The Effect of Degeneration on Intervertebral Disc Herniation: A Human ex vivo Study with Multiscale Structural Analysis

Study design: Human cadaveric structural investigation of mechanical load-induced acute disc herniation across degeneration grades. Objective: To understand the structural effects of loading to failure in discs of different degeneration grades for inferring herniation mechanisms. Summary of background data: Animal models have been extensively used to study disc herniation in non-degenerate discs, but their relevance to human pathology is unclear and validation in human discs is limited. Studying microstructural failure in human discs is therefore essential for investigating mechanisms of herniation and how these are affected by degeneration. Methods: Human cadaveric intervertebral discs (n=16) were imaged using MRI, graded for degeneration using the Pfirrmann classification and assigned to either loaded or unloaded groups. Loaded discs were flexed (13°) to physiological limits and loaded to failure (~90% of disc height). Discs were sectioned and examined macroscopically and microscopically to quantify structural failures (graded ordinally 0-3), facilitating comparison across degeneration grades. Results: Direct comparison of MRI, macroscopic, and microscopic images provided the most comprehensive depiction of the human disc to date. Loaded discs exhibited significantly increased damage scores across radial tears (ordinal rating: 1.46 vs 0.92, P =0.045), lamellae separations (1.12 vs 0.78, P =0.043), endplate tears (0.85 vs 0.50, P =0.033), and nucleus clefts (1.51 vs 0.82, P =0.008). Increased disc degeneration was associated with increased annulus bulging scores (0.42 vs 1.72, P <0.013), and larger clefts being present in the discs. Conclusions: The standardised mechanical loading applied produced consistent macrostructural and microstructural failure of the disc. The findings motivate a hypothesis that mechanisms of herniation may vary with degeneration. Mildly degenerate discs may herniate via extrusion of inner disc material, whereas more degenerate discs may herniate through posterior annulus disc bulging. Treatment strategies, including surgical timing and expectations for spontaneous resorption, may therefore be tailored by degeneration grade.