Annulus Fibrosus Research Articles

Mechanical Characterization of Non-degraded Porcine Annulus Fibrosus Material Properties.

Porcine cervical spines are commonly used as a surrogate for human lumbar spines due to their similar anatomic and mechanical characteristics. Despite their use in spinal biomechanics research, porcine annulus fibrosus (AF) yield and ultimate properties have not been fully evaluated. This study sought to provide a novel dataset of elastic, yield, and ultimate properties of the porcine AF loaded in the circumferential direction. AF specimens were dissected from porcine cervical spines (C3/C4-C6/C7) oriented in the circumferential direction. Specimens were uniformly hydrated before being quasi-statically distracted to failure. Linear modulus, yield stress and strain, ultimate stress and strain, and ultimate strain energy density were calculated. Differences between spinal levels, circumferential regions, and radial regions were identified using multifactor ANOVA tests. AF specimens showed a regionally dependent response between outer and inner radial regions, but not between spinal level and circumferential region. The outer region was significantly stronger and stiffer than the inner regions. In both outer and inner tissue, mechanical yield occurred at approximately 80% of their ultimate properties. This study generated a novel dataset of elastic, yield, and ultimate properties of the porcine AF. The data can be used in future research that requires a robust database of healthy, non-degenerated AF mechanical properties, such as the development of future finite-element models.

Biomechanics of the intervertebral disc : Consequences of degenerative changes

The intervertebral disc represents the flexible connection between two adjacent vertebral bodies. Intervertebral discs, therefore, give the spine its enormous range of motion. At the same time, intervertebral discs distribute the load evenly over the bony vertebral bodies to ensure load transfer from the upper body to the pelvis, provide sufficient stability, and absorb shocks during everyday movements as well as under extreme loads. The two tissue regions of the intervertebral disc, the central fluid-rich core (nucleus pulposus) and the lamellae of the outer fibrous ring (annulus fibrosus) experience different stresses under load and movement. This article summarizes current knowledge on the biomechanical properties of the intervertebral disc and explains how these are altered by degeneration and which surgical treatment options for degenerated and herniated discs are advisable from abiomechanical perspective.

Intervertebral disc deformation in the lower lumbar spine during object lifting measured in vivo using indwelling bone pins

Object lifting is often categorized into squat and stoop techniques, with the former believed to protect the back by maintaining a neutral spine, and the latter considered harmful due to spinal flexion. Despite the widespread promotion of these beliefs, there is no evidence to support such dichotomy, as spinal flexion is not conclusively linked to low back pain. This study aimed to investigate intervertebral disc deformation in the lower lumbar spine during squat and stoop lifting using indwelling bone pins. Five healthy males underwent insertion of Kirschner wires into the L3, L4, and L5 spinous processes, followed by biomechanical data collection using magnetic and optical tracking systems during upright standing, isolated flexion/extension, and object lifting with both squat and stoop techniques. Except for one subject, stoop lifting resulted in up to 90 % greater disc wedging compared to squat lifting, with a significant difference at L4/L5 (p = 0.042). The anterior annulus fibrosus experienced 10 % to 40 % more compression during stoop lifting, but no significant differences were found in posterior annulus fibrosus expansion between techniques. Lever arms were about 35 % longer during stoop compared to squat lifting. These results indicate that even though stoop lifting generally led to greater disc deformation, significant deformation was also observed during squat lifting, challenging the notion of maintaining a neutral spine with this technique. Moreover, the considerable variability observed among participants raises concerns about the suitability of current one-size-fits-all lifting guidelines.

Does the high-intensity zone of lumbar intervertebral disc at magnetic resonance imaging have diagnostic value for discogenic low back pain? A meta-analysis

ObjectiveThe correlation between high-intensity zone (HIZ) of lumbar disc magnetic resonance imaging (MRI) and discogenic low back pain (DLBP) is currently controversial, this study aimed to systematically evaluate the correlation between HIZ of lumbar disc MRI and positive discography, as well as its diagnostic value for DLBP.MethodDatabases were searched to include research literature on high intensity zone (HIZ) related to discography and DLBP diagnosis. HIZ is a separate small, confined area of high signal located at the posterior border of the annulus fibrosus on MRI T2-weighted images of the lumbar spine, which is separated from the nucleus pulposus but has a higher signal than the nucleus pulposus. Studies on the correlation of HIZ with discography and DLBP diagnosis were searched in the Pubmed, EMBASE, Cochrane Central, Science Direct, China Knowledge Network, Wanfang Database, and China Biomedical Literature Databases, Scopus from January 1992 to June 2024. The outcomes were diagnostic values of HIZ for DLBP. The risk assessment was performed by Deeks’ funnel methods in the Stata 17.0 software after 2 investigators independently screened the literature, extracted information and evaluated the risk of bias of the included studies.ResultsA total of 25 studies including 5889 patients were included. meta-analysis showed that the sensitivity of HIZ for the diagnosis of DLBP was (0.49, 95% CI [0.37,0.61]) and specificity was (0.89, 95% CI [0.85,0.93]); the positive likelihood ratio was (4.52, 95% CI [3.28,6.25]) and the negative likelihood ratio was (0.58, 95% CI [0.46,0.71]). The diagnostic ratio was (7.87, 95% CI [5.05,12.26]).ConclusionThe available evidence suggests that HIZ has acceptable sensitivity and high specificity in the diagnosis of DLBP. Due to the limitation of the number and quality of included studies, the above conclusions need to be validated by more high-quality studies.

From structure to therapy: the critical influence of cartilaginous endplates and microvascular network on intervertebral disc degeneration.

The intervertebral disc (IVD) is the largest avascular structure in the human body. The cartilaginous endplate (CEP) is a layer of translucent cartilage located at the upper and lower edges of the vertebral bodies. On one hand, CEPs endure pressure from within the IVD and the tensile and shear forces of the annulus fibrosus, promoting uniform distribution of compressive loads on the vertebral bodies. On the other hand, microvascular diffusion channels within the CEP serve as the primary routes for nutrient supply to the IVD and the transport of metabolic waste. Degenerated CEP, characterized by increased stiffness, decreased permeability, and reduced water content, impairs substance transport and mechanical response within the IVD, ultimately leading to intervertebral disc degeneration (IDD). Insufficient nutrition of the IVD has long been considered the initiating factor of IDD, with CEP degeneration regarded as an early contributing factor. Additionally, CEP degeneration is frequently accompanied by Modic changes, which are common manifestations in the progression of IDD. Therefore, this paper comprehensively reviews the structure and physiological functions of CEP and its role in the cascade of IDD, exploring the intrinsic relationship between CEP degeneration and Modic changes from various perspectives. Furthermore, we summarize recent potential therapeutic approaches targeting CEP to delay IDD, offering new insights into the pathological mechanisms and regenerative repair strategies for IDD.

Approaches to Managing Herniated Disc Surgical vs. Conservative Treatment

Introduction Disc herniation is a displacement of an intervertebral disc, most often caused by degeneration of its outer layer, the annulus fibrosus. This condition can cause various symptoms such as numbness, pain, muscle weakness or lose of sensation. While many patients can be successfully treated with non-surgical methods, some of them some require surgical intervention. Aim of study The objective of this study is to evaluate both surgical and non-surgical treatment methods for herniated disc and seeks to introduce doctors and patients to the advantages and disadvantages associated with them. State of Knowledge Disk herniation occurs when disk material prolapses beyond intervertebral disk’s space. The symptoms may arise when displaced material start to compress major structures located nearby, such as spinal nerves. The most common causes include age-related degeneration, repetitive movements, obesity, trauma or genetic predisposition. Summary (Conclusion) Disk herniation can be managed with various non-surgical and surgical methods. Conservative treatment should be considered as first line treatment showing high success rate for mild to moderate cases in long term relief and preventing recurrence of symptoms. Surgical options offer better short-term relief for sever and more advanced cases but carry greater risks of side effects and involve longer recovery time. Best approach should be carefully selected based on the severity of symptoms and patient needs.

Fiber‐Dependent 3D Anisotropic Stiffness‐Tunable Biomimetic Intervertebral Disc via Multi‐Material Additive Manufacturing

AbstractLumbar intervertebral disc degeneration is a global musculoskeletal disorder. Total disc replacement is an effective treatment for symptomatic degeneration unresponsive to conservative care. However, current artificial discs, with their joint‐like structural design and homogeneous materials, fail to replicate the 3D anisotropic stiffness of natural discs. Inspired by the intricate structure and material gradient of the natural disc, a biomimetic intervertebral disc is designed and fabricated using multi‐material additive manufacturing. The biomimetic disc exhibits 3D anisotropic stiffness similar to natural discs. By adjusting the hardness, diameter, and arrangement of fibers in annulus fibrosus, the biomimetic disc closely matches the 3D anisotropic stiffness of the natural lumbar disc, exceeding 90% similarity and outperforming existing artificial discs. This highlights the crucial role of fiber properties in disc stiffness regulation and enhances the understanding of biomechanical functions of structures and materials in the annulus fibrosus of human discs. These insights may inspire high‐performance artificial disc designs.

Development of a microfluidic system with a bearing micropump for applying fluid shear force in an intervertebral disc degeneration model involving mechanical stimulation

Background: The intervertebral disc (IVD) functions as a shock absorber with viscoelastic tissues, including the gelatinous nucleus pulposus and the collagenous annulus fibrosus (AF). External mechanical loading influences IVD homeostasis but can cause damage and inflammatory reactions, contributing to disc degeneration. There is a lack of in vitro platforms for modeling IVD disease with mechanical stimulation.Methods: This study aimed to create a mechanical stimulation-based model by subjecting AF cells to shear stress using a micropump system. A micropump platform was used to measure pulsation, flow rate, and shear stress. AF cells were exposed to fluid shear stress of 0.5 and 1 dyne/cm², and morphological changes, cytotoxicity, and cell viability were analyzed through a live/dead assay. Perimeter, area, diameter, and elongation were assessed using live cell imaging and imaging analysis software.Results: The micropump platform exhibited optimal rotor characteristics for uniform pulsation and shear stress. Fluid shear stress at 0.5 dyne/cm² showed no significant difference from the control group, while 1 dyne/cm² reduced cell adhesion and survival. Comparing the 0.5 dyne/cm² shear stress group and interleukin-1β group to the control, significant decreases in perimeter, area, and diameter were observed.Conclusion: The study successfully developed a micro-peristaltic pump platform for applying fluid shear stress to cells, identifying an optimal rotor for uniform stress application. The platform effectively modeled IVD disease, revealing reduced cell adhesion and survival under specific shear stress conditions. This platform has potential promise for discovering biomarkers and exploring cellular responsiveness to external stimuli.

Clinical efficacy of single-channel percutaneous endoscopic nucleotomy with annulus fibrosus suturing for lumbar disc herniation: A retrospective study.

This retrospective study aimed to investigate the clinical efficacy of single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing for treating lumbar disc herniation (LDH). The study included 86 patients with LDH treated in our spinal department from August 2020 to January 2022. The suture group consisted of 26 males and 18 females, while the control group (nucleotomy alone) included 25 males and 17 females. All patients were followed for at least 1 year, with follow-up points at 3 days, 3 months, and 12 months postoperatively. Various clinical and radiological indicators were used to evaluate and compare the efficacy and safety of the 2 procedures. No statistically significant differences were observed in age, sex, BMI, surgical segments, degree of disc degeneration, or postoperative length of hospital stay. However, the suture group had a longer operative time (63.28 ± 4.17 minutes vs 54.71 ± 4.89 minutes, t = 8.759, P < .05). At 12 months postoperatively, neither group showed aggravated disc degeneration. There was also no significant difference in excellent rates between the 2 groups (95.45% vs 92.86%, X2=0.265, P = .607). However, the suture group had a lower intervertebral disc height loss rate compared to the control group (22.3% ± 4.6% vs 29.8% ± 6.2%, X2=6.390, P < .001). In conclusion, single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing is a safe and reliable treatment for LDH. It effectively reduces the recurrence rate, slows disc degeneration and loss of disc height, and achieves excellent early outcomes.

Platelet Rich Plasma in the Management of Recurrent Lumbar Disc Surgery; A Study of Ten Cases

Low back pain (LBP) is a very common entity, now regarded as the first cause of disability worldwide. Intervertebral disc (IVD) degeneration leads to posterior rupture annulus fibrosus (AF) with extrusion of Central Nucleus pulposus (NP) through the injured area which has little potential to repair as it has no blood supply and causes mechanical pressure and inflammatory changes in the nerve root causing LBP. Autologous platelet rich plasma (PRP) contain concentrate blood that contain a natural concentration of autologous growth factors and cytokines and currently widely used in the clinical setting for tissue regeneration and repair. PRP had great potential to stimulate cell proliferation and metabolic activity of IVD effectively restoring structural change, improving matrix integrity, IVD regeneration, reducing discogenic back pain. Our Study of 10 cases, where repeat or re-exploration surgery (after primary PLID Surgery, fenestration and discectomy) was done, where removal of recurrent disc 5, release of epidural fibrosis and perineural scarring 4 and surgical debridement for discitis 1 was done. In addition, PRP was given in the disc space &amp; around the nerve root which provides lots of growth factor, cytokines which helps in disc regeneration and prevent adhesion &amp; fibrosis. These dual actions enhance symptomatic recovery of all cases. Large scale studies may be required to confirm the clinical evidence of PRP for the treatment of discogenic LBP Bang. J Neurosurgery 2024; 13(2): 70-74

Inactivation of Tnf-α/Tnfr signaling attenuates progression of intervertebral disc degeneration in mice.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), worsened by chronic inflammatory processes associated with aging. Tumor necrosis factor alpha (Tnf-α) and its receptors, Tnf receptor type 1 (Tnfr1) and Tnf receptor type 2 (Tnfr2), are upregulated in IVDD. However, its pathologic mechanisms remain poorly defined. To investigate the role of Tnfr in IVDD, we generated global Tnfr1/2 double knockout (KO) mice and age-matched control C57BL/6 male mice, and analyzed intervertebral disc (IVD)-related phenotypes of both genotypes under physiological conditions, aging, and lumbar spine instability (LSI) model through histological and immunofluorescence analyses and μCT imaging. Expression levels of key extracellular matrix (ECM) proteins in aged and LSI mice, especially markers of cell proliferation and apoptosis, were evaluated in aged (21-month-old) mice. At 4 months, KO and control mice showed no marked differences of IVDD-related parameters. However, at 21 months of age, the loss of Tnfr expression significantly alleviated IVDD-like phenotypes, including a significant increase in height of the nucleus pulposus (NPs) and reductions of endplates (EPs) porosity and histopathological scores, when compared to controls. Tnfr deficiency promoted anabolic metabolism of the ECM proteins and suppressed ECM catabolism. Tnfr loss largely inhibited hypertrophic differentiation, and, in the meantime, suppressed cell apoptosis and cellular senescence in the annulus fibrosis, NP, and EP tissues without affecting cell proliferation. Similar results were observed in the LSI model, where Tnfr deficiency significantly alleviated IVDD and enhanced ECM anabolic metabolism while suppressing catabolism. The deletion of Tnfr mitigates age-related and LSI-induced IVDD, as evidenced by preserved IVD structure, and improved ECM integrity. These findings suggest a crucial role of Tnf-α/Tnfr signaling in IVDD pathogenesis in mice. Targeting this pathway may be a novel strategy for IVDD prevention and treatment.

3D bioprinting of an intervertebral disc tissue analogue with a highly aligned annulus fibrosus via suspended layer additive manufacture.

Intervertebral disc (IVD) function is achieved through integration of its two component regions: the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is soft (0.3-5 kPa), gelatinous and populated by spherical NP cells in a polysaccharide-rich extracellular matrix (ECM). The AF is much stiffer (~100 kPa) and contains layers of elongated AF cells in an aligned, fibrous ECM. Degeneration of the disc is a common problem with age being a major risk factor. Progression of IVD degeneration leads to chronic pain and can result in permanent disability. The development of therapeutic solutions for IVD degeneration is impaired by a lack of in vitro models of the disc that are capable of replicating the fundamental structure and biology of the tissue. This study aims to investigate if a newly developed suspended hydrogel bioprinting system (termed SLAM) could be employed to fabricate IVD analogues with integrated structural and compositional features similar to native tissue. Bioprinted IVD analogues were fabricated to recapitulate structural, morphological and biological components present in the native tissue. The constructs replicated key structural components of native tissue with the presence of a central, polysaccharide-rich NP surrounded by organised, aligned collagen fibres in the AF. Cell tracking, actin and matrix staining demonstrated that embedded NP and AF cells exhibited morphologies and phenotypes analogous to what is observed in vivo with elongated, aligned AF cells and spherical NP cells that deposited HA into the surrounding environment. Critically, it was also observed that the NP and AF regions contained a defined cellular and material interface and segregated regions of the two cell types, thus mimicking the highly regulated structure of the IVD.

Discogenic chronic low back pain management: intradiscal radiofrequency biacuplasty versus conservative treatment

BackgroundThis prospective bicentric study aims to evaluate and compare the efficacy of intradiscal radiofrequency biacuplasty (IDB) versus conservative management (CM) in treating chronic discogenic low back pain (CDLBP).MethodsForty-four patients with CDLBP were randomly assigned to either the biacuplasty group or the conservative management group. The biacuplasty group received treatment with two radiofrequency (RF) needles, positioned bilaterally on the annulus fibrosus under fluoroscopic guidance and local anaesthesia, to administer bipolar RF. Patients were monitored for 6 months, with the allowance of pain medication as needed. In the conservative management group, patients who continued to experience low back pain after three months were permitted to switch to the biacuplasty group. The study was conducted over two years, starting on July 1, 2020.ResultsThe studied groups had comparable age and gender distributions, with no significant difference in BMI. The Oswestry Disability Index (ODI) was assessed at baseline, 1 month, 3 months, and 6 months. At baseline, no significant difference was observed between the groups (p = 0.263). However, at the 1-month, 3-month, and 6-month follow-up, the biacuplasty group exhibited significantly lower ODI scores compared to the conservative management group (all p < 0.001), indicating that biacuplasty was more effective in reducing disability caused by chronic low back pain.ConclusionsIntradiscal radiofrequency biacuplasty is a minimally invasive interventional technique that has proven effective for patients with CDLBP who do not respond to conservative management.

Discogenic Low Back Pain: Anatomic and Pathophysiologic Characterization, Clinical Evaluation, Biomarkers, AI, and Treatment Options.

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes.

Incidental findings on MRI for the evaluation of endometriosis: prevalence and clinical significance.

This study aimed to analyze the prevalence and clinical significance of incidental findings on MRI for endometriosis. Differences between patients with and without evidence of deep infiltrating endometriosis on MRI were to be examined. This was a retrospective, descriptive cross-sectional single-center study. All patients who received a pelvic MRI for endometriosis between April 2021 and February 2023 were included. The presence and frequency of incidental findings were noted after review of all MR images and radiology reports. The potential clinical significance of the findings was analyzed. Differences in the frequency of incidental findings between patients with and without evidence of deep infiltrating endometriosis on MRI were evaluated, utilizing the Chi-square test, Fisher's exact test and Mann-Whitney U-test. 303 consecutive patients (mean age, 33.4 years ± 8.3) were evaluated. Incidental findings were noted in 299/303 (98.7%) patients. Most frequently, ossification of the hip acetabular rim and degenerative changes of the lumbar spine were noted. In 25/303 (8.3%) patients, incidental findings had high clinical significance. For specific incidental findings, significantly higher prevalences were found in patients with than in patients without evidence of deep infiltrating endometriosis on MRI (hip acetabular rim ossification, p = 0.041; annulus fibrosus fissures, p = 0.006; gallstones, p = 0.042). Incidental findings are very common on pelvic MRI for endometriosis. The detection of incidental findings can lead to the diagnosis of relevant diseases and thus enable early treatment. On the other hand, many incidental findings have no, only minor, or uncertain consequences.

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 SignificanceUnderstanding 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.

Polyphenol-Mediated Adhesive and Anti-Inflammatory Double-Network Hydrogels for Repairing Postoperative Intervertebral Disc Defects.

Hydrogels have garnered tremendous attention for their applications in the repair of intervertebral disk (IVD) degeneration and postoperative IVD defects. However, it is still challenging to develop a hydrogel fulfilling the requirements for high mechanical properties, adhesive capability, biocompatibility, antibacterial properties, and anti-inflammatory performance. Herein, we report a multifunctional double-network (DN) hydrogel composed of physically cross-linked carboxymethyl chitosan (CMCS) and tannic acid (TA) networks as well as chemically cross-linked acrylamide (AM) networks, which integrates the properties of high strength, adhesion, biocompatibility, antimicrobial activity, and anti-inflammation for the repair of postoperative IVD defects. The treatment with CMCS/TA/PAM DN hydrogels can significantly decrease the levels of inflammatory cytokines and degeneration-related factors and upregulated collagen type II alpha 1. In addition, the hydrogels can effectively seal the annulus fibrosus defect, prevent nucleus pulposus degeneration, retain IVD height, and restore the biomechanical properties of the disc to some extent. This polyphenol-mediated DN hydrogel is promising for sealing IVD defects and preventing herniation after lumbar discectomy.

Combining the probabilistic finite element model and artificial neural network to study nutrient levels in the human intervertebral discs

BackgroundDiffusion distance and diffusivity are known to affect nutrient transport rates, but the probabilistic analysis of these two factors remains vacant. There is a lack of effective tools to evaluate disc nutrient levels. MethodsFive-hundred-disc samples with different combinations of morphological and water content parameters were generated, which were used to evaluate nutrient levels in unloaded and loaded states. Spearman correlation coefficients between inputs and responses were calculated. Artificial neural networks were trained to predict nutrient concentrations based on the dataset generated by the probabilistic finite element model. FindingsIn unloaded and loaded states, the minimum oxygen concentration of nucleus pulposus was negatively correlated with disc height (r = −0.83, p < 0.01 and r = −0.76, p < 0.01, respectively), and the minimum glucose concentration of annulus fibrosus was positively correlated with its water content (r = 0.68, p < 0.01 and r = 0.73, p < 0.01, respectively). The maximum lactate concentration of cartilage endplate was affected by endplate thickness (r = 0.94, p < 0.01 and r = 0.95, p < 0.01, respectively). For trained neural networks, nutrient concentrations could be well predicted, with coefficients of determination greater than 0.95 and mean absolute percentage errors less than 5 %. InterpretationThis study underscores the importance of disc height, annulus fibrosus water content, and endplate thickness in regulating nutrient levels, and precise control of these parameters should be prioritized in the design of tissue-engineered discs. Moreover, artificial neural networks might be a promising tool for evaluating nutrient levels.

Pain Characteristics of the Posterior Longitudinal Ligament in Percutaneous Endoscopic Lumbar Discectomy and its Significance: A Retrospective Study.

In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin-eosin (HE) staining and immunohistochemistry. Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P < 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (P < 0.0001). Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.

Osteopontin deficiency promotes cartilaginous endplate degeneration by enhancing the NF-κB signaling to recruit macrophages and activate the NLRP3 inflammasome

Intervertebral disc degeneration (IDD) is a major cause of discogenic pain, and is attributed to the dysfunction of nucleus pulposus, annulus fibrosus, and cartilaginous endplate (CEP). Osteopontin (OPN), a glycoprotein, is highly expressed in the CEP. However, little is known on how OPN regulates CEP homeostasis and degeneration, contributing to the pathogenesis of IDD. Here, we investigate the roles of OPN in CEP degeneration in a mouse IDD model induced by lumbar spine instability and its impact on the degeneration of endplate chondrocytes (EPCs) under pathological conditions. OPN is mainly expressed in the CEP and decreases with degeneration in mice and human patients with severe IDD. Conditional Spp1 knockout in EPCs of adult mice enhances age-related CEP degeneration and accelerates CEP remodeling during IDD. Mechanistically, OPN deficiency increases CCL2 and CCL5 production in EPCs to recruit macrophages and enhances the activation of NLRP3 inflammasome and NF-κB signaling by facilitating assembly of IRAK1-TRAF6 complex, deteriorating CEP degeneration in a spatiotemporal pattern. More importantly, pharmacological inhibition of the NF-κB/NLRP3 axis attenuates CEP degeneration in OPN-deficient IDD mice. Overall, this study highlights the importance of OPN in maintaining CEP and disc homeostasis, and proposes a promising therapeutic strategy for IDD by targeting the NF-κB/NLRP3 axis.