title: Assessment of epidural versus intradiscal biocompatibility of PEEK implant debris: an in vivo rabbit model.
abstract: OBJECTIVE
  To understand the relative histopathological effects of PEEK particulate debris when applied within the epidural versus the intervertebral disc space. We hypothesized that due to the avascular nature of the intervertebral disc acting as a barrier to immune cells, the intradiscal response would be less than the epidural response.
  
  
  METHODS
  The inflammatory effects of clinically relevant doses (3 mg/5-kg rabbit) and sizes (1.15 µm diameter) of PEEK implant debris were assed when placed dry on epidural and intradiscal tissues in an in vivo rabbit model. The size of the particulate was based on wear particulate analysis of wear debris generated from simulator wear testing of PEEK spinal disc arthroplasty devices. Local and systemic gross histology was evaluated at the 3- and 6-month time points. Quantitative immunohistochemistry of local tissues was used to quantify the common inflammatory mediators TNF-α, IL-1β, and IL-6.
  
  
  RESULTS
  Both treatments did not alter the normal appearance of the dura mater and vascular structures; however, limited epidural fibrosis was observed. Epidural challenge of PEEK particles resulted in a significant (30 %) increase (p < 0.007) in TNF-α and IL-1β at both 3 and 6 months compared to that of controls, and IL-6 at 6 months (p < 0.0001). Intradiscal challenge of PEEK particles resulted in a significant increase in IL-1β, IL-6 and TNF-α at 6-months post-challenge (p ≤ 0.03). However, overall there were only moderate increases in the relative amount of these cytokines when compared with surgical controls (10-20 %). In contrast, epidural challenge resulted in a 50-100 % increase.
  
  
  CONCLUSIONS
  The results of this study are similar to past investigations of PEEK, whose results have not been shown to elicit an aggressive immune response. The degree to which these results will translate to the clinical environment remains to be established, but the pattern of subtle elevations in inflammatory cytokines indicated both a mild persistence of responses to PEEK debris, and that intradiscal implant debris will likely result in less inflammation than epidural implant debris.
authors.affiliation: Department of Orthopaedic Surgery, Rush University Medical Center, 1735 West Harrison, Chicago, IL, 60612, USA, nhallab@rush.edu.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Qi-Bin
authors.initials: QB
authors.lastname: Bao
authors.forename: Tim
authors.initials: T
authors.lastname: Brown
mesh_terms: D000818:Animals; D001577:Benzophenones; D016207:Cytokines / Q000276:immunology; D004824:Epidural Space / Q000276:immunology / Q000473:pathology*; D005355:Fibrosis / Q000473:pathology; D005547:Foreign Bodies / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007403:Intervertebral Disc / Q000276:immunology / Q000473:pathology*; D007659:Ketones; D008422:Materials Testing; D023421:Models, Animal; D011092:Polyethylene Glycols; D011108:Polymers; D019736:Prostheses and Implants; D011817:Rabbits; D013131:Spine / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha
chemical_list: D001577:Benzophenones; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D007659:Ketones; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; C063834:polyetheretherketone; D011092:Polyethylene Glycols