Application of the polynomial chaos expansion to approximate the homogenised response of the intervertebral disc

A possibility to simulate the mechanical behaviour of the human spine is given by modelling the stiffer structures, i.e. the vertebrae, as a discrete multi-body system (MBS), whereas the softer connecting tissue, i.e. the softer intervertebral discs (IVD), is represented in a continuum-mechanical sense using the finite-element method (FEM). From a modelling point of view, the mechanical behaviour of the IVD can be included into the MBS in two different ways. They can either be computed online in a so-called co-simulation of a MBS and a FEM or offline in a pre-computation step, where a representation of the discrete mechanical response of the IVD needs to be defined in terms of the applied degrees of freedom (DOF) of the MBS. For both methods, an appropriate homogenisation step needs to be applied to obtain the discrete mechanical response of the IVD, i.e. the resulting forces and moments. The goal of this paper was to present an efficient method to approximate the mechanical response of an IVD in an offline computation. In a previous paper (Karajan et al. in Biomech Model Mechanobiol 12(3):453–466, 2012), it was proven that a cubic polynomial for the homogenised forces and moments of the FE model is a suitable choice to approximate the purely elastic response as a coupled function of the DOF of the MBS. In this contribution, the polynomial chaos expansion (PCE) is applied to generate these high-dimensional polynomials. Following this, the main challenge is to determine suitable deformation states of the IVD for pre-computation, such that the polynomials can be constructed with high accuracy and low numerical cost. For the sake of a simple verification, the coupling method and the PCE are applied to the same simplified motion segment of the spine as was used in the previous paper, i.e. two cylindrical vertebrae and a cylindrical IVD in between. In a next step, the loading rates are included as variables in the polynomial response functions to account for a more realistic response of the overall viscoelastic intervertebral disc. Herein, an additive split into elastic and inelastic contributions to the homogenised forces and moments is applied.     

Load-sharing in the lumbosacral spine in neutral standing & flexed postures – A combined finite element and inverse static study

Understanding load-sharing in the spine during in-vivo conditions is critical for better spinal implant design and testing. Previous studies of load-sharing that considered actual spinal geometry applied compressive follower load, with or without moment, to simulate muscle forces. Other studies used musculoskeletal models, which include muscle forces, but model the discs by simple beams or spherical joints and ignore the articular facet joints.This study investigated load-sharing in neutral standing and flexed postures using a detailed Finite Element (FE) model of the ligamentous lumbosacral spine, where muscle forces, gravity loads and intra-abdominal pressure, as predicted by a musculoskeletal model of the upper body, are input into the FE model. Flexion was simulated by applying vertebral rotations following spine rhythm measured in a previous in-vivo study, to the musculoskeletal model. The FE model predicted intradiscal pressure (IDP), strains in the annular fibers, contact forces in the facet joints, and forces in the ligaments. The disc forces and moments were determined using equilibrium equations, which considered the applied loads, including muscle forces and IDP, as well as forces in the ligaments and facet joints predicted by the FE model. Load-sharing was calculated as the portion of the total spinal load carried along the spine by each individual spinal structure. The results revealed that spinal loads which increased substantially from the upright to the flexed posture were mainly supported by the discs in the upright posture, whereas the ligaments’ contribution in resisting shear, compression, and moment was more significant in the flexed posture.     

Effects of lumbo-pelvic rhythm on trunk muscle forces and disc loads during forward flexion: A combined musculoskeletal and finite element simulation study

Previous in-vivo studies suggest that the ratio of total lumbar rotation over pelvic rotation (lumbo-pelvic rhythm) during trunk sagittal movement is essential to evaluate spinal loads and discriminate between low back pain and asymptomatic population. Similarly, there is also evidence that the lumbo-pelvic rhythm is key for evaluation of realistic muscle and joint reaction forces and moments predicted by various computational musculoskeletal models. This study investigated the effects of three lumbo-pelvic rhythms defined based on in-vivo measurements on the spinal response during moderate forward flexion (60°) using a combined approach of musculoskeletal modeling of the upper body and finite element model of the lumbosacral spine. The muscle forces and joint loads predicted by the musculoskeletal model, together with the gravitational forces, were applied to the finite element model to compute the disc force and moment, intradiscal pressure, annular fibers strain, and load-sharing. The results revealed that a rhythm with high pelvic rotation and low lumbar flexion involves more global muscles and increases the role of the disc in resisting spinal loads, while its counterpart, with low pelvic rotation, recruits more local muscles and engages the ligaments to lower the disc loads. On the other hand, a normal rhythm that has balanced pelvic and lumbar rotations yields almost equal disc and ligament load-sharing and results in more balanced synergy between global and local muscles. The lumbo-pelvic rhythm has less effect on the intradiscal pressure and annular fibers strain. This work demonstrated that the spinal response during forward flexion is highly dependent on the lumbo-pelvic rhythm. It is therefore, essential to adapt this parameter instead of using the default values in musculoskeletal models for accurate prediction of muscle forces and joint reaction forces and moments. The findings provided by this work are expected to improve knowledge of spinal response during forward flexion, and are clinically relevant towards low back pain treatment and disc injury prevention.     

Linking continuous and discrete intervertebral disc models through homogenisation

At present, there are two main numerical approaches that are frequently used to simulate the mechanical behaviour of the human spine. Researchers with a continuum-mechanical background often utilise the finite-element method (FEM), where the involved biological soft and hard tissues are modelled on a macroscopic (continuum) level. In contrast, groups associated with the science of human movement usually apply discrete multi-body systems (MBS). Herein, the bones are modelled as rigid bodies, which are connected by Hill-type muscles and non-linear rheological spring-dashpot models to represent tendons and cartilaginous connective tissue like intervertebral discs (IVD). A possibility to benefit from both numerical methods is to couple them and use each approach, where it is most appropriate. Herein, the basic idea is to utilise MBS in simulations of the overall body and apply the FEM only to selected regions of interest. In turn, the FEM is used as homogenisation tool, which delivers more accurate non-linear relationships describing the behaviour of the IVD in the multi-body dynamics model. The goal of this contribution is to present an approach to couple both numerical methods without the necessity to apply a gluing algorithm in the context of a co-simulation. Instead, several pre-computations of the intervertebral disc are performed offline to generate an approximation of the homogenised finite-element (FE) result. In particular, the discrete degrees of freedom (DOF) of the MBS, that is, three displacements and three rotations, are applied to the FE model of the IVD, and the resulting homogenised forces and moments are recorded. Moreover, a polynomial function is presented with the discrete DOF of the MBS as variables and the discrete forces an moments as function values. For the sake of a simple verification, the coupling method is applied to a simplified motion segment of the spine. Herein, two stiff cylindrical vertebrae with an interjacent homogeneous cylindrical IVD are examined under the restriction of purely elastic deformations in the sagittal plane.     

Embedding of human vertebral bodies leads to higher ultimate load and altered damage localisation under axial compression

Computer tomography (CT)-based finite element (FE) models of vertebral bodies assess fracture load in vitro better than dual energy X-ray absorptiometry, but boundary conditions affect stress distribution under the endplates that may influence ultimate load and damage localisation under post-yield strains. Therefore, HRpQCT-based homogenised FE models of 12 vertebral bodies were subjected to axial compression with two distinct boundary conditions: embedding in polymethylmethalcrylate (PMMA) and bonding to a healthy intervertebral disc (IVD) with distinct hyperelastic properties for nucleus and annulus. Bone volume fraction and fabric assessed from HRpQCT data were used to determine the elastic, plastic and damage behaviour of bone. Ultimate forces obtained with PMMA were 22% higher than with IVD but correlated highly (R² = 0.99). At ultimate force, distinct fractions of damage were computed in the endplates (PMMA: 6%, IVD: 70%), cortex and trabecular sub-regions, which confirms previous observations that in contrast to PMMA embedding, failure initiated underneath the nuclei in healthy IVDs. In conclusion, axial loading of vertebral bodies via PMMA embedding versus healthy IVD overestimates ultimate load and leads to distinct damage localisation and failure pattern.     

Intervertebral disc creep behavior assessment through an open source finite element solver

Degenerative Disc Disease (DDD) is one of the largest health problems faced worldwide, based on lost working time and associated costs. By means of this motivation, this work aims to evaluate a biomimetic Finite Element (FE) model of the Intervertebral Disc (IVD). Recent studies have emphasized the importance of an accurate biomechanical modeling of the IVD, as it is a highly complex multiphasic medium. Poroelastic models of the disc are mostly implemented in commercial finite element packages with limited access to the algorithms. Therefore, a novel poroelastic formulation implemented on a home-developed open source FE solver is briefly addressed throughout this paper. The combination of this formulation with biphasic osmotic swelling behavior is also taken into account. Numerical simulations were devoted to the analysis of the non-degenerated human lumbar IVD time-dependent behavior. The results of the tests performed for creep assessment were inside the scope of the experimental data, with a remarkable improvement of the numerical accuracy when compared with previously published results obtained with ABAQUS^®. In brief, this in-development open-source FE solver was validated with literature experimental data and aims to be a valuable tool to study the IVD biomechanics and DDD mechanisms.     

Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16 ^INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16 ^INK4A . Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16 ^INK4A . Cells from degenerate discs (even from young patients) exhibited increased expression of P16 ^INK4A , increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16 ^INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration.     

Sensitivity of lumbar spine response to follower load and flexion moment: finite element study

The follower load (FL) combined with moments is commonly used to approximate flexed/extended posture of the lumbar spine in absence of muscles in biomechanical studies. There is a lack of consensus as to what magnitudes simulate better the physiological conditions. Considering the in-vivo measured values of the intradiscal pressure (IDP), intervertebral rotations (IVRs) and the disc loads, sensitivity of these spinal responses to different FL and flexion moment magnitudes was investigated using a 3D nonlinear finite element (FE) model of ligamentous lumbosacral spine. Optimal magnitudes of FL and moment that minimize deviation of the model predictions from in-vivo data were determined. Results revealed that the spinal parameters i.e. the IVRs, disc moment, and the increase in disc force and moment from neutral to flexed posture were more sensitive to moment magnitude than FL magnitude in case of flexion. The disc force and IDP were more sensitive to the FL magnitude than moment magnitude. The optimal ranges of FL and flexion moment magnitudes were 900–1100 N and 9.9–11.2 Nm, respectively. The FL magnitude had reverse effect on the IDP and disc force. Thus, magnitude for FL or flexion that minimizes the deviation of all the spinal parameters together from the in-vivo data can vary. To obtain reasonable compromise between the IDP and disc force, our findings recommend that FL of low magnitude must be combined with flexion moment of high intensity and vice versa.     

Quantifying the centre of rotation pattern in a multi-body model of the lumbar spine

Understanding the kinematics of the spine provides paramount knowledge for many aspects of the clinical analysis of back pain. More specifically, visualisation of the instantaneous centre of rotation (ICR) enables clinicians to quantify joint laxity in the segments, avoiding a dependence on more inconclusive measurements based on the range of motion and excessive translations, which vary in every individual. Alternatively, it provides motion preserving designers with an insight into where a physiological ICR of a motion preserving prosthesis can be situated in order to restore proper load distribution across the passive and active elements of the lumbar region. Prior to the use of an unconstrained dynamic musculoskeletal model system, based on multi-body models capable of transient analysis, to estimate segmental loads, the model must be kinematically evaluated for all possible sensitivity due to ligament properties and the initial locus of intervertebral disc (IVD). A previously calibrated osseoligamentous model of lumbar spine was used to evaluate the changes in ICR under variation of the ligament stiffness and initial locus of IVD, when subjected to pure moments from 0 to 15 Nm. The ICR was quantified based on the closed solution of unit quaternion that improves accuracy and prevents coordinate singularities, which is often observed in Euler-based methods and least squares principles. The calculation of the ICR during flexion/extension revealed complexity and intrinsic nonlinearity between flexion and extension. This study revealed that, to accommodate a good agreement between in vitro data and the multi-body model predictions, in flexion more laxity is required than in extension. The results showed that the ICR location is concentrated in the posterior region of the disc, in agreement with previous experimental studies. However, the current multi-body model demonstrates a sensitivity to the initial definition of the ICR, which should be recognised as a limitation of the method. Nevertheless, the current simulations suggest that, due to the constantly evolving path of the ICR across the IVD during flexion–extension, a movable ICR is a necessary condition in multi-body modelling of the spine, in the context of whole body simulation, to accurately capture segmental kinematics and kinetics.     

A combined passive and active musculoskeletal model study to estimate L4-L5 load sharing

A number of geometrically-detailed passive finite element (FE) models of the lumbar spine have been developed and validated under in vitro loading conditions. These models are devoid of muscles and thus cannot be directly used to simulate in vivo loading conditions acting on the lumbar joint structures or spinal implants. Gravity loads and muscle forces estimated by a trunk musculoskeletal (MS) model under twelve static activities were applied to a passive FE model of the L4-L5 segment to estimate load sharing among the joint structures (disc, ligaments, and facets) under simulated in vivo loading conditions. An equivalent follower (FL), that generates IDP equal to that generated by muscle forces, was computed in each task. Results indicated that under in vivo loading conditions, the passive FE model predicted intradiscal pressures (IDPs) that closely matched those measured under the simulated tasks (R² = 0.98 and root-mean-squared-error, RMSE = 0.18 MPa). The calculated equivalent FL compared well with the resultant force of all muscle forces and gravity loads acting on the L4-L5 segment (R² = 0.99 and RMSE = 58 N). Therefore, as an alternative approach to represent in vivo loading conditions in passive FE model studies, this FL can be estimated by available in-house or commercial MS models. In clinical applications and design of implants, commonly considered in vitro loading conditions on the passive FE models do not adequately represent the in vivo loading conditions under muscle exertions. Therefore, more realistic in vivo loading conditions should instead be used.     

The influence of different magnitudes and methods of applying preload on fusion and disc replacement constructs in the lumbar spine: a finite element analysis

In a finite element (FE) analysis of the lumbar spine, different preload application methods that are used in biomechanical studies may yield diverging results. To investigate how the biomechanical behaviour of a spinal implant is affected by the method of applying the preload, hybrid-controlled FE analysis was used to evaluate the biomechanical behaviour of the lumbar spine under different preload application methods. The FE models of anterior lumbar interbody fusion (ALIF) and artificial disc replacement (ADR) were tested under three different loading conditions: a 150 N pressure preload (PP) and 150 and 400 N follower loads (FLs). This study analysed the resulting range of motion (ROM), facet contact force (FCF), inlay contact pressure (ICP) and stress distribution of adjacent discs. The FE results indicated that the ROM of both surgical constructs was related to the preload application method and magnitude; differences in the ROM were within 7% for the ALIF model and 32% for the ADR model. Following the application of the FL and after increasing the FL magnitude, the FCF of the ADR model gradually increased, reaching 45% at the implanted level in torsion. The maximum ICP gradually decreased by 34.1% in torsion and 28.4% in lateral bending. This study concluded that the preload magnitude and application method affect the biomechanical behaviour of the lumbar spine. For the ADR, remarkable alteration was observed while increasing the FL magnitude, particularly in the ROM, FCF and ICP. However, for the ALIF, PP and FL methods had no remarkable alteration in terms of ROM and adjacent disc stress.     

Effect of the intra-abdominal pressure and the center of segmental body mass on the lumbar spine mechanics - a computational parametric study

Determination of physiological loads in human lumbar spine is critical for understanding the mechanisms of lumbar diseases and for designing surgical treatments. Computational models have been used widely to estimate the physiological loads of the spine during simulated functional activities. However, various assumptions on physiological factors such as the intra-abdominal pressure (IAP), centers of mass (COMs) of the upper body and lumbar segments, and vertebral centers of rotation (CORs) have been made in modeling techniques. Systematic knowledge of how these assumptions will affect the predicted spinal biomechanics is important for improving the simulation accuracy. In this paper, we developed a 3D subject-specific numerical model of the lumbosacral spine including T12 and 90 muscles. The effects of the IAP magnitude and COMs locations on the COR of each motion segment and on the joint/muscle forces were investigated using a global convergence optimization procedure when the subject was in a weight bearing standing position. The data indicated that the line connecting the CORs showed a smaller curvature than the lordosis of the lumbar spine in standing posture when the IAP was 0?kPa and the COMs were 10?mm anterior to the geometric center of the T12 vertebra. Increasing the IAP from 0 kPa to 10 kPa shifted the location of CORs toward the posterior direction (from 1.4?±?8.9 mm anterior to intervertebral disc (IVD) centers to 40.5?±?3.1 mm posterior to the IVD centers) and reduced the average joint force (from 0.78?±?0.11 Body weight (BW) to 0.31?±?0.07 BW) and overall muscle force (from 349.3?±?57.7 N to 221.5?±?84.2 N). Anterior movement of the COMs from -30 mm to 70 mm relative to the geometric center of T12 vertebra caused an anterior shift of the CORs (from 25.1?±?8.3 mm posterior to IVD centers to 7.8?±?6.2 mm anterior to IVD centers) and increases of average joint forces (from 0.78?±?0.1 BW to 0.93?±?0.1 BW) and muscle force (from 348.9?±?47.7 N to 452.9?±?58.6 N). Therefore, it is important to consider the IAP and correct COMs in order to accurately simulate human spine biomechanics. The method and results of this study could be useful for designing prevention strategies of spinal injuries and recurrences, and for enhancing rehabilitation efficiency.     

Effect of a Double Helical Spring Decompression Structure Backpack on the Lumbar Spine Biomechanics of School-Age Children: A Finite Element Study

Background: A children’s backpack is one of the important school supplies for school-age children. Long-term excessive weight can cause spinal deformity that cannot be reversed. This study compared a double helical spring decompression structure backpack (DHSB) with a traditional backpack (TB) to explore the optimization of decompression devices on upper body pressure. The finite element (FE) method was then used to explore the simulation of lumbar stress with different backpacks, in order to prove that DHSB can reduce the influence of backpack weight on lumbar vertebrae, avoid the occurrence of muscle discomfort and spinal deformity in children; Methods: 18 male children subjects (age: 12.5 ± 0.6 years; height: 145.5 ± 1.9 cm; bodyweight: 40.8 ± 3.1 kg) ran with DHSB and TB at a speed of 3.3 ± 0.2 m/s. Flexible pressure sensors were used to measure the pressure on the shoulder, back, and waist during running. The pressure data was then inputted into the FE model to simulate the effect of carrying different backpacks on the stress of the lumbar intervertebral disc (IVD); Result: There was a significant difference in shoulder and waist peak pressure between the DHSB and TB during the running posture. At a speed of 3.3 ± 0.2 m/s, the peak pressure of the shoulder and waist decreased. After finite element analysis, it was found that carrying DHSB on the back could effectively reduce the intervertebral disc pressure between L4-5 and L5-S1 by 27.9% and 34.1%, respectively; Conclusion: DHSB can effectively reduce the pressure on the shoulder and waist when children are running and can reduce the influence of backpacks on children’s posture to a certain extent. By finite element analysis, it is found that carrying DHSB can effectively reduce the stress of the lumbar intervertebral disc, and the damage to lumbar vertebrae is lower than with a TB.     

Analysis of large compression loads on lumbar spine in flexion and in torsion using a novel wrapping element

Axial compression on the spine could reach large values especially in lifting tasks which also involve large rotations. Experimental and numerical investigations on the spinal multi motion segments in presence of physiological compression loads cannot adequately be carried out due to the structural instability and artefact loads. To circumvent these problems, a novel wrapping cable element is used in a nonlinear finite element model of the lumbosacral spine (L1-S1) to investigate the role of moderate to large compression loads on the lumbar stiffness in flexion and axial moments/rotations. The compression loads up to 2,700 N was applied with no instability or artefact loads. The lumbar stiffness substantially increased under compression force, flexion moment, and axial torque when applied alone. The presence of compression preloads significantly stiffened the load-displacement response under flexion and axial moments/rotations. This stiffening effect was much more pronounced under larger preloads and smaller moments/rotations. Compression preloads also increased intradiscal pressure, facet contact forces, and maximum disc fibre strain at different levels. Forces in posterior ligaments were, however, diminished with compression preload. The significant increase in spinal stiffness, hence, should be considered in biomechanical studies for accurate investigation of the load partitioning, system stability, and fixation systems/disc prostheses.     

Effects of pulsed electromagnetic field on intervertebral disc cell apoptosis in rats

Despite numerous studies on pulsed electromagnetic field (PEMF) application, its effects of PEMF on intervertebral disc (IVD) have not yet been investigated in vivo. Accordingly, the effects of PEMF upon IVD in rats were evaluated through molecular surveys. Rats were divided into six groups: Group I and II were exposed to low and high frequency of PEMF (LF and HF, respectively). Group III and IV underwent induced disc degeneration and were exposed to low and high frequency of PEMF (LF/IDD and HF/IDD, respectively). Group V underwent induced disc degeneration (IDD), and group VI was control. The values of caspase 3, Bax, Bcl-2 and β-actin band density, as cell apoptotic markers, were obtained from band densitometry. Our results showed that the value of cleaved caspase-3 of cells and Bax/Bcl-2 ratio in IDD group increased significantly compared to the control group (p?p?相似文献   

Effect of autologous platelet-rich plasma-releasate on intervertebral disc degeneration in the rabbit anular puncture model: a preclinical study

Introduction

Platelet-rich plasma (PRP) is a fraction of plasma in which several growth factors are concentrated at high levels. The active soluble releasate isolated following platelet activation of PRP (PRP-releasate) has been demonstrated to stimulate the metabolism of IVD cells in vitro. The in vivo effect of PRP-releasate on degenerated IVD remains unknown. The purpose of this study was to determine the reparative effects of autologous PRP-releasate on degenerated intervertebral discs (IVDs).

Methods

To induce disc degeneration, New Zealand white rabbits (n = 12) received anular puncture in two noncontiguous discs. Autologous PRP and PPP (platelet-poor plasma) were isolated from fresh blood using two centrifugation techniques. Four weeks after the initial puncture, releasate isolated from clotted PPP or PRP (PPP- or PRP-releasate), or phosphate-buffered saline (PBS; control) was injected into the punctured discs. Disc height, magnetic resonance imaging (MRI) T2-mapping and histology were assessed.

Results

Anular puncture produced a consistent disc narrowing within four weeks. PRP-releasate induced a statistically significant restoration of disc height (PRP vs. PPP and PBS, P<0.05). In T2-quantification, the mean T2-values of the nucleus pulposus (NP) and anulus fibrosus (AF) of the discs were not significantly different among the three treatment groups. Histologically, the number of chondrocyte-like cells was significantly higher in the discs injected with PRP-releasate compared to that with PBS.

Conclusions

The administration of active PRP-releasate induced a reparative effect on rabbit degenerated IVDs. The results of this study suggest that the use of autologous PRP-releasate is safe and can lead to a clinical application for IVD degeneration.

     

Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration

Introduction

Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn^−/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn^−/0 mouse model.

Methods

To evaluate ADSC implant efficacy, Bgn^−/0 mice were intradiscally (L1-L2) injected with 8x10⁴ ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn^−/0 mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area.

Results

After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels.

Conclusion

Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn^−/0 mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field.     

The influence of serum,glucose and oxygen on intervertebral disc cell growth <Emphasis Type="Italic">in vitro</Emphasis>: implications for degenerative disc disease

Introduction  

The avascular nature of the human intervertebral disc (IVD) is thought to play a major role in disc pathophysiology by limiting nutrient supply to resident IVD cells. In the human IVD, the central IVD cells at maturity are normally chondrocytic in phenotype. However, abnormal cell phenotypes have been associated with degenerative disc diseases, including cell proliferation and cluster formation, cell death, stellate morphologies, and cell senescence. Therefore, we have examined the relative influence of possible blood-borne factors on the growth characteristics of IVD cells in vitro.     

Loading of the lumbar spine during backpack carriage

Backpack carriage is significantly associated with a higher prevalence of low back pain. Elevated compression and shear forces in the lumbar intervertebral discs are known risk factors. A novel method of calculating the loads in the lumbar spine during backpack carriage is presented by combining physical and numerical modelling. The results revealed that to predict realistic lumbar compression forces, subject-specific lumbar curvature data were not necessary for loads up to 40 kg. In contrast, regarding shear forces, using subject-specific lumbar curvature data from upright MRI measurements as input for the rigid body model significantly altered lumbar joint force estimates.     

The influence of exogenous cross-linking and compressive creep loading on intradiscal pressure

This study involves a biomechanical evaluation of a prospective injectable treatment for degenerative discs. The high osmolarity of the non-degenerated nucleus pulposus attracts water contributing to the hydrostatic behavior of the tissue. This intradiscal pressure is known to drop as fluid is exuded from the matrix due to compressive loading. The objective of this study was to compare the changes in intradiscal pressure in control and genipin cross-linked intervertebral discs. Thirty bovine lumbar motion segments were randomly divided into a phosphate-buffered saline control group and a 0.33% genipin group and soaked at room temperature for 2 days. A needle pressure sensor was held in the center of the disc while short-term and static creep compressive loads were applied. The control group demonstrated a 25% higher average intradiscal pressure compared to genipin-treated discs under 750 N compressive load (p=0.029). Depressurization during static compressive creep was 56% higher in the control than in the genipin group (p=0.014). These results suggest cross-linking induced changes in the poroelastic properties of the involved tissues affected the mechanics of compressive load support in the disc with lower levels of nucleus pressure, a corresponding decrease in the elastic expansion of the annulus, and an increased axial compressive loading of the inner and outer annulus tissues. It is possible that concurrent changes in hydraulic permeability and proteoglycan retention known to be associated with genipin cross-linking were also contributors to poroelastic changes. Reduction of peak pressures and moderation of pressure fluctuations could be beneficial relative to discogenic pain.