Reduction of In Vivo Oxidation induced by Lipid Absorption by Phospholipid Polymer Grafting on Orthopedic Bearings

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1 Reduction of In Vivo Oxidation induced by Lipid Absorption by Phospholipid Polymer Grafting on Orthopedic Bearings Masayuki Kyomoto, Ph.D. 1,2, Toru Moro, M.D., Ph.D. 1, Shihori Yamane, MSc 1,2, Kenichi Watanabe, BS 1,2, Sakae Tanaka, M.D., Ph.D. 1, Kazuhiko Ishihara, Ph.D The University of Tokyo, Tokyo, Japan, 2 KYOCERA Medical Corporation, Osaka, Japan. Disclosures: M. Kyomoto: None. T. Moro: None. S. Yamane: None. K. Watanabe: None. S. Tanaka: None. K. Ishihara: None. Introduction: To decrease wear particle production and eliminate periprosthetic osteolysis, we developed an articular cartilage-based technology that allows surface modification of acetabular liners used in artificial hip joints by using phospholipid polymer grafting, such as poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) for cross-linked polyethylene (CLPE) [1]. Modifying bearing surfaces of an artificial joint with a hydrophilic layer has reported to increase lubrication similar to that for articular cartilage under physiological conditions. Our previous study on the tribological and biological effects of PMPC revealed that such grafting decreases wear particle production and bone resorptive responses [2]. However, wear-resistance is only one of several important indicators of clinical performance of acetabular liners. As well as wear-resistance, oxidation resistance is an important indicator of the clinical performance of acetabular liners. Free radicals during gamma-ray irradiation limit the longevity of artificial hip joints. In vivo oxidation of the CLPE liner occurs, not only by annealing, but also by melting; CLPE absorbs lipids from the synovial fluid in vivo, which accelerates oxidative degradation; however, although the clinical impact of this degradation is unclear, in vivo oxidation is regarded undesirable. Stabilization of residual free radicals with an antioxidant such as vitamin E (VE) is necessary as an additional or alternative process. In the present study, we prepared a highly hydrophilic nanometer-scale surface by grafting a PMPC onto the surface of an antioxidative CLPE substrate, modified by VE blending (CLPE(VE)). Our ultimate goal was to manipulate the surface and substrate of the CLPE liner applied to life-long orthopedic bearings such that the surface not only had high wear resistance, but also had high oxidative resistance [3]. In this study, we investigated (1) the effect of the grafted PMPC layer on the lipid absorption of CLPE and CLPE(VE) samples, and (2) the effect of PMPC layer on oxidative resistance. Methods: A bar stock of 0.1 mass% VE-blended polyethylene (GUR1020E resin) was irradiated with gamma-rays (high dose [HD]; 100 kgy) and annealed at 120 C for 12 h in N 2 gas, to facilitate cross-linking (HD-CLPE(VE)). For the control, a bar stock of polyethylene without any additives (GUR1020 resin) was irradiated with gamma-rays (50 kgy) and annealed at 120 C for 7.5 h in N 2 gas, to facilitate cross-linking (CLPE). The CLPE and HD-CLPE(VE) samples were then machined from the bar stocks and were immersed in aqueous MPC solution. Photo-induced graft polymerization of MPC was performed on the CLPE and HD-CLPE(VE) surfaces by using UV irradiation (intensity, 5 mw/cm 2 ) at 60 C for 90 min. All samples were sterilized using gamma-rays (dose, 25 kgy). Lipid absorption and oxidative properties of the 4 samples (untreated CLPE, PMPC-grafted CLPE, untreated HD-CLPE(VE), and PMPC-grafted HD-CLPE(VE) were investigated. The residual-free radical concentrations in the samples were analyzed using electron spin resonance (ESR). Squalene absorption,

2 after squalene soaking at 120 C for 2 h, was evaluated by Fourier transform-infrared spectroscopy (FT- IR). Squalene index was calculated as the ratio of the peak area at 1145 cm -1 to that at 1895 cm -1. Oxidative stability (oxidation-induction time) was evaluated by differential scanning calorimetry according to ASTM D3895. The oxidative degradation of samples subjected to accelerated aging by exposure to 80 C in air for 21 d was evaluated using FT-IR according to ASTM F2102. Results: In ESR spectra, multiple peaks corresponding to alkyl or allyl radicals were observed in all samples (Fig.1A). The small detectable peaks corresponding to tocopheroxyl radicals were observed only in the untreated and PMPC-grafted HD-CLPE(VE) samples. The residual free-radical concentrations after gamma-ray sterilization did not differ significantly between samples (Fig. 1B). Squalene indices of the PMPC-grafted samples were lower than those of the untreated samples (Fig. 2). Oxidative-induction times were significantly longer in the untreated and PMPC-grafted HD-CLPE(VE) samples than in the untreated and PMPC-grafted CLPE samples (Fig. 3A). Oxidative-induction times of the untreated and PMPC-grafted HD-CLPE(VE) samples were shorter after squalene absorption than those before absorption. In the absence of squalene absorption, oxidative-induction times did not differ significantly between untreated and PMPC-grafted samples. In contrast, after squalene absorption, the oxidative-induction times of PMPC-grafted HD- CLPE(VE) samples was significantly longer than those of the untreated HD-CLPE(VE) samples. Thus, oxidation indices of the accelerated-aged untreated and PMPC-grafted HD-CLPE(VE) samples were significantly lower (almost zero) than those of the untreated CLPE and PMPC-grafted CLPE samples, despite squalene absorption (Fig. 3B). Compared with untreated CLPE, the increased oxidation index after squalene absorption was prevented in PMPC-grafted CLPE. Discussion: Here, we investigated the effects of surface modification with a phospholipid polymer on oxidative resistance of CLPE or HD-CLPE(VE). The PMPC-grafted HD-CLPE(VE) samples had extremely high oxidation resistance, even though the residual-free radical levels were detectable. Even after PMPC grafting, the HD-CLPE(VE) substrate maintained high oxidation resistance. Indeed, VE is an extremely efficient radical scavenger. Interestingly, PMPC-grafted samples were resistant to squalene absorption, probably because of the presence of the PMPC layer: MPC is a methacrylate monomer that has a phospholipid polar group in its side chain and is highly hydrophilic, while PMPC is water-soluble. Therefore, we believe that the presence of a water-fluid film and hydrated PMPC layer is the primary mechanism underlying the high oxidation resistance; water molecules in the hydration layers reduce lipid absorption, thus reducing adhesive interaction or interpenetration. The secondary mechanism is attributed to the suppressed diffusion of squalene into the PMPC layer because squalene is an insoluble molecule in the methacrylate monomer. In conclusion, the PMPC layer grafted on the CLPE or HD-CLPE(VE) surface prevented squalene absorption and its accelerated oxidation degradation. These results provide preliminary evidence that surface modification affected the extent of oxidative stability. This suggests that the PMPC-grafted surface and VE-blended substrate may be a promising approach for longevity of artificial hip joints. Significance: Our in vitro findings indicate some improvements in the oxidation resistance of CLPE acetabular cups in total hip arthroplasty.

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5 ORS 2015 Annual Meeting Poster No: 1807