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 role of the nucleus pulposus in intervertebral disc recovery: Towards improved specifications for nucleus replacement devices.

Nucleus replacement devices (NRDs) have potential to treat degenerated or herniated intervertebral discs (IVDs). However, IVD height loss is a post-treatment complication. IVD height recovery involves the nucleus pulposus (NP), but the mechanism of this in response to physiological loads is not fully elucidated. This study aimed to characterise the non-linear recovery behaviour of the IVD in intact, post-nuclectomy, and post-NRD treatment states, under physiological loading. 36 bovine IVDs (12 intact, 12 post-nuclectomy, 12 post-treatment) underwent creep-recovery protocols simulating Sitting, Walking or Running, followed by 12 h of recovery. A rheological model decoupled the fluid-independent (elastic, fast) and fluid-dependent (slow) recovery phases. In post-nuclectomy and post-treatment groups, nuclectomy efficiency (ratio of NP removed to remaining NP) was quantified following post-test sectioning. Relative to intact, post-nuclectomy recovery significantly decreased in Sitting (-0.3 ± 0.4 mm, p < 0.05) and Walking (-0.6 ± 0.3 mm, p < 0.001) coupled with significant decreases to the slow response (p < 0.05). Post-nuclectomy, the fast and slow responses negatively correlated with nuclectomy efficiency (p < 0.05). In all protocols, the post-treatment group performed significantly worse in recovery (-0.5 ± 0.3 mm, p < 0.01) and the slow response (p < 0.05). Results suggest the NP mainly facilitates slow-phase recovery, linearly dependent on the amount of NP present. Failure of this NRD to recover is attributed to poor fluid imbibition. Additionally, unconfined NRD performance cannot be extrapolated to the in vitro response. This knowledge informs NRD design criteria to provide high osmotic pressure, and encourages testing standards to incorporate long-term recovery protocols.

From drugs to biomaterials: a review of emerging therapeutic strategies for intervertebral disc inflammation.

Chronic low back pain (LBP) is an increasingly prevalent issue, especially among aging populations. A major underlying cause of LBP is intervertebral disc degeneration (IDD), often triggered by intervertebral disc (IVD) inflammation. Inflammation of the IVD is divided into Septic and Aseptic inflammation. Conservative therapy and surgical treatment often fail to address the root cause of IDD. Recent advances in the treatment of IVD infection and inflammation range from antibiotics and small-molecule drugs to cellular therapies, biological agents, and innovative biomaterials. This review sheds light on the complex mechanisms of IVD inflammation and physiological and biochemical processes of IDD. Furthermore, it provides an overview of recent research developments in this area, intending to identify novel therapeutic targets and guide future clinical strategies for effectively treating IVD-related conditions.

Replicating spine loading during functional and daily activities: An in vivo, in silico, in vitro research pipeline.

Lifestyle heavily influences intervertebral disc (IVD) loads, but measuring in vivo loads requires invasive methods, and the ability to apply these loads in vitro is limited. In vivo load data from instrumented vertebral body replacements is limited to patients that have had spinal fusion surgery, potentially resulting in different kinematics and loading patterns compared to a healthy population. Therefore, this study aimed to develop a pipeline for the non-invasive estimation of in vivo IVD loading, and the application of these loads in vitro. A full-body Opensim model was developed by adapting and combining two existing models. Kinetic data from healthy participants performing activities of daily living were used as inputs for simulations using static optimisation. After evaluating simulation results using in vivo data, the estimated six-axis physiological loads were applied to bovine tail specimens. The pipeline was then used to compare the kinematics resulting from the physiological load profiles (flexion, lateral bending, axial rotation) with a simplified pure moment protocol commonly used for in vitro studies. Comparing kinematics revealed that the in vitro physiological load protocol followed the same trends as the in silico and in vivo data. Furthermore, the physiological loads resulted in substantially different kinematics when compared to pure moment testing, particularly in flexion. Therefore, the use of the presented pipeline to estimate the complex loads of daily activities in different populations, and the application of those loads in vitro provides a novel capability to deepen our knowledge of spine biomechanics, IVD mechanobiology, and improve pre-clinical test methods.

The physiological, in-vitro simulation of daily activities in the intervertebral disc using a load Informed kinematic evaluation (LIKE) protocol.

Current spinal testing protocols generally adopt pure moments combined with axial compression. However, daily activities involve multi-axis loads, and multi-axis loading has been shown to impact intervertebral disc (IVD) cell viability. Therefore, integrating in-vivo load data with spine simulators is critical to understand how loading affects the IVD, but doing so is challenging due to load coupling and variable load rates. This study addresses these challenges through the Load Informed Kinematic Evaluation (LIKE) protocol, which was evaluated using the root mean squared error (RMSE) between desired and actual loads in each axis. Stage 1 involves obtaining the kinematics from six-axis load control tests replicating 20 Orthoload activities at a reduced test speed. Stage 2 applies these kinematics in five axes, with axial compression applied in load control, at the reduced speed and at the physiological test rate. Stage 3 enables long-term tests through six-axis kinematic control combined with diurnal height correction to account for the natural height fluctuations of the IVD. Stage 1 yielded RMSEs within twice the load cell noise floor. Low RMSEs were maintained during stage 2 at reduced speed (Tx:0.80 ± 0.30 N; Ty:0.77 ± 0.29 N; Tz:1.79 ± 0.50 N; Rx:0.02 ± 0.01Nm; Ry:0.02 ± 0.01Nm; and Rz:0.02 ± 0.01Nm) and at the physiological test rate (Tx:3.45 ± 1.81 N; Ty:3.82 ± 1.99 N; Tz:11.32 ± 8.69 N; Rx:0.13 ± 0.07Nm; Ry:0.16 ± 0.11Nm; and Rz:0.07 ± 0.04Nm). To address unwanted oscillations observed in longer tests (>2h), Stage 3 was introduced to enable the stable and consistent replication of activities at a physiological test rate. Despite higher RMSEs the axial error was 85.5 ± 24.27 N (equivalent to âˆ¼ 0.16 MPa), with shear RMSEs similar to other testing systems conducting pure moment tests at slower rates. The LIKE protocol enables the replication of physiological loads, providing opportunities for enhanced investigations of IVD mechanobiology, and the pre-clinical evaluation of IVD devices and therapies.

Development and evaluation of sex-specific thoracolumbar spine finite element models to study spine biomechanics.

Musculoskeletal disorders and low back pain (LBP) are common global afflictions, with a higher prevalence observed in females. However, the cause of many LBP cases continues to elude researchers. Current approaches seldom consider differences in male and female spines. Thus, this study aimed to compare the load distribution between male and female spines through finite element modeling. Two finite element models of the spine, one male and one female, were developed, inclusive of sex-specific geometry and material properties. The models consisted of the vertebrae, intervertebral discs (IVD), tendons, surrounding spinal muscles, and thoracolumbar fascia and were subjected to loading conditions simulating flexion and extension. Following extensive validation against published literature, intersegmental rotation, IVD stress, and vertebral body stress were evaluated. The female model demonstrated increased magnitudes for rotation and stresses when compared to the male model. Results suggest that the augmented stresses in the female model indicate an increased load distribution throughout the spine compared to the male model. These findings may corroborate the higher prevalence of LBP in females. This study highlights the importance of using patient- and sex-specific models for patient analyses and care.

A finite element method study of the effect of vibration on the dynamic biomechanical response of the lumbar spine.

BACKGROUND: Studies focusing on lumbar spine biomechanics are very limited, and the mechanism of the effect of vibration on lumbar spine biodynamics is unclear. To provide guidance and reference for lumbar spine biodynamics research and vibration safety assessment, this study aims to investigate the effects of different vibrations on lumbar spine biodynamics. METHODS: A validated finite element model of the lumbosacral spine was utilized. The model incorporated a 40 kg mass on the upper side and a 400 N follower preload. As a comparison, another model without a coupled mass was also employed. A sinusoidal acceleration with an amplitude of 1 m/s2 and a frequency of 5 Hz was applied to the upper and lower sides of the model respectively. FINDINGS: When the coupled mass point is not introduced: in the case of upper-side excitation, the lumbar spine shows a significantly larger response in the x-direction than in the z-direction, while in the case of lower-side excitation, the lumbar spine experiences rigid body displacement in the z-direction without any movement, deformation, rotation, or stress changes in the x-direction. When the coupled mass point is introduced: both upper and lower-side excitations result in significant differences in z-directional displacement, with relatively small differences in vertebral rotation angle, disc deformation, and stress. Under upper excitation, low-frequency oscillations occur in the x-direction. In both types of excitations, the anterior-posterior deformation of the L2-L3 and L4-L5 intervertebral discs is greater than the vertical deformation. The peak (maximum) disc stress exceeds the average stress and stress amplitude across the entire disc. Regardless of the excitation type, the stress distribution within the disc at the moment of peak displacement remains nearly identical, with the maximum stress consistently localized on the anterior side of the L4-L5 disc. INTERPRETATION: Accurately simulating lumbar spine biodynamics requires the inclusion of the upper body mass in the lumbosacral spine model. The physiological curvature of the lumbar spine could escalate the risk of lumbar spine vibration injuries. It is more instructive to apply local high stress in the disc as a lumbar spine vibration safety evaluation parameter.

A multiscale investigation into the role of collagen-hyaluronan interface shear on the mechanical behaviour of collagen fibers in annulus fibrosus - Molecular dynamics-cohesive finite element-based study.

Multi-directional deformation exhibited by annulus fibrosus (AF) is contributed by chemo-mechanical interactions among its biomolecular constituents' collagen type I (COL-I), collagen type II (COL-II), proteoglycans (aggrecan and hyaluronan) and water. However, the nature and role of such interactions on AF mechanics are unclear. This work employs a molecular dynamics-cohesive finite element-based multiscale approach to investigate role of COL-I-COL-II interchanging distribution and water concentration (WC) variations from outer annulus (OA) to inner annulus (IA) on collagen-hyaluronan (COL-HYL) interface shear, and the mechanisms by which interface shear impacts fibril sliding during collagen fiber deformation. At first, COL-HYL interface atomistic models are constructed by interchanging COL-I with COL-II and increasing COL-II and WC from 0 to 75%, and 65%-75% respectively. Thereafter, a multiscale approach is employed to develop representative volume elements (RVEs) of collagen fibers by incorporating COL-HYL shear as traction-separation behaviour at fibril-hyaluronan contact. Results show that increasing COL-II and WC increases interface stiffness from 0.6 GPa/nm to 1.2 GPa/nm and reduces interface strength from 155 MPa to 58 MPa from OA to IA, contributed by local hydration alterations. A stiffer and weaker interface enhances fibril sliding with increased straining at the contact - thereby contributing to reduction in modulus from 298 MPa to 198 MPa from OA to IA. Such reduction further contributes to softer mechanical response towards IA, as reported by earlier studies. Presented multiscale analysis provides deeper understanding of hierarchical structure-mechanics relationships in AF and can further aid in developing better substitutes for AF repair.

Stab lesion of the L4/L5 intervertebral disc in the rat causes acute changes in disc bending mechanics.

Low-back pain often coincides with altered neuromuscular control, possibly due to changes in spine stability resulting from injury or degeneration, or due to effects of nociception. The relative importance of these mechanisms, and their possible interaction, are unknown. In spine bending, the bulk of the load is borne by the IVD, yet the acute effects of intervertebral disc (IVD) injury on bending mechanics have not been investigated. In the present study, we aimed to quantify the acute effects of a stab lesion of the disc on its mechanical properties, because such changes can be expected to elicit compensatory changes in neuromuscular control. L4/L5 spinal segments were collected from 27 Wistar rats within two hours after sacrifice and stored at -20℃. Following thawing, bending tests were performed to assess the intersegmental angle-moment characteristics. Specimens were loaded in right bending, left bending and flexion, before and after a stab lesion of the IVD fully penetrating the nucleus pulposus. In the angle-moment curves, we found reduced moments at equal bending angles after IVD lesion in left bending, right bending and flexion. Peak stiffness, peak moment, and hysteresis were significantly decreased (by 7.8-27.7 %) after IVD lesion in all directions. In conclusion, L4/L5 IVD lesion in the rat caused small to moderate acute changes in IVD mechanical properties. Our next steps will be to evaluate the longer term effects of IVD lesion on spine mechanics and the neural control of trunk muscles.

Development of a novel FE model for investigation of interactions of multi-motion segments of the lumbar spine.

The spinal anatomy is composed of a series of motion segments (MSs). Although finite element (FE) analysis has been extensively used to investigate the spinal biomechanics with various simplifications of the spinal structures, it is still a challenge to investigate the interactions of different MSs. Anatomical studies have shown that there are major spine ligaments connecting not only single-MS (i.e., two consecutive vertebrae) but also spanning multi-vertebral bones or multi-MSs. However, the effects of the multi-MS spanning ligaments on the spine biomechanics have not been investigated previously. This study developed an FE model of the lumbar spine by simulating the anterior longitudinal ligaments (ALLs) in two portions, one connecting a single-MS and the other spanning two MSs, with varying physiological cross-sectional area (PCSA) ratios of the two portions. The spine biomechanics during extension motion were investigated. The results showed that on average, the constraining forces by the two-MS spanning elements were ∼18% of those of the single-MS ALL elements when the PCSA ratio was 50%, but the two-MS ALL elements also applied compressive forces on the anterior surfaces of the vertebrae. Decreases in intradiscal pressure were also calculated when the two-MS spanning ALL elements were included in the spine model. The multi-MS spanning ligaments were shown to synergistically function with the single-MS elements in spine biomechanics, especially in the interactions of different MSs. The novel lumbar FE model could therefore provide a useful analysis tool for investigation of physiological functions of the spine.

Mechanical characterization and design of biomaterials for nucleus pulposus replacement and regeneration.

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re-herniation post-operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices.

Development of a finite element full spine model with active muscles for quantitatively analyzing sarcopenia effects on lumbar load.

BACKGROUND AND OBJECTIVE: The musculoskeletal imbalance caused by disease is one of the most critical factors leading to spinal injuries, like sarcopenia. However, the effects of musculoskeletal imbalances on the spine are difficult to quantitatively investigate. Thus, a complete finite element spinal model was established to analyze the effects of musculoskeletal imbalance, especially concerning sarcopenia. METHODS: A finite element spinal model with active muscles surrounding the vertebrae was established and validated from anatomic verification to the whole spine model in dynamic loading at multiple levels. It was then coupled with the previously developed neuromuscular model to quantitatively analyze the effects of erector spinae (ES) and multifidus (MF) sarcopenia on spinal tissues. The severity of the sarcopenia was classified into three levels by changing the physiological cross-sectional area (PCSA) of ES and MF, which were mild (60% PCSA of ES and MF), moderate (48% PCSA of ES and MF), and severe (36% PCSA of ES and MF). RESULTS: The stress and strain levels of most lumbar tissues in the sarcopenia models were more significant than those of the normal model during spinal extension movement. The sarcopenia caused load concentration in several specific regions. The stress level of the L4-L5 intervertebral disc and L1 vertebra significantly increased with the severity of sarcopenia and showed relatively larger values than other segments. From the normal model to a severe sarcopenia model, the stress value of the L4-L5 intervertebral disc and L1 vertebra increased by 128% and 113%, respectively. The strain level of L5-S1 also inclined significantly with the severity of sarcopenia, and the relatively larger capsule strain values occurred at lower back segments from L3 to S1. CONCLUSIONS: In summary, the validated spinal coupling model can be used for spinal injury risk analysis caused by musculoskeletal imbalance. The results suggested that sarcopenia can primarily lead to high injury risk of the L4-L5 intervertebral disc, L1 vertebrae, and L3-S1 joint capsule regarding significant stress or strain variance.

Physiological and degenerative loading of bovine intervertebral disc in a bioreactor: A finite element study of complex motions.

Intervertebral disc (IVD) degeneration and regenerative therapies are commonly studied in organ-culture experiments with uniaxial compressive loading. Recently, in our laboratory, we established a bioreactor system capable of applying loads in six degrees-of-freedom (DOF) to bovine IVDs, which replicates more closely the complex multi-axial loading of the IVD in vivo. However, the magnitudes of loading that are physiological (able to maintain cell viability) or mechanically degenerative are unknown for load cases combining several DOFs. This study aimed to establish physiological and degenerative levels of maximum principal strains and stresses in the bovine IVD tissue and to investigate how they are achieved under complex load cases related to common daily activities. The physiological and degenerative levels of maximum principal strains and stresses were determined via finite element (FE) analysis of bovine IVD subjected to experimentally established physiological and degenerative compressive loading protocols. Then, complex load cases, such as a combination of compression + flexion + torsion, were applied on the FE-model with increasing magnitudes of loading to discover when physiological and degenerative tissue strains and stresses were reached. When applying 0.1 MPa of compression and ±2-3° of flexion and ±1-2° of torsion the investigated mechanical parameters remained at physiological levels, but with ±6-8° of flexion in combination with ±2-4° of torsion, the stresses in the outer annulus fibrosus (OAF) exceeded degenerative levels. In the case of compression + flexion + torsion, the mechanical degeneration likely initiates at the OAF when loading magnitudes are high enough. The physiological and degenerative magnitudes can be used as guidelines for bioreactor experiments with bovine IVDs.

Bionate® nucleus disc replacement: bench testing comparing two different designs.

BACKGROUND: Intervertebral disc nucleus degeneration initiates a degenerative cascade and can induce chronic low back pain. Nucleus replacement aims to replace the nucleus while the annulus is still intact. Over time, several designs have been introduced, but the definitive solution continues to be elusive. Therefore, we aimed to create a new nucleus replacement that replicates intact intervertebral disc biomechanics, and thus has the potential for clinical applications. MATERIALS AND METHODS: Two implants with an outer ring and one (D2) with an additional midline strut were compared. Static and fatigue tests were performed with an INSTRON 8874 following the American Society for Testing and Materials F2267-04, F2346-05, 2077-03, D2990-01, and WK4863. Implant stiffness was analyzed at 0-300 N, 500-2000 N, and 2000-6000 N and implant compression at 300 N, 1000 N, 2000 N, and 6000 N. Wear tests were performed following ISO 18192-1:2008 and 18192-2:2010. GNU Octave software was used to calculate movement angles and parameters. The statistical analysis package R was used with the Deducer user interface. Statistically significant differences between the two designs were analyzed with ANOVA, followed by a post hoc analysis. RESULTS: D1 had better behavior in unconfined compression tests, while D2 showed a "jump." D2 deformed 1 mm more than D1. Sterilized implants were more rigid and deformed less. Both designs showed similar behavior under confined compression and when adding shear. A silicone annulus minimized differences between the designs. Wear under compression fatigue was negligible for D1 but permanent for D2. D1 suffered permanent height deformation but kept its width. D2 suffered less height loss than D1 but underwent a permanent width deformation. Both designs showed excellent responses to compression fatigue with no breaks, cracks, or delamination. At 10 million cycles, D2 showed 3-times higher wear than D1. D1 had better and more homogeneous behavior, and its wear was relatively low. It showed good mechanical endurance under dynamic loading conditions, with excellent response to axial compression fatigue loading without functional failure after long-term testing. CONCLUSION: D1 performed better than D2. Further studies in cadaveric specimens, and eventually in a clinical setting, are recommended. Level of evidence 2c.

A swelling-based biphasic analysis on the quasi-static biomechanical behaviors of healthy and degenerative intervertebral discs.

BACKGROUND AND OBJECTIVE: The degeneration of intervertebral discs is significantly dependent of the changes in tissue composition ratio and tissue structure. Up to the present, the effects of degeneration on the quasi-static biomechanical responses of discs have not been well understood. The goal of this study is to quantitatively analyze the quasi-static responses of healthy and degenerative discs. METHODS: Four biphasic swelling-based finite element models are developed and quantitatively validated. Four quasi-static test protocols, including the free-swelling, slow-ramp, creep and stress-relaxation, are implemented. The double Voigt and double Maxwell models are further used to extract the immediate (or residual), short-term and long-term responses of these tests. RESULTS: Simulation results show that both the swelling-induced pressure in the nucleus pulposus and the initial modulus decrease with degeneration. In the free-swelling test of discs possessing healthy cartilage endplates, simulation results show that over 80% of the total strain is contributed by the short-term response. The long-term response is dominant for discs with degenerated permeability in cartilage endplates. For the creep test, over 50% of the deformation is contributed by the long-term response. In the stress-relaxation test, the long-term stress contribution occupies approximately 31% of total response and is independent of degeneration. Both the residual and short-term responses vary monotonically with degeneration. In addition, both the glycosaminoglycan content and permeability affect the engineering equilibrium time constants of the rheologic models, in which the determining factor is the permeability. CONCLUSIONS: The content of glycosaminoglycan in intervertebral soft tissues and the permeability of cartilage endplates are two critical factors that affect the fluid-dependent viscoelastic responses of intervertebral discs. The component proportions of the fluid-dependent viscoelastic responses depend also strongly on test protocols. In the slow-ramp test, the glycosaminoglycan content is responsible for the changes of the initial modulus. Since existing computational models simulate disc degenerations only by altering disc height, boundary conditions and material stiffness, the current work highlights the significance of biochemical composition and cartilage endplates permeability in the biomechanical behaviors of degenerated discs.

A neuromuscular human body model for lumbar injury risk analysis in a vibration loading environment.

BACKGROUND AND OBJECTIVE: Long-term intensive exposure to whole-body vibration substantially increases the risk of low back pain and degenerative diseases in special occupational groups, like motor vehicle drivers, military vehicle occupants, aircraft pilots, etc. This study aims to establish and validate a neuromuscular human body model focusing on improvement of the detailed description of anatomic structures and neural reflex control, for lumbar injury analysis in vibration loading environments. METHODS: A whole-body musculoskeletal in Opensim codes was first improved by including a detailed anatomic description of spinal ligaments, non-linear intervertebral disc, and lumbar facet joints, and coupling a proprioceptive feedback closed-loop control strategy with GTOs and muscle spindles modeling in Python codes. Then, the established neuromuscular model was multi-levelly validated from sub-segments to the whole model, from regular movements to dynamic responses to vibration loadings. Finally, the neuromuscular model was combined with a dynamic model of an armored vehicle to analyze occupant lumbar injury risk in vibration loadings due to different road conditions and traveling velocities. RESULT: Based on a series of biomechanical indexes, including lumbar joint rotation angles, the lumbar intervertebral pressures, the displacement of the lumbar segments, and the lumbar muscle activities, the validation results show that the present neuromuscular model is available and feasible in predicting lumbar biomechanical responses in normal daily movement and vibration loading environments. Furthermore, the combined analysis with the armored vehicle model predicted similar lumbar injury risk to the experimental or epidemiologic studies. The preliminary analysis results also showed that road types and travelling velocities have substantial combined effects on lumbar muscle activities, and indicated that intervertebral joint pressure and muscle activity indexes can need to be jointly considered for lumbar injury risk evaluation. CONCLUSION: In conclusion, the established neuromuscular model is an effective tool to evaluate vibration loading effects on injury risk of the human body and assist vehicle design vibration comfort by directly concerning the human body injury itself.

A Microstructure-Based Mechanistic Approach to Detect Degeneration Effects on Potential Damage Zones and Morphology of Young and Old Human Intervertebral Discs.

There is an increasing demand to develop predictive medicine through the creation of predictive models and digital twins of the different body organs. To obtain accurate predictions, real local microstructure, morphology changes and their accompanying physiological degenerative effects must be taken into account. In this article, we present a numerical model to estimate the long-term aging effect on the human intervertebral disc response by means of a microstructure-based mechanistic approach. It allows to monitor in-silico the variations in disc geometry and local mechanical fields induced by age-dependent long-term microstructure changes. Both lamellar and interlamellar zones of the disc annulus fibrosus are constitutively represented by considering the main underlying microstructure features in terms of proteoglycans network viscoelasticity, collagen network elasticity (along with content and orientation) and chemical-induced fluid transfer. With age, a noticeable increase in shear strain is especially observed in the posterior and lateral posterior regions of the annulus which is in correlation with the high vulnerability of elderly people to back problems and posterior disc hernia. Important insights about the relation between age-dependent microstructure features, disc mechanics and disc damage are revealed using the present approach. These numerical observations are hardly obtainable using current experimental technologies which makes our numerical tool useful for patient-specific long-term predictions.

Blocking toll-like receptor 4 mitigates static loading induced pro-inflammatory expression in intervertebral disc motion segments.

While the anabolic effects of mechanical loading on the intervertebral disc (IVD) have been extensively studied, inflammatory responses to loading have not been as well characterized. Recent studies have highlighted a significant role of innate immune activation, particularly that of toll-like receptors (TLRs), in IVD degeneration. Biological responses of intervertebral disc cells to loading depend on many factors that include magnitude and frequency. The goals of this study were to characterize the inflammatory signaling changes in response to static and dynamic loading of IVD and investigate the contributions of TLR4 signaling in response to mechanical loading. Rat bone-disc-bone motion segments were loaded for 3 hr under a static load (20 % strain, 0 Hz) with or without an additional low-dynamic (4 % dynamic strain, 0.5 Hz) or high-dynamic (8 % dynamic strain, 3 Hz) strain, and results were compared to unloaded controls. Some samples were also loaded with or without TAK-242, an inhibitor of TLR4 signaling. The magnitude of NO release into the loading media (LM) was correlated with the applied frequency and strain magnitudes across different loading groups. Injurious loading profiles, such as static and high-dynamic, significantly increased Tlr4 and Hmgb1 expression while this result was not observed in the more physiologically relevant low-dynamic loading group. TAK-242 co-treatment decreased pro-inflammatory expression in static but not dynamic loaded groups, suggesting that TLR4 plays a direct role in mediating inflammatory responses of IVD to static compression. Overall, the microenvironment induced by dynamic loading diminished the protective effects of the TAK-242, suggesting that TLR4 plays a direct role in mediating inflammatory responses of IVD to static loading injury.

Structure-function characterization of the transition zone in the intervertebral disc.

Understanding the structure-function relationship in the intervertebral disk (IVD) is crucial for the development of novel tissue engineering strategies to regenerate IVD and the establishment of accurate computational models for low back pain research. A large number of studies have improved our knowledge of the mechanical and structural properties of the nucleus pulposus (NP) and annulus fibrosus (AF), two of the main regions in the IVD. However, few studies have focused on the AF-NP interface (transition zone; TZ). Therefore, the current study aims to, for the first time, characterize the cyclic and failure mechanical properties of the TZ region under physiological loading (1, 3, and 5%s-1 strain rates) and investigate the structural integration mechanisms between the NP, TZ, and AF regions. The results of the current study reveal significant effects of region (NP, TZ, and AF) and strain rates (1, 3, and 5%s-1) on stiffness (p < 0.001). In addition, energy absorption is significantly higher for the AF compared to the TZ and NP (p <0.001) as well as between the TZ and NP (p <0.001). The current research finds adaptation, direct penetration, and entanglement between TZ and AF fibers as three common mechanisms for structural integration between the TZ and AF regions. STATEMENT OF SIGNIFICANCE: Despite a large number of studies that have mechanically, structurally, and biologically characterized the nucleus pulposus (NP) and annulus fibrosus (AF) regions, few studies have focused on the NP-AF interface region (known as Transition Zone; TZ) in the IVD; hence, our understanding of the TZ structure-function relationship is still incomplete. Of particular importance, the cyclic mechanical properties of the TZ, compared to the adjacent regions (NP and AF), are yet to be explored and the precise nature of the structural integration between the NP and AF via the TZ region is not yet known. The current study explores both the mechanical and structural properties of the TZ region to ultimately identify the mechanism of integration between the NP and AF.

Development of a Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration.

Effective therapeutic approaches to overcome the heterogeneous pro-inflammatory and inhibitory extracellular matrix (ECM) microenvironment are urgently needed to achieve robust structural and functional repair of severely wounded fibrocartilaginous tissues. Herein we developed a dynamic and multifunctional nanohybrid peptide hydrogel (NHPH) through hierarchical self-assembly of peptide amphiphile modified with biodegradable two-dimensional nanomaterials with enzyme-like functions. NHPH is not only injectable, biocompatible, and biodegradable but also therapeutic by catalyzing the scavenging of pro-inflammatory reactive oxygen species and promoting ECM remodeling. In addition, our NHPH method facilitated the structural and functional recovery of the intervertebral disc (IVD) after severe injuries by delivering pro-regenerative cytokines in a sustained manner, effectively suppressing immune responses and eventually restoring the regenerative microenvironment of the ECM. In parallel, the NHPH-enhanced nucleus pulposus cell differentiation and pain reduction in a rat nucleotomy model further validated the therapeutic potential of NHPH. Collectively, our advanced nanoscaffold technology will provide an alternative approach for the effective treatment of IVD degeneration as well as other fibrocartilaginous tissue injuries.