The Studies On Immobilization Of The Direct Thrombin Inhibitor-Bivalirudin On316L Stainless Steel Via Polydopamine

Bivalirudin, a peptidic direct thrombin inhibitor, derived from hirudin, has gained increasing interest in clinical anticoagulant therapy in the recent years. In the present work, a hemocompatible surface was prepared by immobilization of bivalirudin (BV) on316L stainless steel (SS) using a bonding layer of polydopamine (DA). FT-IR spectrometer(FT-IR) and X-ray photoelectron spectroscopy (XPS) was used to determine the chemical composition of the surfaces to characterize polydopamine intermediate layer and the immobilized bivalirudin. The quantity of bound bivalirudin was measured by quartz crystal microbalance (QCM). We also measured the water contact angles of surfaces and the quantity of Acid groups on surfaces. The hemocompatibility in vitro was evaluated by coagulating time of aPTT and PT assay, platelet adhesion and activation, fibrinogen adsorption and activation and whole blood test. The effect of sterilizing method on the bioactivity of immobilized bivalirudin was also evaluated. The results showed that bivalirudin were successfully immobilized on stainless steel surface with the DA interlayer at a density of98ng/cm2. The washing step is reliable, and the major part of immobilized bivalirudin is covalent binding, a few of them was due to the electrostatic self-assembly. Bivalirudin coating surface prolonged aPTT and PT, inhibited the activation of platelet and fibrinogen significantly. Sterilization by ultraviolet (UV) radiation was possible with only marginal loss of activity. Also we have measured the cellular compatibility of samples with endothelial cell (ECs), smooth muscle cell (SMCs) and endothelial progenitor cells (EPCs). The results shows that there is few different for SS and BV samples cultivated with ECs or EPCs. But in early stage of cultivation, ECs or EPCs spread out better on BV than SS. It is worth noting that DA and BV samples which contain polydopamine on surface, showed a great inhibition of SMCs. That may make the polydopamine materials a potential of anti intimal hyperplasia that own to the rapid growth of SMCs. Thus the approach described here may provide a basis for the preparation of316L stainless steel surface modification for use in cardiovascular implants.