Machine learning applications in spine biomechanics.

Spine biomechanics is at a transformation with the advent and integration of machine learning and computer vision technologies. These novel techniques facilitate the estimation of 3D body shapes, anthropometrics, and kinematics from as simple as a single-camera image, making them more accessible and practical for a diverse range of applications. This study introduces a framework that merges these methodologies with traditional musculoskeletal modeling, enabling comprehensive analysis of spinal biomechanics during complex activities from a single camera. Additionally, we aim to evaluate their performance and limitations in spine biomechanics applications. The real-world applications explored in this study include assessment in workplace lifting, evaluation of whiplash injuries in car accidents, and biomechanical analysis in professional sports. Our results demonstrate potential and limitations of various algorithms in estimating body shape, kinematics, and conducting in-field biomechanical analyses. In industrial settings, the potential to utilize these new technologies for biomechanical risk assessments offers a pathway for preventive measures against back injuries. In sports activities, the proposed framework provides new opportunities for performance optimization, injury prevention, and rehabilitation. The application in forensic domain further underscores the wide-reaching implications of this technology. While certain limitations were identified, particularly in accuracy of predictions, complex interactions, and external load estimation, this study demonstrates their potential for advancement in spine biomechanics, heralding an optimistic future in both research and practical applications.

Comparative evaluation of different spinal stability metrics.

Direct in vivo measurements of spinal stability are not possible, leaving computational estimations (such as dynamic time series and structural analyses) as the feasible option. However, differences between different stability assessment approaches and metrics remain unclear. To explore this, we asked 32 participants to perform 35 cycles of repetitive lifts with and without load (4/2.6 kg for males/females). EMG signals and 3D kinematics were collected via 12 surface electrodes and 17 inertial sensors, and three dynamical stability measures were computed: short and long temporal and conventional maximum Lyapunov exponents (LyE) and maximum Floquet multipliers (FM). A dynamic subject-specific EMG-assisted musculoskeletal model computed four structural stability measures (critical muscle stiffness coefficient at which spine becomes unstable, average spine stiffness, minimum and geometric average of Hessian matrix eigenvalues). Across cycles, dynamical and structural stability outcomes varied noticeably. Temporal short-term LyE and all structural stability measures were more influenced by the cycle percentage (posture factor) than by phase (lifting, lowering) or load factor. The effect of all factors were non-significant for FM and long LyE, except for the posture on LyE-L with a small effect size. Pearson's correlations revealed a weak to moderate, or non-existent, correlation between structural and dynamical stability metrics, with small shared variances, underscoring their distinct and independent nature and theoretical foundations. Moreover, the low sensitivity of dynamic measures to posture and load factors, found in this study, calls for further examination. Considering the limitations and shortcomings of both dynamical and structural stability assessment approaches, there is a need for the development of improved musculoskeletal stability evaluation techniques.

Trunk muscle forces and spinal loads during heavy deadlift: Effects of personalization, muscle wrapping, muscle lever arm, and lumbopelvic rhythm.

Heavy deadlift is used as a physical fitness screening tool in the U.S. Army. Despite the relevance of such a screening tool to military tasks performed by Service Members, the biomechanical impact of heavy deadlift and its risk of low-back injury remain unknown. A kinematics-driven musculoskeletal model of spine was implemented to investigate biomechanics of the lower back in a volunteer (23 years old, height of 1.82 m, and body mass of 98.8 kg) during a 68 kg deadlift. In search of protective mechanisms, effects of model personalization and variations in trunk musculature and lumbopelvic rhythm were also investigated. The net moment, compression and shear forces at the L5-S1 reached peaks of 684 Nm, 17.2 and 4.2 kN, respectively. Geometrical personalization and changes in lumbopelvic rhythm had the least effects on predictions while increases in muscle moment arms (40%) had the largest effects that caused, respectively, 32% and 36% decrease in the maximum compressive and shearing forces. Initiating wrapping of back muscles at farther distances from the spine had opposing effects on spinal loads; peak compression at the L5-S1 decreased by 12% whereas shear increased by 19%. Despite mechanisms considered, spinal loads during heavy deadlift exceed the existing evidence concerning the threshold of injury for spinal segments, suggesting the vulnerability to injury. Chronic exposure to such high-spinal loads may lead to (micro) fractures, degeneration, pathoanatomical changes and finally low-back pain.

Validation of an EMG submaximal method to calibrate a novel dynamic EMG-driven musculoskeletal model of the trunk: Effects on model estimates.

BACKGROUND: Multijoint EMG-assisted optimization models are reliable tools to predict muscle forces as they account for inter- and intra-individual variations in activation. However, the conventional method of normalizing EMG signals using maximum voluntary contractions (MVCs) is problematic and introduces major limitations. The sub-maximal voluntary contraction (SVC) approaches have been proposed as a remedy, but their performance against the MVC approach needs further validation particularly during dynamic tasks. METHODS: To compare model outcomes between MVC and SVC approaches, nineteen healthy subjects performed a dynamic lifting task with two loading conditions. RESULTS: Results demonstrated that these two approaches produced highly correlated results with relatively small absolute and relative differences (<10 %) when considering highly-aggregated model outcomes (e.g. compression forces, stability indices). Larger differences were, however, observed in estimated muscle forces. Although some model outcomes, e.g. force of abdominal muscles, were statistically different, their effect sizes remained mostly small (ηG2 ≤ 0.13) and in a few cases moderate (ηG2 ≤ 0.165). CONCLUSION: The findings highlight that the MVC calibration approach can reliably be replaced by the SVC approach when the true MVC exertion is not accessible due to pain, kinesiophobia and/or the lack of proper training.

Submaximal electromyography-driven musculoskeletal modeling of the human trunk during static tasks: Equilibrium and stability analyses.

Conventional electromyography-driven (EMG) musculoskeletal models are calibrated during maximum voluntary contraction (MVC) tasks, but individuals with low back pain cannot perform unbiased MVCs. To address this issue, EMG-driven models can be calibrated in submaximal tasks. However, the effects of maximal (when data points include the maximum contraction) and submaximal calibration techniques on model outputs (e.g., muscle forces, spinal loads) remain yet unknown. We calibrated a subject-specific EMG-driven model, using maximal/submaximal isometric contractions, and simulated different independent tasks. Both approaches satisfactorily predicted external moments (Pearson's correlation ∼ 0.75; relative error = 44%), and removing calibration tasks under axial torques markedly improved the model performance (Pearson's correlation âˆ¼ 0.92; relative error âˆ¼ 28%). Unlike individual muscle forces, gross (aggregate) model outputs (i.e., spinal loads, stability index, and sum of abdominal/back muscle forces) estimated from maximal and submaximal calibration techniques were highly correlated (r > 0.78). Submaximal calibration method overestimated spinal loads (6% in average) and abdominal muscle forces (11% in average). Individual muscle forces estimated from maximal and submaximal approaches were substantially different; however, gross model outputs (especially internal loads and stability index) remained highly correlated with small to moderate relative differences; therefore, the submaximal calibration technique can be considered as an alternative to the conventional maximal calibration approach.

Adjacent segments biomechanics following lumbar fusion surgery: a musculoskeletal finite element model study.

PURPOSE: This study exploits a novel musculoskeletal finite element (MS-FE) spine model to evaluate the post-fusion (L4-L5) alterations in adjacent segment kinetics. METHODS: Unlike the existing MS models with idealized representation of spinal joints, this model predicts stress/strain distributions in all passive tissues while organically coupled to a MS model. This generic (in terms of musculature and material properties) model uses population-based in vivo vertebral sagittal rotations, gravity loads, and an optimization algorithm to calculate muscle forces. Simulations represent individuals with an intact L4-L5, a preoperative severely degenerated L4-L5 (by reducing the disc height by ~ 60% and removing the nucleus incompressibility), and a postoperative fused L4-L5 segment with either a fixed or an altered lumbopelvic rhythm with respect to the intact condition (based on clinical observations). Changes in spine kinematics and back muscle cross-sectional areas (due to intraoperative injuries) are considered based on in vivo data while simulating three activities in upright/flexed postures. RESULTS: Postoperative changes in some adjacent segment kinetics were found considerable (i.e., larger than 25%) that depended on the postoperative lumbopelvic kinematics and preoperative L4-L5 disc condition. Postoperative alterations in adjacent disc shear, facet/ligament forces, and annulus stresses/strains were greater (> 25%) than those found in intradiscal pressure and compression (< 25%). Kinetics of the lower (L5-S1) and upper (L3-L4) adjacent segments were altered to different degrees. CONCLUSION: Alterations in segmental rotations mainly affected adjacent disc shear forces, facet/ligament forces, and annulus/collagen fibers stresses/strains. An altered lumbopelvic rhythm (increased pelvis rotation) tends to mitigate some of these surgically induced changes.

Blood clot behaves as a poro-visco-elastic material.

Mechanical properties of blood clots play a crucial role in hemostasis and embolization. They are time-dependent and often described with viscoelastic models. But blood clots also exhibit some hallmark features of poroelasticity, as most biological tissues exhibit concurrent viscoelasticity and poroelasticity. In this study, we characterized the time-dependent behavior of blood clots, and developed an experimental-computational framework to decouple and model poroelastic and viscoelastic responses. Compression stress relaxation tests were conducted on bovine blood clots with different diameters to evaluate the influence of sample size on the relaxation time. In the compression tests, the mass of blood clots was measured to estimate fluid migration. To capture pure viscoelastic responses, rheological shear stress relaxation tests were carried out. A poroviscoelastic model was also proposed and calibrated to capture the complex multiaxial (compression and shear) relaxation behavior of blood clots. In unconfined compression tests, stresses relaxed markedly (average: 83%; range: 76-90%), and samples with larger diameters showed longer relaxation time. Blood clots lost about 24% of their initial masses, and the mass transport took place gradually in compression tests. Under shear deformation, blood clots relaxed in average 37% (range: 32-39%) which was much less than those under unconfined compression tests (in average 37% versus 83%). Unlike poroelastic and viscoelastic theories, the poroviscoelastic model accurately predicted multiaxial responses of blood clots under compression and shear; additionally, the estimated Darcy's coefficient (4.4×10-9 cm2) was found within the reported physiological range (0.1×10-9 to 36 × 10-9 cm2). The combination of size-dependent stress relaxation and mass loss under compression (due to poroelasticity) as well as substantial stress relaxation under shear deformation (due to viscoelasticity) demonstrate that blood clot behaves as a poroviscoelastic material; therefore, accurate interpretation of transient responses of blood clots requires a validated poroviscoelastic model. This work provides understanding and methodology on blood clot mechanics and will further motivate the development of clot-like biomaterials.

Evaluating stability of human spine in static tasks: a combined in vivo-computational study.

Various interpretations and parameters have been proposed to assess spinal stability such as antagonist muscle coactivity, trunk stiffness and spinal buckling load; however, the correlation between these parameters remains unknown. We evaluated spinal stability during different tasks while changing the external moment and load height and investigated likely relationships between different EMG- and model-based parameters (e.g., EMG coactivity ratio, trunk stiffness, force coactivity ratio) and stability margins. EMG and kinematics of 40 young healthy subjects were recorded during various quasi-static tasks. Muscle forces, trunk stiffness and stability margins were calculated by a nonlinear subject-specific EMG-assisted-optimization musculoskeletal model of the trunk. The load elevation and external moment increased muscle activities and trunk stiffness while all stability margins (i.e., buckling loads) decreased. The force coactivity ratio was strongly correlated with the hand-load stability margin (i.e., additional weight in hands to initiate instability; R2 = 0.54) demonstrating the stabilizing role of abdominal muscles. The total trunk stiffness (Pearson's r = 0.96) and the sum of EMGs of back muscles (Pearson's r = 0.65) contributed the most to the T1 stability margin (i.e., additional required load at T1 for instability/buckling). Force coactivity ratio and trunk stiffness can be used as alternative spinal stability metrics.

Biomechanical effects of lumbar fusion surgery on adjacent segments using musculoskeletal models of the intact, degenerated and fused spine.

Adjacent segment disorders are prevalent in patients following a spinal fusion surgery. Postoperative alterations in the adjacent segment biomechanics play a role in the etiology of these conditions. While experimental approaches fail to directly quantify spinal loads, previous modeling studies have numerous shortcomings when simulating the complex structures of the spine and the pre/postoperative mechanobiology of the patient. The biomechanical effects of the L4-L5 fusion surgery on muscle forces and adjacent segment kinetics (compression, shear, and moment) were investigated using a validated musculoskeletal model. The model was driven by in vivo kinematics for both preoperative (intact or severely degenerated L4-L5) and postoperative conditions while accounting for muscle atrophies. Results indicated marked changes in the kinetics of adjacent L3-L4 and L5-S1 segments (e.g., by up to 115% and 73% in shear loads and passive moments, respectively) that depended on the preoperative L4-L5 disc condition, postoperative lumbopelvic kinematics and, to a lesser extent, postoperative changes in the L4-L5 segmental lordosis and muscle injuries. Upper adjacent segment was more affected post-fusion than the lower one. While these findings identify risk factors for adjacent segment disorders, they indicate that surgical and postoperative rehabilitation interventions should focus on the preservation/restoration of patient's normal segmental kinematics.

Modeling of human intervertebral disc annulus fibrosus with complex multi-fiber networks.

Collagen fibers within the annulus fibrosus (AF) lamellae are unidirectionally aligned with alternating orientations between adjacent layers. AF constitutive models often combine two adjacent lamellae into a single equivalent layer containing two fiber networks with a crisscross pattern. Additionally, AF models overlook the inter-lamellar matrix (ILM) as well as elastic fiber networks in between lamellae. We developed a nonhomogenous micromechanical model as well as two coarser homogenous hyperelastic and microplane models of the human AF, and compared their performances against measurements (tissue level uniaxial and biaxial tests as well as whole disc experiments) and seven published hyperelastic models. The micromechanical model had a realistic non-homogenous distribution of collagen fiber networks within each lamella and elastic fiber network in the ILM. For small matrix linear moduli (<0.2 MPa), the ILM showed substantial anisotropy (>10%) due to the elastic fiber network. However, at moduli >0.2 MPa, the effects of the elastic fiber network on differences in stress-strain responses at different directions disappeared (<10%). Variations in sample geometry and boundary conditions (due to uncertainty) markedly affected stress-strain responses of the tissue in uniaxial and biaxial tests (up to 16 times). In tissue level tests, therefore, simulations should represent testing conditions (e.g., boundary conditions, specimen geometry, preloads) as closely as possible. Stress/strain fields estimated from the single equivalent layer approach (conventional method) yielded different results from those predicted by the anatomically more accurate apparoach (i.e., layerwise). In addition, in a disc under a compressive force (symmetric loading), asymmetric stress-strain distributions were computed when using a layerwise simulation. Although all developed and selected published AF models predicted gross compression-displacement responses of the whole disc within the range of measured data, some showed excessively stiff or compliant responses under tissue-level uniaxial/biaxial tests. This study emphasizes, when constructing and validating constitutive models of AF, the importance of the proper simulation of individual lamellae as distinct layers, and testing parameters (sample geometric dimensions/loading/boundary conditions).

Comparison of different lifting analysis tools in estimating lower spinal loads - Evaluation of NIOSH criterion.

Excessive loads on the human spine is recognized as a risk factor for back injuries/pain. Various lifting analysis tools such as musculoskeletal models, regression equations and NIOSH (National Institute for Occupational Safety and Health) lifting equation (NLE) have been proposed to evaluate and mitigate associated risks during manual material handling activities. Present study aims to compare predicted spinal loads from 5 different lifting analysis tools as well as to critically evaluate the NIOSH recommended weight limit (RWL). Spinal loads were estimated under different symmetric/asymmetric lifting tasks in which hand-load mass at each task was set based on RWL from NLE. Estimated intradiscal pressures (IDPs) of various tools were also compared with in vivo measurements. We compared RWL by NLE versus our estimations of RWL calculated from our regression equations using biomechanical criteria (compression <3400 N with/without shear <1000, 1250 or 1500 N). Our regression equations followed by OpenSim, AnyBody, simple polynomial and 3DSSPP satisfactorily predicted L4-L5 IDPs. Lifting analysis tools estimated comparable spinal compression forces (mean Pearson's r = 0.80; standard deviation of relative difference = 26%) while in shear, differences were greater (mean Pearson's r = 0.68; standard deviation of relative difference = 56%). NLE estimations of RWL were conservative in comparison with our estimations for lean individuals (BMI < 25 kg/m2) when compression <3400 N and shear <1250 N were considered as the biomechanical criteria. For heavier individuals, however, NLE estimations of RWL generated spinal compression >3400 N (NIOSH biomechanical safety threshold) as well as shear >1000 N. Although RWLs estimated by NLE was body weight independent, body weight substantially altered RWLs estimated from our regression equations. For improved estimation of the risk of injury, more accurate failure criteria for spinal segments are essential.

Estimation of Trunk Muscle Forces Using a Bio-Inspired Control Strategy Implemented in a Neuro-Osteo-Ligamentous Finite Element Model of the Lumbar Spine.

Low back pain (LBP), the leading cause of disability worldwide, remains one of the most common and challenging problems in occupational musculoskeletal disorders. The effective assessment of LBP injury risk, and the design of appropriate treatment modalities and rehabilitation protocols, require accurate estimation of the mechanical spinal loads during different activities. This study aimed to: (1) develop a novel 2D beam-column finite element control-based model of the lumbar spine and compare its predictions for muscle forces and spinal loads to those resulting from a geometrically matched equilibrium-based model; (2) test, using the foregoing control-based finite element model, the validity of the follower load (FL) concept suggested in the geometrically matched model; and (3) investigate the effect of change in the magnitude of the external load on trunk muscle activation patterns. A simple 2D continuous beam-column model of the human lumbar spine, incorporating five pairs of Hill's muscle models, was developed in the frontal plane. Bio-inspired fuzzy neuro-controllers were used to maintain a laterally bent posture under five different external loading conditions. Muscle forces were assigned based on minimizing the kinematic error between target and actual postures, while imposing a penalty on muscular activation levels. As compared to the geometrically matched model, our control-based model predicted similar patterns for muscle forces, but at considerably lower values. Moreover, irrespective of the external loading conditions, a near (<3°) optimal FL on the spine was generated by the control-based predicted muscle forces. The variation of the muscle forces with the magnitude of the external load within the simulated range at the L1 level was found linear. This work presents a novel methodology, based on a bio-inspired control strategy, that can be used to estimate trunk muscle forces for various clinical and occupational applications toward shedding light on the ever-elusive LBP etiology.

Internal load-sharing in the human passive lumbar spine: Review of in vitro and finite element model studies.

Human lumbar motion segment is composed of various components with distinct contributions to its gross mechanical response. By employing experimental and computational approaches, many studies have investigated the relative role of each component as well as effects of various factors such as boundary-initial conditions, load magnitude-combination-direction, load temporal regime, preload, posture, degeneration, failures and surgical interventions on load-sharing. This paper reviews and critically discusses the relevant findings of in vitro and finite element model studies on load-sharing in healthy, aged, degenerate and damaged human lumbar motion segments. Two systematic searches were performed in PubMed (October 2018 - March 2019) using three sets of concepts ("lumbar spine", "load-sharing" and "motion segment components") followed by a complementary generic search. The segment overall response as well as the relative role of its constituents are markedly influenced by alterations in resection sequence, boundary conditions, geometry, loading characteristics (rate, magnitude, combinations and preloads), disc hydration, bone quality, posture and time (creep and cyclic). Structural transection order affects both findings and conclusions not only in force-control protocols but also in displacement-control loading regimes. Disc degeneration, endplate fracture and surgical resections significantly alter load transmission in the lumbar spine. In summary, in vitro and finite element model studies have together substantially improved our understanding of functional biomechanics (load-sharing) of human lumbar spine in normal and perturbed conditions acting as invaluable complementary tools in clinical applications.

On the modeling of human intervertebral disc annulus fibrosus: Elastic, permanent deformation and failure responses.

As a primary load-resisting component, annulus fibrosus (AF) maintains structural integrity of the entire intervertebral disc. Experiments have demonstrated that permanent deformation and damage take place in the tissue under mechanical loads. Development of an accurate model to capture the complex behaviour of AF tissue is hence crucial in disc model studies. We, therefore, aimed to develop a non-homogenous model to capture elastic, inelastic and failure responses of the AF tissue and the entire disc model under axial load. Our model estimations satisfactorily agreed with results of existing uniaxial (along fiber, circumferential and axial directions) and biaxial tissue-level tests. The model accurately predicted the failure of the tissue in various directions in uniaxial extension. Collagen fiber content, type and orientation substantially altered AF tissue responses in uni- and bi-axial tests. Although collagen fiber content and type mostly affected failure stress, fiber orientation significantly influenced the tissue failure strain. The entire L2-L3 disc model accurately replicated load-displacement as well as loading-unloading responses of the disc under compression-tension forces. Preconditioning of the disc-body unit substantially stiffened response. Poisson's ratio of both AF and nucleus considerably affected compression-displacement responses of the disc (173% increase in compression at 1.49 mm displacement when it was changed from 0.499 to 0.49999). Any AF constitutive model should be calibrated under various tissue-level loads and directions as well as the entire disc model responses since using a single tissue-level loading (e.g. uniaxial) for calibration can lead to unrealistic responses in other tests (e.g., biaxial). Special attentions should be given to the choice of Poisson's ratio and the realistic consideration of preconditioning load.

Subject-specific loads on the lumbar spine in detailed finite element models scaled geometrically and kinematic-driven by radiography images.

Traditional load-control musculoskeletal and finite element (FE) models of the spine fail to accurately predict in vivo intervertebral joint loads due mainly to the simplifications and assumptions when estimating redundant trunk muscle forces. An alternative powerful protocol that bypasses the calculation of muscle forces is to drive the detailed FE models by image-based in vivo displacements. Development of subject-specific models, however, both involves the risk of extensive radiation exposures while imaging in supine and upright postures and is time consuming in terms of the reconstruction of the vertebrae, discs, ligaments, and facets geometries. This study therefore aimed to introduce a remedy for the development of subject-specific FE models by scaling the geometry of an existing detailed FE model of the T12-S1 lumbar spine. Five subject-specific scaled models were driven by their own radiography image-based displacements in order to predict joint loads, ligament forces, facet joint forces, and disc fiber strains during relaxed upright as well as moderate flexion and extension tasks. The predicted intradiscal pressures were found in adequate agreement with in vivo data for upright, flexion, and extension tasks. There were however large intersubject variations in the estimated joint loads and facet forces.

Temporal and spatial variations of pressure within intervertebral disc nuclei.

Experimental and computational studies often presume that nuclei pulposi of non-degenerated human lumbar discs function as fluid-filled cavities with single hydrostatic pressures throughout that vary neither with time nor location and orientation. Recent simultaneous measurements of the pressure at multiple locations within disc nuclei have however shown time-dependent and nonhomogeneous pressure distributions. This combined in vitro and in silico study aims to re-examine the temporal and spatial variations of the pressure within disc nuclei with special focus on the effect of tissue hydration. After 20h of free swelling, effects of two preload magnitudes (0.06 and 0.28MPa) on nucleus pressure were investigated under 8h of constant preloads followed by 10 cycles of high-low loads each lasting 15min using 6 disc-bone bovine specimens. Changes in pressure at 3 different nucleus locations were recorded as surrogate measures of fluid flow within the discs. To identify the likely mechanisms observed in vitro, a finite element model of a human disc (L4-L5) was employed while simulating foregoing plus additional loading protocols. In vitro and computed results show a clear and substantial pressure gradient within the nucleus, especially early after the load application under higher loads and in more hydrated discs. The pressure reaches its maximum in the nucleus center reducing axially toward endplates and radially toward the nucleus-annulus interface. These cause pressure gradients that substantially diminish with time and at lower hydration levels. With time and as the pore pressure drops, the contribution of the nucleus bulk increases till it reaches equilibrium. The relative share of the annulus bulk in supporting the applied loads markedly increases not only with time but at higher loads and lower hydrations. The hydration state of the disc is hence crucial in the disc pressure distribution and internal response under various static-dynamic loads in vitro and in the replication of in vivo conditions.

Computational study of the role of fluid content and flow on the lumbar disc response in cyclic compression: Replication of in vitro and in vivo conditions.

The intervertebral disc viscoelastic response is governed primarily by its fluid content and flow. Invivo measurements demonstrate that the disc volume, fluid content, height and nucleus pressure completely recover during resting even after diurnal loading with twice longer duration (16 vs. 8 h). In view of much longer periods required for the recovery of disc height and pressure in vitro, concerns have been raised on the fluid inflow through the endplates that might be hampered by clogged blood vessels post mortem. This in silico study aimed to identify fluid-flow dependent response of discs and conditions essential to replicate in vitro and in vivo observations. An osmo-poroelastic finite element model of the human lumbar L4-L5 disc-bone unit was used. Simulating earlier in vitro experiments on bovine discs, the loading protocol started with 8 h preload at 0.06 MPa followed by 30 high/low compression loading cycles each lasting 7.5min at 0.5/0.06 MPa, respectively. Three different endplate configurations were investigated: free in- and outflow, no inflow and closed endplates with no flow. Additionally, the preload magnitude was increased from 0.06 MPa to 0.28 MPa and 0.50 MPa, or the initial nucleus hydration was reduced from 83% to 50%. For 0.06 MPa preload, the model with no inflow best matched in vitro trends. The model with free inflow increased segment height and nucleus pressure while the model with no fluid inflow resulted in a relatively small recovery in segment height and a rather constant nucleus pressure during unloading periods. Results highlight an excessive mobile fluid content as well as a restricted fluid inflow through endplates as likely causes of the discrepancies between in vivo and in vitro studies. To replicate in vivo conditions in vitro and in silico, disc hydration level should be controlled by adequate selection of preload magnitude/period and/or mobile fluid porosity.

Separate the Sheep from the Goats: Use and Limitations of Large Animal Models in Intervertebral Disc Research.

Approximately 5,168 large animals (pigs, sheep, goats, and cattle) were used for intervertebral disc research in identified studies published between 1985 and 2016. Most of the reviewed studies revealed a low scientific impact, a lack of sound justifications for the animal models, and a number of deficiencies in the documentation of the animal experimentation. The scientific community should take suitable measures to investigate the presumption that animal models have translational value in intervertebral disc research. Recommendations for future investigations are provided to improve the quality, validity, and usefulness of animal studies for intervertebral disc research. More in vivo studies are warranted to comprehensively evaluate the suitability of animal models in various applications and help place animal models as an integral, complementary part of intervertebral disc research.