Hallab Nadim J, Bao Qi-Bin, Brown Tim
Department of Orthopaedic Surgery, Rush University Medical Center, 1735 West Harrison, Chicago, IL, 60612, USA,
Eur Spine J. 2013 Dec;22(12):2740-51. doi: 10.1007/s00586-013-2904-4. Epub 2013 Aug 31.
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.
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.
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.
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.
了解聚醚醚酮（PEEK）颗粒碎片应用于硬膜外腔和椎间盘间隙时的相对组织病理学效应。我们假设，由于椎间盘的无血管性质可作为免疫细胞的屏障，椎间盘内的反应会小于硬膜外的反应。
在兔体内模型中，将临床相关剂量（3 mg/5 kg兔）和尺寸（直径1.15 µm）的PEEK植入物碎片干燥放置于硬膜外和椎间盘组织上，评估其炎症效应。颗粒大小基于对PEEK人工椎间盘模拟器磨损试验产生的磨损碎片的磨损颗粒分析。在3个月和6个月时间点评估局部和全身大体组织学。使用局部组织的定量免疫组织化学来量化常见炎症介质肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）。
两种处理均未改变硬脑膜和血管结构的正常外观；然而，观察到有限的硬膜外纤维化。与对照组相比，硬膜外注射PEEK颗粒在3个月和6个月时TNF-α和IL-1β显著增加（30%）（p < 0.007），6个月时IL-6显著增加（p < 0.0001）。椎间盘内注射PEEK颗粒在注射后6个月时IL-1β、IL-6和TNF-α显著增加（p≤0.03）。然而，总体而言，与手术对照组相比，这些细胞因子的相对量仅适度增加（10 - 20%）。相比之下，硬膜外注射导致增加50 - 100%。
本研究结果与过去对PEEK的研究相似，其结果尚未显示会引发强烈的免疫反应。这些结果在临床环境中的转化程度仍有待确定，但炎症细胞因子的细微升高模式表明对PEEK碎片的反应有轻度持续性，并且椎间盘内植入碎片可能比硬膜外植入碎片引起的炎症更少。
