Review 10.1586/17434440.3.2.245 © 2006 Future Drugs Ltd ISSN 1743-4440 245 www.future-drugs.com Is there an alternative to systemic anticoagulation, as related to interventional biomedical devices? Gemma Conn, Asmeret G Kidane, Geoffrey Punshon, Ruben Y Kannan, George Hamilton and Alexander M Seifalian † † Author for correspondence Biomaterials & Tissue Engineering Centre, Academic Division of Surgical and Interventional Sciences, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK Tel.: +44 207 830 2901 a.seifalian@medsch.ucl.ac.uk KEYWORDS: anticoagulant, antiplatelet, cardiovascular bypass graft, catheter, extracorporeal circuit, guide wire, heparin, stent, tissue engineering To reduce the toxic effects, related clinical problems and complications such as bleeding disorders associated with systemic anticoagulation, it has been hypothesized that by coating the surfaces of medical devices, such as stents, bypass grafts, extracorporeal circuits, guide wires and catheters, there will be a significant reduction in the requirement for systemic anticoagulation or, ideally, it will no longer be necessary. However, current coating processes, even covalent ones, still result in leaching followed by reduced functionality. Alternative anticoagulants and related antiplatelet agents have been used for improvement in terms of reduced restenosis, intimal hyperphasia and device failure. This review focuses on existing heparinization processes, their application in clinical devices and the updated list of alternatives to heparinization in order to obtain a broad overview, it then highlights, in particular, the future possibilities of using heparin and related moieties to tissue engineer scaffolds. Expert Rev. Med. Devices 3(2), 245–261 (2006) Heparin is a member of the glycosamino- glycan family and is widely used as an anti- coagulant. T he molecular target of heparin is antithrombin III (ATIII). Once activated by heparin, ATIII binds and inactivates thrombin and/or activated Factor X (Xa) resulting in its anticoagulant activity. Low- molecular-weight heparins (LMWHs), for example enoxaparin, are produced by degra- dation (enzymatic or chemical) of unfraction- ated heparin, and consist of smaller poly- saccharide chains. LMWHs are unable to simultaneously bind ATIII and Factor Xa and preferentially bind to Factor Xa. Heparinizing the surface of biomaterials was the first, and still is the most prevalent, method of improv- ing the hemocompatibility of interventional medical devices used clinically, having been first reported in 1963 [1]. As heparin has a strong anionic property, ionic bonding is readily achieved on surfaces pretreated with a cationic substance such as colloidal graphite. A general disadvantage of this method is the rapid release of heparin upon exposure to blood or plasma [2], although a number of studies on heparin-coated biomedical devices have been shown to enhance various aspects of blood compatibility. The biocompatibility of materials differs depending on factors such as the design of the material, how it interacts with water, usage and their effect on the activation of the cascade systems. Several coating techniques including covalent immo- bilization (TABLE 1) have been investigated and commercialized by various companies due to the limitations of the existing technology. The most commonly used commercially available heparin-coating systems are the Car- meda Bioactive Surface ® and Duralon II ® . T he former uses the principle of ‘end-point immobilization’, which involves the covalent binding of heparin to the substrate causing a chemical modification [3]. As the reaction in heparin occurs only at one end, the overall structure, particularly on the functional anti- thrombogenic site, is not changed. This enables the heparin molecule to be tied to the surface at one end only, with the remainder retaining its bioactivity. Conversely, Duraflo II heparin coating is an ionically CONTENTS Systemic anticoagulation Engineering of surfaces with anticoagulant & antiplatelet agents Clinical applications Conclusion Expert commentary Five-year view Key issues References Affiliations For reprint orders, please contact reprints@future-drugs.com