Disc Degeneration Research Articles

Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.

Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes. Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared. A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties. Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.

LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway.

Intervertebral disc degeneration (IDD)-induced cervical and lumbar herniations are debilitating diseases. The function of intervertebral disc (IVD) mainly depends on the cartilage endplate (CEP), which provides support and waste removal. Therefore, IDD stems from the degeneration of CEP. Our study shows that the expression of lactotransferrin (LTF), an iron-binding protein, is significantly decreased in degenerated human and rat CEP tissues. In addition, we found that LTF knockdown promoted calcification, senescence, and extracellular matrix (ECM) degradation in human endplate chondrocytes. Furthermore, the invivo experiment results confirmed that the JAK2/STAT3 pathway inhibitor AG490 significantly reversed these effects. In addition to investigating the role and mechanism of LTF in CEP degeneration, this study provides a theoretical basis and experimental evidence to improve IDD treatment.

Identification and Validation of Telomere-Related Gene Signature in Intervertebral Disc Degeneration.

This study investigates the role of telomere-related differentially expressed genes (TRDEGs) in intervertebral disc degeneration (IVDD) through comprehensive bioinformatics analyses. Data were sourced from the Gene Expression Omnibus (GEO) with datasets GSE245147 and GSE124272 used for initial identification and validation, respectively. The GSE245147 dataset comprised transcriptional profiles from nucleus pulposus cells of both degenerated and non-degenerated human nucleus pulposus (NP) tissues. Using the limma package, 198TRDEGs were identified by intersecting differentially expressed genes (DEGs) with telomere-related genes (TRGs) from the TelNet database. Functional enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that TRDEGs are significantly involved in cell division, chromosome segregation, and other mitotic processes. Protein-protein interaction (PPI) networks constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized with Cytoscape (Cytoscape Consortium, San Diego, CA, USA) identified key hub genes such as CDK1, CCNA2, and AURKB. Pearson correlation and receiver operating characteristic (ROC) analyses highlighted five hub genes (ASPM, BUB1B, CDC20, KIF2C, TTK) with significant predictive value for IVDD. Additionally, mRNA-microRNA (miRNA) interaction analysis using NetworkAnalyst identified key miRNAs interacting with these hub genes. This study provides insights into the molecular mechanisms of IVDD and identifies potential targets for therapeutic intervention.

Revolutionizing Intervertebral Disc Regeneration: Advances and Future Directions in Three-Dimensional Bioprinting of Hydrogel Scaffolds.

Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.

Changes in the Centers of Rotation in Different Prosthetic Segments Following Continuous Two-Level Cervical Disc Replacement: A Retrospective Study

To observe the short-term to medium-term therapeutic effects and radiological outcomes of adjacent 2-level cervical spondylosis treated with artificial cervical disc replacement (ACDR) using Mobi-C and Bryan discs. To observe changes and discrepancies in the flexion-extension centers of rotation (FE-COR) of different ACDR segments. Twenty-four patients undergoing 2-level (C4/5 and C5/6) ACDR were analyzed retrospectively (11 patients in the Mobi-C group and 13 patients in the Bryan group). Clinical outcomes were assessed using modified Japanese Orthopedic Association score, Neck Disability Index, and visual analog scale. Preoperative and 2years' follow-up radiographs were collected to compare total cervical spine curvature (C2-C7) range of motion (ROM), upper and lower ACDR segmental ROM, and the operated adjacent segmental ROM. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The degree of disc degeneration in the adjacent segment was observed. At the 2years' follow-up, in both group, the modified Japanese Orthopedic Association score increased significantly, and the Neck Disability Index and neck and upper extremity visual analog scale scores decreased significantly compared with preoperative (P<0.05). There were no significant statistical differences in postoperative scores between the 2 groups (P > 0.05). The overall cervical ROM, the upper and lower segmental ROM at the 2years' follow-up showed no significant statistical differences compared with the preoperative period (P > 0.05). There was no statistically significant difference in the adjacent segmental ROMs compared with the preoperative period (P > 0.05). Furthermore, the statistical analysis revealed no significant differences in the measurements of the ROM at each time points between the Mobi-C Group and the Bryan Group (P > 0.05). There was no significant difference in the preoperative FE-COR-X (indicating the horizontal position of the point in the coordinate system) and FE-COR-Y (indicating the vertical position of the point in the coordinate system) of upper or lower ACDR segments between the 2 groups (P > 0.05). At the 2years' follow-up, there were significant differences both in FE-COR-X and FE-COR-Y between the 2 groups (P < 0.05). For the Mobi-C group, in both the upper and lower segment, the FE-COR-X significantly increased compared with preoperative (P < 0.05), while the FE-COR-Y decreased compared with preoperative (P < 0.05). For the Bryan group, no significant changes were observed in the upper or lower segment in both FE-COR-X and FE-COR-Y compared with preoperative (P > 0.05). Fourty-eight adjacent segments (24 superior and 24 inferior segments) were included in the studies of adjacent segment disease. Four segments showed imaging adjacent segment disease (4/48, 8.33%) in 4 patients, of which 2 were mild and 2 were moderate according to the grading criteria. Among them, 2 were from the Mobi-C group and 2 were from the Bryan group. No severe imaging degeneration was observed. In continuous 2-level cervical ACDR surgery, both Mobi-C and Bryan artificial cervical discs achieved satisfactory clinical outcomes in the short to medium term postoperatively. The FE-COR exhibited different trends of change. In the Mobi-C group, the FE-COR for both upper and lower segments shifted anteriorly and inferiorly, whereas in the Bryan group, whether upper or lower, the FE-COR remained closer to the preoperative state. The changes in FE-COR did not significantly affect the short-term to medium-term clinical outcomes postoperatively.

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.

Midterm Follow-Up Of Tlif In Single-Level Lumbar Disc Degeneration

OBJECTIVES This study aims to evaluate the midterm clinical and radiological outcomes of TLIF in patients with single-level lumbar disc degeneration. The focus is on assessing the procedure's effectiveness in terms of pain relief, functional improvement, and any potential complications. METHODOLOGY A retrospective cohort study was conducted at Hayatabad Medical Complex, Peshawar involving 120 patients who underwent single-level TLIF for lumbar disc degeneration between 2018-2023. The patients with a diagnosis of single-level lumbar disc degeneration confirmed by MRI, failure of conservative treatment for at least 6 months, and who underwent TLIF during the study period were included in the study. Data were collected on preoperative and postoperative pain scores, Oswestry Disability Index (ODI), and radiological parameters. SPSS version 24 was used. RESULTSThe mean follow-up period was 36 months (range 24-48 months). There was a statistically significant improvement in both pain scores (p &lt; 0.001) and ODI scores (p &lt; 0.001). Fusion rates were high, with 92% of patients achieving solid fusion by the final follow-up. Complications were observed in 15% of the cases, with adjacent segment disease being the most common. CONCLUSION TLIF provides significant pain relief and functional improvement in patients with single-level lumbar disc degeneration at midterm follow-up. The procedure demonstrates a high fusion rate with an acceptable complication profile, making it a reliable option for this patient population

Integration of bioinformatics and multi-layered experimental validation reveals novel functions of acetylation-related genes in intervertebral disc degeneration

BackgroundThe molecular mechanisms underlying intervertebral disc degeneration (IDD) remain poorly understood. The purpose of this work is to elucidate key molecules and investigate the roles of acetylation-related RNAs and their associated pathways in IDD. MethodDatasets GSE70362 and GSE124272 were obtained from the Gene Expression Omnibus (GEO) and combined to investigate differentially expressed genes (DEGs) associated with acetylation in IDD patients compared to healthy controls. Critical genes were pinpointed by integrating GO, KEGG and PPI networks. Furthermore, CIBERSORTx analysis was used to investigate the differences in immune cell infiltration between different groups and the biological processes (BP), cellular components (CC) and molecular functions (MF) were calculated by GSEA and GSVA. In addition, The single-cell database GSE165722 was incorporated to validate the specific expression patterns of hub genes in cells and identify distinct cell subtypes. This provides a theoretical basis for a more in-depth understanding of the roles played by critical cell subtypes in the process of IDD. Subsequently, tissues from IVD with varying degrees of degeneration were collected to corroborate the key DEGs using western blot, RT-qPCR, and immunofluorescence staining. ResultsBy integrating various datasets and references, we identified a total of 1620 acetylation-related genes. These genes were subjected to a combined analysis with the DEGs from the databases included in this study, resulting in the discovery of 358 acetylation-related differentially expressed genes (ARDEGs). A comparative analysis with differentially expressed genes obtained from three databases yielded 19 ARDEGs. The PPI network highlighted the top 10 genes (IL1B, LAMP1, PPIA, SOD2, LAMP2, FBL, MBP, SELL, IRF1 and KHDRBS1) based on their protein interaction relationships. CIBERSORTx immune infiltration analysis revealed a moderate positive correlation between the gene IL1β and Mast.cells.activated, as well as a similar correlation between the gene IRF1 and Mast.cells.activated. Single-cell dataset was used to identify cell types and illustrate the distribution of hub genes in different cell types. The two cell types with the highest AUCell scores (Neutrophils and Monocytes) were further explored, leading to the subdivision of Neutrophils into two new cell subtypes: S100A9-type Neutrophils and MARCKS-type Neutrophils. Monocytes were labeled as HLA-DRA9-type Monocytes and IGHG3-type Monocytes. Finally, molecular biology techniques were employed to validate the expression of the top 10 hub genes. Among them, four genes (IL1β, SOD2, LAMP2, and IRF1) were confirmed at the gene level, while two (IL1β and SOD2) were validated at the protein level. ConclusionIn this study, we carried out a thorough analysis across three databases to identify and compare ARDEGs between IDD patients and healthy individuals. Furthermore, we validated a subset of these genes using molecular biology techniques on clinical samples. The identification of these differently expressed genes has the potential to offer new insights for diagnosing and treating IDD.

Efficacy of Chemonucleolysis with Condoliase in Patients Aged under 20 Years.

Chemonucleolysis with condoliase is a minimally invasive treatment option for lumbar disk herniation (LDH). However, studies reporting the efficacy of condoliase in patients aged <20 years are scarce. Therefore, the present study aimed to evaluate the efficacy of condoliase therapy for LDH in the aforementioned population. Condoliase administration was determined based on adequate informed consent. The study enrolled 138 patients (mean age, 41.3±15.4 years) with LDH who received condoliase injections with a follow-up period of 1 year. The patients were divided into Group Y (age, <20 years) and Group A (age, 20-70 years). The clinical outcomes were visual analog scale (VAS) scores for leg and back pain and Oswestry Disability Index (ODI) values. Changes in disk height and degeneration were evaluated. These data were obtained at baseline and at the 3-month and 1-year follow-ups. Condoliase therapy was considered to be effective if it improved the VAS score for leg pain by ≥50% at 1 year from baseline and prevented surgery. Groups Y and A consisted of 15 and 123 patients, respectively. Condoliase therapy was effective in 9 patients (60.0%) in Group Y and 96 patients (78.0%) in Group A. The rates of Pfirrmann grade deterioration and recovery were substantially higher in Group Y than in Group A (83.3% vs. 45.8% and 50.0% vs. 16.3%, respectively). While the disk height reduction in Group Y was greater at 3 months, it recovered to the same level as that in Group A at 1 year. In Group Y, patients who did not respond to the treatment exhibited a considerably higher preoperative ODI (P<0.05). Chemonucleolysis with condoliase is considered to have limited efficacy in patients aged <20 years. Caution should be taken when managing cases showing lumbar instability or existing disability. While chemonucleolysis with condoliase is a less invasive treatment option for LDH, the administration should be decided upon with sufficient consent considering the potential limited efficacy and disk degeneration.

Risk factor analysis of persistent low back pain after microdiscectomy: A retrospective study

ObjectiveMicrodiscectomy is an effective and safe treatment for patients with symptomatic lumbar disc herniation (LDH) that is refractory to conservative interventions. However, some patients experience persistent low back pain (PLBP) after microdiscectomy that is secondary to progressive disc degeneration and segmental instability. This study aimed to clarify the definition of PLBP and analyze its prevalence and associated risk factors. MethodsThis retrospective study included patients who underwent microdiscectomy for LDH at our hospital between 2015 and 2019. We divided this cohort into patients who did (PLBP group) or did not (non-PLBP group) experience PLBP after microdiscectomy and compared their clinical, radiological, and anatomical parameters. We analyzed the relationship between PLBP post-microdiscectomy and the following variables: age, sex, disk herniation level, recurrent disk herniation, body mass index (BMI), modic changes on MRI, facet subluxation, preoperative lumbar pain, and lumbosacral transitional vertebrae (LSTV). ResultsPLBP after microdiscectomy was diagnosed in 99 (29.8 %) of the 332 patients enrolled in this study. Based on our multivariate logistic regression analysis, L5-S1 disc herniation level, recurrent disc herniation after microdiscectomy, obesity, modic changes on preoperative MRI, and facet subluxation were independent risk factors for PLBP post-microdiscectomy. Women and patients aged <50 years showed a trend of increased risk for developing PLBP after microdiscectomy; however, this trend did not reach statistical significance. ConclusionsPLBP after microdiscectomy is a frequent and understudied condition. We found that an L5-S1 disc herniation level, recurrent disc herniation, obesity, modic MRI changes, and facet subluxation were risk factors for PLBP after microdiscectomy. These results can help surgeons in developing a better understanding of lumbar microdiscectomy outcomes.

Use of two-point and six-point Dixon MRI for fat fraction analysis in the lumbar vertebral bodies and paraspinal muscles in healthy dogs: comparison with magnetic resonance spectroscopy.

Fatty degeneration of the vertebral bodies and paravertebral muscles is associated with the presence, severity, and prognosis of spinal disease such as intervertebral disc degeneration. Therefore, the fat fraction (FF) of the vertebral bodies and paraspinal muscles has been considered a potential biomarker for assessing the pathophysiology, progression, and treatment response of spinal disease. Magnetic resonance spectroscopy (MRS) is considered the reference standard for fat quantification; however, it has limitations of a long acquisition time and is technically demanding. Chemical shift-encoding water-fat imaging, called the Dixon method, has recently been applied for rapid fat quantification with high spatial resolution. However, the Dixon method has not been validated in veterinary medicine, and we hypothesized that the Dixon method would provide a comparable assessment of the FF to MRS but would be faster and easier to implement in dogs. In this prospective study, we assessed the FF of the lumbar vertebral bodies and paravertebral muscles from the first to sixth lumbar vertebrae using MRS, the two-point Dixon method (LAVA-FLEX), and the six-point Dixon method (IDEAL-IQ) and compared these techniques. The FFs of vertebral bodies and paravertebral muscles derived from LAVA-FLEX and IDEAL-IQ showed significant correlations and agreement with those obtained with MRS. In particular, the FFs obtained with IDEAL-IQ showed higher correlations and better agreement with those obtained with MRS than those derived by LAVA-FLEX. Both Dixon methods showed excellent intra- and interobserver reproducibility for FF analysis of the vertebral bodies and paraspinal muscles. However, the test-retest repeatability of vertebral body and paraspinal muscle FF analysis was low for all three sequences, especially for the paraspinal muscles. The results of this study showed that LAVA-FLEX and IDEAL-IQ have high reproducibility and that their findings were highly correlated with the FFs of the lumber vertebral bodies and paraspinal muscles determined by MRS in dogs. The FF analysis could be performed much more easily and quickly using LAVA-FLEX and IDEAL-IQ than using MRS. In conclusion, LAVA-FLEX and IDEAL-IQ can be used as routine procedures in spinal magnetic resonance imaging in dogs for FF analysis of the vertebral bodies and paraspinal muscles.

Association Between Cumulative G-force Exposure and Cervical Spine Degenerative Changes.

Fighter pilots work in a unique environment and are subject to high G-force loads under simultaneous head movements. Neck pain is reported to be a common health problem among fighter pilots leading to time lost flying and flight duty limitations. The present study aimed to find out if differences in early military flight career G-force exposure levels could increase the risk for degenerative changes in the cervical spine. The study population consisted of 56 20-year-old Finnish Air Force male fighter pilot cadets, who underwent MRI of the cervical spine at baseline and after 5 years. During follow-up, the G-force exposure was measured using the individual Fatigue Index (FI) recordings. The FI data were collected from each flight with BAE Hawks and is determined by the number of times certain levels of G-forces are exceeded during the flights. The incidence or progression of each degenerative change was compared to individual FI values using Pearson correlation coefficients. The pilots flew on average 220 (±21) hours with high performance aircraft during follow-up, resulting in an average FI of 1.98 (±0.47). A statistically significant progression was found in intervertebral disc (IVD) degeneration sum score with no correlation to corresponding FI values. A statistically significant increase was also found in the prevalence of IVD herniations with a negative correlation with FI values. Other degenerative cervical spine changes did not progress or did not correlate with corresponding FI values. The prevalence of IVD degeneration and IVD herniations increases in the early phases of fighter pilots' career. Only the incidence of IVD herniations correlated with FI values and the correlation was negative. The negative correlation may be attributed to avoidance behavior due to neck pain, which was not measured in our study, or other unmeasured confounding factors. This was the first study to compare individual G-force exposure levels to high-quality MRI data over a follow-up of several years. Finnish fighter pilots are known to report increasing cervical symptoms during the Hawk training phase, but longer follow-up periods are likely needed to determine the association between G-force exposure levels and cervical degenerative changes.

Bone graft substitutes used in anterior lumbar interbody fusion: a contemporary systematic review of fusion rates and complications.

Anterior lumbar interbody fusion (ALIF) uses a broad-footprint interbody cage designed to maximize fusion rates for treating degenerative disc disease. Bone graft substitutes are being increasingly utilized during ALIF to replace or supplement autologous iliac crest bone grafts. This approach aims to optimize fusion efficacy while minimizing associated postoperative complications. The objective of this systematic review was to examine recent studies on fusion rates and postoperative complications associated with bone graft substitutes used in ALIF. We conducted a systematic review of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, MEDLINE, and PubMed databases, to critically examine a decade of research (January 1, 2012, to July 6, 2023) on the effectiveness and safety of various bone graft substitutes in ALIF. This timeframe was chosen to build on a previous systematic review published in 2013. The PRISMA guidelines were used. In total, 27 articles met our stringent inclusion and exclusion criteria. A substantial portion of these studies (67%) focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and highlighted its efficacy for achieving high fusion rates. However, the literature presents a dichotomy regarding the association of rhBMP-2 with increased postoperative complications. Notably, the methodologies for evaluating spinal fusion varied across studies. Only one-third of studies employed computed tomography to assess interbody fusion at 12 months postoperatively, highlighting the urgent need to establish uniform fusion criteria to facilitate more accurate comparative analyses. Moreover, there was considerable variability in the criteria used for diagnosing and detecting postoperative complications, significantly influencing the reported incidence rates. This review underscores the need for continued research into bone graft substitutes, particularly focusing on assessment of long-term complications. Future research endeavors should concentrate on developing comprehensive clinical guidelines to aid in the selection of the most suitable bone graft substitutes for use in ALIF, thereby enhancing patient outcomes and surgical efficacy.

Protective effects of alpinetin against interleukin-1β-exposed nucleus pulposus cells: Involvement of the TLR4/MyD88 pathway in a cellular model of intervertebral disc degeneration

Intervertebral disc degeneration (IDD) causes a variety of symptoms such as low back pain, disc herniation, and spinal stenosis, which can lead to high social and economic costs. Alpinetin has an anti-inflammatory potential, but its effect on IDD is unclear. Herein, we investigated the effect of alpinetin on IDD. To mimic an in vitro model of IDD, nucleus pulposus cells (NPCs) were exposed to interleukin 1β (IL-1β). The viability of NPCs was assessed by CCK-8 assay. The expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), aggrecan, collagen-2, and matrix metalloproteinase-3 (MMP-3) was examined by qRT-PCR and western blotting. The protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated protein X (Bax), and cleaved caspase-3 were scrutinized by western blotting. The flow cytometry assay was performed to assess apoptosis of NPCs. The contents of inflammatory factors were examined by ELISA kits. Results showed that alpinetin repressed IL-1β-tempted activation of the TLR4/MyD88 pathway and apoptosis in NPCs. Alpinetin alleviated IL-1β-tempted inflammatory responses and oxidative stress in NPCs. Moreover, alpinetin lessened IL-1β-tempted extracellular matrix (ECM) degeneration in NPCs by enhancing the expression of aggrecan and collagen-2 and reducing the expression of MMP-3. The effects of alpinetin on IL-1β-exposed NPCs were neutralized by TLR4 upregulation. In conclusion, alpinetin repressed IL-1β-tempted apoptosis, inflammatory responses, oxidative stress, and ECM degradation in NPCs through the inactivation of the TLR4/MyD88 pathway.

Positive Cutibacterium acnes Intervertebral Discs Are Not Associated with Subsidence Following Anterior Cervical Discectomy and Fusion at 3 or 6 Months.

Background/Objectives:Cutibacterium acnes (C. acnes), formerly known as Propionibacterium acnes (P. acnes), is an anaerobic, low-virulent bacterium that has been associated with postoperative infections of the shoulder, knee, and cervical spine. Recent studies have highlighted an association between C. acnes and the development of degenerative disc disease (DDD). The aim of this study is to ascertain whether C. acnes increases the risk of subsidence following anterior cervical discectomy and fusion (ACDF). Methods: After IRB approval, consecutive patients undergoing elective ACDF for DDD from 2017 to 2018 were enrolled in this prospective cohort study. Intervertebral disc samples were taken at each affected level and cultured. A total of 66 patients with radiographic follow-ups were included in the final analysis. The extent of subsidence and cervical lordosis was determined immediately postoperatively and at the 3- and 6-month follow-ups. Results: No significant difference in subsidence was observed at 3 months (p = 0.07) or 6 months (p = 0.11) between culture-positive and -negative cohorts. Additionally, there was no significant difference detected in the change in cervical lordosis observed at 3 months (p = 0.16) or 6 months (p = 0.27) between culture-positive and -negative cohorts. For the most inferiorly fused segment, there was a significant difference in subsidence observed at 3 months (1.5 mm, 95% CI: 0.2-2.7 mm, p = 0.02) but not at 6 months (p = 0.17). Conclusions: Intervertebral discs with a positive C. acnes culture were not associated with greater levels of subsidence at 3 or 6 months following ACDF for DDD. Further research is necessary to endorse these results and to gauge the clinical significance of C. acnes infection.

The influence of lumbar vertebra and cage related factors on cage-endplate contact after lumbar interbody fusion: An in-vitro experimental study

Lumbar interbody fusion (LIF) using interbody cages is an established treatment for lumbar degenerative disc disease, but fusion results are known to be affected by risk factors such as bone mineral density (BMD), endplate geometry and cage position. At present, direct measurement of endplate-cage contact variables that affect LIF have not been fully identified. The aim of this study was to use cadaveric experiments to investigate the dependency between BMD, endplate geometry, cage parameters like type, orientation, position, and contact variables like stress and area. One vertebral body specimen from each of the five lumbar positions was harvested from five male donors. The lower half of each vertebra was potted and placed in a material testing machine (Instron 8874). A spinal cage was clamped to the machine then lowered to bring it into contact against the superior endplate. A lockable ball-joint was used to rotate the cage such that its inferior surface was congruent with the local endplate surface. A pressure sensor (Tekscan) was placed between the cage and endplate to record contact area and the peak and average contact pressures. Axial compression of 400 N was performed for five positions using a straight cage, and in one anterior position using a curved cage. The linear mixed model was utilised to perform data analyses for experimental results with statistical significance set at p < 0.05. The results indicated two trends toward significance for contact area, one for volumetric BMD (vBMD) of the vertebra (p = 0.081), and another for predicted contact area (p = 0.057). Peak contact pressure correlated significantly with vBMD (p = 0.041), and there was a trend between average contact pressure and lateral position of cage (p = 0.051). In addition, predicted contact area correlated significantly with cage orientation (p < 0.001). These results indicated that high vBMD of vertebra and a medially positioned cage led to higher contact pressures. Logically, low vBMD of vertebra and transverse cage orientation increased the contact area between the cage and endplate. In conclusion, the study identified significant influence of vBMD of vertebra, cage position and orientation on cage-endplate contact which may help to inform cage selection and design for LIF.

Fibulin-3 Regulates Tissue Inhibitor of Metalloproteinases 3 to Inhibit Senescence in Intervertebral Disc Nucleus Pulposus Cells

To investigate the effect of fibulin-3 on the senescence of intervertebral disc nucleus pulposus cells (NPCs) through the regulation of tissue inhibitor of metalloproteinases 3 (TIMP-3) expression and to elucidate the molecular mechanisms involved. 1). The nucleus pulposus tissues and imaging data of 37 patients who had undergone intervertebral disc surgery were collected. The degree of degeneration of the intervertebral discs were classified according to the Pfirrmann grading system. The senescence degree of NPCs was determined using senescence-associated β-galactosidase (SA-β-gal) staining. Fibulin-3 expression levels were determined using Western blot and ELISA. The relationship between fibulin-3 and disc degeneration and NPCs senescence was investigated. 2). Human intervertebral disc NPCs were cultured in vitro. The proliferation and senescence of NPC across continuous passage were observed via CCK-8 assay and SA-β-gal staining, respectively. Fibulin-3 expression levels and the expression of inflammatory cytokines and matrix metalloproteinases were assessed. Exogenous fibulin-3 was added to verify its effect on the proliferation and senescence of NPCs. 3). The effect of fibulin-3 on the apoptosis and proliferation of NPCs was verified through gene overexpression, which was used in combination with an apoptosis inhibitor for bidirectional verification. 4). Bioinformatics analysis was performed to explore the relationship between fibulin-3 and the TIMP family. Experiments overexpressing fibulin-3 and silencing the TIMP-3 gene were performed to verify their role in NPCs senescence. 1). The intervertebral disc degeneration samples from 37 patients were classified according to the Pfirrmann grading system. The higher the degeneration grade, the lower fibulin-3 expression. Spearman correlation analysis showed that the disc grade was negatively correlated with the NPC senescence grade (r=－0.87, P<0.001) and fibulin-3 expression (r=－0.79, P<0.001). 2). As the passage number of NPCs increased, fibulin-3 expression gradually decreased, cell proliferation ability weakened, and the expression of inflammatory cytokines and matrix metalloproteinases increased. After exogenous fibulin-3 was added, cell morphology and growth status were maintained, cell senescence was significantly inhibited, and the expression of inflammatory cytokines and matrix metalloproteinases was markedly reduced. 3). Gene overexpression experiments showed that fibulin-3 reduced NPC apoptosis and promoted cell proliferation, thereby inhibiting NPC senescence. 4). Bioinformatics analysis revealed a significant association between fibulin-3 and TIMP-3 of the TIMP family. Further experiments confirmed that overexpressing fibulin-3 enhanced TIMP-3 expression, while silencing the TIMP-3 gene significantly weakened the inhibitory effect of fibulin-3 on NPCs senescence. This indicates that, through regulating TIMP-3, fibulin-3 inhibits the activity of matrix metalloproteinases, affects the synthesis and degradation of the extracellular matrix, and ultimately inhibits NPCs senescence. This study demonstrates that fibulin-3 plays a crucial role in inhibiting the senescence of intervertebral disc NPCs by regulating TIMP-3. The specific mechanisms involved are as follows, fibulin-3 upregulates TIMP-3 expression, inhibits matrix metalloproteinase activity, and reduces extracellular matrix degradation, thereby promoting extracellular matrix synthesis. Additionally, fibulin-3 inhibits NPCs senescence by reducing apoptosis and promoting cell proliferation. Therefore, fibulin-3 and TIMP-3 have potential therapeutic significance in maintaining intervertebral disc health and delaying degeneration.

The JNK signaling pathway in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) serves as the underlying pathology for various spinal degenerative conditions and is a primary contributor to low back pain (LBP). Recent studies have revealed a strong correlation between IDD and biological processes such as Programmed Cell Death (PCD), cellular senescence, inflammation, cell proliferation, extracellular matrix (ECM) degradation, and oxidative stress (OS). Of particular interest is the emerging evidence highlighting the significant involvement of the JNK signaling pathway in these fundamental biological processes of IDD. This paper explores the potential mechanisms through the JNK signaling pathway influences IDD in diverse ways. The objective of this article is to offer a fresh perspective and methodology for in-depth investigation into the pathogenesis of IDD by thoroughly examining the interplay between the JNK signaling pathway and IDD. Moreover, this paper summarizes the drugs and natural compounds that alleviate the progression of IDD by regulating the JNK signaling pathway. This paper aims to identify potential therapeutic targets and strategies for IDD treatment, providing valuable insights for clinical application.

Design of a traction neck brace with two degrees-of-freedom via a novel architecture of a spatial parallel mechanism

Abstract Traction of the head-neck is important in the treatment of patients suffering from neck pain due to degeneration of the intervertebral discs. Conventional neck traction is provided manually by experienced physical therapists who maintain a desired orientation of the head-neck relative to the trunk while applying the traction. It is postulated that innovative designs of neck exoskeletons can provide the same function both flexibly and accurately. This article presents a novel architecture of a parallel mechanism whose base sits on the human shoulders with 4 parallel chains, each chain having a revolute-revolute-universal-revolute (RRUR) structure, while the end-effector is connected rigidly to the human head. Each chain has five degrees-of-freedom (DOF) and applies a constraint on the motion of the end-effector. As a result, this parallel mechanism allows two DOFs to the end-effector. These are (i) forward flexion or lateral bending of the head and (ii) vertical translation. An important motivation for the current design with RRUR structure is to characterize the range of forward flexion/lateral bending of the head-neck with this structure and the vertical translation to the end-effector. A physical prototype was constructed and tested to evaluate the performance of this mechanism in hardware for the proposed application.