Cardiovascular diseases determined by arteriosclerosis are the main cause of death in developed nations . Since surgical interventions strongly stress the patient's organism, modern minimal invasive methods have become more and more important . During the last two decades, intravascular coronary stent implantation at the site of acute artery closure has been widely used and has increased the quality of life and life expectancy of patients with coronary diseases. This type of surgery has proved effective in restoring vessel potency and decreasing myocardial ischemia. 316L stainless steel and titanium(alloys) are widely used in the fabrication of coronary stents because of their electrochemical and mechanical properties . However, the exposure to blood flow can result in thrombus formation and smooth muscle cell proliferation, which both ultimately lead to restenosis. To avoid thrombus formation, aggressive anticoagulants are systemically applied, however, this can cause bleeding disorder in long-term application. Thus, a great amount of recent work has attempted to develop non-thrombogenic coatings for these metallic stents, e.g. by chemical coupling of antithrombogenic drugs (heparin, heparan sulfate) to the surface [4,5].
This work aimed to investigate the influence of different coupling agents with varying chain length on the amount and biological performance of surface bound heparin. The principle of the surface modification is demonstrated in Figure 1a for 3-(Trimethoxysilyl)-propylamine (APMS) as commonly used spacer. Alternative coupling agents (Figure 1b) with two or three amino-moieties were N- [3-(Trimethoxysilyl)propyl]ethylenediamine (Diamino-APMS) and N1- [3-(Trimethoxysilyl)-propyl]diethylenetriamine (Triamino-APMS). Surface modification was performed using both TiO2 powder and titanium sheets as substrates. The coupling reaction was followed by means of zeta-potential measurements and the amount of surface bound spacer and heparin and their hydrolytic stability was quantified via the ninhydrin and the toluidine-blue reaction. Determination of the biological activity of the immobilised heparin was performed with the chromogenic substrate Chromozym TH test. Fibrinogen adsorption to the modified surfaces was followed in real time using Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D).