Nucleotomy reduces the effects of cyclic compressive loading with unloaded recovery on human intervertebral discs

Abstract

The first objective of this study was to determine the effects of physiological cyclic loading followed by unloaded recovery on the mechanical response of human intervertebral discs. The second objective was to examine how nucleotomy alters the disc’s mechanical response to cyclic loading. To complete these objectives, 15 human L5-S1 discs were tested while intact and subsequent to nucleotomy. The testing consisted of 10,000 cycles of physiological compressive loads followed by unloaded hydrated recovery. Cyclic loading increased compression modulus (3%) and strain (33%), decreased neutral zone modulus (52%), and increased neutral zone strain (31%). Degeneration was not correlated with the effect of cyclic loading in intact discs, but was correlated with cyclic loading effects after nucleotomy, with more degenerate samples experiencing greater increases in both compressive and neutral zone strain following cyclic loading. Partial removal of the nucleus pulposus decreased the compression and neutral zone modulus while increasing strain. These changes correspond to hypermobility, which will alter overall spinal mechanics and may impact low back pain via altered motion throughout the spinal column. Nucleotomy also reduced the effects of cyclic loading on mechanical properties, likely due to altered fluid flow, which may impact cellular mechanotransduction and transport of disc nutrients and waste. Degeneration was not correlated with the acute changes of nucleotomy. Results of this study provide an ideal protocol and control data for evaluating the effectiveness of a mechanically-based disc degeneration treatment, such as a nucleus replacement.

Evaluation of an In Situ Gelable and Injectable Hydrogel Treatment to Preserve Human Disc Mechanical Function Undergoing Physiologic Cyclic Loading Followed by Hydrated Recovery

“…The mechanical test consisted of six steps ( Fig. 2): (1) overnight hydration, also called initial hydration, (2) measure mechanical parameters (initial), (3) 10,000 cycles of compressive loading, (4) measure mechanical parameters (cyclic), (5) overnight hydration, also called unloaded recovery, and (6) measure mechanical parameters (recovery) [26].…”

“…Following nucleotomy, the samples were frozen until further testing. The results for these nucleotomy tests have already been published [26].…”

“…Mechanical parameters were measured on the 50th cycle of the mechanical measurement steps of the testing procedure (steps 2, 4, and 6) using a previously described custom MATLAB program [26,35]. Compressive range of motion was defined as the displacement between 0 MPa and 0.48 MPa of applied load and compressive stiffness was defined as the slope of the line fit through the data between 0.38 and 0.48 MPa in compression (Fig.…”

“…Reduced hydration decreases disc height, increases stiffness, and increases range of motion, with properties returning to baseline after rehydration (Adams et al, [28]; Wilke et al, [29]). Cyclic loading followed by hydrated recovery in human discs mimics this naturally occurring diurnal response [26]. In a previous study that used cyclic loading to evaluate a hydrogel implant in injured porcine discs, the implant demonstrated recovery of angular stiffness and disc height [30].…”

“…More extensive mechanical testing is completed with the aim of testing failure properties [23,24]. While not commonly used, moderate cyclic loading of discs followed by unloaded hydrated recovery is a valuable testing modality because it is more rigorous than single-cycle tests and captures elements of the time-dependent mechanical response critical for daily function [25,26]. Within the disc, interplay between osmotic pressure and external loads causes 20-25% of the disc's water content to be expressed and re-imbibed daily (Sivan et al [27]).…”