Lysine-PEG-modified polyurethane as a fibrinolytic surface: Effect of PEG chain length on protein interactions, platelet interactions and clot lysis.
Fibrinolytic polyurethane surfaces were prepared by conjugating lysine to the distal terminus of surface-grafted poly(ethylene glycol) (PEG). Conjugation was through the alpha-amino group leaving the epsilon-amino group free. Lysine in this form is expected to adsorb both plasminogen and t-PA specifically from blood. It was shown in previous work that the PEG spacer, while effectively resisting nonspecific protein adsorption, was a deterrent to the specific binding of plasminogen. In the present work, the effects of PEG spacer chain length on the balance of nonspecific and specific protein binding were investigated. PEG-lysine (PEG-Lys) surfaces were prepared using PEGs of different molecular weight (PEG300 and PEG1000). The lysine-derivatized surfaces with either PEG300 or PEG1000 as spacer showed good resistance to fibrinogen in buffer. The PEG300-Lys surface adsorbed plasminogen from plasma more rapidly than the PEG1000-Lys surface. The PEG300-Lys was also more effective in lysing fibrin formed on the surface. These results suggest that the optimum spacer length for protein resistance and plasminogen binding is relatively short. Immunoblots of proteins eluted after plasma contact confirmed that the PEG-lysine surface adsorbed plasminogen while resisting most of the other plasma proteins. The hemocompatibility of the optimized PEG-lysine surface was further assessed in whole blood experiments in which fibrinogen adsorption and platelet adhesion were measured simultaneously. Platelet adhesion was shown to be strongly correlated with fibrinogen adsorption. Platelet adhesion was very low on the PEG-containing surfaces and neither surface-bound lysine nor adsorbed plasminogen promoted platelet adhesion.
Li
Dan
D
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan, People's Republic of China.
Chen
Hong
H
Glenn McClung
W
W
Brash
John L
JL