Controlled bacteriostasis of tea polyphenol loaded ultrahigh molecular weight polyethylene with high crosslink density and oxidation resistance for total joint replacement.

To avoid catastrophic bacterial infection in prosthesis failure, ultrahigh molecular weight polyethylene (UHMWPE), a common bearing material of artificial joints, has been formulated with antibiotics to eliminate bacteria locally at the implant site. However, the pressing issues regarding cytotoxic effects and evolution of drug resistant bacteria necessitates the development of bio-friendly bacteriostat with long bacteriostatic efficacy. Herein, tea polyphenol extracted from nature source was introduced in UHMWPE as a biogenic antimicrobial. Controlled antimicrobial activity was achieved by chemical crosslinking to regulate the release of the tea polyphenol. In addition, the crosslinking efficiency of UHMWPE blends with high loaded tea polyphenol was significantly improved in comparison to radiation crosslinking. The immobilized tea polyphenols also enhanced the oxidation stability of the UHMWPE, which is essential to prolong the service life in vivo and the storage time in vitro. The blends presented good biocompatibility, despite cell repellent on the highly crosslinked surface. Chemically crosslinked tea polyphenol/UHMWPE exhibited feasible properties for total joint implants, which is promising for clinical application.

Antibacterial and anti-inflammatory ultrahigh molecular weight polyethylene/tea polyphenol blends for artificial joint applications.

Periprosthetic joint infection (PJI) is one of the main causes for the failure of joint arthroplasty. In view of the limited clinical effect of oral/injectable antibiotics and the drug resistance problem, there is a pressing need to develop antibacterial implants with therapeutic antimicrobial properties. In this work, we prepared a highly antibacterial ultrahigh molecular weight polyethylene (UHMWPE) implant by incorporating tea polyphenols. The presence of tea polyphenols not only improved the oxidation stability of irradiated UHMWPE, but also gave it the desirable antibacterial property. The potent antibacterial activity was attributed to the tea polyphenols that produced excess intracellular reactive oxygen species and destroyed the bacterial membrane structure. The tea polyphenol-blended UHMWPE had no biological toxicity to human adipose-derived stem cells and effectively reduced bacteria-induced inflammation in vivo. These results indicate that tea polyphenol-blended UHMWPE is promising for joint replacement prostheses with multifunctionality to meet patient satisfaction.

High Oxidation Stability of Tea Polyphenol-stabilized Highly Crosslinked UHMWPE Under an in Vitro Aggressive Oxidative Condition.

BACKGROUND: Synovial fluid components, especially lipids, can trigger oxidation of ultrahigh-molecular-weight polyethylene (UHMWPE) artificial joint components in vivo. The use of antioxidants such as vitamin E effectively diminishes the oxidative cascade by capturing free radicals and reducing the oxidation potential of UHMWPE implants. Using a thermo-oxidative aging method, we recently found that tea polyphenols can enhance the oxidation resistance of irradiated UHMWPE in comparison with commercial vitamin E. However, it is yet unknown whether tea polyphenols can reduce lipid-induced oxidation. QUESTIONS/PURPOSES: We explored whether tea polyphenol-stabilized UHMWPE would exhibit (1) lower squalene absorption; (2) stronger oxidation resistance; and (3) lower content of free radicals than vitamin E-stabilized UHMWPE under a physiologically-motivated in vitro accelerated-aging model. METHODS: Tea polyphenol (lipid-soluble epigallocatechin gallate [lsEGCG]) and vitamin E were blended with UHMWPE powders followed by compression molding and electron beam irradiation at 100 and 150 kGy. Small cubes (n = 3, 60 mg, 4 × 4 × 4 mm) cut from the blocks were doped in squalene at 60°, 80°, 100°, and 120° C for 2 hours. Gravimetric change of the cubes after squalene immersion was measured to assess absorption. Thin films (n = 3, ∼60 µm) were also microtomed from the blocks and were doped at 120° C for 24 hours. Oxidation induction time (n = 3, 5 mg of material from the cubes) and incipient oxidation temperature (n = 3, thin films) were obtained to determine the oxidation stability. Signal intensity of the free radicals, obtained by electron spin resonance spectroscopy, was used to qualitatively rank the antioxidant ability of vitamin E and lsEGCG. RESULTS: Squalene absorption was comparable between lsEGCG/UHMWPE and vitamin E/UHMWPE at a given temperature and radiation dose. The oxidation induction time of 100 kGy-irradiated UHMWPE was increased with lsEGCG compared with vitamin E except at 120° C. For example, the oxidation induction time value of 100 kGy-irradiated lsEGCG/UHMWPE immersed at 60 C was 25.3 minutes (24.2-27.8 minutes), which was 8.3 minutes longer than that of 100 kGy-irradiated vitamin E/UHMWPE which was 17.0 minutes (15.0-17.1 minutes) (p = 0.040). After squalene immersion at 120° C, the incipient oxidation temperature of 100 and 150 kGy irradiated lsEGCG/UHMWPE was 234° C (227-240° C) and 227° C (225-229° C), which was higher than vitamin E-stabilized counterparts with value of 217° C (214-229° C; p = 0.095) and 216° C (207-218° C; p = 0.040), respectively. The electron spin resonance signal of 150 kGy irradiated lsEGCG/UHMWPE was qualitatively weaker than that of 150 kGy irradiated vitamin E/UHMWPE. CONCLUSIONS: lsEGCG-stabilized UHMWPE demonstrated higher oxidation resistance than vitamin E-stabilized UHMWPE after squalene immersion, likely because lsEGCG donates more protons to eliminate macroradicals than vitamin E. CLINICAL RELEVANCE: Our in vitro findings provide support that lsEGCG may be effective in protecting against oxidation that may be associated with synovial fluid-associated oxidation of highly crosslinked UHMWPE joint replacement components.

Enhanced oxidation stability of highly cross-linked ultrahigh molecular weight polyethylene by tea polyphenols for total joint implants.

Despite being currently state-of-the-art to prevent the oxidation of irradiated ultrahigh molecular weight polyethylene (UHMWPE) bearings, vitamin E (VE) poses concerns in the loss of cross-linking efficiency and is limited to be used at very low concentrations. It thus emphasizes the urgent demand for more efficient stabilizers. In this study, oxidation stability of highly cross-linked UHMWPE was demonstrated to be enhanced by tea polyphenols, such as lipid-soluble tea polyphenols (lsPPT), epigallocatechin gallate (EGCG), and lipid-soluble epigallocatechin gallate (lsEGCG). These antioxidants were blended with UHMWPE granules and consolidated by compression molding prior to E-beam irradiation. The presence of tea polyphenols substantially prolonged oxidation induction time of the irradiated UHMWPE before and after accelerated aging. Especially, lsEGCG was significantly superior to VE in terms of stabilizing capacity. Explained by the hydrogen donation mechanism, tea polyphenols with multiple phenolic hydroxyls could scavenge more radiation-induced free radicals than VE with only one phenolic hydroxyl, which was verified by the electron spin resonance spectra. Intriguingly, tea polyphenols showed less inhibitive effect on the cross-link density of irradiated UHMWPE than VE. Besides, there is no significant difference in crystallinity, mechanical performance as well as in vitro biocompatibility between the irradiated UHMWPE stabilized by tea polyphenols and VE. These findings highlight tea polyphenols, especially lsEGCG, are promising alternatives to extend the life span of UHMWPE implants.