Modelling arterial thrombus formation in vitro

Abstract

Purpose of review Models of arterial thrombus formation represent a vital experimental tool to investigate platelet function and test novel antithrombotic drugs. This review highlights some of the recent advances in modelling thrombus formation in vitro and suggests potential future directions. Recent findings Microfluidic devices and the availability of commercial chips in addition to enhanced accessibility of 3D printing has facilitated a rapid surge in the development of novel in vitro thrombosis models. These include progression towards more sophisticated, ‘vessel on a chip’ models which incorporate vascular endothelial cells and smooth muscle cells. Other approaches include the addition of branches to the traditional single channel to yield an occlusive model; and developments in the adhesive coating of microfluidic chambers to better mimic the thrombogenic surface exposed following plaque rupture. Future developments in the drive to create more biologically relevant chambers could see a move towards the use of human placental vessels, perfused ex-vivo. However, further work is required to determine the feasibility and validity of this approach. Summary Recent advances in thrombus formation models have significantly improved the pathophysiological relevance of in vitro flow chambers to better reflect the in vivo environment and provide a more translational platform to test novel antithrombotics.

Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation

“…Results indicating that platelet responses are altered when collagens are exposed in the presence of vascular proteoglycans, such as those found in both plaque rupture and plaque erosion, may have implications on antiplatelet efficacy, which is routinely investigated in vitro using type I collagen in isolation [28][29][30][31][32]. The differences observed between 'rupture' and 'erosion' matrices also indicated that different mechanisms may be involved in the formation of arterial thrombi; therefore, the efficacy of antithrombotic drugs may differ depending on plaque type.…”