A Comparison of the Efficacy of Various Antioxidants on the Oxidative Stability of Irradiated Polyethylene

Ultrahigh-molecular-weight polyethylene (UHMWPE) is subjected to radiation crosslinking to form highly crosslinked polyethylene (HXLPE), which has improved wear resistance. First-generation HXLPE was subjected to thermal treatment to reduce or quench free radicals that can induce long-term oxidative degeneration. Most recently, antioxidants have been added to HXLPE to induce oxidative resistance rather than by thermal treatment. However, antioxidants can interfere with the efficiency of radiation crosslinking. We sought to identify (1) which antioxidant from among those tested (vitamin E, beta-carotene, butylated hydroxytoluene, or pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate]) causes the least reduction of crosslinking; (2) which promotes the greatest oxidative stability; and (3) which had the lowest ratio of oxidation index to crosslink density. Medical-grade polyethylene (PE) resin was blended with 0.1 weight % of the following stabilizers: alpha tocopherol (vitamin E), beta-carotene, butylated hydroxytoluene (BHT), and pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate] (a hindered phenol antioxidant [HPAO]). These blends were compression-molded into sheets and subjected to electron beam irradiation to a dose of 100 kGy. Equilibrium swelling experiments were conducted to calculate crosslink density. Each PE was subjected to accelerated aging for a period of 2 weeks and Fourier transform infrared spectroscopy was used to measure the maximum oxidation. Statistical analysis was conducted using analysis of variance with Fisher's protected least significant difference in which a p value of < 0.05 was used to define a significant difference. The least reduction of crosslinking in antioxidant-containing HXLPE was observed with HPAO, which had a crosslink density (n = 6) of 0.167 (effect size [ES] = 0.87; 95% confidence interval [CI], 0.162-0.173) mol/dm(3) compared with 0.139 (ES = 1.57; 95% CI, 0.132-0.146) mol/dm(3) (p = 0.020) for BHT, 0.131 (ES = 1.77; 95% CI, 0.123-0.139) mol/dm(3) (p = 0.004) for beta-carotene, and 0.130 (ES = 1.79; 95% CI, 0.124-0.136) mol/dm(3) (p = 0.003) for vitamin E, whereas pure HXLPE had a crosslink density of 0.203 (95% CI, 0.170-0.235) mol/dm(3) (p = 0.005). BHT-PE had an oxidation index of 0.21 (ES = 13.14; 95% CI, 0.19-0.22) followed by HPAO-PE, vitamin E-PE and beta-carotene-PE, which had oxidation indices of 0.28 (ES = 9.68; 95% CI, 0.28-0.29), 0.29 (ES = 9.59; 95% CI, 0.27-0.30), and 0.35 (ES = 6.68; 95% CI, 0.34-0.37), respectively (p < 0.001 for all groups). BHT-PE had the lowest ratio of oxidation index to crosslink density of the materials tested (1.49, ES = 1.94; 95% CI, 1.32-1.66) followed by HPAO-PE (1.70, ES = 1.52; 95% CI, 1.61-1.80), vitamin E-PE (2.21, ES = 0.52; 95% CI, 2.05-2.38), and beta-carotene-PE (2.69, ES = -0.43; 95% CI, 2.46-2.93) compared with control PE (2.47, 95% CI, 2.07-2.88) with beta-carotene (p = 0.208) and vitamin E (p = 0.129) not being different from the control. BHT-modified HXLPE was found in this study to have the lowest oxidation index as well as the lowest ratio of oxidation index to crosslink density compared with vitamin E, HPAO, and beta-carotene-modified HXLPEs. More comprehensive studies are required such as wear testing using joint simulators as well as biocompatibility studies before BHT-modified HXLPE can be considered for clinical use. BHT is a synthetic antioxidant commonly used in the polymer industry to prevent long-term oxidative degradation and has been approved by the FDA for use in cosmetics and foodstuffs. It may be an attractive potential stabilizer for HXLPE in total joint replacements.