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To provide reference and theoretical guidance for establishing human body dynamics models and studying biomechanical vibration behavior, this study aimed to develop and verify a computational model of a three-dimensional seated human body with detailed anatomical structure under complex biomechanical characteristics to investigate dynamic characteristics and internal vibration behaviors of the human body. Fifty modes of a seated human body were extracted by modal method. The intervertebral disc and head motions under uniaxial white noise excitation (between 0 and 20 Hz at 1.0, 0.5 and 0.5 m/s 2 r.m.s. for vertical, fore-aft and lateral direction, respectively) were computed by random response analysis method. It was found that there were many modes of the seated human body in the low-frequency range, and the modes that had a great impact on seated human vibration were mainly distributed below 13 Hz. The responses of different positions of the spine varied greatly under the fore-aft and lateral excitation, but the maximum stress was distributed in the lumbar under different excitations, which could explain why drivers were prone to lower back pain after prolonged driving. Moreover, there was a large vibration coupling between the vertical and fore-aft direction of an upright seated human body, while the vibration couplings between the lateral and other directions were very small. Overall, the study could provide new insights into not only the overall dynamic characteristics of the human body, but also the internal local motion and biomechanical characteristics under different excitations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mechanical testing machines are used to evaluate kinematics, kinetics, wear, and efficacy of spinal implants. The simulation of "physiological" spinal loading conditions necessitates the simultaneous use of multiple actuators. The challenge in achieving a desired loading profile lies in achieving close synchronization of these actuators. Errors in load application can be attributed to both the control system and the intrinsic sample response. Moreover, the presence of friction in the setup can have an impact on the measured outcome. The optimization of setup parameters can substantially improve the ability to simulate spinal loading conditions and obtain reliable data on implant performance. In this study, a reproducible kinematic test protocol was developed to evaluate the sensitivity of the kinetic response (i.e., measured loads, moments, and stiffnesses) of a cervical disc prosthesis to several testing parameters. In this context, five ceramic ball and socket sample implants were mounted in a 6 DOF material testing machine and tested with a constant axial compressive force of 100 N in two motion modes: 1) flexion-extension (±7.5°) and 2) lateral bending (±6°). Parameters including rotation rate, slider friction, friction between the samples' articulating surfaces, and moment arm were considered to determine their effects on measured kinetic parameters. The sensitivity analysis indicated that all setup parameters except friction between the samples' articulating surfaces had a substantial effect on the results. The findings were then compared to predictions from a free body diagram to determine the optimal setup parameters. Consequently, the setup with the lowest rotation rate and employing passive sliders yielded results that were consistent with the free body diagram. This study demonstrated the significance of a comprehensive setup evaluation for reliable and reproducible testing of spinal implants, also for comparison between labs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this original paper., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)

The annuus fibrosus (AF) and nucleus pulposus (NP) of the intervertebral disc (IVD) work in conjunction to dissipate spinal loads. In this study we have isolated the contribution of the NP to the overall response of the disc and investigated the effect of extreme structural changes to the disc on the mechanical behaviour. Linear stiffness, overall load range, hysteresis area and total energy were used to evaluate the impact of these changes on the spine and surrounding structures. Six porcine lumbar isolated disc specimens were tested in 6 DOFs with a 400 N compressive axial preload at low strain rates in three conditions: intact (IN), after total nucleotomy (NN) and after the injection of bone cement into the nuclear void (SN). The latter two conditions, NN and SN, were chosen to emulate the effect of extreme changes to the NP on disc behaviour. When comparing with intact specimens, significant changes were noted primarily in axial compression-extension, mediolateral bending and flexion-extension. NN and SN cases demonstrated significant increases in linear stiffness, overall load range and total energy for mediolateral bending and flexion-extension compared to the intact (IN) state. SN also demonstrated a significant increase in total energy for axial compression-extension, and significant decreases in the elastic contribution to total energy in all axes except flexion-extension. These changes to total energy indicate that surrounding spinal structures would incur additional loading to produce the same motion in vivo after structural changes to the disc., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

The objective of the study is to investigate the vibration behavior of the entire spine inside the human body and the influence of muscle soft tissue and lower limbs on spinal response under vertical whole-body vibration. This study conducted modal and random response analyses to simulate the modal displacements and stress of all intervertebral discs in the vertical principal mode in the skeleton, upper, and whole body. Additionally, the acceleration response of intervertebral discs under vertical random excitation was investigated. The results revealed that removing muscle soft tissue and lower limbs significantly changed the resonant frequency, modal displacement, and stress. Particularly, there was a rapid increase in vertical displacement of the lumbar spine in the skeleton model. The reason for that was due to the lack of soft tissue to provide stability, leading to significant lumbar spine bending. Under random excitation, the fore-aft acceleration of intervertebral discs in the skeleton model was considerably larger than that in the whole body, especially in the lumbar spine where it can reach up to four times higher. Conversely, the vertical response of the intervertebral discs inside the human body model was 1.4-2.4 times larger than that of the skeleton model. Muscle soft tissue contributes to the strength of the spine, reducing fore-aft response. The muscle soft tissue in the gluteal region, connected below the spine, can lower the vertical natural frequency and attenuate spinal impact. Although the lower limbs enhance spinal stability, stimulation from the feet can superimpose vibrational responses in the spine., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The intervertebral disc is an important structure for load transfer through the spine. Its injury and degeneration have been linked to pain and spinal fractures. Disc injury and spine fractures are associated with high stresses; however, these stresses cannot be measured, necessitating the use of finite element (FE) models. These models should include the disc's complex structure, as changes in disc geometry have been linked to altered mechanical behavior. However, image-based models using disc-specific structures have yet to be established. This study describes a multiphasic FE modeling approach for noninvasive estimates of subject-specific intervertebral disc mechanical behavior based on medical imaging. The models (n = 22) were used to study the influence of disc geometry on the predicted global mechanical response (moments and forces), internal local disc stresses, and tractions at the interface between the disc and the bone. Disc geometry was found to have a strong influence on the predicted moments and forces on the disc (R 2  = 0.69-0.93), while assumptions regarding the side curvature (bulge) of the disc had only a minor effect. Strong variability in the predicted internal disc stresses and tractions was observed between the models (mean absolute differences of 5.1%-27.7%). Disc height had a systematic influence on the internal disc stresses and tractions at the disc-to-bone interface. The influence of disc geometry on mechanics highlights the importance of disc-specific modeling to estimate disc injury risk, loading on the adjacent vertebral bodies, and the mechanical environment present in disc tissues., (© 2024 Orthopaedic Research Society.)

The aim of this study was to design physics-preserving and precise surrogate models of the nonlinear elastic behaviour of an intervertebral disc (IVD). Based on artificial force-displacement data sets from detailed finite element (FE) disc models, we used greedy kernel and polynomial approximations of second, third and fourth order to train surrogate models for the scalar force-torque -potential. Doing so, the resulting models of the elastic IVD responses ensured the conservation of mechanical energy through their structure. At the same time, they were capable of predicting disc forces in a physiological range of motion and for the coupling of all six degrees of freedom of an intervertebral joint. The performance of all surrogate models for a subject-specific L4 | 5 disc geometry was evaluated both on training and test data obtained from uncoupled (one-dimensional), weakly coupled (two-dimensional), and random movement trajectories in the entire six-dimensional (6d) physiological displacement range, as well as on synthetic kinematic data. We observed highest precisions for the kernel surrogate followed by the fourth-order polynomial model. Both clearly outperformed the second-order polynomial model which is equivalent to the commonly used stiffness matrix in neuro-musculoskeletal simulations. Hence, the proposed model architectures have the potential to improve the accuracy and, therewith, validity of load predictions in neuro-musculoskeletal spine models., (© 2024. The Author(s).)

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10 -16  m 4 /Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The intervertebral disc exhibits not only strain rate dependence (viscoelasticity), but also significant asymmetry under tensile and compressive loads, which is of great significance for understanding the mechanism of lumbar disc injury under physiological loads., Objective: In this study, the strain rate sensitive and tension-compression asymmetry of the intervertebral disc were analyzed by experiments and constitutive equation., Method: The Sheep intervertebral disc samples were divided into three groups, in order to test the strain rate sensitive mechanical behavior, and the internal displacement as well as pressure distribution., Results: The tensile stiffness is one order of magnitude smaller than the compression stiffness, and the logarithm of the elastic modulus is approximately linear with the logarithm of the strain rate, showing obvious tension-compression asymmetry and rate-related characteristics. In addition, the sensitivity to the strain rate is the same under these two loading conditions. The stress-strain curves of unloading and loading usually do not coincide, and form a Mullins effect hysteresis loop. The radial displacement distribution is opposite between the anterior and posterior region, which is consistent with the stress distribution. By introducing the damage factor into ZWT constitutive equation, the rate-dependent viscoelastic and weakening behavior of the intervertebral disc can be well described., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: The intervertebral disc being avascular depends on diffusion and load-based convection for essential nutrient supply and waste removal. There are no reliable methods to simultaneously investigate them in humans under natural loads. For the first time, present study aims to investigate this by strategically employing positional MRI and post-contrast studies in three physiological positions: supine, standing and post-standing recovery., Methods: A total of 100 healthy intervertebral discs from 20 volunteers were subjected to a serial post-contrast MR study after injecting 0.3 mmol/kg gadodiamide and T1-weighted MR images were obtained at 0, 2, 6, 12 and 24 h. At each time interval, images were obtained in three positions, i.e. supine, standing and post-standing recovery supine. The signal intensity values at endplate zone and nucleus pulposus were measured. Enhancement percentages were calculated and analysed comparing three positions., Results: During unloaded supine position, there was slow gradual increase in enhancement reaching peak at 6 h. When the subjects assumed standing position, there was immediate loss of enhancement at nucleus pulposus which resulted in reciprocal increase in enhancement at endplate zone (washout phenomenon). Interestingly, when subjects assumed the post-standing recovery position, the nucleus pulposus regained the enhancement and endplate zone showed reciprocal loss (pumping-in phenomenon)., Conclusions: For the first time, present study documented acute effects of physiological loading and unloading on nutrition of human discs in vivo. While during rest, solutes diffused gradually into disc, the diurnal short loading and unloading redistribute small solutes by convection. Standing caused rapid solute depletion but promptly regained by assuming resting supine position., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. International Federation for Medical and Biological Engineering.)

Background: The static sitting position contributes to increased pressure on the lumbar intervertebral disc, which can lead to dehydration and decreased disc height., Objective: To systematically investigate the of sitting posture on degeneration of the lumbar intervertebral disc., Materials and Methods: One researcher carried out a systematic literature search of articles with no language or time limits. Studies from 2006 to 2018 were found. The searches in all databases were carried out on January 28, 2022, using the following databases: Pubmed, Scopus, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro) databases, and for the grey literature: Google scholar, CAPES Thesis and Dissertation Bank, and Open Grey. The acronym PECOS was used to formulate the question focus of this study: P (population) - male and female subjects; E (exposure) - sitting posture; C (comparison) - other posture or sitting posture in different periods; O (outcomes) - height and degeneration of the lumbar intervertebral disc(s), imaging exam; and S (study) - cross-sectional and case control., Results: The risk of bias was in its moderate totality in its outcome: height and degeneration of the lumbar intervertebral disc(s) - imaging. Of the four selected studies, three found a decrease in the height of the disc(s) in sitting posture., Conclusion: The individual data from the manuscripts suggest that the sitting posture causes a reduction in the height of the lumbar intervertebral disc. It was also concluded that there is a need for new primary studies with a more in-depth design and sample size., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NS was involved in the development and patenting of hydrogel-based technologies for Synthes Spine as Director of Non Fusion Technologies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Jing, Wang and Jia.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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/s 2 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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 ∼ 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

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., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Intervertebral disc (IVD) degeneration and accompanying lower back pain impose global medical and societal challenges, affecting over 600 million people worldwide. The IVD complex fibrocartilaginous structure is responsible for the spine biomechanical function. The nucleus pulposus (NP), composed of swellable glycosaminoglycan (GAG), transfers compressive loads to the surrounding fiber-reinforced annulus fibrosus (AF) lamellae, which stretches under tension. Together, these substructures allow the IVD to withstand extremely high and complex loads. Key to mimic the complete disc must consider the properties of its substructures. This study presents three novel substructures-a biomimetic silk-reinforced composite lamella for the AF, a GAG analog for the NP, and a novel biomimetic combined AF-NP construct. The biomimetic AF demonstrates nonlinear, hyperelastic, and anisotropic behavior similar to the native human AF, while the NP analog demonstrates mechanical behavior similar to the human NP. The synergized biomimetic AF-NP demonstrates similar behavior to the unconfined NP, with significantly increased deformations indicating improved performance. Validation of the AF-NP construct mechanics using a finite element model yields results compatible with native human IVD under various physiological loadings. The ability of our AF-NP construct to mimic the native IVD offers a revolutionary concept for the potential development of a fully functional IVD., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier B.V.)

In spine research, two possibilities to generate models exist: generic (population-based) models representing the average human and subject-specific representations of individuals. Despite the increasing interest in subject specificity, individualisation of spine models remains challenging. Neuro-musculoskeletal (NMS) models enable the analysis and prediction of dynamic motions by incorporating active muscles attaching to bones that are connected using articulating joints under the assumption of rigid body dynamics. In this study, we used forward-dynamic simulations to compare a generic NMS multibody model of the thoracolumbar spine including fully articulated vertebrae, detailed musculature, passive ligaments and linear intervertebral disc (IVD) models with an individualised model to assess the contribution of individual biological structures. Individualisation was achieved by integrating skeletal geometry from computed tomography and custom-selected muscle and ligament paths. Both models underwent a gravitational settling process and a forward flexion-to-extension movement. The model-specific load distribution in an equilibrated upright position and local stiffness in the L4/5 functional spinal unit (FSU) is compared. Load sharing between occurring internal forces generated by individual biological structures and their contribution to the FSU stiffness was computed. The main finding of our simulations is an apparent shift in load sharing with individualisation from an equally distributed element contribution of IVD, ligaments and muscles in the generic spine model to a predominant muscle contribution in the individualised model depending on the analysed spine level., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

Low back pain is the major cause of disability worldwide, and intervertebral disc degeneration (IVDD) is one of the most important causes of low back pain. Currently, there is no method to treat IVDD that can reverse or regenerate intervertebral disc (IVD) tissue, but the recent development of disc tissue engineering (DTE) offers a new means of addressing these disadvantages. Among numerous biomaterials for tissue engineering, silk fibroin (SF) is widely used due to its easy availability and excellent physical/chemical properties. SF is usually used in combination with other materials to construct biological scaffolds or bioactive substance delivery systems, or it can be used alone. The present article first briefly outlines the anatomical and physiological features of IVD, the associated etiology and current treatment modalities of IVDD, and the current status of DTE. Then, it highlights the characteristics of SF biomaterials and their latest research advances in DTE and discusses the prospects and challenges in the application of SF in DTE, with a view to facilitating the clinical process of developing interventions related to IVD-derived low back pain caused by IVDD.

Finite element models (FEMs) of the spine commonly use a limited number of simplified geometries. Nevertheless, the geometric features of the spine are important in determining its FEM outcomes. The link between a spinal segment's shape and its biomechanical response has been studied, but the co-variances of the shape features have been omitted. We used a principal component (PCA)-based statistical shape modelling (SSM) approach to investigate the contribution of shape features to the intradiscal pressure (IDP) and the facets contact pressure (FCP) in a cohort of synthetic L4/L5 functional spinal units under axial compression. We quantified the uncertainty in the FEM results, and the contribution of individual shape modes to these results. This parameterisation approach is able to capture the variability in the correlated anatomical features in a real population and sample plausible synthetic geometries. The first shape mode ([Formula: see text]) explained 22.6% of the shape variation in the subject-specific cohort used to train the SSM, and had the largest correlation with, and contribution to IDP (17%) and FCP (11%). The largest geometric variation in ([Formula: see text]) was in the annulus-nucleus ratio., (© 2022. The Author(s).)

Objectives: Bags such as handbags, shoulder bags, and backpacks are commonly used. However, it is difficult to assess the biomechanical effects of bag-carrying styles on the lumbar spine and paraspinal muscles using traditional methods. This study aimed to evaluate the biomechanical effects of bag-carrying styles on the lumbar spine., Methods: We developed a hybrid model that combined a finite element (FE) model of the lumbar spine and musculoskeletal models of three bag-carrying styles. The image data was collected from a 26-years-old, 176 cm and 70 kg volunteer. OpenSim and ABAQUS were used to do the musculoskeletal analysis and finite analysis. Paraspinal muscle force, intervertebral compressive force (ICF), and intervertebral shear force (ISF) on L1 were calculated and loaded into the FE model to assess the stress distribution on the lumbar spine., Results: Different paraspinal muscle activation occurred in the three bag-carrying models. The increase in the ICF generated by all three bags was greater than the bags' weights. The handbag produced greater muscle force, ICF, ISF, and peak stress on the nucleus pulposus than the backpack and shoulder bag of the same weight. Peak stress on the intervertebral discs in the backpack model and the L1-L4 segments of the shoulder bag model increased linearly with bag weight, and increased exponentially with bag weight in the handbag model., Conclusion: Unbalanced bag-carrying styles (shoulder bags and handbags) led to greater muscle force, which generated greater ICF, ISF, and peak stress on the lumbar spine. The backpack produced the least burden on the lumbar spine and paraspinal muscles. Heavy handbags should be used carefully in daily life., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Many previous studies have found that occupational drivers commonly suffered from low back pain, and low back pain and degeneration of the intervertebral disc might be associated with vibration conditions. However, the biomechanical mechanisms of whole-body vibration that caused pain and injury were not clear. In this study, a validated whole human body finite element model was used, and vibration loads at frequencies of 3, 5, 7 and 9 Hz were loaded to evaluate the frequency effects on the spine. The results showed that the responses of the spine were strong at the 5 Hz vibration load. Vibration loads would produce alternating stresses and bulges in the annulus fibrosus and change the direction of the pressure in the nucleus pulposus. The posterior region of the intervertebral disc showed greater stress fluctuations than the anterior region. The Risk Factors showed that long-term exposure to whole-body vibrations at 5 and 7 Hz might have greater adverse effects on the spine. The findings of this study confirmed that vibrations near the resonance frequency of the human body would cause more injuries to the spine than other frequencies. Alternating stress and bulge might cause fatigue and the degeneration of the intervertebral disc, which might be the mechanisms of spinal injury caused by whole-body vibration, and the posterior regions of the intervertebral disc were more susceptible to degeneration. Some appropriate measures should be taken to reduce the adverse effects of whole-body vibration on spinal health.

Finite element analysis is a powerful tool that is often used to study the biomechanical response of the spine. The primary objective of this study was to illustrate the mechanical behavior of a previously proposed parametric CAD spine model in comparison with a segmented FSU model and the literature. In this study, two finite element models of the L4-L5 spinal level were developed from the same patient's CT scan data. The first was developed using well-known segmentation methods, whereas the second was developed from the new by using a novel parametric CAD model. Both models were subjected to the same loading and boundary conditions to perform flexion, extension, lateral bending and axial rotation motions. The segmented finite element model was observed to be in good agreement with the literature. The parametric finite element model results were also observed to be in good agreement with the segmented finite element model and with the literature except under extension., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2022 IPEM. Published by Elsevier Ltd. All rights reserved.)

The intervertebral disc has an intrinsic circadian rhythm, elimination of which leads to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Disruption or deletion of Bmal1 (a core transcription factor) results in complete loss of circadian rhythms, make mice susceptibility to IDD. However, the underlying mechanism by which Bmal1 mediates IDD is remains enigmatic, and whether there are other upstream factors regulating Bmal1 in NPCs. In our study, we first found that the decrease of Bmal1 was significantly correlated with the grades of IDD. With gain- and loss-of-function, Bmal1 shown a protective effect on NPC viability and functions. Transcriptomic and proteomic landscape reveals the functional contributions of Bmal1, and phosphoproteomic analysis links to autophagy. Bioinformatics analysis identified that a novel miRNA hsa-let-7f-1-3p was directly target Bmal1 3'UTR and negatively correlated with NPC function. Finally, our animal model confirmed the protective role of Bmal1 in rat IDD and this effect could be attenuated by hsa-let-7f-1-3p. The hsa-let-7f-1-3p/Bmal1/autophagy axis provides a potential therapeutic strategy for the clinical treatment of IDD., Competing Interests: Declarations of Interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Current intervertebral disc finite element models are hard to validate since they describe multi-physical phenomena and contain a huge number of material properties. This work aims to simplify numerical validation/identification studies by prioritizing the sensitivity of intervertebral disc behavior to mechanical properties. A 3D fiber-reinforced hyperelastic model of a C6-C7 intervertebral disc is used to carry out the parametric study. 10 parameters describing the extracellular matrix and the collagen network behaviors are included in the parametric study. The influence of varying these parameters on the disc response is estimated during physiological movements of the head, including compression, lateral bending, flexion, and axial rotation. The obtained results highlight the high sensitivity of the disc behavior to the stiffness of the annulus fibrosus extracellular matrix for all the studied loads with a relative increase in the disc apparent stiffness by 67% for compression and by 57% for axial rotation when the annulus stiffness increases from 0.4 to 2 MPa. It is also shown that varying collagen network orientation, stiffness, and stiffening in the studied configuration range have a noticeable effect on rotational motions with a relative apparent stiffness difference reaching 6.8%, 10%, and 22%, respectively, in lateral bending. However, the collagen orientation does not affect disc response to axial load., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 IPEM. Published by Elsevier Ltd. All rights reserved.)

This study quantified the effect of subthreshold loading histories that differed by joint posture (neutral, flexed), peak loading variation (10%, 20%, 40%), and loading duration (1000, 3000, 5000 cycles) on the post-loading Ultimate Compressive Tolerance (UCT), yield force, and regional Cartilaginous End Plate (CEP) indentation responses (loading stiffness and creep displacement). One hundred and fourteen porcine spinal units were included. Following conditioning and cyclic compression exposures, spinal units were transected and one endplate from each vertebra underwent subsequent UCT or microindentation testing. UCT testing was conducted by compressing a single vertebra at a rate of 3 kN/s using an indenter fabricated to a representative intervertebral disc size and shape. Force and actuator position were sampled at 100 Hz. Non-destructive uniaxial CEP indentation was performed at five surface locations (central, anterior, posterior, right, left) using a Motoman robot and aluminum indenter (3 mm hemisphere). Force and end-effector position were sampled at 10 Hz. A significant three-way interaction was observed for UCT (p = 0.038). Compared to neutral, the UCT was, on average, 1.9 kN less following each flexed loading duration. No effect of variation was observed in flexion; however, 40% variation caused the UCT to decrease by an average of 2.13 kN and 2.06 kN following 3000 and 5000 cycles, respectively. The indentation stiffness in the central CEP mimicked the UCT response. These results demonstrate a profound effect of posture on post-loading UCT and CEP behaviour. Control of peak compression exposures became particularly relevant only when a neutral posture was maintained and beyond the midpoint of the predicated lifespan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The annulus fibrosus is the ring-like exterior of the intervertebral disc, which is composed of concentrically organized layers of collagen fiber bundles. The mechanical properties of the annulus have been studied extensively; however, tests are typically performed on extracted fragments or multilayered samples of the annulus and not on the annulus as a whole. The purpose of this study was twofold: (1) to develop a novel testing technique to measure the mechanical properties of the intact, isolated annulus; and (2) to perform a preliminary analysis of the rate-dependency of these mechanical properties. Twenty-nine whole annulus ring samples were dissected from 11 skeletally mature Sprague Dawley rat tails and underwent a tensile failure test at either 2%/s (n = 16) or 20%/s (n = 13). Force and displacement were sampled at 100 Hz and were subsequently normalized to stress and strain. Various mechanical properties were derived from the stress-strain curves and statistically compared between the rates. All mechanical variables, with the exception of initial failure stress, were found to be unaffected by rate. Interestingly, initial failure stress was higher for samples tested at the slower rate compared to the higher rate which is atypical for viscoelastic tissues. Although in general rate did not appear to impact the annulus ring response to tensile loading, this novel, intact annular ring testing technique provides an alternative way to quantify mechanical properties of the annulus., (Copyright © 2022 by ASME.)

Intervertebral discs are fibrocartilage structures, which play a role in buffering the compression applied to the vertebral bodies evenly while permitting limited movements. According to several previous studies, degenerative changes in the intervertebral disc could be accelerated by factors, such as aging, the female sex, obesity, and smoking. As degenerative change progresses, the disc height could be reduced due to the dehydration of the nucleus pulposus. This study aimed to quantitatively analyze the pressure that each structure of the spine receives according to the change in the disc height and predict the physiological effect of disc height on the spine. We analyzed the biomechanical effect on spinal structures when the disc height was decreased using a finite-element method investigation of the lumbar spine. Using a 3D FE model, the degree and distribution of von-Mises stress according to the disc height change were measured by applying the load of four different motions to the lumbar spine. The height was changed by dividing the anterior and posterior parts of the disc, and analysis was performed in the following four motions: flexion, extension, lateral bending, and axial rotation. Except for a few circumstances, the stress applied to the structure generally increased as the disc height decreased. Such a phenomenon was more pronounced when the direction in which the force was concentrated coincided with the portion where the disc height decreased. This study demonstrated that the degree of stress applied to the spinal structure generally increases as the disc height decreases. The increase in stress was more prominent when the part where the disc height was decreased and the part where the moment was additionally applied coincided. Disc height reduction could accelerate degenerative changes in the spine. Therefore, eliminating the controllable risk factors that cause disc height reduction may be beneficial for spinal health., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Jae-Gyeong Jeong et al.)

In vitro testing has been conducted to provide a comprehensive understanding of the biomechanics of the cervical spine. This has allowed a characterization of the stability of the spine as influenced by the intrinsic properties of its tissue constituents and the severity of degeneration or injury. This also enables the preclinical estimation of spinal implant functionality and the success of operative procedures. The purpose of this review paper was to compile methodologies and results from various studies addressing spinal kinematics in pre- and postoperative conditions so that they could be compared. The reviewed literature was evaluated to provide suggestions for a better approach for future studies, to reduce the uncertainties and facilitate comparisons among various results. The overview is presented in a way to inform various disciplines, such as experimental testing, design development, and clinical treatment. The biomechanical characteristics of the cervical spine, mainly the segmental range of motion (ROM), intradiscal pressure (IDP), and facet joint load (FJL), have been assessed by testing functional spinal units (FSUs). The relative effects of pathologies including disc degeneration, muscle dysfunction, and ligamentous transection have been studied by imposing on the specimen complex load scenarios imitating physiological conditions. The biomechanical response is strongly influenced by specimen type, test condition, and the different types of implants utilized in the different experimental groups., (Copyright © 2022 by ASME.)

A new generation of bioreactors with integrated six degrees of freedom (6 DOF) aims to mimic more accurately the natural intervertebral disc (IVD) load. We developed and validated in a biological and mechanical study a specimen holder and corresponding ex vivo IVD organ model according to the bioreactor requirements for multiaxial loading and a long-term IVD culture. IVD height changes and cell viability were compared between the 6 DOF model and the standard 1 DOF model throughout the 3 weeks of cyclic compressive loading in the uniaxial bioreactor. Furthermore, the 6 DOF model and holder were loaded for 9 days in the multiaxial bioreactor under development using the same conditions, and the IVDs were evaluated for cell viability. The interface of the IVD model and specimen holder, enhanced with fixation screws onto the bone, was tested in compression, torsion, lateral bending, and tension. Additionally, critical motions such as tension and bending were assessed for a combination of side screws and top screws or side screws and adhesive. The 6 DOF model loaded in the uniaxial bioreactor maintained similar cell viability in the IVD regions as the 1 DOF model. The viability was high after 2 weeks throughout the whole IVD and reduced by more than 30% in the inner annulus fibrous after 3 weeks. Similarly, the IVDs remained highly viabile when cultured in the multiaxial bioreactor. In both models, IVD height changes after loading were in the range of typical physiological conditions. When differently directed motions were applied, the holder-IVD interface remained stable under hyper-physiological loading levels using a side screw approach in compression and torsion and the combination of side and top screws in tension and bending. We thus conclude that the developed holding system is mechanically reliable and biologically compatible for application in a new generation of multiaxial bioreactors.

Background: The intervertebral disc is a known back pain generator and is frequently the focus of spinal manipulative therapy evaluation and treatment. The majority of our current knowledge regarding intradiscal pressure (IDP) changes related to spinal manual therapy involves cadaveric studies with their inherent limitations. Additional in vivo animal models are needed to investigate intervertebral disc physiological and molecular mechanisms related to spinal manipulation and spinal mobilization treatment for low back disorders., Methods: Miniature pressure catheters (Millar SPR-1000) were inserted into either the L4-L5 or L5-L6 intervertebral disc of 3 deeply anesthetized adult cats (Oct 2012-May 2013). Changes in IDP were recorded during delivery of instrument-assisted spinal manipulation (Activator V® and Pulstar®) and motorized spinal flexion with/without manual spinous process contact., Results: Motorized flexion of 30° without spinous contact decreased IDP of the L4-L5 disc by ~ 2.9 kPa, while physical contact of the L4 spinous process decreased IDP an additional ~ 1.4 kPa. Motorized flexion of 25° with L5 physical contact in a separate animal decreased IDP of the L5-L6 disc by ~ 1.0 kPa. Pulstar® impulses (setting 1-3) increased IDP of L4-L5 and L5-L6 intervertebral discs by ~ 2.5 to 3.0 kPa. Activator V® (setting 1-4) impulses increased L4-L5 IDP to a similar degree. Net changes in IDP amplitudes remained fairly consistent across settings on both devices regardless of device setting suggesting that viscoelastic properties of in vivo spinal tissues greatly dampen superficially applied manipulative forces prior to reaching deep back structures such as the intervertebral disc., Conclusions: This study marks the first time that feline in vivo changes in IDP have been reported using clinically available instrument-assisted spinal manipulation devices and/or spinal mobilization procedures. The results of this pilot study indicate that a feline model can be used to investigate IDP changes related to spinal manual therapy mechanisms as well as the diminution of these spinal manipulative forces due to viscoelastic properties of the surrounding spinal tissues. Additional investigation of IDP changes is warranted in this and/or other in vivo animal models to provide better insights into the physiological effects and mechanisms of spinal manual therapy at the intervertebral disc level., (© 2022. The Author(s).)

Passive finite element (FE) models of the spine are commonly used to simulate intact and various pre- and postoperative pathological conditions. Being devoid of muscles, these traditional models are driven by simplistic loading scenarios, e.g., a constant moment and compressive follower load (FL) that do not properly mimic the complex in vivo loading condition under muscle exertions. We aim to develop novel passive FE models that are driven by more realistic yet simple loading scenarios, i.e., in vivo vertebral rotations and pathological-condition dependent FLs (estimated based on detailed musculoskeletal finite element (MS-FE) models). In these novel force-displacement control FE models, unlike the traditional passive FE models, FLs vary not only at different spine segments (T12-S1) but between intact, pre- and postoperative conditions. Intact, preoperative degenerated, and postoperative fused conditions at the L4-L5 segment for five static in vivo activities in upright and flexed postures were simulated by the traditional passive FE, novel force-displacement control FE, and gold-standard detailed MS-FE spine models. Our findings indicate that, when compared to the MS-FE models, the force-displacement control passive FE models could accurately predict the magnitude of disc compression force, intradiscal pressure, annulus maximal von Mises stress, and vector sum of all ligament forces at adjacent segments (L3-L4 and L5-S1) but failed to predict disc shear and facet joint forces. In this regard, the force-displacement control passive FE models were much more accurate than the traditional passive FE models. Clinical recommendations made based on traditional passive FE models should, therefore, be interpreted with caution., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Recently, more and more people suffer from low back pain triggered by lumbar degenerative disc disease. The mechanical factor is one of the most significant causes of disc degeneration. This study aims to explore the biomechanical responses of the intervertebral disc, and investigate the process of disc injury by the theory of continuum damage mechanics., Methods: A finite element model of the L4-L5 lumbar spine was developed and validated. The model not only considered changes in permeability coefficient with strain, but also included physiological factors such as osmotic pressure. Three loading conditions were simulated: (A) static loads, (B) vibration loads, (C) injury process., Findings: The simulation results revealed that the facet joints shared massive stresses of the intervertebral discs, and prevented excessive lumbar spine movement. However, their asymmetrical position may have led to degeneration. The von Mises stress and pore pressure of annulus fibrosus showed significantly different trends under static loads and vibration loads. The von Mises stress of nucleus pulposus was not sensitive to vibration loads, but its pore pressure was conspicuously influenced by vibration loads. The injury first appeared at the posterior centre, and then, it gradually expanded along the edge of the intervertebral disc. With an increase in the loading steps, the damage rate of the intervertebral disc increased logarithmically., Interpretation: The variation in the biomechanical performance of the intervertebral disc could be attributed to the periodic movement of internal fluids. This study might be helpful for understanding the mechanism of intervertebral disc degeneration., (Copyright © 2022. Published by Elsevier Ltd.)

Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging, mechanical trauma, lifestyle factors, and certain genetic abnormalities, leads to loss of nucleus pulposus, alteration in the composition of the extracellular matrix, excessive oxidative stress, and inflammation in the intervertebral disc. Pharmacological and surgical interventions are considered a boon for the treatment of IVDD, but the effectiveness of those strategies is limited. Mesenchymal stem cells (MSCs) have recently emerged as a possible promising regenerative therapy for IVDD due to their paracrine effect, restoration of the degenerated cells, and capacity for differentiation into disc cells. Recent investigations have shown that the pleiotropic effect of MSCs is not related to differentiation capacity but is mediated by the secretion of soluble paracrine factors. Early studies have demonstrated that MSC-derived exosomes have therapeutic potential for treating IVDD by promoting cell proliferation, tissue regeneration, modulation of the inflammatory response, and reduced apoptosis. This paper highlights the current state of MSC-derived exosomes in the field of treatment of IVDD with further possible future developments, applications, and challenges.

The objective of this study was to quantitatively analyze the effect of lumbar spinal muscle atrophy on the compressive (perpendicular to the upper surface of the disc) and shear (parallel to the upper surface of the disc in the anterior-posterior direction) forces change on lumbar intervertebral discs using a full body musculoskeletal modeling approach. Muscles atrophy was modeled with reduction of the functional cross-sectional area (FCSA) of the muscles. Compressive and shear forces under two levels of lumbar muscle atrophy (20% and 40%) at eight daily postures (lying on back, seating slouched, seating straight, standing, standing flexed (36°), standing lift a 20 kg weight close to chest, standing lift a 20 kg weight flexed (38°), and standing lift a 20 kg weight with arm stretched) were analyzed. There was small increase in compressive forces on lumbar discs with muscle atrophy at most postures except lying and sitting straight. The maximum increase of compressive forces on lumbar discs were 23 N (6%), 28 N (5%), 34 N (2%), 71 N (6%), 89 N (4%), and 190 N (10%) with 20% atrophy, and 66 N (19%), 77 N (12%), 98 N (6%), 169 N (14%), 256 N (12%), 501 N (24%) with 40% atrophy at seating slouched, standing, standing flexed, standing lift close, standing lift flexed, and standing stretched arm, respectively. The shear force did not change significantly on lumbar discs with muscle atrophy. This study is important for understanding the biomechanical mechanisms of how lumbar muscle atrophy may affect the lumbar IVD health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)