Vitamin E-stabilised UHMWPE for surgical orthopaedic implants: Quantification of vitamin E and characterisation of its transformation products

Abstract

The fate of vitamin E and the formation and identification of its transformation products were investigated at different stages of the manufacturing process of commercially produced cross-linked (by γ-irradiation) UHMWPE stabilised with vitamin E (vitamin E infused-post irradiation) used for tibia-components (as articulating surfaces) in total knee arthroplasty (total knee replacement). Vitamin E (α-tocopherol) and its transformation products were extracted from microtomed Tibia films and the different products were separated, isolated, purified using high performance liquid chromatography (HPLC), and characterised by spectroscopic methods and LC-MS. The amount of vitamin E and that of the products formed in the different Tibia samples and in their extracts were also quantified using FTIR and HPLC analysis and calibration curves. Thorough analysis of the Tibia extracts has shown that a number of vitamin E transformation products were formed at different concentrations at two selected stages of the implant manufacturing process that is before and after sterilisation by γ-irradiation. The identified products were found to correspond mainly to different stereoisomeric forms of a small number of vitamin E transformation products. Most of the observed products were of dimeric and trimeric nature with their identity confirmed through a detailed study of their spectral and chromatographic characteristics. It was found that the products of vitamin E, prior to the sterilisation step but after the crosslinking and doping of vitamin E, were mainly the dihydroxydimers and trimers (Tibia samples at this stage are referred to as "Tibia-VEPE"). After sterilisation and completion of the manufacturing process, additional dimers of vitamin E were also formed (Tibia samples at this stage are referred to as 'Tibia-VEPE-Sterile'), Furthermore, two tocopherol-derived aldehydes (aldehyde 5formyl-γ-tocopherol and aldehyde 7-formyl-γ-tocopherol) were also formed but at very low concentrations especially in the Tibia-VEPE-Sterile samples. The question of whether vitamin E becomes chemically reacted (grafted) onto the polymer matrix during the manufacturing process of the Tibia is also addressed.

Characterizing the free volume of ultrahigh molecular weight polyethylene to predict diffusion coefficients in orthopedic liners

“…Therefore, some may not view this trend as universally applicable to every irradiated UHMWPE/Vitamin E blend material. For example, Doudin and Al‐Malaika reported 84% of Vitamin E introduced by a soaking method was extractable after a 25 kGy sterilization dose . These authors also identified and quantified various Vitamin E photochemical transformation products.…”

“…As described in Supporting Information, Figs. S3 and S4, we made a screening‐level estimation of the maximum amount of total ungrafted photoproducts present after irradiation based on a simple reaction model powered by the available literature data of Doudin and Al‐Malaika . For an initial loading of 0.1 wt % Vitamin E in UHMWPE, our analysis suggests at most 0.01 wt % of an individual transformation product (trimers) could be formed by irradiation.…”

“…For example, Doudin and Al-Malaika reported 84% of Vitamin E introduced by a soaking method was extractable after a 25 kGy sterilization dose. 19 These authors also identified and quantified various Vitamin E photochemical transformation products. These photoproducts are similar in structural size and configuration (Ald-5, Ald-7, and Tocopherol-3-ene) or significantly larger (dihydroxydimers and trimers) than the parent structure, meaning that an estimate based on Vitamin E will not underpredict leaching and subsequent patient exposure.…”

“…For example, Vitamin E is often added to UHMWPE in small quantities as an antioxidant during processing . When subsequently exposed to γ‐irradiation for crosslinking or sterilization, various Vitamin E photochemical transformation products are generated . While recent clinical results suggest that Vitamin E elution from retrieved joint arthroplasty devices is low, exposure to sufficiently high quantities of these photoproducts could hypothetically elicit a toxicological response in patients .…”

“…[15][16][17][18] When subsequently exposed to g-irradiation for crosslinking or sterilization, various Vitamin E photochemical transformation products are generated. 19 While recent clinical results suggest that Vitamin E elution from retrieved joint arthroplasty devices is low, 20 exposure to sufficiently high quantities of these photoproducts could hypothetically elicit a toxicological response in patients. 21,22 Additionally, small reactive oxidizing species (ROS, e.g., O 2 , •OH, H 2 O 2 , and so forth) and/or pro-oxidizing biological molecules, such as squalene or cholesterol, may penetrate the liner 23 and result in in vivo oxidation of the liner.…”