Synthesis of a novel small diameter polyurethane vascular graft with reactive binding sites.

Abstract

Development of a small diameter (4 mm inner diameter [ID]) prosthetic vascular graft with functional groups accessible for covalent binding of recombinant hirudin (a potent anticoagulant) should create a more hemocompatible surface. The purpose of this study was to develop a technique for generating carboxylic acid groups on the surface of precast 4 mm ID poly-(carbonate urea)-urethane vascular grafts and to evaluate the accessibility of these groups. A polycarbonate based urethane with the chain extender 2,2-bis(hydroxymethyl)propionic acid was synthesized. A precast 4 mm ID poly(carbonate urea)-urethane vascular graft (Chronoflex [CF]; CardioTech International, Woburn, MA) was then placed into a 4% carboxylated polyurethane (cPU) solution (in 1% dimethyl acetamide) and incubated for 30 minutes (cPU graft). To determine the accessibility of the carboxylic acid groups, a standard textile technique using methylene blue dye was used. Macroscopic cross-sections, which were cut and evaluated for dye penetration, showed greatest concentration of carboxylic acid groups at the luminal and capsule surfaces, with minimal penetration into the mid-portion of the graft. Analysis of dye baths for absorbance reduction resulted in the cPU grafts having 3.7-fold and 5.4-fold more accessible carboxylic acid groups compared with untreated and dimethyl acetamide dipped CF grafts. Thus, a novel small diameter vascular graft has been developed that contains reactive carboxylic acid groups accessible for protein binding.