Immobilization of the direct thrombin inhibitor-bivalirudin on 316L stainless steel via polydopamine and the resulting effects on hemocompatibility in vitro

摘要

Bivalirudin (BV), a peptidic direct thrombin inhibitor, derived from hirudin, has gained increasing interest in clinical anticoagulant therapy in the recent years. In this work, a hemocompatible surface was prepared by immobilization of BV on 316L stainless steel (SS) using a bonding layer of polydopamine (DA). X-ray photoelectron spectros-copy (XPS) was used to determine the chemical composition of the surfaces to characterize polydopamine intermediate layer and the immobilized BV. The quantity of bound BV was measured by quartz crystal microbalance (QCM). The hemocompatibility in vitro was evaluated by coagulating time of activated partial thromboplastin time (aPTT) and prothrombin time (PT) assay, platelet adhesion and activation, fibrinogen adsorption, and activation and whole blood test. The effect of sterilizing method on the bioactivity of immobilized BV was also evaluated. The results showed that BVs were successfully immobilized on SS surface with the DA interlayer at a density of 98 ng/cm2. BV coating surface prolonged aPTT and PT, inhibited the activation of platelet and fibrinogen significantly. Sterilization by ultraviolet radiation was possible with only marginal loss of activity. Thus, the approach described here may provide a basis for the preparation of 316L SS surface modification for use in cardiovascular implants.