ABSTRACT
Reducing the local thrombogenicity of an implanted stent remains an important and clinically significant goal (e.g. in cases of unstable angina, treatment following recanalization of an acute or chronic occlusion, primary stenting of type C lesions, venous grafts, and after brachytherapy). Aside from preventing thrombosis (early response), a primary reduction in local thrombogenicity can also be expected to have a positive influence on the late response by reducing mitogenic factors, including plateletderived growth factor (PDGF).1 Other known factors that influence early and late local responses can be traced back to the adhesion and activation of leukocytes.2 Sawyer et al. studied the physical nature of contact activation of blood.3 They demonstrated that the electrolysis of blood only causes clotting at the anode, and this was the first indication of the participation of electrons in the interaction between blood and metal surfaces. Subsequently, Baurschmidt and Schaldach described the biophysical principle of thrombogenesis on metallic surfaces as an electron transfer from fibrinogen to the metal.4 This knowledge was technologically applied in developing a new therapeutic principle, that of using hybrid materials made of a metallic substrate coated with a semiconducting layer.5 Subsequently, as the result of a scientific development strategy, a novel and effective stent coating was derived from these biophysical descriptions-the silicon coating.6 This principle is demonstrated in the TenaxR stent (Biotronik, Berlin, Germany), which was proven comprehensively in vitro,7 and also clinically in a variety of patient groups.8-11
COATING CHARACTERISTICS/BIOPHYSICAL PRINCIPLES
Electron transfer processes are fundamental interactions between implant materials and proteins or cells. This is due to the fact that the basic physical structure of all proteins, which are dominated by the chain structure of interacting amino acids, is very similar. Proteins have the electronic properties of a semiconductor (Figure 11.1a). With the knowledge of the electronic structure of fibrinogen, and with the metallic surface as the reaction partner (the
energy levels of the electrons), it is possible to define the physical parameters that lead to permanent surface passivation. Electron transfer, the basic mechanism for fibrinogen degradation, is prevented when the alloplastic material has an energy ‘band gap’ >1.4 eV and when the electric conductivity is higher than 10−5 S/cm.5 An optimized (coating) material that meets these electronic requirements is amorphous hydrogen-rich
phosphorus-doped silicon carbide (a-SiC:H) (Figure 11.1b). The behavior of a-SiC:H, the proof of this concept, can be verified by comparing materials with different electronic properties in a solution containing fibrinogen by using scanning force microscopy (SFM) (Figure 11.2). On silicon (Si), which has the smallest energy gap (Egap= 1.1 eV), electron transfer is possible and conversion to fibrin occurs. In contrast, in the substrate’s mica (Egap>3 eV) and a-SiC:H (Egap= 2.0 eV), the gaps are large enough to prevent the tunneling of electrons.12 Because of the fundamental principles of the described interaction between proteins and alloplastic surfaces, similar behavior can be expected regarding the activation between the solids and the proteins of cell membranes of platelets and leukocytes. An example of results after 90 seconds contact between both silicon carbide-coated and uncoated 316L stainless steel and a platelet-containing electrolyte (100000 platelets/µl) is demonstrated in Figure 11.3.
