Preparation of nonthrombogenic polymer surfaces: Immobilization of heparin and dextran oligosaccharides

Blood compatibility is a major concern in the development of synthetic biomaterials since most synthetic polymers will induce thrombosis formation on their surfaces once contact with blood or tissue. The objective of this thesis is to develop surface modification procedures for existing biomaterials, that will specifically inhibit the surface induced thrombosis and extend the lifetime of blood-contacting biomedical implants and devices. Three approaches have been developed to prepare the nonthrombogenic interfaces for biomaterials and devices.;The first approach involved the surface modification of biomaterials by radiofrequency plasma discharge. Two plasma polymer thin films (approx. 110 nm) were deposited on PE. Plasma polymer modified polyethylene surfaces exhibited significant water contact angle hysteresis and a much lower value of advancing water contact angle than that of unmodified polyethylene. Interfacial reduction of the plasma modified surfaces by an aqueous solution of sodium borohydride converted surface carbonyl groups into hydroxyl groups which served as active sites for further derivatization and heparin immobilization.;The second approach involved the immobilization of heparin on the biomaterial surfaces. Both cleaved heparin and high affinity heparin were immobilized onto the surfaces of PE, pyrolytic carbon heart valve material and Dacron vascular graft. These materials were modified by hydroxylated plasma polymers followed by coupling with amino-terminated poly(ethylene-oxide) (N-PEO) and 3-amino-propyltriethoxysilane (APTS) before the immobilization of heparin. The anticoagulant activity of heparin immobilized surfaces was determined by a chromogenic assay for the inhibition of factor Xa. Visual confirmation of the presence of HA-heparin on PE was demonstrated by a gold-labeled double antibody method with imaging by SEM and AFM. The presence of heparin on the immobilized surfaces was also confirmed by ESCA analysis.;The third approach involved the physisorption of dextran-containing surfactant on the biomaterial surface. A triblock polymers with hydrophobic hydrocarbon in the middle and hydrophilic dextran molecules in the end has been synthesized. This triblock polymer adsorbed strongly on the biomaterial surfaces in the aqueous condition through the hydrophobic interaction between the hydrophobic surface and the hydrophobic segment in the triblock polymer. The adsorbed triblock polymer exhibited fairly stable and significant protein resistance on PE surfaces.