Polymers in Drug Delivery: Fundamentals

Abstract

Blood-material interactions are critical to the success of implantable medical devices that are used in thousands of patients every day. Some common blood-contacting devices include catheters, stents, vascular grafts, heart valve prostheses, and extracorporeal circulation/membrane oxygenation systems. Among other complications, thrombosis and clot formation remains one of the major challenges in clinical application of these devices. The initial biological response of blood to a foreign surface is the rapid adsorption of plasma proteins, which is followed by platelet adhesion and activation, and ultimately thrombus formation. The key factors in clot formation are the chemical and physical nature of the surfaces and their interactions with the blood components, such as platelets and plasma proteins. Despite decades of research, an ideal non-thrombogenic surface is still yet to be identified and clinical use of these blood-contacting devices requires use of anticoagulation agents, increasing the risk of bleeding in patients. In this chapter, we will review some of the current and most promising strategies that have been used over the years to develop polymeric materials with improved hemocompatibility, including highly hydrophilic or hydrophobic surfaces, albumin coated surfaces, zwitterionic polymers, attached endothelial cells, patterned surfaces, immobilized heparin, and nitric oxide (NO) releasing/generating surfaces. We will also discuss some of the important techniques employed (using in vitro and in vivo models) to assess the hemocompatibility of any new material, including the measurement of platelet preservation, platelet and protein adhesion, the effect of flow rates on thrombosis, and the ultimate surface clot area.