Intervertebral Disc Mechanics Research Articles

Overloading effect on the osmo-viscoelastic and recovery behavior of the intervertebral disc.

In vitro studies investigating the effect of high physiological compressive loads on the intervertebral disc mechanics as well as on its recovery are rare. Moreover, the osmolarity effect on the disc viscoelastic behavior following an overloading is far from being studied. This study aims to determine whether a compressive loading-unloading cycle exceeding physiological limits could be detrimental to the cervical disc, and to examine the chemo-mechanical dependence of this overloading effect. Cervical functional spine units were subjected to a compressive loading-unloading cycle at a high physiological level (displacement of 2.5 mm). The overloading effect on the disc viscoelastic behavior was evaluated through two relaxation tests conducted before and after cyclic loading. Afterward, the disc was unloaded in a saline bath during a rest period, and its recovery response was assessed by a third relaxation test. The chemo-mechanical coupling in the disc response was further examined by repeating this protocol with three different saline concentrations in the external fluid bath. It was found that overloading significantly alters the disc viscoelastic response, with changes statistically dependent on osmolarity conditions. The applied hyper-physiological compressive cycle does not cause damage since the disc recovers its original viscoelastic behavior following a rest period. Osmotic loading only influences the loading-unloading response; specifically, increasing fluid osmolarity leads to a decrease in disc relaxation after the applied cycle. However, the disc recovery is not impacted by the osmolarity of the external fluid.

The influence of geometry on intervertebral disc stiffness

Geometry plays an important role in intervertebral disc (IVD) mechanics. Previous computational studies have found a link between IVD geometry and stiffness. However, few experimental studies have investigated this link, possibly due to difficulties in non-destructively quantifying internal geometric features. Recent advances in ultra-high resolution MRI provides the opportunity to visualise IVD features in unprecedented detail. This study aimed to quantify 3D human IVD geometries using 9.4 T MRIs and to investigate correlations between geometric variations and IVD stiffness. Thirty human lumbar motion segments (fourteen non-degenerate and sixteen degenerate) were scanned using a 9.4 T MRI and geometric parameters were measured. A 1kN compressive load was applied to each motion segment and stiffness was calculated. Degeneration caused a reduction (p < 0.05) in IVD height, a decreased nucleus-annulus area ratio, and a 1.6 ± 3.0 mm inward collapse of the inner annulus. The IVD height, anteroposterior (AP) width, lateral width, cross-sectional area, nucleus-annulus boundary curvature, and nucleus-annulus area ratio had a significant (p < 0.05) influence on IVD stiffness. Linear relationships (p < 0.05, r > 0.47) were observed between these geometric features and IVD compressive stiffness and a multivariate regression model was generated to enable stiffness to be predicted from features observable on clinical imaging (stiffness, N/mm = 6062 – (61.2 × AP width, mm) – (169.2 × IVD height, mm)). This study advances our understanding of disc structure–function relationships and how these change with degeneration, which can be used to both generate and validate more realistic computational models.

Automated segmentation and prediction of intervertebral disc morphology and uniaxial deformations from MRI

ObjectiveThe measurement of in vivo intervertebral disc (IVD) mechanics may be used to understand the etiology of IVD degeneration and low back pain (LBP). To this end, our lab has developed methods to measure IVD morphology and uniaxial compressive deformation (% change in IVD height) resulting from dynamic activity, in vivo, using magnetic resonance images (MRI). However, due to the time-intensive nature of manual image segmentation, we sought to validate an image segmentation algorithm that could accurately and reliably reproduce models of in vivo tissue mechanics. DesignTherefore, we developed and evaluated two commonly employed deep learning architectures (2D and 3D U-Net) for the segmentation of IVDs from MRI. The performance of these models was evaluated for morphological accuracy by comparing predicted IVD segmentations (Dice similarity coefficient, mDSC; average surface distance, ASD) to manual (ground truth) measures. Likewise, functional reliability and precision were assessed by evaluating the intraclass correlation coefficient (ICC) and standard error of measurement (SEm) of predicted and manually derived deformation measures. ResultsPeak model performance was obtained using the 3D U-net architecture, yielding a maximum mDSC ​= ​0.9824 and component-wise ASDx ​= ​0.0683 ​mm; ASDy ​= ​0.0335 ​mm; ASDz ​= ​0.0329 ​mm. Functional model performance demonstrated excellent reliability ICC ​= ​0.926 and precision SEm ​= ​0.42%. ConclusionsThis study demonstrated that a deep learning framework can precisely and reliably automate measures of IVD function, drastically improving the throughput of these time-intensive methods.

A fully three-dimensional model of interpenetrating collagen fibrillar networks for intervertebral disc mechanics

In this work, a fully three-dimensional model of the human intervertebral disc is proposed within a purely analytical framework in the final goal to create time and cost-efficient patient-specific models. The constitutive representation considers the deformation-induced damage along with the hydration effects on the regional disc mechanics. Special functions are introduced to generate versatile and anatomically accurate disc geometries taking into account morphology regional variation. The complex interpenetrating collagen fibrillar networks are explicitly introduced in the three-dimensional model considering the regional variation throughout the disc. A quantitative evaluation of the predictive capabilities of a human lumbar disc model shows a good agreement with compression and torsion experiments from the literature both for the overall disc stiffness and for the direct MRI kinematic fields. Model predictions are then performed and critically discussed on axially/torsionally loaded human lumbar discs.

A Robust Multiscale and Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc.

A comprehensive understanding of multiscale and multiphasic intervertebral disc mechanics is crucial for designing advanced tissue engineered structures aiming to recapitulate native tissue behavior. The bovine caudal disc is a commonly used human disc analog due to its availability, large disc height and area, and similarities in biochemical and mechanical properties to the human disc. Because of challenges in directly measuring subtissue-level mechanics, such as in situ fiber mechanics, finite element models have been widely employed in spinal biomechanics research. However, many previous models use homogenization theory and describe each model element as a homogenized combination of fibers and the extrafibrillar matrix while ignoring the role of water content or osmotic behavior. Thus, these models are limited in their ability in investigating subtissue-level mechanics and stress-bearing mechanisms through fluid pressure. The objective of this study was to develop and validate a structure-based bovine caudal disc model, and to evaluate multiscale and multiphasic intervertebral disc mechanics under different loading conditions and with degeneration. The structure-based model was developed based on native disc structure, where fibers and matrix in the annulus fibrosus were described as distinct materials occupying separate volumes. Model parameters were directly obtained from experimental studies without calibration. Under the multiscale validation framework, the model was validated across the joint-, tissue-, and subtissue-levels. Our model accurately predicted multiscale disc responses for 15 of 16 cases, emphasizing the accuracy of the model, as well as the effectiveness and robustness of the multiscale structure-based modeling-validation framework. The model also demonstrated the rim as a weak link for disc failure, highlighting the importance of keeping the cartilage endplate intact when evaluating disc failure mechanisms in vitro. Importantly, results from this study elucidated important fluid-based load-bearing mechanisms and fiber-matrix interactions that are important for understanding disease progression and regeneration in intervertebral discs. In conclusion, the methods presented in this study can be used in conjunction with experimental work to simultaneously investigate disc joint-, tissue-, and subtissue-level mechanics with degeneration, disease, and injury.

Disc Regeneration Using MSC Transplanted via the Endplate Route

Introduction Stem cell based intervertebral disc (IVD) regeneration is quickly moving toward clinical applications.1 However, many aspects need to be investigated to routinely translate this therapy to clinical applications, in particular, the most efficient way to deliver cell to the IVD. Cells are commonly delivered to the IVD through the annulus fibrosus (AF) injection. However, recent studies have shown serious drawbacks of this approach2–4 suggesting that intradiscal injection through the AF route itself is not completely innocuous and may disable the treatments to therapeutic agents delivered. As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicular approach). The Purpose of the study was to test MSCs/hydrogel transplantation for IVD regeneration in a grade IV preclinical model of IDD on large size animals via the transpeducular approach5 with cell dose escalation. Material and Methods Adult sheep ( n = 18) underwent bone marrow aspiration for autologous MSC isolation and expansion. MSC were suspended in autologous PRP and conjugated with Hyaluronic Acid and Batroxobin at the time of transplant (MSCs/hydrogel). Nucleotomy was performed via the transpedicular approach under fluoroscopy6 in four lumbar IVDs and that were injected with 1) hydrogel, 2) Low doses of MSC/hydrogel [5x106 cell/ml] 3) High doses of MSC/hydrogel [1x107 cell/ml], 4) no injection (CTRL). The endplate tunnel was sealed using a polyurethane scaffold.7 X-ray and MRI were performed at baseline and 1,3,6,12 months. Disc height and MRI indexes were calculated at each time point. Disc macro- and micro-morphology were analyzed at each time point. Results The MRI index showed a significant decrease in the untreated group, the disc injected with hydrogel and those injected with low MSC dose compared with healthy discs in all time points. The discs treated with high dose of MSC showed maintenance of the MRI index compared with the healthy disc. Morphologically, the grade of degeneration evaluated using the Thompson grade system8 was in agreement with the grades observed at the MRI. The High MSC dose treated discs demonstrated abundant cartilage formation at 3 months, and to a lesser extent at 6 and 12 months. For the carrier and low MSC dose treated groups, however, there was less proteoglycan matrix. Conclusion An effective dose of autologous MSC [1x107 cell/ml] delivered via the alternative transpedicular approach regenerates the NP in a preclinical model of grade IV IDD. These data highlight as the disc regeneration can be achieved maintaining the AF intact via the end-plate route. This preclinical study has high translational value as large animal model with the long fallow up were used, MSCs were expanded in GMP facility simulating the clinical scenario, and the hydrogel were composed of clinically available drags and materials. This study bring a significant contribution toward the translation of regenerative therapies for the biological restoration of degenerative changes in the IVD, which is crucial to improve present clinical treatment and life quality of several patients. Acknowledgment The support of the Italian Ministry of Instruction, University and Research Grant (PRIN-200938NT8Z), the Young Investigator Research Grant of the Italian Ministry of Health (GR-2010–2318448) and the BIOSPINA Award of the Italian Society of Spine Surgery (SICV&amp;GIS) are gratefully acknowledged. References Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 2011;92(7):822–828 Carragee EJ, Don AS, Hurwitz EL, Cuellar JM, Carrino JA, Herzog R. 2009 ISSLS Prize Winner: Does discography cause accelerated progression of degeneration changes in the lumbar disc: a ten-year matched cohort study. Spine 2009;34(21):2338–2345 Korecki CL, Costi JJ, Iatridis JC. Needle puncture injury affects intervertebral disc mechanics and biology in an organ culture model. Spine 2008;33(3):235–241 Vadalà G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 2012;6(5):348–355 Vadalà G, Russo F, Pattappa G, et al. The transpedicular approach as an alternative route for intervertebral disc regeneration. Spine 2013;38(6):E319–E324 Vadalà G, De Strobel F, Bernardini M, Denaro L, D'Avella D, Denaro V. The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization. Eur Spine J 2013;22(Suppl 6):S972–S978 Vadala G, et al. A nucleotomy model with intact annulus fibrosus to test intervertebral disc regeneration strategies. Tissue Eng Part C Methods 2015;21(11):1117–1124 Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine 1990;15(5):411–415

Lubricin deficiency in the murine lumbar intervertebral disc results in elevated torsional apparent modulus

The purpose of this study was to investigate the mechanical consequences of proteoglycan 4 (Prg4) deficiency on intervertebral disc mechanics using a Prg4 knockout mouse model. Prg4, also called lubricin, was first identified as the boundary lubricant in synovial fluid but has subsequently been localized within a number of musculoskeletal tissues in areas subjected to shear and tensile stresses, including the intervertebral disc. The function of lubricin in the intervertebral disc has not been determined. Lumbar level 1–2 vertebral body-disc-vertebral body motion segments were isolated from Prg4 null mice and wild type (WT) litter mate controls. Disc dimensions were measured and motion segments were tested in axial loading and torsion. Torque measurements and disc dimensions were used to calculate the torsional apparent modulus for discs from Prg4 null and WT discs. Discs from Prg4 null mice had a significantly smaller mean transverse disc area (p=0.0057), with a significantly larger proportion of this area occupied by the nucleus pulposus (p<0.0001), compared to WT specimens. Apparent torsional moduli were found to be elevated in Prg4 null lumbar discs compared to WT controls at 10–10° (p=0.0048) and 10–30° (p=0.0127) rotation. This study suggests a functional role for Prg4 in the murine intervertebral disc. The absence of Prg4 was associated with an increased apparent torsional modulus and the structural consequences of Prg4 deficiency in the intervertebral disc, with expansion of the area of the nucleus pulposus relative to the transverse disc area in Prg4 null specimens.

Validation and application of an intervertebral disc finite element model utilizing independently constructed tissue-level constitutive formulations that are nonlinear, anisotropic, and time-dependent

Finite element (FE) models are advantageous in the study of intervertebral disc mechanics as the stress–strain distributions can be determined throughout the tissue and the applied loading and material properties can be controlled and modified. However, the complicated nature of the disc presents a challenge in developing an accurate and predictive disc model, which has led to limitations in FE geometry, material constitutive models and properties, and model validation. The objective of this study was to develop a new FE model of the intervertebral disc, to validate the model׳s nonlinear and time-dependent responses without tuning or calibration, and to evaluate the effect of changes in nucleus pulposus (NP), cartilaginous endplate (CEP), and annulus fibrosus (AF) material properties on the disc mechanical response. The new FE disc model utilized an analytically-based geometry. The model was created from the mean shape of human L4/L5 discs, measured from high-resolution 3D MR images and averaged using signed distance functions. Structural hyperelastic constitutive models were used in conjunction with biphasic-swelling theory to obtain material properties from recent tissue tests in confined compression and uniaxial tension. The FE disc model predictions fit within the experimental range (mean±95% confidence interval) of the disc׳s nonlinear response for compressive slow loading ramp, creep, and stress-relaxation simulations. Changes in NP and CEP properties affected the neutral-zone displacement but had little effect on the final stiffness during slow-ramp compression loading. These results highlight the need to validate FE models using the disc׳s full nonlinear response in multiple loading scenarios.

Acute Mechanical Injury to the Human Intervertebral Disc Initiates Events Implicated in Disc Degeneration

Introduction Low back pain is a prevalent chronic disorder among individuals worldwide. Intervertebral disc degeneration is a major cause of low back pain in adults. Mechanical overload has been proposed as a potential initiating mechanism of degeneration, and previous studies have demonstrated that complex mechanical loading of lumbar motion segments can disrupt disc cell metabolism.1 Furthermore, mechanical wedge loading of bovine caudal discs induced cell death and causes induction of catabolic genes such as IL-1β and members of the metalloproteinase and ADAMTS family of proteases which leads to loss of aggrecan.2 The aim of this study was to investigate the effect of acute mechanical injury on cellular responses and changes in matrix composition in human intervertebral discs. Materials and Methods Lumbar spine segments were harvested from consenting donors via the Transplant Quebec organ donation program in Montreal, Quebec. This was performed in accordance with the Institutional Review Board guidelines of the Montreal General Hospital. Discs with intact cartilaginous endplates were isolated from the lumbar spine. A single ramp compression of either 5 or 30% resulted in approximately 0.2 MPa (low noninjurious load or LNL) or approximately 1.5 MPa (acute traumatic injury or ATI) peak stress. The rate of compression was 30% strain per second. This compression protocol for acute traumatic injury consistently yields endplate fracture. Discs were, after loading, immediately put in low-serum containing media. The media was changed and collected at days 3 and 7. Proteoglycan release was evaluated in media from all culture days and in guanidium hydrochloride extracts of tissue from the loaded discs. Proteoglycan size distribution was visualized by fractionating conditioned media from low noninjurious load and acute traumatic injury samples by agarose gel electrophoresis. At day 14, disc cultures were terminated and Live/Dead analysis was performed on biopsies from seven different regions of the discs and confocal microscopy was used to quantify live and dead cells. PC12 cells, a neuronal-like cell line, were exposed to conditioned media from the cultured discs to study the potential for neurite sprouting. Nerve growth factor (NGF) levels were measured using a commercially available ELISA assay. Commercially, available cytokine arrays were used to investigate protein levels of cytokines. Disc tissue was fixed in 80% methanol and prepared for cryosectioning and histological analysis with Safranin O, hematoxylin, and Fast Green. Results Considerable cell death was observed in discs subjected to acute traumatic injury 14 days after the load event (NP 40% viable and AF 50% viable). Discs subjected to the low noninjurious load maintained a cell viability of 85% in the NP and the AF (Fig. 1A). Investigation of GAG levels revealed that acute traumatic injury induced a considerable release of GAG from the tissue as compared with low noninjurious load samples (Fig. 1B). This was confirmed by histological analysis where a loss of Safranin O staining was apparent in the tissue of discs subjected to acute traumatic injury. Fractionation of the conditioned media by agarose gel electrophoresis revealed a wider size distribution of the proteoglycans released from the discs after acute traumatic injury as compared with the discs subjected to low noninjurious load. Elevated levels of inflammatory cytokines and pain mediators were detected in the culture media from discs subjected to acute traumatic injury group compared with discs subjected to low noninjurious load. Furthermore, conditioned media from the acute traumatic injury disc cultures caused significantly more neurite outgrowth in PC12 cells compared with disc cultures from discs subjected to low noninjurious load. Conclusion Cell death and cytokine production combined with loss of GAG indicate that acute mechanical injury initiated degradative processes that could lead to disc degeneration. A wider size distribution of proteoglycans in conditioned media from discs subjected to acute traumatic injury further confirmed that this type of load induced expression and/or activation of proteases in the disc. Acute injury also stimulated the remaining viable cells to produce elevated levels of inflammatory cytokines. Once the proteoglycan content in the matrix has been degraded, elevated levels of NGF could lead to neuronal in-growth and directly cause pain. Further investigation may yield insights to novel diagnostics and therapies for degenerative disc disease. Disclosure of Interest None declared References Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P. Mechanical initiation of intervertebral disc degeneration. Spine 2PO.004;25(13):1625–1636 Walter BA, Korecki CL, Purmessur D, Roughley PJ, Michalek AJ, Iatridis JC. Complex loading affects intervertebral disc mechanics and biology. Osteoarthritis Cartilage 2011;19(8):1011–1018

The Ability of Physiological Load to Restore Disc Function

Introduction The nucleus pulposus (NP) of a healthy intervertebral disc (IVD) is rich in collagen type II fibers that are arranged in a random fashion to entrap the highly anionic proteoglycan aggrecan which confers the swelling properties important for resistance to compression. A hallmark of IVD degeneration is the decrease in proteoglycan content. Matrix degradation and proteoglycan loss from the NP result in a decrease in weight bearing capacity and loss of disc height. In the final stages of IVD degradation fissures appear in the annular ring allowing extrusion of the NP. It is crucial to understand the interplay between mechanobiology, disc composition, and metabolism to understand the underlying cause of disc degeneration and to be able to study ways to regenerate the degenerate disc. To address such questions, a bioreactor has been developed that facilitates organ culture of intact discs in a controlled dynamically loaded environment.1 The bioreactor can be used in combination with an isolation and degeneration method which maintains the integrity of the intervertebral discs by preserving the noncalcified part of the cartilage endplate.2,3 To allow repair strategies to be studied, a degeneration method utilizing trypsin injection to deplete proteoglycans (PGs) from the matrix has been established.2 Materials and Methods Intact bovine and human discs were prepared as previously described.2,3 Degeneration was induced by trypsin in the bovine discs.2 Human and bovine discs were loaded in the bioreactor system over 14 days. Cell viability or metabolic activity was assessed using a Live/Dead and/or Alamar Blue metabolic assay. The proteoglycan content was assessed by DMMB assay and Safranin O staining of histological sections. CHAD and collagen type II were examined by western blotting. Stress profilometry was performed at 0.6 MPa static load.4 Results After PG depletion, the discs were loaded in the bioreactor under physiological cyclic dynamic load. Cell viability and metabolic activity at the end of the culture period was assessed. Bovine discs treated with trypsin maintained high cell viability when cultured for 14 days both loaded and unloaded. PG content was measured using the DMMB assay and by Safranin O staining of tissue sections. Unloaded discs lost approximately 60% of their proteoglycan content, whereas discs loaded under physiological dynamic load completely replenished the proteoglycan content. Collagen type II and CHAD protein levels were also increased under physiological dynamic loading. In a separate set of discs, stress profilometry was performed at 0.6 MPa static load and stress profiles were generated. No significant change in the load profiles were found for a low trypsin dose, however, the discs treated with the experimental dose of trypsin showed an 11% reduction of the internal pressure. The system has also been used to culture and load intact human discs under three different load magnitudes (high 0-3-1.2 MPa, medium 0.1-0.6, and low 0.1-0.3 MPa). The load curves and cell viability were followed over a 2-week period. Discs cultured under low load maintained a viability of &gt; 90%, discs loaded under medium load showed a viability of &gt; 86%, whereas the cell viability decreased to below 55% in discs loaded under high loads. Conclusion This study shows that physiological load has the ability to stimulate PG synthesis and to fully restore PG content after 14 days of axial dynamic loading at a physiological level. It also allows the response to load to be evaluated. The bioreactor can also be used to evaluate changes in mechanical properties of the disc following biologically induced changes, or to induce biomechanical stimulus of the disc to generate a biological change. As such, it is equally useful for studying the role of load in inducing disc degeneration or the role of biological stimuli in restoring disc function. It provides an experimental platform useful to evaluate if biologic repair is feasible over a range of loading conditions, or is impaired outside this range. Such knowledge is important for patient advice on lifestyle following a biological repair procedure. Disclosure of Interest None declared References Haglund L, Moir J, Beckman L, et al. Development of a bioreactor for axially loaded intervertebral disc organ culture. Tissue Eng Part C Methods 2011;17(10):1011–1019 Jim B, Steffen T, Moir J, Roughley P, Haglund L. Development of an intact intervertebral disc organ culture system in which degeneration can be induced as a prelude to studying repair potential. Eur Spine J 2011;20(8):1244–1254 Gawri R, Mwale F, Ouellet J, et al. Development of an organ culture system for long-term survival of the intact human intervertebral disc. Spine 2011;36(22):1835–1842 McNally DS, Adams MA. Internal intervertebral disc mechanics as revealed by stress profilometry. Spine 1992;17(1):66–73

Human L3L4 intervertebral disc mean 3D shape, modes of variation, and their relationship to degeneration

Intervertebral disc mechanics are affected by both disc shape and disc degeneration, which in turn each affect the other; disc mechanics additionally have a role in the etiology of disc degeneration. Finite element analysis (FEA) is a favored tool to investigate these relationships, but limited data for intervertebral disc 3D shape has forced the use of simplified or single-subject geometries, with the effect of inter-individual shape variation investigated only in specialized studies. Similarly, most data on disc shape variation with degeneration is based on 2D mid-sagittal images, which incompletely define 3D shape changes. Therefore, the objective of this study was to quantify inter-individual disc shape variation in 3D, classify this variation into independently-occurring modes using a statistical shape model, and identify correlations between disc shape and degeneration. Three-dimensional disc shapes were obtained from MRI of 13 human male cadaver L3L4 discs. An average disc shape and four major modes of shape variation (representing 90% of the variance) were identified. The first mode represented disc axial area and was significantly correlated to degeneration (R2=0.44), indicating larger axial area in degenerate discs. Disc height variation occurred in three distinct modes, each also involving non-height variation. The statistical shape model provides an average L3L4 disc shape for FEA that is fully defined in 3D, and makes it convenient to generate a set of shapes with which to represent aggregate inter-individual variation. Degeneration grade-specific shapes can also be generated. To facilitate application, the model is included in this paper׳s supplemental content.

Intervertebral Disc Local Biochemistry and Mechanics are Correlated with Quantitative T2* MRI Mapping

Intervertebral Disc Local Biochemistry and Mechanics are Correlated with Quantitative T2* MRI Mapping

Commentary: The spine and vibration: whole lotta shaking going on

Commentary on: Holguin N, Martin JT, Elliott DM, Judex S. Low-intensity vibrations partially maintain intervertebral disc mechanics and spinal muscle area during deconditioning. Spine J 2013;13:428-36 (in this issue).

Low-intensity vibrations partially maintain intervertebral disc mechanics and spinal muscle area during deconditioning

Background contextReduced spinal loading degrades the intervertebral disc and alters the muscle size. PurposeTo determine the ability of high-frequency and low-intensity vibrations to maintain disc biomechanics and prevent muscle changes during hindlimb unloading. Study designThree groups of Sprague-Dawley rats were hindlimb unloaded for 4 weeks. In two hindlimb unloaded groups, unloading was interrupted for 15 min/d and the rats were positioned upright on a 90 Hz vertically oscillating plate or a sham control inactive plate. One author owns (provisional) patents regarding the application of vibrations to the musculoskeleton. MethodsThe motion segments L4–L5 were mechanically evaluated in compression-tension, axial creep, and torsion loading. In vivo microcomputed tomography was used to determine longitudinal psoas and paraspinal muscle area. This work was supported by National Institutes of Health, National Aeronautics and Space Administration (NASA), Alliance for Graduate Education and the Professoriate, and NASA-Harriett G. Jenkins Predoctoral and W. Burghardt Turner Fellowships. The author (SJ) holds (provisional) patents regarding the application of vibrations. ResultsThere were no differences between the discs of uninterrupted unloading and sham animals and these groups were pooled. Compared with normally ambulating age-matched controls, hindlimb unloaded discs had altered properties in every loading modality. Psoas area of the unloaded rats increased at L4 and L5 and the paraspinal area decreased at L4. Vibrations (90 Hz) maintained compression-tension properties, partially maintained creep properties, but did not mitigate torsional weakening because of unloading. Low-intensity vibrations prevented the increase in psoas area but did not abate paraspinal muscle loss. ConclusionsIn support of clinical studies, unloading deconditioned the rodent disc and altered the muscle area. Although brief exposures to upright posture provided only limited benefits, low-intensity vibrations superimposed on upright posture served to preserve disc mechanics during unloading.

Complex loading affects intervertebral disc mechanics and biology

Complex loading develops in multiple spinal motions and in the case of hyperflexion is known to cause intervertebral disc (IVD) injury. Few studies have examined the interacting biologic and structural alterations associated with potentially injurious complex loading, which may be an important contributor to chronic progressive degeneration. This study tested the hypothesis that low magnitudes of axial compression loading applied asymmetrically can induce IVD injury affecting cellular and structural responses in a large animal IVD ex-vivo model. Bovine caudal IVDs were assigned to either a control or wedge group (15°) and placed in organ culture for 7 days under static 0.2MPa load. IVD tissue and cellular responses were assessed through confined compression, qRT-PCR, histology and structural and compositional measurements, including Western blot for aggrecan degradation products. Complex loading via asymmetric compression induced cell death, an increase in caspase-3 staining (apoptosis), a loss of aggrecan and an increase in aggregate modulus in the concave annulus fibrosis. While an up-regulation of MMP-1, ADAMTS4, IL-1β, and IL-6 mRNA, and a reduced aggregate modulus were induced in the convex annulus. Asymmetric compression had direct deleterious effects on both tissue and cells, suggesting an injurious loading regime that could lead to a degenerative cascade, including cell death, the production of inflammatory mediators, and a shift towards catabolism. This explant model is useful to assess how injurious mechanical loading affects the cellular response which may contribute to the progression of degenerative changes in large animal IVDs, and results suggest that interventions should address inflammation, apoptosis, and lamellar integrity.

Role of load history in intervertebral disc mechanics and intradiscal pressure generation

Solid-fluid interactions play an important role in mediating viscoelastic behaviour of biological tissues. In the intervertebral disc, water content is governed by a number of factors, including age, disease and mechanical loads, leading to changes in stiffness characteristics. We hypothesized that zonal stress distributions depend on load history, or the prior stresses experienced by the disc. To investigate these effects, rat caudal motion segments were subjected to compressive creep biomechanical testing in vitro using a protocol that consisted of two phases: a Prestress Phase (varied to represent different histories of load) followed immediately by an Exertion Phase, identical across all Prestress groups. Three analytical models were used to fit the experimental data in order to evaluate load history effects on gross and zonal disc mechanics. Model results indicated that while gross transient response was insensitive to load history, there may be changes in the internal mechanics of the disc. In particular, a fluid transport model suggested that the role of the nucleus pulposus in resisting creep during Exertion depended on Prestress conditions. Separate experiments using similarly defined load history regimens were performed to verify these predictions by measuring intradiscal pressure with a fibre optic sensor. We found that the ability for intradiscal pressure generation was load history-dependent and exhibited even greater sensitivity than predicted by analytical models. A 0.5MPa Exertion load resulted in 537.2kPa IDP for low magnitude Prestress compared with 373.7kPa for high magnitude Prestress. Based on these measurements, we developed a simple model that may describe the pressure-shear environment in the nucleus pulposus. These findings may have important implications on our understanding of how mechanical stress contributes to disc health and disease etiology.

Quantifying intervertebral disc mechanics: a new definition of the neutral zone

BackgroundThe neutral zone (NZ) is the range over which a spinal motion segment (SMS) moves with minimal resistance. Clear as this may seem, the various methods to quantify NZ described in the literature depend on rather arbitrary criteria. Here we present a stricter, more objective definition.MethodsTo mathematically represent load-deflection of a SMS, the asymmetric curve was fitted by a summed sigmoid function. The first derivative of this curve represents the SMS compliance and the region with the highest compliance (minimal stiffness) is the NZ. To determine the boundaries of this region, the inflection points of compliance can be used as unique points. These are defined by the maximum and the minimum in the second derivative of the fitted curve, respectively. The merits of the model were investigated experimentally: eight porcine lumbar SMS's were bent in flexion-extension, before and after seven hours of axial compression.ResultsThe summed sigmoid function provided an excellent fit to the measured data (r2 > 0.976). The NZ by the new definition was on average 2.4 (range 0.82-7.4) times the NZ as determined by the more commonly used angulation difference at zero loading. Interestingly, NZ consistently and significantly decreased after seven hours of axial compression when determined by the new definition. On the other hand, NZ increased when defined as angulation difference, probably reflecting the increase of hysteresis. The methods thus address different aspects of the load-deflection curve.ConclusionsA strict mathematical definition of the NZ is proposed, based on the compliance of the SMS. This operational definition is objective, conceptually correct, and does not depend on arbitrarily chosen criteria.

010 Restoration of intervertebral disc mechanics after endplate deformity reduction using structural kyphoplasty

Introduction/Purpose: Recent studies suggest endplate fracture incurred during vertebral compression fracture (VCF) increases nucleus volume which alters intervertebral disc mechanics. Altered disc behavior has been theorized to increase adjacent fracture...

Degenerative Anular Changes Induced by Puncture Are Associated With Insufficiency of Disc Biomechanical Function

In vivo experiments to examine physiologic consequences and in vitro tests to determine immediate biomechanical effects of anular injury by needle puncture. To determine whether a relationship exists between induction of degenerative changes in anulus fibrosus (AF) and compromised disc biomechanical function according to injury size. Various studies in intervertebral disc mechanics, degeneration, and regeneration involve the creation of a defect in the anulus fibrosus (AF). However, the impact of the puncture, itself, on biomechanical function and disc health are not understood. For in vivo experiments, rat caudal discs subjected to percutaneous anular punctures using different gauge size hypodermic needles (18, 22, 26 g) and nonpunctured controls were examined histologically up to 4 weeks postsurgery. For in vitro biomechanical testing, healthy motion segments were isolated and their creep compression response assessed immediately after needle puncture. We found that needle size-dependence of creep compression behavior paralleled the size-dependence of degenerative changes in the AF. Specifically, 18-g punctures resulted in inward bulging of the AF, lamellar disorganization, and cellular changes. These changes were not seen in 22- and 26-g punctured discs. Biomechanical tests showed that only 18-g needle punctures led to significant changes in disc mechanics. Importantly, a statistically significant association was found between needle sizes that caused biomechanical changes and induction of degenerative changes in the AF. Our findings suggest that injury sizes large enough to disrupt biomechanical function are needed to drive degenerative changes in rat caudal disc AF. Based on the data, we believe that small anular defects become sealed, allowing the disc to function normally and the AF to heal. Larger defects appear to require longer wound closure times, and may prolong the duration of impaired disc function.

The effect of nucleus implant parameters on the compressive mechanics of the lumbar intervertebral disc: A finite element study

A simplified finite element model of the human lumbar intervertebral disc was utilized for understanding nucleus pulposus implant mechanics. The model was used to assess the effect of nucleus implant parameter variations on the resulting compressive biomechanics of the lumbar anterior column unit. The effects of nucleus implant material (modulus and Poisson's ratio) and geometrical (height and diameter) parameters on the mechanical behavior of the disc were investigated. The model predicted that variations in implant modulus contribute less to the compressive disc mechanics compared to the implant geometrical parameters, for the ranges examined. It was concluded that some threshold exists for the nucleus implant modulus, below which little variations in load-displacement behavior were shown. Compressive biomechanics were highly affected by implant volume (under-filling the nucleus cavity, line-to-line fit, or over-filling the nucleus cavity) with a greater restoration of compressive mechanics observed with the over-filled implant design. This work indicated the effect of nucleus implant parameter variations on the compressive mechanics of the human lumbar intervertebral disc and importance of the "fit and fill" effect of the nuclear cavity in the restoration of the human intervertebral disc mechanics in compression. These findings may have clinical significance for nucleus implant design.