Epidural Application of Spinal Instrumentation Particulate Wear Debris: An In-Vivo Animal Model

Introduction: The effect of unintended particulate wear debris, resulting from micromotion at spinal implant interconnections remains a clinical concern. Using an in-vivo rabbit model, the current study investigated the in-vivo histopathologic response following epidural application of four different types of spinal instrumentation particulate wear debris.

Methods: Fifty New Zealand White rabbits were equally randomized into five groups based on treatment material: 1) Sham (control) (n=10), 2) Stainless Steel (n=10), 3) Titanium Alloy (n=10), 4) Cobalt Chrome Alloy (n=10) and 5) Ultrahigh molecular weight polyethylene (UHMWPE) (n=10). The microsurgical procedure consisted of posterior resection of the ligamentum flavum at L6-L7 - permitting interlaminar exposure of the dural sac. 4mg of the appropriate treatment (Groups 2-5) was then topically applied to the dura in sterile, dry form. The sham procedure consisted of epidural exposure alone. All particles (size 1-5µm dia.) were verified endotoxin free based on Limulus assay prior to implantation. Five animals from each treatment group were sacrificed at three-months and five at six-months post-operatively. Post-mortem analysis included epidural cultures, blood chemistry profiles, cerebrospinal fluid (CSF) analysis / cytology and histopathological assessment of local and systemic tissues. Immunocytochemical analysis of the spinal cord and overlying fibrosis quantified the extent of cellular apoptosis, pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-±, TNF-², PGE2) and histiocytosis.

Results: Post-mortem blood chemistry profiles were within normal limits and cultures were negative for all 50 cases. The CSF analyses indicated no overt inflammatory reactions, infectious agents, pleocytosis or neoplasia. However, two cases from the three-month cobalt chrome treatments contained scant granular and amorphous debris in the CSF and activated macrophages. There was no evidence of particulate debris or pathology in the systemic tissues. Gross histopathology at the operative site demonstrated increased levels of epidural fibrosis in the metallic treatments versus the sham and UHMWPE groups. The epidural fibrous tissues (H&E and macrophage stains) indicated a histiocytic reaction containing phagocytized inert particles and foci of local inflammatory changes in all treatments, except the sham procedures. No significant spinal cord lesions or pathology were observed in any treatment. However, two cases from the cobalt chrome group indicated a chronic macrophage response to particulate debris, which had diffused intrathecally to the innermost spinal meninx - pia mater.

Discussion: The implementation of mobile spinal instrumentation systems for fusionless correction of spinal deformity and total disc replacement necessitates improved understanding of the neurohistopathologic response to the wear debris generated. The current study provides an experimental model to assess the local/systemic response to four of the most commonly used materials in spinal instrumentation.

Conclusions: Epidural application of particulate debris elicits a chronic histiocytic reaction localized primarily within the epidural fibrous layers. Particles have the capacity to diffuse intrathecally, eliciting a macrophage response within the CSF and innermost spinal meninx. Overall, based on the post-operative time periods evaluated, there was no evidence of acute neural or systemic histopathologic responses to the materials included in the current project.