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.

Safety and immunogenicity of heterologous boosting with orally administered aerosolized bivalent adenovirus type-5 vectored COVID-19 vaccine and B.1.1.529 variant adenovirus type-5 vectored COVID-19 vaccine in adults 18 years and older: a randomized, double blinded, parallel controlled trial.

Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×1010viral particles) and B.1.1.529 variant (5×1010viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×1010viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.

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.

Polyphenol-Assisted Chemical Crosslinking: A New Strategy to Achieve Highly Crosslinked, Antioxidative, and Antibacterial Ultrahigh-Molecular-Weight Polyethylene for Total Joint Replacement.

Highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) bearings are wear-resistant to reduce aseptic loosening but are susceptible to oxidize in vivo/in vitro, as reported in clinical studies. Despite widespread acceptance of antioxidants in preventing oxidation, the crosslinking efficiency of UHMWPE is severely impacted by antioxidants, the use of which was trapped in a trace amount. Herein, we proposed a new strategy of polyphenol-assisted chemical crosslinking to facilitate the formation of a crosslinking network in high-loaded tea polyphenol/UHMWPE blends. Epigallocatechin gallate (EGCG), a representative of tea polyphenol, was mixed with UHMWPE and peroxide. Multiple reactive phenolic hydroxyl groups of tea polyphenol coupled with the nearby free radicals to form extra crosslinking sites. The crosslinking efficiency was remarkably enhanced with increasing tea polyphenol content, even at a concentration of 8 wt %. Given by the hydrogen donation principle, the high-loaded tea polyphenol also enhanced the oxidation stability of the crosslinked UHMWPE. The antioxidative performance was preserved even after tea polyphenol elution. Moreover, superior antibacterial performance was achieved by the in situ tea polyphenol release from the interconnected pathways in the present design. The strategy of polyphenol-assisted chemical crosslinking is applicable for producing highly crosslinked, antioxidative, and antibacterial UHMWPE, which has promising prospects in clinical applications.

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.