Atomic Force Microscopy Imaging of Fibrinogen on Different Surfaces: Implications for Implantation Materials Design

Abstract number: P1381

Lim¹ B, Ariens¹ R, Weisel² J, Grant¹ P

¹¹University of Leeds, Leeds, UK ¹¹University of Leeds, Leeds, UK ²²University of Pennsylvania, Philadelphia, USA

Restenosis has been the Achilles' heel of interventional cardiology over the last decade. The recent introduction of drug eluting stents has reduced the incidence of restenosis dramatically but has not eradicated it. Fibrinogen via its influence on the fibrin scaffold has been shown to modulate interactions with remodelling cells and fibroblasts to result in increased atherogenesis and prothrombosis. Interactions between fibrinogen and biomaterials surfaces can, via changes in the conformation and behaviour of fibrinogen, modulate events downstream to influence interactions with remodelling cells and therefore atherogenesis and subsequently restenosis. A Digital Instruments multimode atomic force microscopy was employed for imaging and the liquid tapping mode was used. Different surface materials were used in the experiments to compare the properties of fibrinogen on the different surfaces including mica, mica coated with nickel chloride and highly oriented pyrolithic graphite. Fibrinogen was allowed to adsorb to the various surfaces and imaged. There was a difference in the behaviour of fibrinogen on the different surfaces. There was poor interaction between fibrinogen and untreated mica surfaces, such that the atomic force probe often ‘sweeps’ away the fibrinogen molecules. On mica surfaces that were pretreated with nickel chloride so that there is a positively charged surface, the fibrinogen molecules interacted more strongly with the surface and the atomic force probe did not sweep the molecules away. On the highly oriented pyrolithic graphite which is a hydrophobic surface, conformational changes in fibrinogen were observed suggesting strong interactions with the surface material. Furthermore, a frequent observation was that the fibrinogen molecules were aggregating. The different behaviour of the fibrinogen molecules on different surfaces suggest that modifying the surface to reduce interactions between fibrinogen and the surface may provide an antithrombotic profile to angioplasty stents that may lower restenosis rates.