In the context of hemodialysis vascular accesses, the best practice encouraged by international guidelines is the creation of a native fistula, i.e., the direct surgical connection between an artery and a vein, which however is not always feasible in all patients (e.g. elderly, diabetics, patients with high Body Mass Index), and usually takes 6-8 weeks to reach a sufficient maturation stage to allow for puncturing. Therefore, in case of compromised vasculature and/or when early cannulation (within 24-48 hours after access creation) is needed, synthetic grafts are used, e.g. made of ePTFE (expanded polytetrafluoroethylene) or polyurethane. However, prosthetic grafts carry a lifetime risk of thrombosis, stenosis and infection and the 2-year primary patency for ePTFE arteriovenous grafts for hemodialysis ranges from 30% to 40%.
The most common mechanisms of failure for autologous (venous) and synthetic grafts, implanted either in arteriovenous or arterial districts, are known to be thrombosis due to platelet activation in the short term (≈ weeks) and stenosis due to neointimal hyperplasia in the midterm (≈ months).
Platelet activation – the initial step towards thromboembolic events – may occur due to the contact of blood cells with non-endothelial surfaces, but also as a consequence of shear-related phenomena.
Neointimal hyperplasia, instead, refers to a process in which the intima gets thicker due to the presence of vascular smooth muscle cells and proteoglycan-rich extracellular matrix located between the endothelium and the internal elastic lamina.
Although there is not a general consensus on the molecular mechanisms leading to grafts’ failure, researchers agree that the common denominator at the basis of platelet activation and neointimal hyperplasia may be the difference in mechanical properties – and specifically in radial compliance – between grafts and recipient vessels (phenomenon known as “compliance mismatch”), which leads to disturbances in shear stress due to non-physiological hemodynamics and to stress concentration at the anastomosis