A data-driven microstructure-based model for predicting circumferential behavior and failure in degenerated human annulus fibrosus.

The degeneration of the intervertebral disc annulus fibrosus poses significant challenges in understanding and predicting its mechanical behavior. In this article, we present a novel approach, enriched with detailed insights into microstructure and degeneration progression, to accurately predict the mechanics of the degenerated human annulus. Central to this framework is a fully three-dimensional continuum-based model that integrates hydration state and multiscale structural features, including proteoglycan macromolecules and interpenetrating collagen fibrillar networks across various hierarchical levels within the multi-layered lamellar/inter-lamellar soft tissue, capable of sustaining deformation-induced damage. To ensure accurate and comprehensive predictions of the degenerated annulus mechanical behavior, we establish a data-driven correlation between disc degeneration grade and individual age, which influences the composition and mechanical integrity of annulus constituents while accounting for regional variations. The methodology includes a thorough identification of age- and grade-related evolutions of model inputs, followed by a detailed quantitative evaluation of the model predictive capabilities, with a focus on circumferential behavior and failure. The model successfully replicates experimental data, accurately capturing stiffness, transverse response (Poisson's ratio), and ultimate properties across different annulus regions, while also accommodating the modulation of the age/grade relationship. The reduction rates between normal and severe degeneration align reasonably well with experimental data, with the inner region exhibiting the largest decrease in stiffness (34.63%) and no significant change observed in the outer region. Failure stress drops considerably in both regions (49.86% in the inner and 45.33% in the outer), while failure strain decreases by 36.39% in the outer and 24.74% in the inner. Our findings demonstrate that the proposed framework significantly enhances the predictive accuracy of annulus mechanics across a spectrum of degeneration levels, from normal to severely degenerated states. This approach promises improved predictive accuracy, deeper insights into disc health and injury risk, and a robust foundation for further research on the impact of degeneration on disc integrity. STATEMENT OF SIGNIFICANCE: Understanding and predicting the mechanical behavior of degenerated human annulus fibrosus remains a significant challenge due to the complex interplay of structural, biochemical, and age-related factors. This study presents a microstructure-based approach to address this challenge by integrating hydration state, detailed structural features across hierarchical scales, and deformation-induced damage and failure, alongside age-related changes and degeneration grade factors. This approach enables accurate simulations of annulus mechanics across regions, with model results thoroughly compared to available data, reinforcing its applicability in capturing degeneration effects. By capturing the intricate interactions between microstructure and mechanical behavior in degenerated discs, the model lays a strong foundation for improving clinical assessments and guiding future treatment strategies for disc-related conditions.

Comprehensive analysis of damage evolution in human annulus fibrosus: Numerical exploration of mechanical sensitivity to biological age-dependent alteration.

BACKGROUND AND OBJECTIVE: The annulus fibrosus is an essential part of the intervertebral disc, critical for its structural integrity. Mechanical deterioration in this component can lead to complete disc failure, particularly through tears development, with radial tears being the most common. These tears are often the result of both mechanical and biological factors. This study aims to numerically investigate the mechanisms of radial failure in the annulus tissue, taking into account the mechanical and age-dependent biological damage origins. A newly developed microstructure-based model was upgraded to predict damage evolution in the different annulus regions. METHODS: The study employs a computational model to predict mechanical failures in various annulus regions, using experimental data for comparison. The model incorporates age-dependent microstructural changes to evaluate the effects of biological aging on the mechanical behavior. It specifically includes a detailed analysis of the temporal changes in circumferential rigidity and failure strain of the annulus. RESULTS: The model demonstrated a strong ability to replicate the experimental responses of the different annulus regions to failure. It revealed that age-related microstructural changes significantly impact the rigidity and failure response of the annulus, particularly in the posterior regions and as well the anterior inner side. These changes increase susceptibility to rupture with aging. A correlation was also observed between the composition of collagen fibers, water content, and the annulus transversal response in both radial and axial directions. CONCLUSION: The findings challenge previous assumptions, showing that age-dependent microstructural changes have a notable effect on the annulus mechanical properties. The computational model closely aligns with experimental observations, underscoring the determinant role of oriented collagen fibers in radial failure. This study enhances the understanding of annulus failure and provides a foundation for further research on the impact of aging on disc mechanical integrity and failure.

Overloading effect on the osmo-viscoelastic and recovery behavior of the intervertebral disc.

In vitro studies investigating the effect of high physiological compressive loads on the intervertebral disc mechanics as well as on its recovery are rare. Moreover, the osmolarity effect on the disc viscoelastic behavior following an overloading is far from being studied. This study aims to determine whether a compressive loading-unloading cycle exceeding physiological limits could be detrimental to the cervical disc, and to examine the chemo-mechanical dependence of this overloading effect. Cervical functional spine units were subjected to a compressive loading-unloading cycle at a high physiological level (displacement of 2.5 mm). The overloading effect on the disc viscoelastic behavior was evaluated through two relaxation tests conducted before and after cyclic loading. Afterward, the disc was unloaded in a saline bath during a rest period, and its recovery response was assessed by a third relaxation test. The chemo-mechanical coupling in the disc response was further examined by repeating this protocol with three different saline concentrations in the external fluid bath. It was found that overloading significantly alters the disc viscoelastic response, with changes statistically dependent on osmolarity conditions. The applied hyper-physiological compressive cycle does not cause damage since the disc recovers its original viscoelastic behavior following a rest period. Osmotic loading only influences the loading-unloading response; specifically, increasing fluid osmolarity leads to a decrease in disc relaxation after the applied cycle. However, the disc recovery is not impacted by the osmolarity of the external fluid.

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

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

Surgical management of isthmic spondylolisthesis: A comparative study of postoperative outcomes between ALIF and TLIF.

INTRODUCTION: Circumferential fusion by the anterior (ALIF) or transforaminal (TLIF) approach combined with posterior instrumentation is currently used for the surgical treatment of low-grade isthmic spondylolisthesis. But few studies have compared the clinical and radiological outcomes of various interbody fusion techniques. The objective of this study was to compare the clinical and radiological results at 2 years postoperative of two fusion techniques-TLIF versus ALIF plus posterior instrumentation-for low-grade isthmic spondylolisthesis in adults. MATERIALS AND METHODS: This was an observational multicenter study done at nine French healthcare facilities specialized in spine surgery. The inclusion criteria were minimum age of 18 years, grade 1-3 isthmic spondylolisthesis, ALIF+posterior fixation (ALIF+PS) or TLIF, minimum follow-up of 2 years. Clinical and radiological evaluations were done preoperatively and at 2 years of follow-up. A lumbar CT scan was done at 1 year postoperative to evaluate fusion. RESULTS: The cohort consisted of 89 patients (50 women, 39 men) with a mean age of 47.7±12.3 (18-79) years. The patients in the ALIF groups (n=71) had a significantly longer hospital stay than those in the TLIF group (n=18): 5.7 days versus 4.6 days (p=.04). However, their medical leave from work was significantly shorter: 31.0 weeks versus 40.7 (p=.003). Lumbar pain VAS diminished faster in the ALIF groups, with a significantly larger drop than the TLIF group in the first 3 months postoperative. Only the increase in lumbar disc lordosis was larger in the ALIF group: 11.7°±12.0° versus 6.0°±11.7° (p=.036). There was a significant correlation between the increase in global lordosis and reduction in lumbar VAS at 2 years postoperative (ρ=-0.3295; p=.021). CONCLUSION: ALIF+PS provides a faster relief of postoperative low back pain than TLIF but there are no significant clinical differences between techniques at 2 years of follow-up. Despite better restoration of disc lordosis in the ALIF+PS group, there was no difference in the restoration of global lordosis. LEVEL OF EVIDENCE: III; multicenter comparative study.

Fusion and clinical outcomes of lumbar interbody fusion for low-grade isthmic spondylolisthesis.

INTRODUCTION: Low-grade isthmic spondylolisthesis (ISPL) is generally treated by circumferential fusion with interbody graft, although there is no consensus on technique. HYPOTHESIS: The various interbody fusion strategies provide satisfactory fusion rates and clinical results. METHODS: A multicenter retrospective study analyzed lumbar interbody fusion for low-grade ISPL performed between March 2016 and March 2019. Techniques comprised: circumferential fusion on a posterior or a transforaminal approach (PLIF, TLIF: n=57), combined anterior (ALIF)+posterolateral fusion (ALIF+PLF: n=60), and ALIF+percutaneous posterior fixation (ALIF+PPF: n=55). Function was assessed on a lumbar and a radicular visual analog scale (AVS-L, VAS-R), Oswestry Disability Index (ODI) and Short Form 12 (SF12). RESULTS: Among the 129 patients, 85.3% showed fusion (Lenke 1 or 2), with no significant differences between the ALIF-PLF or ALIF-PPF groups and the PLIF or TLIF groups (p=0.3). Likewise, there was no difference in fusion rates between the ALIF-PPF and ALIF-PLF subgroups (p=0.28). VAS-L (p<0.001) and VAS-R (p<0.0001), ODI (p<0.001) and SF12 physical (PCS) (p<0.01) and mental component sores (MCS) (p<0.001) all showed significant improvement at 12months. Combined approaches provided greater clinical efficacy than TLIF or PLIF for lumbar (p<0.0001) and radicular pain (p<0.05), ODI (p<0.0001) and SF12 PCS (p<0.01). At 12months, there was no clinical difference between the ALIF-PPF and ALIF-PLF subgroups. However, patents with interbody non-union (Lenke 3 or 4) had lower SF12 PCS scores (p<0.004) and VAS-L ratings (p<0.001) than Lenke 1-2 patients. CONCLUSION: Low-grade ISPL treated by circumferential arthrodesis and interbody graft showed 85.3% consolidation at 2years, with equivalent outcomes between anterior and posterior techniques. Successful fusion was associated with better clinical results. LEVEL OF EVIDENCE: IV.

Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival.

Molecular heterogeneity is a key feature of glioblastoma that impedes patient stratification and leads to large discrepancies in mean patient survival. Here, we analyze a cohort of 96 glioblastoma patients with survival ranging from a few months to over 4 years. 46 tumors are analyzed by mass spectrometry-based spatially-resolved proteomics guided by mass spectrometry imaging. Integration of protein expression and clinical information highlights three molecular groups associated with immune, neurogenesis, and tumorigenesis signatures with high intra-tumoral heterogeneity. Furthermore, a set of proteins originating from reference and alternative ORFs is found to be statistically significant based on patient survival times. Among these proteins, a 5-protein signature is associated with survival. The expression of these 5 proteins is validated by immunofluorescence on an additional cohort of 50 patients. Overall, our work characterizes distinct molecular regions within glioblastoma tissues based on protein expression, which may help guide glioblastoma prognosis and improve current glioblastoma classification.

Modeling multiaxial damage regional variation in human annulus fibrosus.

In the present article, a fully three-dimensional human annulus fibrosus model is developed by considering the regional variation of the complex structural organization of collagen network at different scales to predict the regional anisotropic multiaxial damage of the intervertebral disc. The model parameters are identified using experimental data considering as elementary structural unit, the single annulus lamellae stretched till failure along the micro-sized collagen fibers. The multi-layered lamellar/inter-lamellar annulus model is constructed by considering the effective interactions between adjacent layers and the chemical-induced volumetric strain. The regional dependent model predictions are analyzed under various loading modes and compared to experimental data when available. The stretching along the circumferential and radial directions till failure serves to check the predictive capacities of the annulus model. Model results under simple shear, biaxial stretching and plane-strain compression are further presented and discussed. Finally, a full disc model is constructed using the regional annulus model and simulations are presented to assess the most likely failed areas under disc axial compression. STATEMENT OF SIGNIFICANCE: The damage in annulus soft tissues is a complex multiscale phenomenon due to a complex structural arrangement of collagen network at different scales of hierarchical organization. A fully three-dimensional constitutive representation that considers the regional variation of the structural complexity to estimate annulus multiaxial mechanics till failure has not yet been developed. Here, a model is developed to predict deformation-induced damage and failure of annulus under multiaxial loading histories considering as time-dependent physical process both chemical-induced volumetric effects and damage accumulation. After model identification using single lamellae extracted from different disc regions, the model predictability is verified for various multiaxial elementary loading modes representative of the spine movement. The heterogeneous mechanics of a full human disc model is finally presented.

A microstructure-based model for a full lamellar-interlamellar displacement and shear strain mapping inside human intervertebral disc core.

The determinant role of the annulus fibrosus interlamellar zones in the intervertebral disc transversal and volumetric responses and hence on their corresponding three-dimensional conducts have been only revealed and appreciated recently. Their consideration in disc modeling strategies has been proven to be essential for the reproduction of correct local strain and displacement fields inside the disc especially in the unconstrained directions of the disc. In addition, these zones are known to be the starting areas of annulus fibrosus circumferential tears and disc delamination failure mode, which is often judged as one of the most dangerous disc failure modes that could evolve with time leading to disc hernia. For this latter reason, the main goal of the current contribution is to incorporate physically for the first time, the interlamellar zones, at the scale of a complete human lumbar intervertebral disc, in order to allow a correct local vision and replication of the different lamellar-interlamellar interactions and an identification of the interlamellar critical zones. By means of a fully tridimensional chemo-viscoelastic constitutive model, which we implemented into a finite element code, the physical, mechanical and chemical contribution of the interlamellar zones is added to the disc. The chemical-induced volumetric response is accounted by the model for both the interlamellar zones and the lamellae using experimentally-based fluid kinetics. Computational simulations are performed and critically discussed upon different simple and complex physiological movements. The disc core and the interlamellar zones are numerically accessed, allowing the observation of the displacement and shear strain fields that are compared to direct MRI experiments from the literature. Important conclusions about the correct lamellar-interlamellar-nucleus interactions are provided thanks to the developed model. The critical interlamellar spots with the highest delamination potentials are defined, analyzed and related to the local kinetics and microstructure.

Diagnosis of reoperated cervical non-union: Multicenter retrospective study about 45 patients.

INTRODUCTION: Non-union is one of the main complications of single- or multi-level cervical spine fusion, considerably impairing functional results. The aim of this study was to evaluate the respective contributions of imaging examinations in the diagnostic process, the challenge being to avoid inappropriate surgery and unnecessary complementary examinations. MATERIAL AND METHOD: A retrospective multicenter study included all patients managed for cervical spine non-union between 2008 and 2018. We evaluated the imaging examinations performed on each patient and determined signs of non-union in each image. RESULTS: The study included 45 patients in 4 centers: 55% female; mean age, of 48±8.0 years; 57% smokers. Systematic static radiography showed signs of non-union in 55% of cases. Dynamic X-ray was performed in 34% of patients, and showed hypermobility of the level in 80% of cases. CT supported diagnosis of non-union in 97% of cases, and MRI in 48%. SPECT-CT was positive in all cases of non-union. DISCUSSION: Dynamic X-ray is rarely prescribed, but frequently provided an objective measure of hypermobility of the level in non-union, justifying first-line use. Millimetric-slice CT was reliable for diagnosis. MRI is relevant only once diagnosis has been made, as part of preoperative work-up. Nuclear imaging can be useful in order to solve doubtful cases. CONCLUSION: In suspected cervical spine non-union, we recommend dynamic X-rays (flexion/extension) and CT-scan as first-line diagnosis examinations. LEVEL OF EVIDENCE: IV.

A microstructure-based modeling approach to assess aging-sensitive mechanics of human intervertebral disc.

BACKGROUND AND OBJECTIVE: The human body soft tissues are hierarchic structures interacting in a complex manner with the surrounding biochemical environment. The loss of soft tissues functionality with age leads to more vulnerability regarding to the external mechanical loadings and increases the risk of injuries. As a main example of the human body soft tissues, the intervertebral disc mechanical response evolution with age is explored. Although the age-dependence of the intervertebral disc microstructure is a well-known feature, no noticeable age effect on the disc stiffness is evidenced in the in-vitro experimental studies of the literature. So, if the disc intrinsic mechanics remains constant, how to explain the correlation of disc degeneration and disc functionality loss with age. METHODS: A microstructure-based modeling approach was developed to assess in-silico the aging-sensitive mechanics of human intervertebral disc. The model considers the relationship between stress/volumetric macro-response and microstructure along with effective age effects acting at the lamellar and multi-lamellar scales. The stress-stretch and transversal responses of the different disc regions were computed for various age groups (13-18, 36, 58, 69 and 82 years old) and their evolution with age was studied. RESULTS: While matching with in-vitro experimental data, the predicted stiffness was found to increase while passing from adolescent young discs to mature older discs and then to remain almost constant for the rest of life. Important age-related changes in the disc transversal behavior were also predicted affecting the flexibility of the disc, changing its volumetric behavior, and modifying its dimensions. CONCLUSION: The developed approach was found able to bring new conclusions about age-dependent mechanical properties including regional dependency. The disc mechanics in terms of rigidity, radial and axial transversal responses were found to alter going from adolescent to middle age where the disc reaches a certain maturity. After reaching maturity, the mechanical properties undergo very slight changes until becoming almost constant with age.

Relevance of a novel external dynamic distraction device for treating back pain.

Low back pain is a common, expensive, and disabling condition in industrialized countries. There is still no consensus for its ideal management. Believing in the beneficial effect of traction, we developed a novel external dynamic distraction device. The purpose of this work was to demonstrate that external distraction allows limiting the pressure exerted in standing-up position on the lower intervertebral discs. Numerical and cadaveric studies were used as complementary approaches. Firstly, we implemented the device into a numerical model of a validated musculoskeletal software (Anybody Modeling System) and we calculated the lower disc pressure while traction forces were applied. Secondly, we performed an anatomical study using a non-formalin preserved cadaver placed in a sitting position. A pressure sensor was placed in the lower discs under fluoroscopic control through a Jamshidi needle. The intradiscal pressure was then measured continuously at rest while applying a traction force of 200 N. Both numerical and cadaveric studies demonstrated a decrease in intradiscal pressures after applying a traction force with the external device. Using the numerical model, we showed that tensile forces below 500 N in total were sufficient. The application of higher forces seems useless and potentially deleterious. External dynamic distraction device is able to significantly decrease the intradiscal pressure in a sitting or standing position. However, the therapeutic effects need to be proven using clinical studies.

Interlamellar matrix governs human annulus fibrosus multiaxial behavior.

Establishing accurate structure-property relationships for intervertebral disc annulus fibrosus tissue is a fundamental task for a reliable computer simulation of the human spine but needs excessive theoretical-numerical-experimental works. The difficulty emanates from multiaxiality and anisotropy of the tissue response along with regional dependency of a complex hierarchic structure interacting with the surrounding environment. We present a new and simple hybrid microstructure-based experimental/modeling strategy allowing adaptation of animal disc model to human one. The trans-species strategy requires solely the basic knowledge of the uniaxial circumferential response of two different animal disc regions to predict the multiaxial response of any human disc region. This work demonstrates for the first time the determining role of the interlamellar matrix connecting the fibers-reinforced lamellae in the disc multiaxial response. Our approach shows encouraging multiaxial predictive capabilities making it a promising tool for human spine long-term prediction.

How Osmoviscoelastic Coupling Affects Recovery of Cyclically Compressed Intervertebral Disc.

STUDY DESIGN: Osmoviscoelastic behavior of cyclically loaded cervical intervertebral disc. OBJECTIVE: The aim of this study was to evaluate in vitro the effects of physiologic compressive cyclic loading on the viscoelastic properties of cervical intervertebral disc and, examine how the osmoviscoelastic coupling affects time-dependent recovery of these properties following a long period of unloading. SUMMARY OF BACKGROUND DATA: The human neck supports repetitive loadings during daily activities and recovery of disc mechanics is essential for normal mechanical function. However, the response of cervical intervertebral disc to cyclic loading is still not very well defined. Moreover, how loading history conditions could affect the time-dependent recovery is still unclear. METHODS: Ten thousand cycles of compressive loading, with different magnitudes and saline concentrations of the surrounding fluid bath, are applied to 8 motion segments (composed by 2 adjacent vertebrae and the intervening disc) extracted from the cervical spines of mature sheep. Subsequently, specimens are hydrated during 18 hours of unloading. The viscoelastic disc responses, after cyclic loading and recovery phase, are characterized by relaxation tests. RESULTS: Viscoelastic behaviors are significantly altered following large number of cyclic loads. Moreover, after 18-hour recovery period in saline solution at reference concentration (0.15 mol/L), relaxation behaviors were fully restored. Nonetheless, full recovery is not obtained whether the concentration of the surrounding fluid, that is, hypo-, iso-, or hyper-osmotic conditions. CONCLUSION: Cyclic loading effects and full recovery of viscoelastic behavior after hydration at iso-osmotic condition (0.15 mol/L) are governed by osmotic attraction of fluid content in the disc due to imbalance between the external load and the swelling pressure of the disc. After removal of the load, the disc recovers its viscoelastic properties following period of rest. Nevertheless, the viscoelastic recovery is a chemically activated process and its dependency on saline concentration is governed by fluid flow due to imbalance of ions between the disc tissues and the surrounding fluid. LEVEL OF EVIDENCE: 3.

Osmo-inelastic response of the intervertebral disc annulus fibrosus tissue.

The aim of this article is to provide some insights on the osmo-inelastic response under stretching of annulus fibrosus of the intervertebral disc. Circumferentially oriented specimens of square cross section, extracted from different regions of bovine cervical discs (ventral-lateral and dorsal-lateral), are tested under different strain-rates and saline concentrations within normal range of strains. An accurate optical strain measuring technique, based upon digital image correlation, is used in order to determine the full-field displacements in the lamellae and fibers planes of the layered soft tissue. Annulus stress-stretch relationships are measured along with full-field transversal strains in the two planes. The mechanical response is found hysteretic, rate-dependent and osmolarity-dependent with a Poisson's ratio higher than 0.5 in the fibers plane and negative (auxeticity) in the lamellae plane. While the stiffness presents a regional-dependency due to variations in collagen fibers content/orientation, the strain-rate sensitivity of the response is found independent on the region. A significant osmotic effect is found on both the auxetic response in the lamellae plane and the stiffness rate-sensitivity. These local experimental observations will result in more accurate chemo-mechanical modeling of the disc annulus and a clearer multi-scale understanding of the disc intervertebral function.

French Spine Surgery Society guidelines for management of spinal surgeries during COVID-19 pandemic.

Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in China, various measures have been adopted in order to attenuate the impact of the virus on the population. With regard to spine surgery, French physicians are devoted to take place in the national plan against COVID-19, the French Spine Surgery Society therefore decided to elaborate specific guidelines for management of spinal disorders during COVID-19 pandemic in order to prioritize management of patients. A three levels stratification was elaborated with Level I: Urgent surgical indications, Level II: Surgical indications associated to a potential loss of chance for the patient and Level III: Non-urgent surgical indications. We also report French experience in a COVID-19 cluster region illustrated by two clinical cases. We hope that the guidelines formulated by the French Spine Surgery Society and the experience of spine surgeons from a cluster region will be helpful in order optimizing the management of patients with urgent spinal conditions during the pandemic.

How pre-strain affects the chemo-torsional response of the intervertebral disc.

BACKGROUND: The role of the axial pre-strain on the torsional response of the intervertebral disc remains largely undefined. Moreover, the chemo-mechanical interactions in disc tissues are still unclear and corresponding data are rare in the literature. The paper deals with an in-vitro study of the pre-strain effect on the chemical sensitivity of the disc torsional response. METHODS: Fifteen non-frozen 'motion segments' (two vertebrae and the intervening soft tissues) were extracted from the cervical spines of mature sheep. The motion segments were loaded in torsion at various saline concentrations and axial pre-strain levels in order to modulate the intradiscal pressure. After preconditioning with successive low-strain compressions at a magnitude of 0.1 mm (10 cycles at 0.05 mm/s), the motion segment was subjected to a cyclic torsion until a twisting level of 2 deg. at 0.05 deg./s while a constant axial pre-strain (in compression or in tension) is maintained, the saline concentration of the surrounding fluid bath being changed from hypo-osmotic condition to hyper-osmotic condition. FINDINGS: Analysis of variance shows that the saline concentration influences the torsional response only when the motion segments are pre-compressed (p < .001) with significant differences between hypo-osmotic condition and hyper-osmotic condition. INTERPRETATION: The combination of a compressive pre-strain with twisting amplifies the nucleus hydrostatic pressure on the annulus and the annulus collagen fibers tensions. The proteoglycans density increases with the compressive pre-strain and leads to higher chemical imbalances, which would explain the increase in chemical sensitivity of the disc torsional response.

Interlamellar-induced time-dependent response of intervertebral disc annulus: A microstructure-based chemo-viscoelastic model.

The annulus fibrosus of the intervertebral disc exhibits an unusual transversal behavior for which a constitutive representation that considers as well regional effect, chemical sensitivity and time-dependency has not yet been developed, and it is hence the aim of the present contribution. A physically-based model is proposed by introducing a free energy function that takes into account the actual disc annulus structure in relation with the surrounding biochemical environment. The response is assumed to be dominated by the viscoelastic contribution of the extracellular matrix, the elastic contribution of the oriented collagen fibers and the osmo-induced volumetric contribution of the internal fluid content variation. The regional dependence of the disc annulus response due to variation in fibers content/orientation allows a micromechanical treatment of the soft tissue. A finite element model of the annulus specimen is designed while taking into consideration the 'interlamellar' ground substance zone between lamellae of the layered soft tissue. The kinetics is designed using full-field strain measurements performed on specimens extracted from two disc annulus regions and tested under different osmotic conditions. The time-dependency of the tissue response is reported on stress-free volumetric changes, on hysteretic stress and transversal strains during quasi-static stretching at different strain-rates and on their temporal changes during an interrupted stretching. Considering the effective contributions of the internal fluid transfer and the extracellular matrix viscosity, the microstructure-based chemo-mechanical model is found able to successfully reproduce the significant features of the macro-response and the unusual transversal behavior including the strong regional dependency from inner to outer parts of the disc: Poisson's ratio lesser than 0 (auxetic) in lamellae plane, higher than 0.5 in fibers plane, and their temporal changes towards usual values (between 0 and 0.5) at chemo-mechanical equilibrium. The underlying time-dependent mechanisms occurring in the tissue are analyzed via the local numerical fields and important insights about the effective role of the interlamellar zone are revealed for the different disc localizations. STATEMENT OF SIGNIFICANCE: The structural complexity of the annulus fibrosus has only been appreciated through recent experimental contributions and a constitutive representation that considers as well regional effect, chemical sensitivity and time-dependency of the unusual transversal behavior has not yet been developed. Here, a microstructure-based chemo-viscoelastic model is developed to highlight the interlamellar-induced time-dependent response by means of a two-scale strategy. The model provides important insights about the origin of the time-dependent phenomena in disc annulus along with regional dependency, essential for understanding disc functionality.

A chemo-mechanical model for osmo-inelastic effects in the annulus fibrosus.

The annulus fibrosus exhibits complex osmotic and inelastic effects responsible for unusual transversal behavior with a Poisson's ratio higher than 0.5 in fibers plane and negative (i.e., auxetic) in lamellae plane. In this paper, we present a new chemo-mechanical approach for the intrinsic osmo-inelastic response of the annulus fibrosus in relation to the microstructure of the layered reinforced soft tissue, the biochemical environment and the mechanical loading conditions. The constitutive model introduces the coupling between the deformation-induced inelastic stress in the tangled extracellular matrix and the stress-free swelling due to internal fluid content variation by osmosis. The proposed formulation is implemented into a finite element code, and numerical simulations on annulus specimens, including explicitly lamellae and interlamellar zones, are presented. To illustrate the capability of the approach to capture experimental observations quantitatively, the simulated results are compared to experimental results obtained by monitoring the full-field strain in annulus specimens using digital image correlation method. Some material constants are found by matching the free swelling in a water bath with different salt concentrations, and others are found by matching tensile results in terms of loading-unloading stress-stretch curve and transversal behavior. The constitutive model is found to successfully capture the variations in osmolarity and strain-rate conditions (both statistically significant, p < 0.05) on the intrinsic response and the auxeticity. The stress/strain patterns in the model simulation provide valuable insights into the role of the interlamellar zone in the osmo-inelastic mechanisms.