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In vitro models of thrombosis and hemostasis

Abnormalities in hemostatic response are responsible for a large number of life-threatening conditions, however, despite many decades of research, today there are no reliable ways to correct hemostasis without significant risks of thrombosis or bleeding. This situation reflects a poor understanding of the key mechanisms that regulate the hemostatic response. To uncover the principles underlying the regulation of hemostasis, both experimental models and theoretical approaches are actively used. This review focuses on current in vitro models of thrombosis and hemostasis and describes key approaches and tools for studying blood coagulation outside the human/animal body. To reconstruct this process, both microfluidic technologies and approaches based on manufacturing artificial vessels using a variety of hydrogels are actively used. In vitro models of thrombosis traditionally mimic non-penetrating damage to the vessel wall and have been used for more than 30 years to uncover the key processes responsible for the formation of arterial thrombi. Models of in vitro hemostasis have been actively developed only in recent years and are focused ono crucial mechanisms governing the formation of hemostatic plugs - clots that stop bleeding upon a penetrating vascular injury. Modern in vitro models of thrombosis and hemostasis are used not only as tools for fundamental research but are also introduced into clinical practice.

Fabrication of PDMS-based flow chamber: a) A master mold is prepared using photolithography. The relief (typically made of photoresist on a silicon wafer, shown in orange) usually contains several patterns to be imprinted on PDMS; b) The relief form (master mold) is poured with the liquid mixture of PDMS base with curing agent; с-d) A part of polymerized PDMS is then сut and extracted from the mold e) inlet and outlet holes are made and the required tubings are connected. The chamber is attached onto the glass or plastic coverslip (gray) using plasma bonding or vacuum-sealing.
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#hemostasis#platelets#microfluidics#hydrogel#whole blood#in vitro models#thrombosis

Platelet functional responses and signalling: the molecular relationship. Part 1: responses.

Blood platelets are small anucleated cells whose main function is to form a plug upon vascular damage to stop bleeding. This role involves a number of functional responses induced by different agonists and coordinated by an intricate network of signal transduction pathways. Understanding this network is vital from both basic research point of view and for the purposes of drug target identification in thrombosis and hemostasis. This review series will focus on the regulation of platelet signalling, on tracking the molecular relationship between receptor activation and functional responses, and on the networking aspects of these pathways. The present paper, first one out of two, focuses on the description of platelet functional responses and of the conditions for their triggering.
Platelet functional responses within arterial thrombus.
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#hemostasis#platelet activation#platelet intracellular signaling#thrombosis#thrombus formation

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