Vascular grafting in the management of thrombotic disorders

Currently available vascular prostheses yield lower patency rates than do autogenous vascular grafts when implanted into small and medium caliber arteries, in part due to the relatively thrombogenic nature of the tissue reactions that they elicit. Our laboratory has developed techniques for enhancing spontaneous reendothelialization of blood-contacting biomaterials. Prostheses are constructed of bioresorbable lactide-glycolide copolymers that are phagocytized by macrophages. After implantation into animal models, they elicit extensive transinterstitial capillary infiltration and an early endothelialized luminal surface that responds to sodium arachidonate by production of 6-keto-PGF1 alpha at rates resembling normal control artery. Concurrent cell culture studies have shown that macrophages in culture with these copolymers release into their media growth factors mitogenic for quiescent endothelial cells. Additional studies have developed a method of affixing (ECGF) to biomaterial surfaces. The future development of more clinically efficacious small vessel prostheses will depend on optimization of the tissue reactions, including either enhancement of spontaneous endothelialization, endothelial cell transplantation, or prostheses pre-endothelialized in culture, and on the function of these endothelialized surfaces in an anticoagulant fashion.