title: A Novel Technique for Assessing Antioxidant Concentration in Retrieved UHMWPE.
abstract: BACKGROUND
  Antioxidants added to UHMWPE to prevent in vivo oxidation are important to the long-term performance of hip and knee arthroplasty. Diffused vitamin E antioxidant polyethylene raised questions about potential in vivo elution that could cause inflammatory reactions in periprosthetic tissues and also potentially leave the implant once again prone to oxidation. Currently, there is no information on the elution, if any, of antioxidants from implant polyethylene materials in vivo.
  
  
  OBJECTIVE
  (1) Do antioxidants, especially diffused vitamin E, elute from antioxidant polyethylene in vivo? (2) Can extraction of the retrieved antioxidant polyethylene (to remove absorbed species from the in vivo environment near the articular and nonarticular surfaces) improve the identification of antioxidant content? (3) Can actual antioxidant content be estimated from calculated antioxidant indices by accounting for ester content (from absorbed species) near the articular and nonarticular surfaces?
  
  
  METHODS
  An institutional review board-approved retrieval laboratory received 39 antioxidant polyethylene hip and knee retrievals at revision from 25 surgeons with in vivo time of 0.02 to 3.6 years (median, 1.3 years). These consecutive antioxidant polyethylene retrievals, received between May 2010 and February 2016, were made from three different antioxidant highly crosslinked polyethylene materials: diffused vitamin E, blended vitamin E, and hindered phenol antioxidant pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)] propionate (here and after referred to as PBHP). Retrievals were analyzed using Fourier transform infrared (FTIR) spectroscopy. Absorbed ester index (1725-1740 cm-1normalized to 1365-1371 cm-1), and vitamin E index (1245-1275 cm-1) and PBHP index (1125-1150 cm-1), normalized to 1850-1985 cm-1, were defined. Microtomed thin sections of PBHP and vitamin E retrievals were hexane-extracted to remove absorbed species from the in vivo environment in an effort to improve identification of antioxidant content. Paired Student's t-tests were used to compare as-retrieved articular antioxidant index with expected antioxidant index (the bulk value for blended antioxidants where constant antioxidant content is expected throughout and the extrapolated original vitamin E concentration at the articular surface based on the as-manufactured vitamin E concentration gradient). Linear regression was used for each of the retrievals to evaluate the correlation of antioxidant index to ester content with the goal of extrapolation to the antioxidant index at zero ester content.
  
  
  RESULTS
  On average, vitamin E index at the articular surface (0.04 ± 0.03) was reduced compared with expected vitamin E index (0.09 ± 0.04; 95% confidence interval [CI] of the difference, 0.04-0.07; p < 0.001), and PBHP index at the articular surface (0.06 ± 0.02) was elevated compared with the average PBHP index from the bulk (0.03 ± 0.00; 95% CI of the difference, 0.03-0.05; p < 0.001). Extraction returned the PBHP index at the articular surface (0.03 ± 0.00) to bulk values (95% CI of the difference, -0.001 to 0.004; p = 0.326); diffused vitamin E was removed by extraction. Crossplots of vitamin E index and PBHP index with ester index showed significant (p < 0.001 for 32 of the 35 retrievals with sufficient data) linear trends (r ≥ 0.89) that allowed extrapolation of the articular surface antioxidant indices at zero absorbed ester index.
  
  
  CONCLUSIONS
  Absorbed esters from time in vivo caused erroneous values of antioxidant index to be calculated. However, hexane extraction to remove absorbed species also removed diffused vitamin E. Correlating antioxidant indices with ester content, measured by FTIR in unextracted antioxidant retrievals, provides a nonaltered method for estimating actual articular surface vitamin E index and demonstrates that there was no measurable elution in these short-term retrievals.
  
  
  CONCLUSIONS
  Assessing antioxidant content in retrieved polyethylene inserts is important to determine how much of the antioxidant remains in place to prevent oxidation of the polyethylene over time in vivo. Retrieval analyses reporting antioxidant content must account for absorbed species to be valid. Because standard hexane extraction removes both absorbed species and vitamin E from diffused vitamin E retrievals, the correlation method presented in this study is the recommended analysis alternative.
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA. barbara.h.currier@dartmouth.edu.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Currier
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Van Citters
mesh_terms: D065966:Absorption, Physicochemical; D000704:Analysis of Variance; D000975:Antioxidants / Q000032:analysis*; D019644:Arthroplasty, Replacement, Hip / Q000295:instrumentation*; D019645:Arthroplasty, Replacement, Knee / Q000295:instrumentation*; D020878:Device Removal; D004058:Diffusion; D004952:Esters / Q000032:analysis; D006622:Hip Prosthesis; D006801:Humans; D007720:Knee Prosthesis; D016014:Linear Models; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000032:analysis*; D011095:Polyethylenes / Q000737:chemistry*; D011474:Prosthesis Design; D012086:Reoperation; D015203:Reproducibility of Results; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014810:Vitamin E / Q000032:analysis*
chemical_list: D000975:Antioxidants; D004952:Esters; D010666:Phenylpropionates; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D014810:Vitamin E