Thromboresistant surface modification of expanded polytetrafluoroethylene vascular graft by impregnating covalently crosslinked gel of heparin and alginate

Background: The expanded polytetrafluoroethylene (ePTFE) vascular grafts hold promise for enhanced healing, extended suture retention, kink reduction and compression resistance. But thrombus formation still limits its use for revascularization of small-caliber vessels. It is the surface of ePTFE vascular graft that contacts with the blood. The current study focused on surface modification of ePTFE materials to improve its blood compatibility. Objective: To characterize the heparin/alginate (H/A) gel modified ePTFE vascular graft and investigate the hemocompatibility and histocompatibility of the graft. Design: Observation experiment. Setting: Laboratory for Nanomedicine and Biosensor, Biomedicine Engineering Center, Harbin Institute of Technology. Materials: The GORE-TEX ePTFE vascular grafts were 4 mm in internal diameter. Sodium alginate and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) were purchased from Sigma. Heparin sodium salt was obtained from Calbiochem. Nafion and chitosan were purchased from Aldrich company. Human α -thrombin and AT III were purchased from Haematologic Technologies, Inc. S-2238 was purchased from Chromogenix. Methods: This study was performed at the Laboratory for Nanomedicine and Biosensor, Biomedicine Engineering Center, Harbin Institute of Technology between May 2006 and June 2007. The graft was first modified with Nafion and then Chitosan/Nafion/Chitosan multilayer. Following the impregnation of heparin and alginate, covalent crosslinking was performed using ethylenediamine and EDC. Some characterization methods were employed: stastic water contact angle for the hydrophilicity; SEM for the surface morphology; ATR-FTIR for the surface chemical characteristics; APTT and PT, percent hemolysis and Chromogenic assay for the hemocompatibility of the ePTFE vascular graft after modification. Main outcome measures: 1 Static water contact angles. 2 Characterization of the surface morphology and platelet adhesion by SEM. 3 ATR-FTIR 4 APTT and PT. 5 Percent hemolysis 6 Chromogenic assay for heparin activity. Results: 1 ATR-FTIR revealed the presence of -CO-NH- at 1626 cm^-1. 2 The water contact angle was greatly decreased from (125 ± 1)° to (84 ± 2)°. 3 The prolonged APTT and PT, low percent hemolysis(0.065%) and low amount of platelet adhesion assay showed the H/A gel impregnated graft had good blood compatibility. 4 Chromogenic assay showed the modified graft was less thrombogenic than the bare one, and the H/A coating had good stability in. PBS buffer. Conclusion: The H/A modified ePTFE vascular graft has great potential in applications utilizing small-diameter vascular grafts.