Disc Degeneration Research Articles

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.

Regenerative Outcomes of Combining siCOL1A2 Hydrogel with Acupuncture in a Rat Model of Chronic Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is a significant cause of chronic pain and disability, necessitating innovative therapeutic strategies. This study investigates the combined effect of a novel siCOL1A2-encapsulated hydrogel and acupuncture on IVDD in a rat model. We developed a hydrogel system, siCOL1A2-encapsulated G5-PBA hydrogel (siCOL1A2@G5-PBA@Gel), designed for sustained siRNA delivery to the degenerated discs and assessed its therapeutic efficacy alongside acupuncture treatment. Key inflammatory genes were identified through RNA-seq analysis, with COL1A2 highlighted as a crucial regulator of inflammatory responses in IVDD. Our in vivo experiments involved treating rats with hydrogel alone, acupuncture alone, and combining both. The treatments were evaluated through behavioral pain assessments, imaging techniques (X-ray and MRI), and histological analyses. Results indicated that the combination therapy significantly alleviated pain, reduced inflammation, and promoted disc regeneration more effectively than individual treatments. The hydrogel proved biocompatible and facilitated targeted gene silencing, while acupuncture enhanced therapeutic outcomes by improving local blood circulation and modulating inflammatory responses. These findings suggest that integrating siCOL1A2 hydrogel with acupuncture offers a promising approach to treating IVDD.

A strong association between Modic changes type 2 and endplate defects at non-fused segments after ACDF

To determine the association between Modic changes (MC) with other MRI parameters and clinical symptoms of cervical degenerative disc disease (DDD). A retrospective analysis of data on patients with cervical DDD who underwent single-level anterior cervical discectomy and fusion. Preoperative demographic data (age, sex, surgical data) were collected, cervical MRI parameters (disc degeneration grade, MC and endplate defects, each determined at each cervical level) and clinical data (Numerical pain rating scale (NPRS) neck and arm, the Neck Disability Index (NDI)) were compared to preoperative data. The study included 121 patients at Visit 1 and 83 patients at Visit 2. The median follow-up duration was 26.5 [18.9; 33.1] months. Patients with MC had more intense NPRS-based neck pain before surgery compared to patients without MC (p=0.001). There were significant changes in MC rate at the C5-C6 levels due to a significant number of new MCs type 1 and MCs type 2 (p=0.002 and p<0.001, respectively). MC type 2 was associated with disc degeneration, endplate defects defects, patients' age and clinical scales (NDI, NPRS) (p<0.05). The endplate defects defect score threshold for predicting MC type 2 at the С3-С7 cervical levels was 5. The factor predicting MC type 2 at the C3-C7 cervical levels is submaximal damage to the endplate. The MC rate is increased due to MC type 1 and MC type 2. MC types at the cervical levels may not represent consecutive stages of the same process.

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

Combined effect of artificial cervical disc replacement and facet tropism on the index-level facet joints: a finite element study

BackgroundArtificial Cervical Disc Replacement (ACDR) is an effective treatment for cervical degenerative disc diseases. However, clinical information regarding the facet joint alterations after ACDR was limited. Facet tropism is common in the sub-axial cervical spine. Our previous research indicated that facet tropism could lead to increased pressure on the cervical facet joints. This study aimed to assess the impact of facet tropism on the facet contact force and facet capsule stress after ACDR.MethodsA C2–T1 cervical finite element model was constructed from computed tomography (CT) scans of a 28-year-old male volunteer. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by altering the facet orientation at the C5-C6 level. The C5/C6 ACDR was simulated in the intact, moderate asymmetrical and severe asymmetrical models. A 75-N follower load with 1.0-Nm moments was applied to the top of C2 vertebra in the models to simulate flexion, extension, lateral bending, and axial rotation with the T1 vertebra fixed. The range of motions (ROMs) under all moments, facet contact forces (FCFs) and facet capsule strains were tested.ResultsIn the asymmetrical model, the right FCFs considerably increased under flexion, extension, right bending, left rotation, especially under right bending the right sided FCF of the severe asymmetrical model was about 5.44 times of the neutral position, and 3.14 times of the symmetrical model. and concentrated on the cephalad part of the facets. The facet capsule stresses on both sides remarkably increased under extension, lateral bending and right rotation. In the moderate and severe asymmetrical models, the capsule strain was greater on both sides of each position than in the symmetric model.ConclusionsThe face tropism increased facet contact force and facet capsule strain after ACDR, especially under extension, lateral bending, and rotation, and also could result in abnormal stress distribution on the facet joint surface and facet joint capsule. The results suggest that face tropism might be a risk factor for post-operative facet joint degeneration progression after ACDR. Facet tropism may be noteworthy when ACDR is considered as a surgical option.

Vertebral Body Tethering for Thoracolumbar Curvatures in Adolescent Idiopathic Scoliosis: Radiographic and Clinical Outcomes at 2–6-Year Follow-Up

Background: The gold standard treatment for adolescent idiopathic scoliosis (AIS) is posterior spinal fusion (PSF). However, long-term consequences of PSF can include reduced spinal flexibility, back pain, and intervertebral disc degeneration. Vertebral body tethering (VBT) is a non-fusion alternative that preserves motion. We investigated the outcomes of VBT for the treatment of thoracolumbar (TL) major AIS in the largest single-surgeon series with a minimum 2-year follow-up (FU). Methods: We performed a retrospective single-center review. Inclusion criteria were AIS, Lenke 5/6 curvature, and skeletally immature Variables were compared using Student’s t-tests, Wilcoxon rank sum tests, Chi-square, and Fisher’s exact tests. Results: A total of 37 consecutive patients, age 14.1 ± 1.6 years, 86.5% F, 35.9 ± 11.5-month FU, were examined. Overall, 27 patients (73%) had Lenke 5 and 10 (27%) had Lenke 6 curvatures. Instrumentation of the TL curve alone was performed in 59.5%, and thoracic (T) and TL in 40.5% of patients. Overall, 45.9% of patients had two tethers placed in the TL spine; no patients had double tethers placed at the main thoracic curves. The TL (51 ± 8° to 20 ± 11°; p &lt; 0.0001) and T (37 ± 13° to 17 ± 10°; p &lt; 0.0001) curvatures improved from baseline to the latest FU. Overall, 89% of patients achieved major Cobb &lt; 35°; the three patients who did not experienced at least one cord breakage or required PSF. T5-T12 kyphosis increased (p = 0.0401) and lumbar lordosis was maintained (p = 0.9236). Both the TL inclinometer (16 ± 4º to 4 ± 2°; p &lt; 0.0001) and T (6 ± 4° to 4 ± 3°; p = 0.0036) measurements improved. There was a 49% tether breakage rate as follows: 60% for single-cord TL constructs and 35% for double cords (p = 0.0991). There was an 8.1% re-operation rate as follows: one conversion to T PSF and revision of the TL tether; one release of the T tether and revision of the TL tether; one screw revision for radiculopathy. One patient was re-admitted for poor pain control. Conclusions: Patients with TL major curvature treated with VBT experienced a high rate of clinically successful outcomes with maintenance of lumbar lordosis and relatively low complication rates at the latest FU.

A M-PEEK rod system to stabilize spinal motion after graded facetectomy: a finite element study

BackgroundResecting the facet joint to relieve nerve pain can lead to spinal instability, deformity, and abnormal pressure on the anterior of the intravertebral disc. To mitigate these issues, surgeons often limit the amount of bone removed during facetectomy or stabilize the spine by fusion to maintain lumbar stability. This study aimed to assess how a M-PEEK rod system influenced the stability of the lumbar spine during graded facetectomy.MethodsFacetectomy was performed on a validated L1-L5 finite element model which was then simulated both with and without the M-PEEK rod system.ResultsIn extension, models implanted with M-PEEK in the interspinous space of L3/L4 experienced a 35.2% decrease in range of motion (ROM) at L3/L4, while others saw an 8.4–24.8% increase. For axial rotation, the ROM at L3/L4 increased by 2.2–5.4% in models with the M-Rod, and by 4.9–12.9% in models without the implant. In lateral flexion, the ROM at L3/L4 increased by 8.4–14.3% in models without a PEEK M-Rod (facetectomy only), with adjacent segments experiencing a 6.5% decrease in ROM in the implanted models. Overall, the difference in ROM between the intact and implanted models was minimal.ConclusionsFacetectomy involving the removal of 50% or more of the facet joint significantly increases range of motion and maximum intradiscal pressure, potentially accelerating disc degeneration, as shown in our finite element study. Stabilizing the segment with an M-PEEK rod may limit excessive motion, providing stability and maintaining intradiscal pressure closer to that of an intact model.

PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription.

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses a considerable burden to society. However, the molecular mechanisms underlying IVDD remain to be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, and inflammatory responses in various diseases. Despite these regulatory functions, the mechanism of action of PRDM1 in IVDD remains unexplored. In this study, we investigated the role and underlying mechanisms of action of PRDM1 in IVDD progression. The expression of PRDM1 in nucleus pulposus (NP) tissues and NP cells (NPCs) was assessed using western blotting, immunohistochemistry, and immunofluorescence. The effects of PRDM1 on IVDD progression were investigated in vitro and in vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to confirm that PRDM1 triggered CASP1 transcription. Our study demonstrated for the first time that PRDM1 expression was substantially upregulated in degenerated NP tissues and NPCs. PRDM1 overexpression promoted NPCs pyroptosis by inhibiting mitophagy and exacerbating IVDD progression, whereas PRDM1 silencing exerted the opposite effect. Furthermore, PRDM1 activated CASP1 transcription, thereby promoting NPCs pyroptosis in vitro. Notably, CASP1 silencing reversed the effects of PRDM1 on the NPCs. To the best of our knowledge, this study is the first to demonstrate that PRDM1 silencing inhibits NPCs pyroptosis by repressing CASP1 transcription, which may be a promising new therapeutic target for IVDD.

The role of micronutrients and serum metabolites in intervertebral disk degeneration: insights from a Mendelian randomization study and mediation analysis.

Intervertebral disk degeneration (IVDD) is a complex degenerative skeletal condition, potentially influenced by micronutrients and serum metabolites in its etiology. However, the exact causal relationship between these factors and IVDD remains ambiguous. The research employed a Two-Sample Mendelian Randomization (2SMR) analysis to thoroughly evaluate the causal relationship between 15 micronutrients (consisting of 7 minerals and 8 vitamins) as exposure variables, 1,091 blood metabolites, and 309 metabolite ratios as intermediary factors, and IVDD as the outcome. Additionally, reverse MR analysis and mediation analysis were carried out to validate the reliability of the results and explore the underlying mechanism by which micronutrients influence the risk of IVDD by regulating metabolites. Among the micronutrients examined, vitamin B12 exhibited a noteworthy negative correlation with the incidence of IVDD (OR: 0.752, 95% [CI]: 0.573-0.987, p = 0.040), indicating a potential reduction in IVDD risk with increased vitamin B12 consumption. Of the 1,091 blood metabolites and 309 metabolite ratios analyzed, 52 metabolites displayed significant associations with IVDD, primarily linked to amino acid, fatty acid, nucleotide, and sphingolipid metabolic pathways. Mediation analysis identified 4-acetaminophen sulfate as a potential mediator in the protective effect of vitamin B12 against IVDD. This study has shown that vitamin B12 may reduce the risk of IVDD and has identified 52 serum metabolites that are associated with IVDD. Furthermore, it proposes that 4-acetaminophen sulfate could serve as a potential mechanism by which vitamin B12 exerts its inhibitory effects on IVDD.

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells

Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1β) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.

Regional variations of mechanical responses of IVD to 7 different motions: An in vivo study combined with FEA and DFIS

The abnormal mechanical behaviour of a lumbar intervertebral disc (IVD) is commonly recognized as a direct indicator of intervertebral disc degeneration (IDD). However, current methods cannot evaluate the patient-specific mechanical performance of an IVD in vivo during movement. This study establishes a patient-specific (PS) model that combines the kinematics parameters of the lumbar spine obtained with a dual fluoroscopic imaging system (DFIS) and a finite-element (FE) method for the first time to reveal the mechanical behaviours of IVDs in vivo under seven motions. Three healthy participants were recruited for this study. CT images were obtained to create finite-element models of L3-L5 spine segments. Meanwhile, participants were required to take specific positions including upright standing, flexion, extension, left and right lateral bending, as well as left and right axial torsion in the DFIS. The in vivo kinematic parameters, calculated by registering the CT images with images obtained with DFIS, were considered as loading conditions in FE simulations. Significant differences of von Mises stresses and principal strains were found between PS model and GN model which employing a generalized moment as loading conditions, former resulting in up to 76.74 % lower strain than the GN model. Also, considerable differences were observed for five anatomical regions of the IVD (L3-L5). Under all motions, the stress in the centre region (nucleus pulposus) was the lowest, while the stress in the posterior region was the highest in extension motion. Therefore, activities such as stretching with an extension, should be avoided by patients with a herniated disc, in which the posterior region was the herniation site. The PS model combining in vivo kinematics and FE simulations shows the potential in the design and assessment of patient-specific implants.

The association of spinal morning stiffness with lumbar disc degeneration and C-reactive protein: The back complaints in older adults (BACE) study

ObjectiveTo determine the association between patient-reported spinal morning stiffness and lumbar disc degeneration (LDD) and systemic inflammation, as measured by C-reactive protein (CRP), in older patients with non-specific back pain. The ultimate objective is to help shape a future definition of spinal osteoarthritis (OA). DesignBaseline data from the Dutch “Back Complaints in the Older Adults” (BACE) study was used. The relationship between the severity and duration of patient-reported spinal morning stiffness, LDD (i.e., multilevel disc space narrowing and multilevel osteophytes), and CRP was assessed. Regression models adjusted for confounding variables were performed. ResultsSix hundred and seventy-five patients were included. The mean age was 66.52 years (SD 7.69), with a mean CRP of 3.20 ​mg/L (SD 7.61). The severity of spinal morning stiffness was associated with multilevel disc space narrowing: OR 2.89 (95 ​% CI: 1.24 to 6.74) for ‘mild’, OR 2.97 (95 ​% CI: 1.18 to 7.44) for ‘moderate’, OR 3.23 (95 ​% CI: 1.17 to 8.90) for ‘severe’, and OR 5.62 (95 ​% CI: 1.70 to 18.60) for ‘extreme’ morning stiffness severity. However, spinal morning stiffness severity was not associated with multilevel osteophytes, and both multilevel features of LDD showed no associations with the duration of spinal morning stiffness. No associations were found between spinal morning stiffness severity or duration, and CRP levels. ConclusionsOur results suggest that the severity of patient-reported spinal morning stiffness might be considered in future definitions of symptomatic spinal OA and that spinal morning stiffness is probably a symptom of a degenerative process in the spine rather than a symptom of systemic inflammation in patients with back pain.

New perspectives on YTHDF2 O-GlcNAc modification in the pathogenesis of intervertebral disc degeneration

This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.

Identifying critical modules and biomarkers of intervertebral disc degeneration by using weighted gene co-expression network.

Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein-protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.

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

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

EXPLORING THE FEASIBILITY OF PLATELET-RICH PLASMA INJECTIONS FOR INTERVERTEBRAL DISCOPATHY: A PILOT STUDY.

This longitudinal pilot study aimed to evaluate the feasibility, safety and potential benefits of Platelet-Rich Plasma injections into the lumbar intervertebral discs in patients with low back pain and degenerative intervertebral monodiscopathy, assessing potential efficacy on disability. Longitudinal pilot study. Six participants with chronic low back pain and lumbar degenerative intervertebral disc (monodiscopathy) disease underwent 1 Platelet-Rich Plasma injection, with a 1-year follow-up. Platelet-Rich Plasma injections were administered into the lumbar intervertebral disc, and outcomes were measured using the Roland Morris Disability Questionnaire, numeric rating scale for pain, Tampa scale for kinesiophobia and lumbar flexion range. Magnetic resonance imaging analysis assessed disc changes. No adverse events were reported. At the end of the 1-year follow-up, half of the patients showed significant improvements in disability scores at 1 year, while 3 of the 6 patients had no change. Magnetic resonance imaging revealed no significant disc changes. Platelet-Rich Plasma injections show promise for some patients with low back pain and degenerative intervertebral discopathy patients. However, caution is warranted due to study limitations, including small sample size and lack of a control group. Further research is needed to define Platelet-Rich Plasma therapy protocols.

3D Bioprinted Chondrogenic Gelatin Methacrylate-Poly(ethylene glycol) Diacrylate Composite Scaffolds for Intervertebral Disc Restoration

Abstract Degenerative spine pathologies, including intervertebral disc (IVD) degeneration, present a significant healthcare challenge due to their association with chronic pain and disability. This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology, specifically visible light-based digital light processing (VL-DLP), to fabricate tissue scaffolds that closely mimic the native architecture of the IVD. Utilizing a hybrid bioink composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) at a 10% concentration, we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD. Preconditioning rat bone marrow-derived mesenchymal stem cell (rBMSC) spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system. Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses. The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders, highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.

Comparative study of clinical effects between oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine

Objective: To compare the clinical effects of oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine. Method: This was a retrospective study. The clinical data of 80 patients with lumbar disc degenerative disease who underwent surgery in Affiliated Hospital of Beihua University from May 2018 to May 2023 were selected. The patients were divided into LLIF group and OLIF group according to surgical methods. Compare the 36-Item Short-Form Health Survey(SF-36), Visual Analog Scale(VAS) scores, Oswesterly Disability Index(ODI), Japanese Orthopedic Association(JOA) scores, Cobb angle, and intervertebral height changes between two groups of patients pre- and posttreatment, and evaluate the differences in clinical efficacy and surgical complications. Result: Postsurgery, the SF-36 score, VAS score, ODI index, and JOA score of two groups were significantly better than presurgery(p&lt;0.05); After three months of treatment, the improvement in OLIF group was better than LLIF group(p&lt;0.05), while there was no statistically significant difference between the two groups at six months postsurgery(p&gt;0.05). Six months postsurgery, the intervertebral space height and Cobb angle of the two groups were significantly improved compared to presurgery (p&lt;0.05), but there was no significant difference between the groups(p&gt;0.05). There was no difference in clinical efficacy and incidence between the two groups(p&gt;0.05). Conclusion: LLIF and OLIF may be both safe and effective minimally invasive surgical methods for the treatment of degenerative disc disease of the lumbar spine. doi: https://doi.org/10.12669/pjms.40.10.9344 How to cite this: Wang Y, Song Y, Ma Y, Sun X, Wang H. Comparative study of clinical effects between oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine. Pak J Med Sci. 2024;40(10):2238-2242. doi: https://doi.org/10.12669/pjms.40.10.9344 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Short Link N Modulates Inflammasome Activity in Intervertebral Discs Through Interaction with CD14.

Intervertebral disc degeneration and pain are associated with the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome activation and the processing of interleukin-1 beta (IL-1β). Activation of thehm inflammasome is triggered by Toll-like receptor stimulation and requires the cofactor receptor cluster of differentiation 14 (CD14). Short Link N (sLN), a peptide derived from link protein, has been shown to modulate inflammation and pain in discs in vitro and in vivo; however, the underlying mechanisms remain elusive. This study aims to assess whether sLN modulates IL-1β and inflammasome activity through interaction with CD14. Disc cells treated with lipopolysaccharides (LPS) with or without sLN were used to assess changes in Caspase-1, IL-1β, and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). Peptide docking of sLN to CD14 and immunoprecipitation were performed to determine their interaction. The results indicated that sLN inhibited LPS-induced NFκB and Caspase-1 activation, reducing IL-1β maturation and secretion in disc cells. A significant decrease in inflammasome markers was observed with sLN treatment. Immunoprecipitation studies revealed a direct interaction between sLN and the LPS-binding pocket of CD14. Our results suggest that sLN could be a potential therapeutic agent for discogenic pain by mitigating IL-1β and inflammasome activity within discs.

Overloaded Vertebral Body Following Consecutive Three-Level Hybrid Surgery Comparing with Anterior Cervical Discectomy and Fusion.

Based on the varying number and relative positions of cervical disc replacement (CDR) and anterior cervical discectomy and fusion (ACDF) procedures, three-segment hybrid surgery (HS) presents a diverse structural approach. Currently, the potential differential effects of HS with different segment combinations and surgical procedures on overloaded vertebral body (OVB) occurrence remain unexplored. The purpose of this retrospective study is to compare the clinical and radiological outcomes of HS and ACDF in treating cervical degenerative disc disease (CDDD), aiming to provide further insights into OVB. This study included patients with three-level CDDD who underwent ACDF or HS at our institution. Eligible patients were divided into three groups: Type I (one-level CDR and two-level ACDF), Type II (two-level CDR and one-level ACDF), and ACDF (three-level ACDF). For radiographic analysis, patients were further divided into the Replacement Segment Group and the Nonreplacement Segment Group based on the presence of replacement segments above and below the OVB. Clinical outcomes were evaluated using visual analog scale (VAS) scores for neck and arm pain, Japanese Orthopedic Association (JOA) scores, and neck disability index (NDI) scores. The cervical radiological parameters assessed included (1) vertebral cross-sectional area (CSA), (2) wedge angle (WA), (3) anterior vertebral height (AH), (4) posterior vertebral height (PH), and (5) Hounsfield unit (HU) values. Statistical methods included paired t-test, ANOVA test, and chi-square test. Independent samples t-test, Mann-Whitney U test, and Wilcoxon signed-rank test were used to compare the differences between two groups according to the results of normal distribution test. A total of 123 patients, evenly distributed among three groups, were included and were well matched in terms of demographic characteristics. The likelihood of vertebral body collapse (VBC) was notably higher in the ACDF group (41.5%) compared with the Type I (17.9%) and Type II (8.9%) groups (p < 0.01). Following surgery, both at 3 and 6 months, the ACDF group demonstrated higher VAS neck scores and NDI scores compared with the Type I and Type II groups (p < 0.01). Additionally, the WA and AH values of the upper and lower adjacent OVB were consistently lower in the ACDF group than in the Type I and Type II groups at 6 and 12 months and at the final follow-up (p < 0.01). Notably, in the Nonreplacement Segment Group, WA significantly decreased at 12 months postoperatively and at the final follow-up compared with the Replacement Segment Group (p < 0.01). Three levels of HS appear to reduce stress concentrations and alleviate morphological changes in OVB. The occurrence of more VBC patients with OVB was associated with the use of Zero-P or Zero-P VA implants.