ABSTRACT
Figure 27.1 Schematic illustration of interaction of blood components at the blood-biomaterial interface. Metals and polymers are the most commonly used synthetic materials for blood-contacting applications. Implants made of metal (e.g., stainless steel and titanium) are widely used in trauma surgery, orthopedics, and oral medicine [16]. Polymeric materials including poly(vinyl chloride) (PVC) and polyethylene (PE) are also extensively used for blood storage devices, vascular catheters, extracorporeal tubing, etc. [17-20]. There is significant attention recently on the blood compatibility of the drug delivery vehicles and macromolecular imaging agents especially used for parenteral administration [21-24]. Due to the poor hemocompatibility of the existing biomaterials, numerous studies have been carried out to improve their compatibility with blood. Conventional strategies focus on surface modifications, including surface plasma treatment [25], coating or immobilization of surfaces with biomacromolecules such as albumin and anticoagulants like heparin [26, 27], and grafting of biocompatible hydrophilic polymers (“graft to”) [28]. Other approaches, including the change in physical geometry of surface as well as bulk modifications of substrates, were also reported [29]. Although traditional approaches gave some useful improve-ments, they were limited by several factors. For example, the activity of surface-bound heparin used to prevent surface-associated blood
coagulation is relatively poor compared with its soluble versions due to the steric constraints. Moreover, one type of surface modifica-tion targets only a particular biological reaction, and other biological pathways can still be activated. An emerging strategy for improving hemocompatibility of synthetic materials is to grow a densely grafted layer of highly biocompatible polymer chains on the surface. Due to the steric repulsion between the polymer chains, the polymer chains stretch away from the surface and form a brush kind of arrangement on the surface. Such surface-confined, covalently attached polymer chains on the surface are referred to as polymer brushes. Synthesis and theoretical description of polymer brushes have significantly advanced in the past decade [30] and are reviewed in chapter 8. In this chapter we will review the recent advances in the use of polymer brushes for the generation of hemocompatible surfaces. 27.2 Hemocompatible Surfaces Based on
It is believed that nonspecific protein adsorption is the primary process taking place when an artificial surface interacts with blood, followed by platelet activation and adhesion. The origins of these reactions are due to different types of interactions. Among them, hydrophobic interaction and electrostatic interactions between the proteins and surfaces are most important. Figure 27.2 illustrates a possible mechanism by which hydrophilic polymer brushes prevent nonspecific protein adsorption and cellular interactions. A densely grafted polymer brush can function as an inert shielding layer, or “barrier,” to reduce the undesirable interactions between the surface and the biological fluid. Halperin first proposed a theoretical model to study the protein-resistant property of hydrophilic polymer brushes [31]. As shown in Fig. 27.3, when a protein encounters a bare adsorbing surface (such as hydrophobic plastic or a metallic surface), it experiences a purely attractive interaction potential Ubare(z). The interaction potential is qualitatively modified when the surface is coated with a hydrophilic polymer brush. The overlap of the impenetrable, dense protein with
the brush gives rise to a free-energy penalty (Fig. 27.3, curve C). The increased energy level disfavors the insertion of proteins into the polymer brush, which becomes the driving force of the polymer brush to prevent protein adsorption.
