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377i

Antiwearable and Biocompatible Surface of Artificial Hip Joints by Nano-Scaled Grafting with Phospholipid Polymers

Kazuhiko Ishihara1, Toru Moro2, Yoshio Takatori2, Hiroshi Kawaguchi2, Kozo Nakamura2, and Tomohiro Konno1. (1) Department of Materials Engineering, Center for NanoBio Integration, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan, (2) Department of Sensory and Motor System Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

Aseptic loosening is the most common and important long-term complication associated with total joint replacements. It has become apparent that aseptic loosening relates to periprosthetic osteolysis caused by the foreign-body reaction of macrophages to wear particles. Among the several potential sources of wear particles, the articulation between the acetabular liner and the femoral head is most significant. Moreover, recent studies revealed that periprosthetic osteolysis closely related to the rate of polyethylene (PE) liner wear and the characteristics of the particles. We hypothesized that creation of molecular assembly of phospholipids such as cell membrane provides excellent surface both biocompatible and low friction surfaces. That is, a grafting phospholipid polymer chains on the surface of PE liner will suppress wear and the wear particles, which will become biologically inert even when wear will be occurred. So, we prepare a novel PE liner grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) and investigated its potential for the longevity of artificial joints. Surface grafting of the MPC polymer on the PE liner was carried out by photoinduced polymerization using benzophenone as a photosensitizer. The grafting was confirmed with X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and wettability measurement. To assess the lubricity and the production of wear particles, we performed hip simulator tests (1x107 cycles) using cross-linked polyethylene(CL-PE) liners and that with nano-grafting (depth of the MPC polymer grafting layer is in the range of 100-150 nm: confirmed with SEM) of MPC polymer (MPC liner) against 26mm Co-Cr-Mo heads. The surface treated with the MPC polymer reduce contact angle of water dramatically. Throughout 1 x 107 cycles, the friction torque was about 90% lower in MPC liners than CL-PE liners. The friction torque of PE was as the same level as that of CE-PL liner. That is, cross-linking is not affect to the surface lubrications. However, the wear of PE liner after 1 x 107 cycles was about 180mg, however, that of CL-PE liners showed a total weight loss of 45 } 5 mg. In contrast, MPC liners continued to gain weights, and showed a total weight gain of 2 } 1mg. MPC liners also showed no or very little wear after correcting for weight gain due to water absorption, suggesting marked reduction in wears. The field emission-transmission electron microscope (FE-TEM) analysis showed that most of the liner surface was still covered by the MPC polymer layer even after the loading. In vitro murine osteolysis model, although large amounts of non-treated polymer particles were phagocytosed by macrophages, the MPC polymer particles were not taken into the cells, probably because biocompatible MPC polymer prevented macrophages from recognizing the particles as foreign bodies. Concentrations of TNF-, IL-1, IL-6 and PGE2 in the culture medium of mouse macrophage-like cell line J774 cells were stimulated by the exposure to non-treated particles up to 4-20 times those without the exposure; however, the exposure to the MPC polymer particles affected none of them. In the mouse osteoblast culture, the receptor of NF-kB ligend(RANKL) expression was strongly induced by the conditioned medium exposed to non-treated particles, but not by that exposed to MPC polymer particles. Osteoclastogenesis from cultured bone marrow cells were about 7-fold increased by the conditioned medium of J774 cells exposed to non-treated polymer particles, and this stimulation was significantly inhibited by addition of anti-TNF-, anti-IL-1 or anti-IL-6 antibody, a cyclooxygenase-2 (COX-2) inhibitor, and a RANKL inhibitor. Contrarily, the conditioned medium of exposed to MPC polymer particles did not increase osteoclastogenesis. The MPC polymer is our original biocompatible polymer whose side chain is composed of phosphorylcholine resembling phospholipids of biomembrane [1,2]. That means, the MPC polymer grafting provided a biomimetic surface like cell surface. The treatment with the MPC polymer onto the surface of medical devices has already been approved to suppress biological reactions even when they are in contact with living organisms. Hence, aiming at the prevention of periprosthetic osteolysis, the present study investigated the mechanical and biological effects of the MPC polymer grafting onto the surface of the PE liner of artificial hip joints. The lines of results obtained in this study clearly demonstrate that the MPC grafting on the surface of PE liner markedly decrease the friction and the wear. In addition, even if wear particles are produced, they are biologically inert in respect to phagocytosis by macrophahes and subsequent bone resorptive actions. Furthermore, the MPC grafting can successfully inhibit the bone resorptive response to wear particles to levels similar to those of recently developed pharmacological therapies such as cytokine antagonists, COX-2 inhibitors and osteoprotegerin, suggesting that this grafting will surpass the pharmacologic therapies that possibly cause serious side effects during a long period of administration after surgery. We will also discuss the mechanism of the lowering of wear on MPC polymer grafted PE surface with attention to the state of water at the interface. Ref. [1] K.Ishihara, et al., Polym.J., 22, 355 (1990), [2] K.Ishihara, et al., JBMR., 26, 1543 (1992)