Addressing thrombogenicity in vascular graft construction.
Thrombosis is a major cause of poor patency in synthetic vascular grafts for small diameter vessel (< 6 mm) bypass. Arteries have a host of structural mechanisms by which they prevent triggering of platelet activation and the clotting cascade. Many of these are present in vascular endothelial cells. These mechanisms act together with perpetual feedback at different levels, providing a constantly fine-tuned non-thrombogenic environment. The arterial wall anatomy also serves to promote thrombosis as a healing mechanism when it has been severely injured. Surface modification of synthetic graft surfaces to attenuate the coagulation cascade has reduced thrombosis levels and improved patency in vitro and in animal models. Success in this endeavor is critically dependent on the methods used to modify the surface. Platelets adhere to positively charged surfaces due to their own negative charge. They also preferentially attach to hydrophobic surfaces. Therefore synthetic graft development is concerned with hydrophilic materials with negative surface charge. However, fibrinogen has both hydrophilic and hydrophobic binding sites-amphiphilic materials reduce its adhesion and subsequent platelet activation. The self-endothelializing synthetic graft is an attractive proposition as a confluent endothelial layer incorporates many of the anti-thrombogenic properties of arteries. Surface modification to promote this has shown good results in animal models. The difficulties experienced in achieving spontaneous endothelialisation in humans have lead to the investigation of pre-implantation in vitro endothelial cell seeding. These approaches ultimately aim to result in novel synthetic grafts which are anti-thrombogenic and hence suitable for coronary and distal infrainguinal bypass.
Sarkar
Sandip
S
Biomaterials and Tissue Engineering Centre (BTEC), Academic Division of Surgical and Interventional Sciences, University College London, London, United Kingdom.
Sales
Kevin M
KM
Hamilton
George
G
Seifalian
Alexander M
AM
D001158:Arteries / Q000166:cytology*; D001777:Blood Coagulation / Q000502:physiology*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D011474:Prosthesis Design; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control*