Construction of Hemocompatible and Histocompatible Surface by Grafting Antithrombotic Peptide ACH11 and Hydrophilic PEG.

Abstract

Blood-contacting materials with antiplatelet aggregation and anticoagulant properties are in great demand in biomedical field. Herein, hydrophilic poly(ethylene glycol) (PEG) and antithrombotic peptide ACH11 were coimmobilized onto Au to develop a multifunctional surface with remarkable hemocompatibility, antiprotein adsorption, antiplatelet aggregation, anticoagulant properties, and good histocompatibility. PEG can not only help the surface resist nonspecific protein adsorption and improve its hemocompatibility but also be a benefit for the immobilized ACH11 to maintain its bioactivity in plasma. The anticoagulant peptide ACH11 can endow the surface with the ability of activated coagulation factor Xa (FXa) inhibition and antiplatelet aggregation activities. Au was first aminated with 2-aminoethanethiol through strong Au-S bond, and then it was reacted with PEG-ACH11 through active ester chemistry to prepare the multifunctional surface Au-PEG-ACH11, among which the heterobifunctional PEG served as a linker to immobilize antithrombotic ACH11. The surface chemical structure and composition quantified by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy convinced us of the successful preparation of the PEG-ACH11 modified Au surface. The surface micromorphology and topography of the modified surfaces were observed by field emission scanning electron microscopy and atomic force microscopy. The good hydrophilicity of the modified Au surface was confirmed by water contact analysis. Enzyme immunoassay analysis demonstrated that the activation level of FXa in plasma after incubation with Au-PEG-ACH11 was obviously lower than that in control groups. In vitro hemocompatibility evaluation, including hemolysis rate, denaturation of adsorbed fibrinogen, and platelet adhesion and activation, indicated that Au-PEG-ACH11 possessed good hemocompatibility. In vivo subcutaneous implantation assay also confirmed the milder tissue response of Au-PEG-ACH11. These results indicated that the multifunctional surface has great potential for biomedical application.