Finite element study of human lumbar disc nucleus replacements

Currently, there are a number of nucleus replacements under development. The important concern is how well these implants duplicate the mechanical function of the native nucleus. This finite element model study aimed to investigate the influence of different nucleus replacements on the mechanical response of the disc. Models included partial, full, over-sized, partially saturated, elastic and poroelastic solid replacements. Over-sized nucleus replacements up to 25% yielded results that were comparable to those in the intact state. Differences were much greater in cases with under-sized nucleus replacements. The effect was most pronounced for the 75% under-sized replacement that resembled the condition with a full nucleotomy. Nucleus implants with elastic properties substantially altered load transmission when 10% under-sized and over-sized replacements were considered. Compared to intact, the under-sized implants should be avoided when using biphasic materials with properties similar to the native nucleus, whereas for elastic replacements both under- and over-sized implants should not be used.     

Characterization of Krt19CreERT allele for targeting the nucleus pulposus cells in the postnatal mouse intervertebral disc

Intervertebral disc degeneration and associated back pain are relatively common but sparsely understood conditions, affecting over 70% of the population during some point of life. Disc degeneration is often associated with a loss of nucleus pulposus (NP) cells. Genetic mouse models offer convenient avenues to understand the cellular and molecular regulation of the disc during its formation, growth, maintenance, and aging. However, due to the lack of inducible driver lines to precisely target NP cells in the postnatal mouse disc, progress in this area of research has been moderate. NP cells are known to express cytokeratin 19 (Krt19), and tamoxifen (Tam)-inducible Krt19^CreERT allele is available. The current study describes the characterization of Krt19^CreERT allele to specifically and efficiently target NP cells in neonatal, skeletally mature, middle-aged, and aged mice using two independent fluorescent reporter lines. The efficiency of recombination at all ages was validated by immunostaining for KRT19. Results show that following Tam induction, Krt19^CreERT specifically drives recombination of NP cells in the spine of neonatal and aged mice, while no recombination was detected in the surrounding tissues. Knee joints from skeletally mature Tam-treated Krt19^CreERT/+; R26^tdTOM mouse show the absence of recombination in all tissues and cells of the knee joint. Thus, this study provides evidence for the use of Krt19^CreERT allele for genetic characterization of NP cells at different stages of the mouse life.     

Computational biomechanics of a lumbar motion segment in pure and combined shear loads

Anterior shear has been implicated as a risk factor in spinal injuries. A 3D nonlinear poroelastic finite element model study of a lumbar motion segment L4-L5 was performed to predict the temporal shear response under various single and combined shear loads. Effects of nucleotomy and facetectomy as well as changes in the posture and facet gap distance were analyzed as well.     

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.     

Finite elements/Taguchi method based procedure for the identification of the geometrical parameters significantly affecting the biomechanical behavior of a lumbar disc

The aim of this work is to show a quick and simple procedure able to identify the geometrical parameters of the intervertebral disc that strongly affect the behavior of the FEM model. First, we allocated a selection criterion for the minimum number of geometrical parameters that describe, with a good degree of approximation, a healthy human vertebra. Next, we carried out a sensitivity analysis using the ‘Taguchi orthogonal array’ to arrive at a quick identification of the parameters that strongly affect the behavior of the Fem model.     

Overexpressed IGFBP5 promotes cell proliferation and inhibits apoptosis of nucleus pulposus derived from rats with disc degeneration through inactivating the ERK/MAPK axis

It is previously suggested that insulin-like growth factor binding proteins (IGFBPs) potentially share an association with disc degeneration (DD) that causes back pain. This study aimed at exploring the functional relevance of IGFBP5 in DD by establishing a rat model of DD. The nucleus pulposus (NP) cells were transduced with IGFBP5-shRNA or IGFBP5 overexpression to determine the cellular processes (proliferation, apoptosis, as well as colony formation). The protein levels of apoptosis-related proteins were evaluated. Furthermore, NP cells were treated with the extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK/MAPK) pathway inhibitor (PD98059) followed by measurement of ERK protein level and ERK phosphorylation content. The NP cells showed suppressed proliferation and colony formation ability, yet promoted apoptosis after transfection with IGFBP5-shRNA. It was found that silencing of IGFBP5 could lead to the ERK/MAPK axis activation, as indicated by an elevated ERK protein level and ERK phosphorylation content. However, overexpression of IGFBP5 could reverse all the reaction induced by silenced IGFBP5. These key findings demonstrate that overexpressed IGFBP5 inactivates the ERK/MAPK axis to stimulate the proliferation and inhibit apoptosis of NP cells in a rat model of DD.     

Downregulation of microRNA-129-5p increases the risk of intervertebral disc degeneration by promoting the apoptosis of nucleus pulposus cells via targeting BMP2

miR-129-5p is implicated in many diseases, such as laryngeal cancer and breast cancer. In this study, we studied the mechanism underlying the role of BMP2 in intervertebral disc degeneration (IDD). We used a luciferase assay system to determine the relationship between BMP2 and miR-129-5 expression. In addition, Western blot and real-time PCR were used to confirm the regulatory relationship between miR-129-5p and its targets, while flow cytometry was used to evaluate the effect of miR-129-5p on the apoptosis of neural progenitor cells (NPCs). BMP2 was confirmed as a direct target of miR-129-5p. Furthermore, the expression of miR-129 was downregulated along with upregulated BMP2 expression in IDD patients. Meanwhile, BMP2 was validated as the target of miR-129-5p in cells transfected with miR-129-5p and BMP2 siRNA. Also, compared with NPCs transfected with blank/scramble controls or miR-129-5p inhibitors, the NPCs treated with miR-129-5p mimics or BMP2 siRNA exhibited evidently elevated viability and inhibited apoptosis. The data demonstrated that miR-129-5p was poorly expressed in IDD patients, and the dysregulation of miR-129-5p might contribute to the development of IDD by targeting BMP2 expression.     

The effect of degenerative morphological changes of the intervertebral disc on the lumbar spine biomechanics: a poroelastic finite element investigation

Intervertebral disc degeneration involves changes in the spinal anatomical structures. The mechanical relevance of the following changes was investigated: disc height, endplate sclerosis, disc water content, permeability and depressurisation. A poroelastic nonlinear finite element model of the L4–L5 human spine segments was employed. Loads represented a daily cycle (500 N compression combined with flexion–extension motion for 16 h followed by 200 N compression for 8 h). In non-degenerative conditions, the model predicted a diurnal axial displacement of 1.32 mm and a peak intradiscal pressure of 0.47 MPa. Axial displacement, facet force and range of motion in flexion–extension are decreased by decreasing disc height. By decreasing the initial water content, axial displacement, facet force and fluid loss were all reduced. Endplate sclerosis did not have a significant influence on the calculated results. Depressurisation determined an increase of the disc effective stress, possibly inducing failure. Degenerative instability was not calculated in any simulations.     

Uncertainty analysis of material properties and morphology parameters in numerical models regarding the motion of lumbar vertebral segments

Abstract

The kinematics of a spinal motion segment is determined by the material properties of the soft-tissue and the morphology. The material properties can vary within subjects and between vertebral levels, leading to a wide possible range of motion of a spinal segment independently on its morphology. The goal of this numerical study was to identify the most influential material parameters concerning the kinematics of a spinal motion segment and their plausible ranges. Then, a method was tested to deduce the material properties automatically, based on a given ROM and morphology. A fully parametric finite element model of the morphology and material properties of a lumbar spinal motion segment was developed. The impact of uncertainty of twelve spinal material parameters, as well as the size of the gap between the articular surfaces of the facet joints was examined. The simulation results were compared to our own in vitro data. The flexibility of a lumbar segment was especially influenced by the properties of the anterior annulus region, the facet gap size and the interspinous ligament. The high degree of uncertainty in the material properties and facet gap size published in the literature can lead to a wide scatter in the motion of a spinal segment, with a range of 6°-17° in the intact condition in flexion/extension, from 5°-22° in lateral bending and from 3°-14° in axial rotation. Statistical analysis of the variability might help to estimate the sensitivity and total uncertainty propagated through biomechanical simulations, affecting the reliability of the predictions.     

Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice

Prolonged exposure to microgravity has shown to have deleterious effects on the human spine, indicated by low back pain during spaceflight and increased incidence of post-spaceflight herniated nucleus pulposus. We examined the effect of microgravity on biomechanical properties of lumbar and caudal discs from mice having been on 15-day shuttle mission STS-131. Sixteen C57BL/C mice (spaceflight group, n=8; ground-based control group, n=8) were sacrificed immediately after spaceflight. Physiological disc height (PDH) was measured in situ, and compressive creep tests were performed to parameterize biomechanical properties into endplate permeability (k), nuclear swelling pressure strain dependence (D), and annular viscoelasticity (G). For caudal discs, the spaceflight group exhibited 32% lower PDH, 70% lower D and crept more compared to the control mice (p=0.03). For lumbar discs, neither PDH nor D was significantly different between murine groups. Initial modulus, osmotic pressure, k and G for lumbar and caudal discs did not appear influenced by microgravity (p>0.05). Decreases in both PDH and D suggest prolonged microgravity effectively diminished biomechanical properties of caudal discs. By contrast, differences were not noted for lumbar discs. This potentially deleterious interaction between prolonged weightlessness and differential ranges of motion along the spine may underlie the increased cervical versus lumbar disc herniation rates observed among astronauts.     

Influence of anisotropic bone properties on the biomechanical behavior of the acetabular cup implant: a multiscale finite element study

Although the biomechanical behavior of the acetabular cup (AC) implant is determinant for the surgical success, it remains difficult to be assessed due to the multiscale and anisotropic nature of bone tissue. The aim of the present study was to investigate the influence of the anisotropic properties of peri-implant trabecular bone tissue on the biomechanical behavior of the AC implant at the macroscopic scale. Thirteen bovine trabecular bone samples were imaged using micro-computed tomography (μCT) with a resolution of 18 μm. The anisotropic biomechanical properties of each sample were determined at the scale of the centimeter based on a dedicated method using asymptotic homogenization. The material properties obtained with this multiscale approach were used as input data in a 3D finite element model to simulate the macroscopic mechanical behavior of the AC implant under different loading conditions. The largest stress and strain magnitudes were found around the equatorial rim and in the polar area of the AC implant. All macroscopic stiffness quantities were significantly correlated (R² > 0.85, p < 6.5 e-6) with BV/TV (bone volume/total volume). Moreover, the maximum value of the von Mises stress field was significantly correlated with BV/TV (R² > 0.61, p < 1.6 e-3) and was always found at the bone-implant interface. However, the mean value of the microscopic stress (at the scale of the trabeculae) decrease as a function of BV/TV for vertical and torsional loading and do not depend on BV/TV for horizontal loading. These results highlight the importance of the anisotropic properties of bone tissue.     

Effects of age,replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases

Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.     

Computational biomechanical analysis of postoperative inferior tibiofibular syndesmosis: a modified modeling method

To analyze the biomechanical effect of syndesmotic screw through three and four cortices, a total of 12 finite element models simulating healthy ankles, tibiofibular syndesmosis injured ankles, and post-operative ankles by screw fixations through three or four cortices were built. A set of biomechanical data were obtained to find that screw fixation methods for inferior tibiofibular syndesmosis can help recover most of the biomechanical relations of the ankle especially the tricortical fixation, while the screw of quadricortical fixation bear more stress than the tricortical fixation. The modeling method for finite element models was also modified for saving more time and realizing personalized modeling for clinical application.     

Biomechanical effects of posterior pedicle fixation techniques on the adjacent segment for the treatment of thoracolumbar burst fractures: a biomechanical analysis

Abstract

Posterior pedicle fixation technique is a common method for treating thoracolumbar burst fractures, but the effect of different fixation techniques on the postoperative spinal mechanical properties has not been clearly defined, especially on adjacent segments. A finite element model of T10-L2 with moderate T12 vertebra burst fracture was constructed to investigate biomechanical behavior of three posterior pedicle screw fixation techniques. Compared with traditional short-segment 4 pedicle screw fixation (TS-4) and intermediate long-segment 6 pedicle screw fixation (IL-6), mono-segment 4 pedicle screw fixation (MS-4) provides a safer surgical selection to prevent the secondary degeneration of adjacent segments in the long-term.     

Comparative role of disc degeneration and ligament failure on functional mechanics of the lumbar spine

Understanding spinal kinematics is essential for distinguishing between pathological conditions of spine disorders, which ultimately lead to low back pain. It is of high importance to understand how changes in mechanical properties affect the response of the lumbar spine, specifically in an effort to differentiate those associated with disc degeneration from ligamentous changes, allowing for more precise treatment strategies. To do this, the goals of this study were twofold: (1) develop and validate a finite element (FE) model of the lumbar spine and (2) systematically alter the properties of the intervertebral disc and ligaments to define respective roles in functional mechanics. A three-dimensional non-linear FE model of the lumbar spine (L3-sacrum) was developed and validated for pure moment bending. Disc degeneration and sequential ligament failure were modelled. Intersegmental range of motion (ROM) and bending stiffness were measured. The prediction of the FE model to moment loading in all three planes of bending showed very good agreement, where global and intersegmental ROM and bending stiffness of the model fell within one standard deviation of the in vitro results. Degeneration decreased ROM for all directions. Stiffness increased for all directions except axial rotation, where it initially increased then decreased for moderate and severe degeneration, respectively. Incremental ligament failure produced increased ROM and decreased stiffness. This effect was much more pronounced for all directions except lateral bending, which is minimally impacted by ligaments. These results indicate that lateral bending may be more apt to detect the subtle changes associated with degeneration, without being masked by associated changes of surrounding stabilizing structures.     

Augmentation and repair tissue formation of the nucleus pulposus after partial nucleotomy in a rabbit model

Disc degeneration alters disc height and mechanics of the spinal column and is associated with lower back pain. In preclinical studies gel-like materials or resorbable polymer-based implants are frequently used to rebuild the nucleus pulposus, aiming at tissue regeneration and restoration of tissue function. To compare the outcome of tissue repair, freeze-dried resorbable polyglycolic acid–hyaluronan (PGA/HA) implants without any bioactive components or bioactivated fibrin (fibrin-serum) was used in a degenerated disc disease model in New Zealand white rabbits. Animals with partial nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity in the nuclear region of operated discs as assessed by magnet resonance imaging was reduced in operated compared to healthy discs, indicating loss of water and did not change from week 1 to month 6 after surgery. Quantification of histological and immunohistochemical staining indicated that the implantation of PGA/HA leads to significantly more repair tissue compared to nucleotomy only. Type II collagen content of the repair tissue formed after PGA/HA or fibrin-serum treatment is significantly increased compared to controls with nucleotomy only. The data indicate that intervertebral disc augmentation after nucleotomy has a positive effect on repair tissue formation and type II collagen deposition as shown in the rabbit model.     

Implication of obesity on motion,posture and internal stress of the foot: an experimental and finite element analysis

Obesity causes increased loading on the foot which can damage the soft tissue and bone ultimately leading to foot problems. Experimental and computational methods were used to analyse the chain of biomechanical changes in the lower limb due to obesity. The experimental study shows some changes in foot posture and gait where obese subjects were more likely to have pronated feet, smaller joint angles in the sagittal and frontal planes, smaller cadence, and smaller stride length. Anatomically correct finite element models generated on obese subjects showed increased and altered internal and plantar stress. Altered foot posture was identified as a key indicator of increased internal stress indicating the importance of foot posture correction.