Improved blood compatibility and decreased VSMC proliferation of surface-modified metal grafted with sulfonated PEG or heparin

Abstract

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.

Facile immobilization of heparin on bioabsorbable iron via mussel adhesive protein (MAPs)

“…In addition, it had been confirmed that heparin could inhibit the proliferation of vascular smooth muscle cells (VSMCs) [8]. In the research by Lee [9], heparin was covalently bonded to stainless steel, and an effective inhabitation of VSMCs adhesion and improvement of blood compatibility were achieved. However, the immobilization methods mentioned above are toxic solvent containing, time consuming and relatively complicating with low grafted dense heparin.…”

Regulation of polyurethane hemocompatibility and endothelialization by tethered hyaluronic acid oligosaccharides

“…Immobilization of polyethylene glycol (PEG) is the most common approach used to render surfaces resistant to protein adsorption and subsequent cell and platelet adhesion [13][14][15]. However, PEG-modified surfaces are capable of only indirectly and passively inhibiting platelet adhesion and aggregation [16], and PEG indiscriminately blocks cell adhesion, thereby also inhibiting graft endothelialization.…”

Quantitative spatial distribution of sirolimus and polymers in drug‐eluting stents using confocal Raman microscopy

“…XPS has been used to characterize surfaces of several drug-polymer stent coatings including confirmation of drug identity and the determination of possible chemical reactions with the matrix components. 5,6,[15][16][17] Dynamic time-of-flight mass spectrometry performs destructive depth profiles through drug-polymer coatings for chemically specific information. 13,[18][19][20][21][22] Spectroscopic methods such as near infrared (NIR), Fourier transform infrared (FTIR), and Raman spectroscopy are nondestructive approaches that provide the chemical specificity needed to distinguish an active pharmaceutical ingredient (API) from the matrix components.…”

“…Combining the methods with microscopy has provided the ability to map the distribution of polymer blends, pharmaceutical formulations, and drug-polymer coatings on stents. 11,[15][16][17][23][24][25][26][27][28][29][30] Although NIR and FTIR imaging provide chemical selectivity, both suffer from poor spatial resolution and cannot depth profile through coatings. Fluorescence microscopy requires chemical labeling of the drug or a fluorophore inherent to the system.…”