Thromboresistant alkyl derivatized polyurethanes

We have developed an alkylation process of synthetic polymers that selectively increases their affinity for albumin. Evidence from in vitro and in vivo experiments supports the concept that alkyl-derivatized polymers, in this case polyurethanes (Biomer and Pellethane 2363 80A), bind a thromboresistant albumin coat. In vitro kinetic studies with alkylated polyurethanes indicated that albumin was rapidly and massively adsorbed, and that albumin adsorption was substantially favored in competitive albumin-fibrinogen uptake studies. Alkylation almost eliminated red and white thrombus formation on 4 mm ID Biomer grafts in the canine femoral artery in short-term exposures in which no anticoagulation or prealbumination was employed. When albumin was preadsorbed and systemic heparinization was employed, superior thromboresistance was still observed for alkylated grafts. In both cases, scanning electron micrographs (SEM) of alkylated grafts revealed regions of single white cell and/or platelet adhesion, or no cell adhesion, and virtually no fibrin. In contrast, scans of ¹²⁵I fibrinogen distributions for 24-hour graft exposures revealed progressive buildup of fibrinogen at the anastomotic lines. This material eventually deposited in significant amounts on the alkylated grafts, but at substantially lower rates than observed with control grafts. These observations support the concept that preferentially bound endogenous albumin promotes thromboresistance in short term exposure to blood. According to our hypothesis, albumin may be reversibly sorbed on alkyl-derivatized surfaces and thus may impart substantial thromboresistance to blood-contacting devices for clinically significant periods of time.