REVIEW Yasuhiko Iwasaki Æ Kazuhiko Ishihara Phosphorylcholine-containing polymers for biomedical applications Received: 1 June 2004 / Revised: 2 August 2004 / Accepted: 6 August 2004 / Published online: 10 November 2004 Ó Springer-Verlag 2004 Introduction Numerous polymeric materials have been used in the manufacture of medical devices, especially for applica- tion as artificial organs where the polymer is in contact with blood [1]. The polymers currently in use, however, are commodity materials, such as poly(vinyl chloride) (PVC), polyethylene (PE), poly(methyl methacrylate) poly(MMA), segmented polyetherurethane (SPU), polydimethylsiloxane, polytetrafluoroethylene (PTFE), cellulose, and polysulfone (PSf). Thrombus formation is one of the most serious host responses to artificial materials. Because conventional polymer materials do not have sufficient blood compatibility and anti- thrombogenicity, infusion of an anticoagulant is re- quired during clinical treatment using these medical devices to avoid thrombus formation. As a means of improving blood compatibility, some methods of surface modification using newly designed polymeric materials have been studied. The molecular design of blood- compatible polymers for making artificial organs is classified into four categories based on the approach to the regulation of blood–material interaction. These categories are listed in Table 1. One of the most effective methods of making a blood-compatible polymer is to modify conventional materials with polymers having a phospholipid polar group mimicking a biomembrane surface. Phosphorylcholine-containing polymers 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymer The biomembrane surface is regarded as the best surface for smooth interaction with blood components such as proteins and cells. A model of the structure of a bio- membrane, which is well-known as the fluid-mosaic model, was proposed by Singer and Nicolson (Fig. 1) [2]. According to this model, amphiphilic phospholipids are arranged in a bilayer structure and proteins are lo- cated in or upon it. The distribution of these compo- nents is asymmetric. The phospholipids always flow dynamically, and the biomembrane maintains its strength by the supporting proteins. In all cells for which lipid compositional asymmetry has been described, negatively charged phospholipids such as phosphati- dylserine are predominantly found on the inner, cyto- plasmic side of the membrane, whereas the neutral, zwitterionic phosphorylcholine lipids such as phosphat- idylcholines are located in the outer leaflet. The phos- phatidylcholine surface provides an inert surface for biological reactions of proteins and glycoproteins to occur smoothly on the membrane. This provides very significant information for the development of novel blood-compatible polymers. Nakabayashi et al. [3] designed a methacrylate monomer with a phospholipid polar group, 2-methac- ryloyloxyethyl phosphorylcholine (MPC), to obtain new medical polymer materials (Fig. 2). At that time, how- ever, the purity and yield of MPC were insufficient to evaluate their functions. Ishihara et al. [4] then improved the synthetic route to MPC and succeeded in producing MPC as a white powder by recrystallization. MPC, which contains the polymerizable methacrylate group, can readily be co-polymerized and enables the design of numerous polymers having a wide variety of molecular architectures including random [4, 5], block [6–9], graft [10], charged [11, 12], and end functional polymers [10]. Y. Iwasaki (&) Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan E-mail: yasu.org@tmd.ac.jp Tel.: +81-3-52808026 Fax: +81-3-52808027 K. Ishihara Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Anal Bioanal Chem (2005) 381: 534–546 DOI 10.1007/s00216-004-2805-9