In vitro models of thrombosis and hemostasis
List of abbreviations:
PDMS — polydimethylsiloxane
HUVEC — Human Umbilical Vein Endothelial Cells
СFD – computational fluid dynamics
TF - tissue factor
GelMA - methacrylate-gelatin
Introduction
The human hemostasis system remains the subject of active research primarily due to its great clinical significance: complications caused by arterial thrombosis alone are the most common cause of death and disability in people worldwide
Arterial thrombosis—insidious, unpredictable and deadly
S. Jackson
Nature Medicine. 2011, 17, 1423-1436
Murine Models of Vascular Thrombosis
R. Westrick, M. Winn, D. Eitzman
Arteriosclerosis, Thrombosis, and Vascular Biology. 2007, 27, 2079-2093
High-throughput measurement of human platelet aggregation under flow: application in hemostasis and beyond
S. Brouns, J. van Geffen, J. Heemskerk
Platelets. 2018, 29, 662-669
The use of microfluidics in hemostasis
K. Neeves, A. Onasoga, A. Wufsus
Current Opinion in Hematology. 2013, 20, 417-423
Subcommittee on Biorheology. In vitro flow‐based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis.
5. Mangin PH, Neeves KB, Lam WA, Cosemans JM, Korin N, Kerrigan SW, Panteleev MA
Journal of Thrombosis and Haemostasis. 2021, 19, 582-7
In Silico Hemostasis Modeling and Prediction
D. Nechipurenko, A. Shibeko, A. Sveshnikova, M. Panteleev
Hämostaseologie. 2020, 40, 524-535
In vitro models make it possible to reconstruct the processes of hemostatic response outside the body under well-controlled conditions, which is crucial due to the extreme complexity of the hemostatic system. Such models are also of great importance as potential systems for assessing the state of hemostasis in clinical settings, as well as tools for the development of new drugs since they allow working with human blood.
This review highlights the most significant in vitro approaches proposed in recent years for the study of thrombosis and hemostasis. Following traditional concepts, the structure of this work implies the separation of thrombosis models, which simulate the formation of intravascular clots, and hemostasis models, which aim to reconstruct the processes that occur in response to penetrating damage to the vessel.
Here we will focus on the technological features of these models, rather than the biological or clinical results obtained with their help.
In vitro models of thrombosis
Microfluidic models
The current in vitro models of thrombosis represent flow devices, usually termed flow chambers, which allow perfusion of whole blood or its components through a specially designed channel that mimic blood vessels. One of the most popular and proven approaches to the creation of flow chambers for modeling thrombosis is based on PDMS as a material that forms the geometry of the channels. The optical transparency of PDMS, its biological inertness, as well as an excellent combination with photolithography technology, led to the rapid development of microfluidics and its active application in various problems of biology and medicine. The use of this technology to reconstruct the process of blood coagulation outside the body makes it possible to regulate a significant part of the experimental parameters: the geometry of the channel which imitates the vessel, the pressure in the channel, the flow and the surface shear rates, the location of the activator that initiates the formation of a thrombus, and the introduction of various solutions into the system. To create such a flow chamber, the so-called microfluidic chips are widely used. These chips (moulds, masters) are created by photolithography technology and determine the geometry of the channels. The tandem of photolithography and polymerizing elastomer (PDMS) is called soft lithography and is illustrated with Fig. 1.

The key parameters of experiments on thrombus formation under flow conditions include channel geometry (shape, characteristic size), wall shear rate (usually ranging from 100 to 2000 s-1), biochemical composition and geometry of the area with an activator molecules (usually type I fibrillar collagen and tissue factor are used), the source and composition of the blood (the organism from which the blood was drawn, the type of anticoagulants, the presence of additional substances in the blood).
An example of the elegant application of microfluidic technology to study thrombus formation is the classic work of researchers from the University of Pennsylvania
Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates
K. NEEVES, S. MALONEY, K. FONG, A. SCHMAIER, M. KAHN, L. BRASS, S. DIAMOND
Journal of Thrombosis and Haemostasis. 2008, 6, 2193-2201
Microfluidics technology allows manufacturing flow systems with much more complex geometries. Researchers from the same group led by Scott L. Diamond have demonstrated the use of a microfluidic device that allows fluorescent probe (FITC, fluorescein isothiocyanate) to be pumped through a growing thrombus formed on collagen or collagen with TF scaffold. This technique makes it possible to measure the permeability of platelet and platelet/fibrin deposited layers, while independently controlling the pressure gradient and shear rate
Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient
R. Muthard, S. Diamond
Lab on a Chip. 2013, 13, 1883
![Microfluidic devices for analysis of thrombus formation under controlled shear. a) A 100 μm strip of collagen (red) was deposited and immobilized with a microfluidic pattern along the length of the slide. b) A microfluidic device with a set of channels was oriented perpendicular to the collagen pattern (red). Adapted from [7]. с-e) Microfluidic device with adjustable pressure gradients. The constant flow rate Q1 was provided by the syringe pump. The presence of pressure transducers (P1, P2 and P3) and additional inlet Q2 allowed controllable pressure gradient in the thrombus formation zone (e,f). f) Thrombus (orange) was formed on a collagen (blue) located between the PDMS pillars (white circles). Adapted from [8].](https://astore.sbpreports.com/issues/articles/7/figures/fig_1.png?v=ayzfl)
Hydrogel-based models
The most commonly used approaches to the design of microfluidic chambers are convenient in use, but their degree of correspondence to a real vessel is rather low, because they are characterized by non-physiological geometry (rectangular/square channel section), the absence of endothelial cells and mechanically rigid PDMS walls. The most realistic models of vessels today are created based on combining hydrogel technology and cell culture methods, and such systems are gaining popularity in a variety of biomedical fields
Tissue‐engineered 3D microvessel and capillary network models for the study of vascular phenomena
M. Bogorad, J. DeStefano, A. Wong, P. Searson
Microcirculation. 2017, 24, None
Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms
S. Ahn, Y. Sei, H. Park, J. Kim, Y. Ryu, J. Choi, H. Sung, T. MacDonald, A. Levey, Y. Kim
Nature Communications. 2020, 11, None
Engineering of Hydrogel Materials with Perfusable Microchannels for Building Vascularized Tissues
R. Xie, W. Zheng, L. Guan, Y. Ai, Q. Liang
Small. 2020, 16, 1902838
Yu Shrike Zhang et al. used 3D bioprinting technology to create a highly biomimetic model of thrombosis
Bioprinted thrombosis-on-a-chip
Y. Zhang, F. Davoudi, P. Walch, A. Manbachi, X. Luo, V. Dell'Erba, A. Miri, H. Albadawi, A. Arneri, X. Li, X. Wang, M. Dokmeci, A. Khademhosseini, R. Oklu
Lab on a Chip. None, 16, 4097-4105
Another popular approach for design of realistic vessel is based on capillary removal technique (Fig 3, d-f) and has been successfully applied for various tasks
Tissue‐engineered 3D microvessel and capillary network models for the study of vascular phenomena
M. Bogorad, J. DeStefano, A. Wong, P. Searson
Microcirculation. 2017, 24, None
![Various approaches for using hydrogels to fabricate artificial vessels. a) - c): bioprinting of vascularized hydrogels, schematic of the bioprinting process (adapted from [12]). a) bioprinting vessels and the wall; b) scaffold for GelMA; c) final GelMA block after curing with ultraviolet light and dissolving of the sacrificial layer (made from pluronic). d) - f): the tissue-engineered 3D microvessel, schematic of the construction process: d) PDMS mold, which contains input and output ports, is vacuum-sealed to the glass slide and serves as the shell. Cylindrical template rod (e.g. glass capillary) is positioned in the middle of the chamber into the special functional holes; e) PDMS mold is filled with hydrogel in a liquid state; f) after the gelation, the rod is physically removed by pulling it out from one side. After the removal of the template rod, the chamber is ready to use for blood/plasma perfusion or could be perfused for endothelial cell seeding and cultivation. Adapted from [9].](https://astore.sbpreports.com/issues/articles/7/figures/fig_2.png?v=meqfe)
Parallel-plate flow chambers
It should be noted that flow chambers of standard parallel-plate geometry, despite their simplicity, are actively and successfully applied in fundamental research of the hemostasis system today
Pharmacological Blockade of Glycoprotein VI Promotes Thrombus Disaggregation in the Absence of Thrombin
M. Ahmed, V. Kaneva, S. Loyau, D. Nechipurenko, N. Receveur, M. Le Bris, E. Janus-Bell, M. Didelot, A. Rauch, S. Susen, N. Chakfé, F. Lanza, E. Gardiner, R. Andrews, M. Panteleev, C. Gachet, M. Jandrot-Perrus, P. Mangin
Arteriosclerosis, Thrombosis, and Vascular Biology. 2020, 40, 2127-2142
Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface
D. Nechipurenko, N. Receveur, A. Yakimenko, T. Shepelyuk, A. Yakusheva, R. Kerimov, S. Obydennyy, A. Eckly, C. Léon, C. Gachet, E. Grishchuk, F. Ataullakhanov, P. Mangin, M. Panteleev
Arteriosclerosis, Thrombosis, and Vascular Biology. 2019, 39, 37-47
Core and shell platelets of a thrombus: A new microfluidic assay to study mechanics and biochemistry
M. DeCortin, L. Brass, S. Diamond
Research and Practice in Thrombosis and Haemostasis. 2020, 4, 1158-1166
Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting
N. Podoplelova, A. Sveshnikova, Y. Kotova, A. Eckly, N. Receveur, D. Nechipurenko, S. Obydennyi, I. Kireev, C. Gachet, F. Ataullakhanov, P. Mangin, M. Panteleev
Blood. 2016, 128, 1745-1755
Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow
F. Swieringa, C. Baaten, R. Verdoold, T. Mastenbroek, N. Rijnveld, K. van der Laan, E. Breel, P. Collins, M. Lancé, Y. Henskens, J. Cosemans, J. Heemskerk, P. van der Meijden
Arteriosclerosis, Thrombosis, and Vascular Biology. 2016, 36, 692-699
Researchers at the University of Maastricht, using a standard flow chamber with parallel-plate geometry, have demonstrated the ability of cell-free homogenates from human atherosclerotic plaques to promote platelet adhesion and aggregate formation under relatively high shear rates (1000 s-1)
Contribution of platelet glycoprotein VI to the thrombogenic effect of collagens in fibrous atherosclerotic lesions
J. Cosemans, M. Kuijpers, C. Lecut, S. Loubele, S. Heeneman, M. Jandrot-Perrus, J. Heemskerk
Atherosclerosis. 2005, 181, 19-27
Identification of platelet function defects by multi-parameter assessment of thrombus formation
S. de Witt, F. Swieringa, R. Cavill, M. Lamers, R. van Kruchten, T. Mastenbroek, C. Baaten, S. Coort, N. Pugh, A. Schulz, I. Scharrer, K. Jurk, B. Zieger, K. Clemetson, R. Farndale, J. Heemskerk, J. Cosemans
Nature Communications. 2014, 5, None
Models with stenotic geometries
To study the impact of flow disturbance on the dynamics of thrombus formation, flow chambers with a special geometry are used, wherein a stenosis is added to the standard shape of the channel, affecting the surface shear rate distribution.
Such systems make it possible to study thrombus formation in case when local spatial shear rate changes by over an order of magnitude. The creation of stenotic geometry is usually accomplished by microfluidic technique (using soft lithography) and was realized by imitating the atherosclerotic geometry with a semicircle
Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner
E. Westein, A. van der Meer, M. Kuijpers, J. Frimat, A. van den Berg, J. Heemskerk
Proceedings of the National Academy of Sciences. 2013, 110, 1357-1362
A shear gradient–dependent platelet aggregation mechanism drives thrombus formation
W. Nesbitt, E. Westein, F. Tovar-Lopez, E. Tolouei, A. Mitchell, J. Fu, J. Carberry, A. Fouras, S. Jackson
Nature Medicine. 2009, 15, 665-673
Shear rate gradients promote a bi-phasic thrombus formation on weak adhesive proteins, such as fibrinogen in a von Willebrand factor-dependent manner.
Receveur, Nicolas, Dmitry Nechipurenko, Yannick Knapp, Aleksandra Yakusheva, Eric Maurer, Cécile V. Denis, François Lanza, Mikhail Panteleev, Christian Gachet, and Pierre H. Mangin.
Haematologica. 2020, 105, None
![Schematic of a microfluidic flow chamber designed to generate shear gradients. (а) Schematic of a polydimethylsiloxane (PDMS) microfluidic flow chamber containing a straight rectangular channel 1 mm wide and 0.1 mm height, and a stenotic channel of similar dimensions, but providing a 90% width reduction in the central region (zone 3). Zones 1 through 5 are labeled in the bottom of the schematics showing 3D view. (b) Microphotograph of a microfluidic flow chamber from a fluorescent microscope: transition from zone 2 to zone 3 of the stenotic channel. Image was obtained with x20 objective. (c) Map of velocity magnitude at mean height in the stenotic canal, obtained using velocimetry imaging of microparticles: transition from zone 2 to zone 3. (d) Dimensionless velocity profiles U⁄Umax as a function of Y⁄Ymax or Z ⁄Zmax (U is the magnitude velocity, Ymax - stenosis half-width, Zmax - half-height) at the average height and average width of the microfluidic flow chamber in zone 3. (e) Computational fluid dynamics analysis representing the shear rate at the bottom of the chamber (z = 0) throughout the chamber and in the enlarged area, corresponding to the entrance to zone 3. The geometry of the channel in the computational fluid dynamics (CFD) model corresponded to the stenotic version of the chamber shown in panel (a). Figure adapted from [20].](https://astore.sbpreports.com/issues/articles/7/figures/fig_3.png?v=xdjpt)
Miscellaneous: beyond traditional tasks and techniques
In several works, microfluidic approaches have also been successfully used to analyze fibrin polymerization under flow conditions, but in the absence of platelets
Thrombin Flux and Wall Shear Rate Regulate Fibrin Fiber Deposition State during Polymerization under Flow
K. Neeves, D. Illing, S. Diamond
Biophysical Journal. 2010, 98, 1344-1352
Thrombin generation and fibrin formation under flow on biomimetic tissue factor-rich surfaces
A. Onasoga-Jarvis, T. Puls, S. O'Brien, L. Kuang, H. Liang, K. Neeves
Journal of Thrombosis and Haemostasis. 2014, 12, 373-382
In most current models of thrombosis, the flow in the system is kept constant by using syringe pumps, leading to drastic increase of local pressure gradients in case when thrombus significantly alters hydraulic resistance of a system. Such conditions of a constant flow are non-physiological; therefore, in some models, researchers use special bypass channels, thereby realizing the conditions of a quasi-stationary pressure drop
Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear
V. Govindarajan, S. Zhu, R. Li, Y. Lu, S. Diamond, J. Reifman, A. Mitrophanov
Biophysical Journal. 2018, 114, 978-991
Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network
J. Zilberman-Rudenko, J. Sylman, H. Lakshmanan, O. McCarty, J. Maddala
Cellular and Molecular Bioengineering. 2017, 10, 16-29
High Shear Thrombus Formation under Pulsatile and Steady Flow
L. Casa, D. Ku
Cardiovascular Engineering and Technology. 2014, 5, 154-163
The influence of the pulsatility of the blood flow on the extent of platelet adhesion.
Zhao XM, Wu YP, Cai HX, Wei R, Lisman T, Han JJ, Xia ZL, de Groot PG
Thrombosis research. 2008, 121, 821-5
Either syringe pumps or hydrostatic pressure is commonly used to provide fluid perfusion through the flow chamber. A more complicated approach, ex vivo autoperfusion system, has recently been proposed to study the behavior of mouse leukocytes and platelets under realistic hemodynamic conditions
A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function
A. Hafezi-Moghadam, K. Thomas, C. Cornelssen
American Journal of Physiology-Cell Physiology. 2004, 286, C876-C892
The studies of thrombus formation under blood flow conditions in vitro in most aim to reproduce processes that occur in vivo in case of non-penetrating damage to the inner layer of the vascular wall above the atherosclerotic plaque and thus correspond to arterial thrombosis. Another pathological scenario of thrombus formation is the formation of a so-called red venous thrombi in the area ofstagnant zones near the venous valves. To simulate this process, a special microfluidic flow chamber was proposed, in which, due to the selection of geometric and hemodynamic parameters, a stagnant zone is formed that simulates the situation in a living organism
Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI–Dependent Manner in an In Vitro Venous Thrombosis Model
M. Lehmann, R. Schoeman, P. Krohl, A. Wallbank, J. Samaniuk, M. Jandrot-Perrus, K. Neeves
Arteriosclerosis, Thrombosis, and Vascular Biology. 2018, 38, 1052-1062
Today, in vitro models of thrombosis are much more often used in basic research than in clinical practice, which is mainly associated with the problems of standartizing such systems. Nevertheless, flow chambers are slowly gaining popularity in clinical studies as novel diagnostic tools
High-throughput measurement of human platelet aggregation under flow: application in hemostasis and beyond
S. Brouns, J. van Geffen, J. Heemskerk
Platelets. 2018, 29, 662-669
The use of microfluidics in hemostasis
K. Neeves, A. Onasoga, A. Wufsus
Current Opinion in Hematology. 2013, 20, 417-423
Subcommittee on Biorheology. In vitro flow‐based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis.
5. Mangin PH, Neeves KB, Lam WA, Cosemans JM, Korin N, Kerrigan SW, Panteleev MA
Journal of Thrombosis and Haemostasis. 2021, 19, 582-7
Point-of-Care Diagnostic Assays and Novel Preclinical Technologies for Hemostasis and Thrombosis
C. Caruso, W. Lam
Seminars in Thrombosis and Hemostasis. 2021, 47, 120-128
In vitro models of hemostasis
A Microfluidic Model of Hemostasis Sensitive to Platelet Function and Coagulation
R. Schoeman, K. Rana, N. Danes, M. Lehmann, J. Di Paola, A. Fogelson, K. Leiderman, K. Neeves
Cellular and Molecular Bioengineering. 2017, 10, 3-15
![Scheme of a microfluidic model of hemostasis with an injury channel. Citrated whole blood and recalcification buffer were combined at a 9:1 volumetric flow ratio. Recalcified whole blood (red) and wash buffer (blue) were injected into two different vertical channels of the extravascular injury device. A horizontal injury channel (consisting of collagen and/or TF) connects two vertical channels. Adapted from [32].](https://astore.sbpreports.com/issues/articles/7/figures/fig_4.png?v=nqhyb)
A microengineered vascularized bleeding model that integrates the principal components of hemostasis
Y. Sakurai, E. Hardy, B. Ahn, R. Tran, M. Fay, J. Ciciliano, R. Mannino, D. Myers, Y. Qiu, M. Carden, W. Baldwin, S. Meeks, G. Gilbert, S. Jobe, W. Lam
Nature Communications. 2018, 9, None
![Multilayer microfluidic model of bleeding. (a) Three PDMS-layers: 1-vascular layer, consisting of a vascular channel and a bleeding channel, 2-PDMS valve layer, 3-layer that deforms the valve due to pressure reduction; (b) The schematics of the assembled device; c) General scheme of the system: first, endothelial cells (pink) are cultured to form a monolayer in the vascular channel (blue). d) Further, whole blood (red) is perfused and the valve layer is displaced by decrease of the pressure in the valve actuator chamber (white). Blood, while the valve is in the open position, flows through the vascular channel, as well as through the newly created channel, simulating bleeding due to penetrating damage. Adapted from [33].](https://astore.sbpreports.com/issues/articles/7/figures/fig_5.png?v=sdpvd)
A Human Vascular Injury‐on‐a‐Chip Model of Hemostasis
I. Poventud‐Fuentes, K. Kwon, J. Seo, M. Tomaiuolo, T. Stalker, L. Brass, D. Huh
Small. 2021, 17, 2004889
![In vitro model of hemostasis with artificial vessel. a) The system is encapsulated into PDMS shell. Basic components are shown in the schematics and labeled accordingly b) Consecutive steps of the puncturing process performed by the needle. The needle is moved from right to the left and first penetrates the blood chamber (right section), then punctures the endothelial layer (shown red) and collagen gel section (middle), and finally reaches the “extravascular” domain, denoted as bleeding chamber. Adapted from [34].](https://astore.sbpreports.com/issues/articles/7/figures/fig_6.png?v=hwjji)
Conclusion
Funding
References of this article:
Arterial thrombosis—insidious, unpredictable and deadly
S. Jackson
Nature Medicine. 2011, 17, 1423-1436
Murine Models of Vascular Thrombosis
R. Westrick, M. Winn, D. Eitzman
Arteriosclerosis, Thrombosis, and Vascular Biology. 2007, 27, 2079-2093
High-throughput measurement of human platelet aggregation under flow: application in hemostasis and beyond
S. Brouns, J. van Geffen, J. Heemskerk
Platelets. 2018, 29, 662-669
The use of microfluidics in hemostasis
K. Neeves, A. Onasoga, A. Wufsus
Current Opinion in Hematology. 2013, 20, 417-423
Subcommittee on Biorheology. In vitro flow‐based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis.
5. Mangin PH, Neeves KB, Lam WA, Cosemans JM, Korin N, Kerrigan SW, Panteleev MA
Journal of Thrombosis and Haemostasis. 2021, 19, 582-7
In Silico Hemostasis Modeling and Prediction
D. Nechipurenko, A. Shibeko, A. Sveshnikova, M. Panteleev
Hämostaseologie. 2020, 40, 524-535
Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates
K. NEEVES, S. MALONEY, K. FONG, A. SCHMAIER, M. KAHN, L. BRASS, S. DIAMOND
Journal of Thrombosis and Haemostasis. 2008, 6, 2193-2201
Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient
R. Muthard, S. Diamond
Lab on a Chip. 2013, 13, 1883
Tissue‐engineered 3D microvessel and capillary network models for the study of vascular phenomena
M. Bogorad, J. DeStefano, A. Wong, P. Searson
Microcirculation. 2017, 24,
Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms
S. Ahn, Y. Sei, H. Park, J. Kim, Y. Ryu, J. Choi, H. Sung, T. MacDonald, A. Levey, Y. Kim
Nature Communications. 2020, 11,
Engineering of Hydrogel Materials with Perfusable Microchannels for Building Vascularized Tissues
R. Xie, W. Zheng, L. Guan, Y. Ai, Q. Liang
Small. 2020, 16, 1902838
Bioprinted thrombosis-on-a-chip
Y. Zhang, F. Davoudi, P. Walch, A. Manbachi, X. Luo, V. Dell'Erba, A. Miri, H. Albadawi, A. Arneri, X. Li, X. Wang, M. Dokmeci, A. Khademhosseini, R. Oklu
Lab on a Chip. , 16, 4097-4105
Pharmacological Blockade of Glycoprotein VI Promotes Thrombus Disaggregation in the Absence of Thrombin
M. Ahmed, V. Kaneva, S. Loyau, D. Nechipurenko, N. Receveur, M. Le Bris, E. Janus-Bell, M. Didelot, A. Rauch, S. Susen, N. Chakfé, F. Lanza, E. Gardiner, R. Andrews, M. Panteleev, C. Gachet, M. Jandrot-Perrus, P. Mangin
Arteriosclerosis, Thrombosis, and Vascular Biology. 2020, 40, 2127-2142
Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface
D. Nechipurenko, N. Receveur, A. Yakimenko, T. Shepelyuk, A. Yakusheva, R. Kerimov, S. Obydennyy, A. Eckly, C. Léon, C. Gachet, E. Grishchuk, F. Ataullakhanov, P. Mangin, M. Panteleev
Arteriosclerosis, Thrombosis, and Vascular Biology. 2019, 39, 37-47
Core and shell platelets of a thrombus: A new microfluidic assay to study mechanics and biochemistry
M. DeCortin, L. Brass, S. Diamond
Research and Practice in Thrombosis and Haemostasis. 2020, 4, 1158-1166
Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting
N. Podoplelova, A. Sveshnikova, Y. Kotova, A. Eckly, N. Receveur, D. Nechipurenko, S. Obydennyi, I. Kireev, C. Gachet, F. Ataullakhanov, P. Mangin, M. Panteleev
Blood. 2016, 128, 1745-1755
Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow
F. Swieringa, C. Baaten, R. Verdoold, T. Mastenbroek, N. Rijnveld, K. van der Laan, E. Breel, P. Collins, M. Lancé, Y. Henskens, J. Cosemans, J. Heemskerk, P. van der Meijden
Arteriosclerosis, Thrombosis, and Vascular Biology. 2016, 36, 692-699
Contribution of platelet glycoprotein VI to the thrombogenic effect of collagens in fibrous atherosclerotic lesions
J. Cosemans, M. Kuijpers, C. Lecut, S. Loubele, S. Heeneman, M. Jandrot-Perrus, J. Heemskerk
Atherosclerosis. 2005, 181, 19-27
Identification of platelet function defects by multi-parameter assessment of thrombus formation
S. de Witt, F. Swieringa, R. Cavill, M. Lamers, R. van Kruchten, T. Mastenbroek, C. Baaten, S. Coort, N. Pugh, A. Schulz, I. Scharrer, K. Jurk, B. Zieger, K. Clemetson, R. Farndale, J. Heemskerk, J. Cosemans
Nature Communications. 2014, 5,
Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner
E. Westein, A. van der Meer, M. Kuijpers, J. Frimat, A. van den Berg, J. Heemskerk
Proceedings of the National Academy of Sciences. 2013, 110, 1357-1362
A shear gradient–dependent platelet aggregation mechanism drives thrombus formation
W. Nesbitt, E. Westein, F. Tovar-Lopez, E. Tolouei, A. Mitchell, J. Fu, J. Carberry, A. Fouras, S. Jackson
Nature Medicine. 2009, 15, 665-673
Shear rate gradients promote a bi-phasic thrombus formation on weak adhesive proteins, such as fibrinogen in a von Willebrand factor-dependent manner.
Receveur, Nicolas, Dmitry Nechipurenko, Yannick Knapp, Aleksandra Yakusheva, Eric Maurer, Cécile V. Denis, François Lanza, Mikhail Panteleev, Christian Gachet, and Pierre H. Mangin.
Haematologica. 2020, 105,
Thrombin Flux and Wall Shear Rate Regulate Fibrin Fiber Deposition State during Polymerization under Flow
K. Neeves, D. Illing, S. Diamond
Biophysical Journal. 2010, 98, 1344-1352
Thrombin generation and fibrin formation under flow on biomimetic tissue factor-rich surfaces
A. Onasoga-Jarvis, T. Puls, S. O'Brien, L. Kuang, H. Liang, K. Neeves
Journal of Thrombosis and Haemostasis. 2014, 12, 373-382
Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear
V. Govindarajan, S. Zhu, R. Li, Y. Lu, S. Diamond, J. Reifman, A. Mitrophanov
Biophysical Journal. 2018, 114, 978-991
Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network
J. Zilberman-Rudenko, J. Sylman, H. Lakshmanan, O. McCarty, J. Maddala
Cellular and Molecular Bioengineering. 2017, 10, 16-29
High Shear Thrombus Formation under Pulsatile and Steady Flow
L. Casa, D. Ku
Cardiovascular Engineering and Technology. 2014, 5, 154-163
The influence of the pulsatility of the blood flow on the extent of platelet adhesion.
Zhao XM, Wu YP, Cai HX, Wei R, Lisman T, Han JJ, Xia ZL, de Groot PG
Thrombosis research. 2008, 121, 821-5
A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function
A. Hafezi-Moghadam, K. Thomas, C. Cornelssen
American Journal of Physiology-Cell Physiology. 2004, 286, C876-C892
Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI–Dependent Manner in an In Vitro Venous Thrombosis Model
M. Lehmann, R. Schoeman, P. Krohl, A. Wallbank, J. Samaniuk, M. Jandrot-Perrus, K. Neeves
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