Bioinspired Blood Compatible Surface Having Combined Fibrinolytic and Vascular Endothelium-Like Properties via a Sequential Coimmobilization Strategy

Developing surfaces with antithrombotic properties is of great interest for the applications of blood-contacting biomaterials and medical devices. It is promising to coimmobilize two or more biomolecules with different and complementary functions to improve blood compatibility. However, the general one-pot strategy usually adopted by previous studies suffers the problems of inevitable competition between diverse biomolecules and uncontrollability of the relative quantities of the immobilized biomolecules. To solve these problems, a new sequential coimmobilization strategy is proposed and applied to fabricate a blood compatible surface. Polyurethane surface is modified with a copolymer, poly(2-hydroxyethyl methacrylate-co-1-adamantan-1-ylmethyl methacrylate), which serves as a linker-spacer for sequential attachment of two functional molecules, a hexapeptide containing REDV (Arg-Glu-Asp-Val) sequence, and a modified cyclodextrin bearing 7 lysine ligands, through covalent bonding and host-guest interaction, respectively. The resulting surface combines the antithrombogenic properties of the vascular endothelium and the clot lysing properties of the fibrinolytic system. Importantly, neither of the two functions of REDV peptide and lysine is compromised by the presence of the other, suggesting the enhanced blood compatibility. These results suggest a new strategy to engineer multifunctional surfaces by coimmobilization of bioactive molecules having unique functionalities.