Improved blood compatibility and decreased VSMC proliferation of surface-modified metal grafted with sulfonated PEG or heparin.
Although the technique of coronary stenting has remarkably improved long-term results in recent years, (sub)acute thrombosis and late restenosis still remain problems to be solved. Metallic surfaces were regarded as thrombogenic, due to their positive surface charges, and stenosis resulted from the activation and proliferation of vascular smooth muscle cells (VSMCs). In this study, a unique surface modification method for metallic surfaces was studied using a self-assembled monolayer (SAM) technique. The method included the deposition of thin gold layers, the chemisorption of disulfides containing functional groups, and the subsequent coupling of PEG derivatives or heparin utilizing the functional groups of the disulfides. All the reactions were confirmed by ATR-FTIR and XPS. The surface modified with sulfonated PEG (Au-S-PEG-SO3) or heparinized PEG (Au-S-PEG-Hep) exhibited decreased static contact angles and therefore increased hydrophilicity to a great extent, which resulted from the coupling of PEG and the ionic groups attached. In vitro fibrinogen adsorption and platelet adhesion onto the Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces decreased to a great extent, indicating enhanced blood compatibility. This decreased interaction of the modified surfaces should be attributed to the non-adhesive property of PEG and the synergistic effect of sulfonated PEG. The effect of the surface modification on the adhesion and proliferation of VSMCs was also investigated. The modified Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces also exhibited decreased adhesion of VSMCs, while the deposited gold layer itself was effective. The enhanced blood compatibility and the decreased adhesion of VSMCs on the modified metallic surfaces may help to decrease thrombus formation and suppress restenosis. It would therefore be very useful to apply these modified surfaces to stents for improved functions. A long-term in vivo study using animal models is currently under way.
Lee
Hee Jung
HJ
Biomaterials Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongnyang, Seoul 130-650, Korea.
Hong
Jong-Kyu
JK
Goo
Hyun Chul
HC
Lee
Won Kyu
WK
Park
Ki Dong
KD
Kim
Soo Hyun
SH
Yoo
Young Mi
YM
Kim
Young Ha
YH
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology / Q000592:standards; D001777:Blood Coagulation / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008670:Metals / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis; D015607:Stents / Q000592:standards; D013499:Surface Properties
D001672:Biocompatible Materials; D004220:Disulfides; D008670:Metals; D011092:Polyethylene Glycols; D005340:Fibrinogen; D006493:Heparin