Engineering antithrombogenic surfaces in synthetic small-diameter vascular grafts: A review of passive strategies

Small-diameter vascular grafts are indispensable in coronary and peripheral artery bypass surgeries to reestablish the blood flow when blood vessels block. Despite advances in biomaterials' design, current clinical practice still relies heavily on autologous vessels, as synthetic grafts for small-diameter applications present high failure rates due to thrombosis and neointimal hyperplasia. Hence, there is a need for antithrombogenic synthetic small-diameter vascular grafts. Antithrombogenicity can be ensured by passive strategies, which aim to minimize nonspecific protein adsorption and platelet adhesion/activation onto the biomaterial's surface, hence preventing the onset steps of thrombus formation. This review aims to shed light on passive strategies reported in literature to improve antithrombogenicity and performance of vascular grafts. Such strategies include either surface modifications of pre-existing materials composing the backbone of vascular grafts (such as expanded polytetrafluorethylene or polyethylene terephthalate), or the creation of novel intrinsically antithrombogenic bulk materials for fabrication of such conduits. Endowing vascular grafts with antithrombogenic properties has been attempted using a variety of macromolecules, from hydrophilic polymers such as the classically-explored poly(ethylene glycol), to more recently proposed hydrophobic lubricant-infused surfaces. Here, the physicochemical phenomena underlying each surface type is carefully analyzed, reporting both in vitro and in vivo results. By critically examining both theoretical and translational aspects of each strategy, this review provides key insights to guide future innovations in vascular graft design and development. STATEMENT OF SIGNIFICANCE: Small-diameter vascular grafts, used in bypass surgeries when blood vessels block, still fail due to thrombosis. This review highlights passive strategies - i.e. strategies which aim to minimize nonspecific protein adsorption and platelet adhesion - to prevent thrombosis in vascular grafts. By looking into the types of polymers explored, evaluating their molecular mechanisms, reporting in vitro and in vivo results, and critically analyzing translational aspects, it provides a comprehensive guide and future perspective of passive strategies. As such, it appeals to authors interested in the development of vascular grafts, as well as other blood-contacting devices.