kipp M, Naghilouy-Hidaji H, Adam D, Kühn C, Natanov R, Niehaus A, Haverich A, Wiegmann B. Biohybrid lung Development: Towards Complete Endothelialization of an Assembled Extracorporeal Membrane Oxygenator. Bioengineering 2023;10(1). https://doi.org/10.3390/bioengineering10010072 .
Haritz JL, Pflaum M, Güntner HJ, Katsirntaki K, Hegermann J, Hehnen F, Lommel M, Kertzscher U, Arens J, Haverich A, Ruhparwar A, Wiegmann B. Citrate-Coated Iron Oxide Nanoparticles Facilitate Endothelialization of Left Ventricular Assist Device Impeller for Improved Antithrombogenicity. Adv Sci. 2025;12(6). https://doi.org/10.1002/advs.202408976 .
Grande Gutiérrez N, Mukherjee D, Bark D. Decoding thrombosis through code a review of computational models. 2024. https://doi.org/10.1016/j.jtha.2023.08.021 . (PMID: 10.1016/j.jtha.2023.08.021)
Wu W-T, Jamiolkowski MA, Wagner WR, Aubry N, Massoudi M, Antaki JF. Multi-Constituent Simulation of Thrombus Deposition. Sci Rep. 2017;7(1):42720. https://doi.org/10.1038/srep42720 , arXiv:1601.06717.
Zhussupbekov M, Méndez Rojano R, Wu WT, Massoudi M, Antaki JF. A continuum model for the unfolding of von Willebrand Factor. Ann Biomed Eng. 2021;49(9):2646–58. https://doi.org/10.1007/s10439-021-02845-5 . (PMID: 10.1007/s10439-021-02845-5344019709847011)
He W, Ibrahim AM, Karmakar A, Tuli S, Butcher JT, Antaki JF. Computational Fluid Dynamic Optimization of Micropatterned Surfaces: Towards Biofunctionalization of Artificial Organs. Bioengineering 2024;11(11). https://doi.org/10.3390/bioengineering11111092 .
Andrews AM, Jaron D, Buerk DG, Kirby PL, Barbee KA. Direct, real-time measurement of shear stress-induced nitric oxide produced from endothelial cells in vitro. Nitric Oxide. 2010;23(4):335–42. https://doi.org/10.1016/j.niox.2010.08.003 . (PMID: 10.1016/j.niox.2010.08.003207192522965060)
Malinski T, Taha Z, Grunfeld S, Patton S, Kapturczak M, Tomboulian P. Diffusion of Nitric Oxide in the Aorta Wall Monitored in Situ by Porphyrinic Microsensors. Biochem Biophys Res Commun. 1993;193(3):1076–82. https://doi.org/10.1006/bbrc.1993.1735 . (PMID: 10.1006/bbrc.1993.17358323533)
Fadel AA, Barbee KA, Jaron D. A computational model of nitric oxide production and transport in a parallel plate flow chamber. Ann Biomed Eng. 2009;37(5):943–54. https://doi.org/10.1007/s10439-009-9658-5 . (PMID: 10.1007/s10439-009-9658-519242805)
Tsai M, Kita A, Leach J, Rounsevell R, Huang JN, Moake J, et al. In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J Clin Investig. 2012;122(1):408–18. https://doi.org/10.1172/JCI58753 . (PMID: 10.1172/JCI5875322156199)
Ramamurthi A, Lewis RS. Influence of Agonist, Shear Rate, and Perfusion Time on Nitric Oxide Inhibition of Platelet Deposition. Ann Biomed Eng. 2000;28(2):174–81. https://doi.org/10.1114/1.242 . (PMID: 10.1114/1.24210710189)
Ramamurthi A, Robson SC, Lewis RS. Effects of Nitric Oxide (NO) and Soluble Nucleoside Triphosphate Diphosphohydrolase (NTPDase) on Inhibition of Platelet Deposition In Vitro. Thromb Res. 2001;102(4):331–41. https://doi.org/10.1016/S0049-3848(01)00244-4 . (PMID: 10.1016/S0049-3848(01)00244-411369426)
Costa PF, Albers HJ, Linssen JEA, Middelkamp HHT, Hout LVD, Passier R, et al. Mimicking arterial thrombosis in a 3d-printed microfluidic: In vitro vascular model based on computed tomography angiography data. Lab Chip. 2017;17:2785–92. https://doi.org/10.1039/c7lc00202e . (PMID: 10.1039/c7lc00202e28717801)
Sorensen EN, Burgreen GW, Wagner WR, Antaki JF. Computational Simulation of Platelet Deposition and Activation: I. Model Development and Properties. Annals Biomed Eng. 1999;27(4):436–48. https://doi.org/10.1114/1.200 . (PMID: 10.1114/1.200)
Sorensen EN, Burgreen GW, Wagner WR, Antaki JF. Computational Simulation of Platelet Deposition and Activation: II. Results for Poiseuille Flow over Collagen. Annals Biomed Eng. 1999;27(4):449–58. https://doi.org/10.1114/1.201 . (PMID: 10.1114/1.201)
Li S, Yang S, Sun X, Ma T, Zheng Y, Liu X. Nitric oxide distribution correlates with intraluminal thrombus in abdominal aortic aneurysm: A computational study. Bioengineering 2025;12. https://doi.org/10.3390/bioengineering12020191 .
Brouns SL, Provenzale I, Geffen JP, Meijden PE, Heemskerk JW. Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study. J Thromb Haemost. 2020;18(4):931–41. (PMID: 10.1111/jth.14719318635487187151)
Lancaster JR. Simulation of the diffusion and reaction of endogenously produced nitric oxide. Proc Natl Acad Sci USA. 1994;91(17):8137–41. https://doi.org/10.1073/pnas.91.17.8137 . (PMID: 10.1073/pnas.91.17.8137805876944560)
Laurent M, Lepoivre M, Tenu JP. Kinetic modelling of the nitric oxide gradient generated in vitro by adherent cells expressing inducible nitric oxide synthase. Biochemical Journal. 1996;314(1):109–13. https://doi.org/10.1042/bj3140109 . (PMID: 10.1042/bj314010986602701217012)
Vaughn MW, Kuo L, Liao JC. Estimation of nitric oxide production and reactionrates in tissue by use of a mathematical model. American Journal of Physiology-Heart and Circulatory Physiology. 1998;274(6):2163–76. https://doi.org/10.1152/ajpheart.1998.274.6.H2163 .
Grant Information:
HL089456 United States HL NHLBI NIH HHS
Contributed Indexing:
Keywords: Endothelial cell; Nitric oxide; Platelets; Thrombosis
Substance Nomenclature:
31C4KY9ESH (Nitric Oxide)
Entry Date(s):
Date Created: 20260218 Date Completed: 20260219 Latest Revision: 20260218
Update Code:
20260219
DOI:
10.1007/s12265-026-10749-9
PMID:
41709029
Database:
MEDLINE
*Further Information*
*The development of blood-wetted artificial organs is limited by thrombosis on synthetic biomaterial surfaces. In contrast, the endothelium of the vasculature creates a natural barrier to both thrombosis and pannus growth. Consequently, efforts have been made to endothelialize synthetic biomaterials used in blood-wetted devices. Therefore, this study was undertaken to provide a numerical model to simulate the inhibitory effects of EC-derived nitric oxide (NO) on platelet deposition. An existing multi-constituent continuum model of thrombosis was amended to incorporate shear-dependent generation of NO as an anticoagulant. A simulation was performed of blood flow through a bipartite parallel plate channel having an endothelialized upstream layer followed by a pro-coagulant collagen surface downstream. The simulation showed that endothelial-derived NO inhibited downstream platelet deposition, reducing thrombus growth and creating a thrombus-free zone immediately downstream. This enhanced simulation model of thrombosis provides insights into factors that may guide future endothelialization of artificial organs and other blood-wetted devices.
(© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)*
*Declarations. Conflicts of Interest/Competing interests: The authors have no conflict of interest to declare. Human Subjects: No human studies were carried out by the authors for this article. Animal Studies: No animal studies were carried out by the authors for this article.*