Intervertebral disc degeneration (IVDD) is increasingly prevalent in aging societies and poses a significant health challenge. Due to the limited blood supply to the disc, oral medications and systemic treatments are often ineffective. Consequently, localized injection therapies, which deliver therapeutic agents directly to the degenerated disc, have emerged as more efficient. Self-healing injectable hydrogels are particularly promising due to their potential for minimally invasive delivery, precise implantation, and targeted drug release into hard-to-reach tissue sites, including those requiring prolonged healing. Their dynamic viscoelastic properties accurately replicate the mechanical environment of the natural nucleus pulposus, providing cells with an adaptive biomimetic microenvironment. This review will initially discuss the anatomy and pathophysiology of intervertebral discs, current treatments, and their limitations. Subsequently, we conduct bibliometric analysis to explore the research hotspots and trends in applying injectable hydrogel technology to treat IVDD. It will then explore the promising features of injectable hydrogels in biomedical applications such as drug, protein, cells and gene delivery, tissue engineering and regenerative medicine. We discuss the construction mechanisms of injectable hydrogels via physical interactions, chemical and biological crosslinkers, and discuss the selection of biomaterials and fabrication methods for developing novel hydrogels for IVD tissue engineering. The article concludes with future perspectives on the application of injectable hydrogels in this field.

Retrospective observational study.

We aim to evaluate whether age is a risk factor for cage subsidence, and whether other patient characteristics, preoperative radiological or imaging parameters are associated with cage subsidence and the need for revision surgery in patients undergoing transforaminal lumbar interbody fusion (TLIF).

Patient demographics and surgery-related information were extracted. Cage subsidence was evaluated using upright standing sagittal plane X-rays and defined as more than 2 mm migration of the cage into the adjacent vertebral body. Patients who received revision surgery within 1 year for any reason were recorded. Radiographic parameters were measured. Univariable logistic regression models were used to evaluate the risk factors for cage subsidence and need for revision surgery.

At 3-month and 1-year follow-up, cage subsidence was observed in 28 patients (16.5%) and 58 patients (34.1%), respectively. Twenty-seven patients received revision surgery within the first year after TLIF. Age (odds ratio (OR): 1.07 per year) and male sex (OR: 2.76) had a significantly increased odds ratio for cage subsidence 3 months after TLIF. Male sex (OR: 2.55) but not age was a significant risk factor for cage subsidence 1 year after TLIF. Of all assessed risk factors, only BMI (OR: 1.11 per kg/m2) had a significantly increased risk for the need of revision surgery.

Age was associated with cage subsidence 3 months but not 1 year after TLIF suggesting that age is only a risk factor for early cage subsidence and not in a longer follow-up.

Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in the pathology and potential treatment of disc degeneration.

To investigate the effects of disc-specific Piezo1 deletion, we generated Aggrecan CreERT2 ; Piezo1 fl/fl mice and examined both lumbar spine instability (LSI)- and aging-induced disc degeneration. Additionally, the effect of pharmacological inhibition of Piezo1 was evaluated using GsMTx4, a potent Piezo1 antagonist, in an ex vivo model stimulated with IL-1β to induce disc degeneration. Assessments included histological examinations, immunofluorescence, and western blot analyses to thoroughly characterize the alterations in the intervertebral discs.

Elevated expression of Piezo1 was detected in the nucleus pulposus (NP) of intervertebral discs with advanced disc degeneration in both aged mice and human patients. Inducible deletion of Piezo1 expression in aggrecan-expressing disc cells significantly reduced lumbar disc degeneration, decreased extracellular matrix (ECM) degradation, and lowered apoptosis in NP cells, observed in both aged mice and those undergoing LSI surgery. Excessive compression loading (CL) upregulated Piezo1 expression, induced ECM disruption, and increased apoptosis in NP cells, whereas inhibition of Piezo1 with GsMTx4 effectively mitigated these pathological changes. Furthermore, in ex vivo cultured mouse discs, GsMTx4 treatment significantly alleviated IL-1β-induced degenerative damages, restored ECM anabolism, and reduced apoptosis.

The findings suggest that Piezo1 plays a critical role in the development of disc degeneration and highlight its potential as a therapeutic target. Inhibiting Piezo1 could offer a novel strategy for treating or preventing this critical disease.

This research highlights the involvement of Piezo1 in the development of intervertebral disc degeneration and emphasizes the potential for targeting Piezo1 as a therapeutic strategy to delay or reverse this condition.

With a prevalence of over 90% in people over 50, intervertebral disc degeneration (IVDD) is a major health concern. This weakening of the intervertebral discs can lead to herniation, where the nucleus pulpus (NP) leaks through the surrounding Annulus Fibrosus (AF). Considering the limited self-healing capacity of AF tissue, an implant is needed to restore its architecture and function. Here, we developed a biomimetic electrospun nanofibrous biodegradable scaffold that could be potentially used to repair AF defects. To that aim, we synthesized copolymers and blends of ε-caprolactone and lactide to create poly(ε-caprolactone-co-lactide) (PCLA) and PCL/PLA scaffolds with 10, 20, or 30% PLA. Properties of the initial nanofibrous scaffolds and the impact of gamma irradiation sterilization on the mechanical, thermal, and in vitro degradation properties are assessed and discussed with respect to the AF application. It was shown that ovine AF cells colonize the nanofibrous layers with increased metabolic activity over time. As an outcome of these studies, two copolymers were chosen to design a device composed of a 3D nanofibrous stacked scaffold associated with a degradable anchoring system to maintain the scaffold in an AF defect. The implantability of this device was tested in a cadaveric sheep lumbar IVD.

We utilized the Fast Low Angle Shot (FLASH) sequence to document the sequential changes in cartilaginous (CEP) and bony end plate (BEP) to study the influence on disc degeneration (DD).

Routine MRI and FLASH sequences were used in 500 lumbar discs in 100 each of healthy volunteers (HV), low back pain patients treated conservatively (CG) and surgically (SG) to document CEP and BEP status, Pfirrmann Grade (PG) and various MRI parameters.

The three groups were identical demographically but had a significantly different number of healthy discs (p < 0.01) and changes in CEP and BEP (p < 0.01), with patients having a higher severity of end plate changes and DD, even in asymptomatic discs. CEP abnormalities always appeared first, followed by a sequence of BEP defects of different severity, allowing the development of an 'Integrated Total End Plate Score' (I-TEPS). There was a good correlation between I-TEPS and PG, with a steep escalation of DD after a score of 7. A score of ≥ 7 was also associated with higher surgical incidence in patients with both degenerated and herniated discs. The most significant influencing factors for surgery was a combination of I-TEPS ≥ 7 with herniation (OR7.7;p-0.00), smoking (OR4.63;p-0.02), and an I-TEPS ≥ 7 (OR3.37;p-0.04).

CEP changes identified by FLASH preceded BEP defects and DD. I-TEPS was superior to TEPS in identifying a subgroup of discs that had CEP abnormalities without BEP. An I-TEPS ≥ 7 had a significant correlation to the severity of DD, influenced variations in herniation and also surgical incidence.

Degenerative disc disease is a common disorder that can significantly impact patients' quality of life, leading to chronic pain and disability. Platelet-rich plasma (PRP) therapy is emerging as a potential treatment for degenerative disc disease. The purpose of this review is to summarize the role of PRP in the management of degenerative disc disease types III and IV. This is a scoping literature review. The online database PUBMED was used, and papers were searched using the keywords: ("PRP" OR "platelet-rich plasma") AND ("degenerative disk disease" OR "disk degeneration" OR "intradiscal injection" OR "discogenic pain" OR "intervertebral disc degeneration" OR "degenerative disk disease" OR "intervertebral disc disease"). Clinical studies evaluating the role of PRP in the management of stage III and IV degenerative disc disease were included in the study. Systematic reviews, animal studies, in vitro studies, case reports, study designs, case reports, and studies in languages other than English were excluded. The present study includes 14 studies. PRP has been found to promote tissue regeneration and modulate inflammatory response in degenerated discs. PRP can be administered mostly intradiscally but also epidurally. The benefits of PRP use include pain reduction, improvement of functionality, and low risk of adverse events. The effect of intradiscal PRP injections is similar to steroid injections. A higher concentration of platelets is associated with enhanced clinical outcomes. PRP therapy represents a promising avenue for tissue healing and regeneration across degenerative disc disease. While the evidence supporting its efficacy is encouraging, further research is needed to elucidate its mechanisms of action, optimize treatment protocols, and expand its clinical applications.

Intervertebral disc degeneration disease (IVDD) is a major cause of disability and reduced work productivity worldwide. Annulus fibrosus degeneration is a key contributor to IVDD, yet its mechanisms remain poorly understood. Autophagy, a vital process for cellular homeostasis, involves the lysosomal degradation of cytoplasmic proteins and organelles. This study aimed to investigate the role of autophagy in IVDD using a hydrogen peroxide (H2O2)-induced model of rat annulus fibrosus cells (AFCs).

AFCs were exposed to H2O2 to model oxidative stress-induced degeneration. Protein expression levels of collagen I, collagen II, MMP3, and MMP13 were quantified. GEO database analysis identified alterations in miR-2355-5p expression, and its regulatory role on the mTOR pathway and autophagy was assessed. Statistical tests were used to evaluate changes in protein expression and pathway activation.

H2O2 exposure reduced collagen I and collagen II expression to approximately 50% of baseline levels, while MMP3 and MMP13 expression increased twofold. Activation of autophagy restored collagen I and II expression and decreased MMP3 and MMP13 levels. GEO analysis revealed significant alterations in miR-2355-5p expression, confirming its role in regulating the mTOR pathway and autophagy.

Autophagy, mediated by the miR-2355-5p/mTOR pathway, plays a protective role in AFCs degeneration. These findings suggest a potential therapeutic target for mitigating IVDD progression.

Lumbar disc herniation (LDH) affects millions globally, with annual healthcare costs exceeding $100 billion in the United States alone, driving increasing interest in minimally invasive radiological interventions as treatment alternatives. This narrative review examines developments in collagenase chemonucleolysis for LDH, integrating a literature analysis with clinical experience. Key advancements include the transition from single-agent to combination therapies, exploration of diverse injection routes, and the progression from C-arm fluoroscopy to multi-slice CT guidance. The synergistic use of collagenase, oxygen-ozone, and anti-inflammatory analgesics has enhanced efficacy. Safety measures such as aspiration tests, contrast agent tests, and lidocaine tests implemented to mitigate procedural risks. However, challenges persist, including non-standardized dosages and potential complications arising from intradiscal injections. Future research should focus on establishing accreditation systems, refining patient selection criteria, optimizing drug dosages, and exploring advanced image-guided technologies. While chemonucleolysis offers advantages such as minimal invasiveness and cost-effectiveness, its complexity necessitates a multidisciplinary approach. Key findings demonstrate that combination therapy achieves superior outcomes compared to monotherapy, with long-term efficacy rates reaching 90% and 6-month success rates of 95%. Additionally, CT guidance has significantly improved procedural precision and safety compared to traditional fluoroscopy. This review provides insights for clinicians and researchers, highlighting the potential of chemonucleolysis in LDH management to ensure its safe and effective integration into mainstream treatment protocols.

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.

Intervertebral disc degeneration (IVDD) stands as a prevalent chronic orthopedic ailment, profoundly impacting patients' well-being due to incapacitating low back pain. Studies have highlighted a close correlation between IVDD and the programmed cell death of nucleus pulposus (NP) cells orchestrated by interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and caspase-3 (CASP3). Puerarin, renowned for its anti-inflammatory attributes and its influence on IL-1β and TNF-α, emerges as a promising candidate for IVDD treatment. However, the precise mechanism by which it regulates apoptosis via these pathways remains ambiguous. This investigation utilizes bioinformatics to unveil the molecular intricacies of puerarin-mediated apoptosis regulation in IVDD, substantiated by preliminary in vitro experiments. Analysis exposes aberrant expression of pivotal apoptosis-associated proteins (IL-1β, TNF-α, CASP3, CASP8, and BCL2) in IVDD patients, with network pharmacology indicating puerarin's potential efficacy in IVDD treatment by modulating apoptosis and cellular senescence pathways. Further experiments elucidate puerarin's capacity to stimulate NP cell proliferation while inhibiting apoptosis, potentially contributing to IVDD mitigation. Western blot and PCR outcomes reveal escalated expression of apoptosis-related proteins (IL-1β, TNF-α, and CASP3) in lipopolysaccharide-treated NPCs, ameliorated by puerarin intervention. Molecular docking simulations demonstrate favorable binding properties of puerarin with apoptotic proteins, while flow cytometry analysis indicates its ability to diminish NPC apoptosis. These discoveries imply that puerarin might alleviate NPC apoptosis by modulating key targets, thereby potentially ameliorating IVDD. In summary, this study unveils the intrinsic mechanism of puerarin in regulating NPC apoptosis to alleviate IVDD, underscoring its therapeutic promise.

To systematically review relevant animal models of disk degeneration induced through the endplate injury pathway and to provide suitable animal models for exploring the intrinsic mechanisms and treatment of disk degeneration.

PubMed, Web of Science, Cochrane and other databases were searched for literature related to animal models of disk degeneration induced by the endplate injury pathway from establishment to August 2024, and key contents in the literature were screened and extracted to analyze and evaluate each type of animal model using the literature induction method.

Fifteen animal experimental studies were finally included in the literature, which can be categorized into direct injury models and indirect injury models, of which direct injury models include transvertebral injury models and transpedicular approach injury models, and indirect injury models include endplate ischemia models and vertebral fracture-induced endplate injury models. The direct injury models have a minimum observation period of 2 months and a maximum of 32 wk. All direct injury models were successful in causing disk degeneration, and the greater the number of interventions, the greater the degree of disk degeneration caused. The observation period for the indirect injury models varied from 4 wk to 70 wk. Of the 9 studies, only one study was unsuccessful in inducing disk degeneration, and this was the first animal study in this research to attempt to intervene on the endplate to cause disk degeneration.

The damage to the direct injury model is more immediate and controllable in extent and can effectively lead to disk degeneration. The indirect injury models do not directly damage the endplate structure, making it easier to observe the physiological and pathological condition of the endplate and associated structures of the disk. None of them can completely simulate the corresponding process of endplate injury-induced disk degeneration in humans, and there is no uniform clinical judgment standard for this type of model. The most appropriate animal model still needs further exploration and discovery.

As the aging process progresses, age-related intervertebral disc degeneration (IVDD) is becoming an emerging public health issue. Site-1 protease (S1P) has recently been found to be associated with abnormal spinal development in patients with mutations and has multiple biological functions. Here, we discovered a reduction of S1P in degenerated and aging intervertebral discs, primarily regulated by DNA methylation. Furthermore, through drug treatment and siRNA-mediated S1P knockdown, nucleus pulposus cells were more prone to exhibit degenerative and aging phenotypes. Conditional KO of S1P in mice resulted in spinal developmental abnormalities and premature aging. Mechanistically, S1P deficiency impeded COP II-mediated transport vesicle formation, which leads to protein retention in the endoplasmic reticulum (ER) and subsequently ER distension. ER distension increased the contact between the ER and mitochondria, disrupting ER-to-mitochondria calcium flow and resulting in mitochondrial dysfunction and energy metabolism disturbance. Finally, using 2-APB to inhibit calcium ion channels and the senolytic drug dasatinib and quercetin (D + Q) partially rescued the aging and degenerative phenotypes caused by S1P deficiency. In conclusion, our findings suggest that S1P is a critical factor in causing IVDD in the process of aging and highlight the potential of targeting S1P as a therapeutic approach for age-related IVDD.

This study aimed to discover micro-ribonucleic acids (microRNAs) involved in the degeneration of cartilage endplates through next-generation sequencing and lay the foundation for further research.

The cartilage endplate was obtained from patients who underwent interbody fusion surgery at the Department of Spine Surgery, Shanghai East Hospital Affiliated to Tongji University, from 1 January 2020 to 1 January 2023. Total RNA was extracted from the cartilage endplate tissue. Discover differential genes through NGS. To annotate gene functions, all target genes were aligned against the Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) databases. The GO enrichment and KEGG enrichment analyses of target genes were performed using phyper, a function of R. The p-value was corrected using the Bonferroni method, and a corrected p-value of ≤0.05 was taken as the threshold. GO terms or KEGG terms fulfilling this condition were defined as significantly enriched terms. The screened miRNAs and their target protein were verified in vitro using quantitative polymerase chain reaction (qPCR) and Western blotting (WB).

RNA was extracted from normal and degenerated cartilage endplate tissues for NGS. Eight downregulated differentially expressed genes (DEGs) and 22 upregulated DEGs were found. The KEGG pathway analysis of these target genes revealed that differential microRNAs and target genes were enriched in different signaling pathways, and the regulated signaling pathways were mainly mitochondrial autophagy and autophagy. The qPCR results demonstrated a significant upregulation of miR-25-3p and miR-345-5p in degenerative cartilage endplate tissues (p ≤ 0.001). Western blot analysis revealed that BRD4 exhibited a marked increase in protein expression levels in degenerative cartilage endplate tissues (p ≤ 0.0001), while BECN1 showed a significant decrease in protein expression levels within these samples (p ≤ 0.0001).

We found that DEG hsa-miR-25-3p and hsa-miR-345-5p can be used as diagnostic and therapeutic targets for IDD. The significant target proteins of miR-25-3p and miR-345-5p were BRD4 and BECN1, respectively.

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.

Intervertebral disc (IVD) degeneration damaging the extracellular matrix (ECM) of IVDs is the main cause of spine-associated disorders. Degenerative disc disease (DDD) is a multifaceted disorder, where environmental factors, inflammatory cytokines and catabolic enzymes act together. DDD starts typically due to imbalance between ECM biosynthesis and degradation within IVDs, especially through unbalanced degradation of aggrecan and collagen II in nucleus pulposus (NP). Current treatment approaches are primarily based on conservative or surgical therapies, which are insufficient for biological regeneration. The disintegrins and metalloproteinases with thrombospondin motifs (ADAMTSs) and matrix metalloproteinases (MMPs) are the key proteolytic enzymes for degradation of aggrecan and collagens. Previously, high expression levels of ADAMTS4, ADAMTS5, MMP3 and MMP13, which are accompanied with low levels of aggrecan and collagen II, were demonstrated in degenerative human NP cells. Moreover, self-complementary adeno-associated virus type 6 (scAAV6) mediated inhibitions of ADAMTS4 and ADAMTS5 by RNA-interference (RNAi) could specifically enhance aggrecan level. Thus, MMPs are apparently the main degrading enzymes of collagen II in NP. Furthermore, scAAV6-mediated inhibitions of MMP3 and MMP13 have not yet been investigated. Therefore, we attempted to enhance the level of collagen II in degenerative NP cells by scAAV6-RNAi-mediated inhibitions of MMP3 and MMP13. MRI was used to determine preoperative grading of IVD degeneration in patients. After isolation and culturing of NP cells, cells were transduced with scAAV6-shRNAs targeting MMP3 or MMP13; and analysed by fluorescence microscopy, FACS, MTT assay, RT-qPCR, ELISA and western blotting. scAAV6-shRNRs have no impact on cell viability and proliferation, despite high transduction efficiencies (98.6%) and transduction units (1383 TU/Cell). Combined knockdown of MMP3 (92.8%) and MMP13 (90.9%) resulted in highest enhancement of collagen II (143.2%), whereby treatment effects were significant over 56 days (p < 0.001). Conclusively, scAAV6-RNAi-mediated inhibitions of MMP3 and MMP13 help to progress less immunogenic and enduring biological treatments in DDD.

Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD.

Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section.

Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed.

These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.

We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration.

We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1-2), moderate (grade 3-4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality.

In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3-4) and good image quality (median 4; interquartile range 4-4).

DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs.

Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated.

A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI.

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral K3Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K3Citrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated K3Citrate did not alter the mineral composition and revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, K3Citrate reduced calcification incidence without altering the pathological endplate chondrocyte hypertrophy, suggesting mitigation of disc calcification primarily occurred through Ca2+ chelation, a conclusion supported by chondrogenic differentiation and Seahorse metabolic assays. Overall, this study underscores the therapeutic potential of K3Citrate as a systemic intervention strategy for disc calcification.

This study explores the potential of Omilancor in treating Intervertebral Disc Degeneration (IDD) through MAP2K6 targeting.

We analyzed mRNA microarray datasets to pinpoint MAP2K6 as a key regulator implicated in IDD progression. Follow-up studies demonstrated that cisplatin (DDP) could prompt cellular senescence in vitro by upregulating MAP2K6 expression. Through molecular docking and other analyses, we identified Omilancor as a compound capable of binding to MAP2K6. This interaction effectively impeded the cellular senescence induced by DDP.

We further showed that administration of Omilancor could significantly alleviate the degeneration of IVDs in annulus fibrosus puncture-induced rat model.

Omilancor shows promise as a treatment for IDD by targeting MAP2K6-mediated cellular senescence.

Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months.

Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded.

Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend.

This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.

Intervertebral disc degeneration (IVDD) is rising worldwide and leading to significant health issues and financial strain for patients. Traditional treatments for IVDD can alleviate pain but do not reverse disease progression, and surgical removal of the damaged disc may be required for advanced disease. The inflammatory microenvironment is a key driver in the development of disc degeneration. Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD. Several treatment options, including glucocorticoids, non-steroidal anti-inflammatory drugs, and biotherapy, are being studied for their potential to reduce inflammation. However, anti-inflammatories often have a short half-life when applied directly and are quickly excreted, thus limiting their therapeutic effects. Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment. This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems. We discuss the strengths, shortcomings, and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment, thus providing guidance for future breakthroughs in IVDD treatment.

The decellularized extracellular matrix (ECM) of cartilage is a widely used natural bioscaffold for constructing tissue-engineered cartilage due to its good biocompatibility and regeneration properties. However, current decellularization methods for accessing decellularized cartilaginous tissues require multiple steps and a relatively long duration to produce decellularized cartilage. In addition, most decellularization strategies lead to damage of the microstructure and loss of functional components of the cartilaginous matrix. In this study, a novel decellularization strategy based on a hydrostatic pressure (HP) bioreactor was introduced, which aimed to improve the efficiency of producing integral decellularized cartilage pieces by combining physical and chemical decellularization methods in a perfusing manner. Two types of cartilaginous tissues, auricular cartilage (AC) and nucleus pulposus (NP) fibrocartilage, were selected for comparison of the effects of ordinary, positive, and negative HP-based decellularization according to the cell clearance ratio, microstructural changes, ECM components, and mechanical properties. The results indicated that applying positive HP improved the efficiency of producing decellularized AC, but no significant differences in decellularization efficiency were found between the ordinary and negative HP-treated groups. However, compared with the ordinary HP treatment, the application of the positive or negative HP did not affect the efficiency of decellularized NP productions. Moreover, neither positive nor negative HP influenced the preservation of the microstructure and components of the AC matrix. However, applying negative HP disarranged the fibril distribution of the NP matrix and reduced glycosaminoglycans and collagen type II contents, two essential ECM components. In addition, the positive HP was beneficial for maintaining the mechanical properties of decellularized cartilage. The recellularization experiments also verified the good biocompatibility of the decellularized cartilage produced by the present bioreactor-based decellularization method under positive HP. Overall, applying positive HP-based decellularization resulted in a superior effect on the production of close-to-natural scaffolds for cartilage tissue engineering. Impact statement In this study, we successfully constructed a novel hydrostatic pressure (HP) bioreactor and used this equipment to produce decellularized cartilage by combining physical and chemical decellularization methods in a perfusing manner. We found that positive HP-based decellularization could improve the production efficiency of integral decellularized cartilage pieces and promote the maintenance of matrix components and mechanical properties. This new decellularization strategy exhibited a superior effect in the production of close-to-natural scaffolds and positively impacts cartilage tissue engineering.

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.

Proteoglycans through their sulfated glycosaminoglycans regulate cell-matrix signaling during tissue development, regeneration, and degeneration processes. Large extracellular proteoglycans such as aggrecan, versican, and perlecan are especially important for the structural integrity of the intervertebral disc and cartilage during development. In these tissues, proteoglycans are responsible for hydration, joint flexibility, and the absorption of mechanical loads. Loss or reduction of these molecules can lead to disc degeneration and skeletal dysplasia, evident from loss of disc height or defects in skeletal development respectively. In this review, we discuss the common proteoglycans found in the disc and cartilage and elaborate on various murine models and skeletal dysplasias in humans to highlight how their absence and/or aberrant expression causes accelerated disc degeneration and developmental defects.

Low back pain (LBP) mainly emerges from intervertebral disc (IVD) degeneration. However, the failing mechanism of IVD ́s components, like the annulus fibrosus (AF) and nucleus pulposus (NP), leading to IVD degeneration/herniation is still poorly understood. Moreover, the specific role of cellular populations and molecular pathways involved in the inflammatory process associated with IVD herniation remains to be highlighted. The limited knowledge of inflammation associated with the initial steps of herniation and the lack of suitable models to mimic human IVD ́s complexity are some of the reasons for that. It has become essential to enhance the knowledge of cellular and molecular key players for AF and NP cells during inflammatory-driven degeneration. Due to unique properties of immunomodulation and pluripotency, mesenchymal stem cells (MSCs) have attained diverse recognition in this field of bone and cartilage regeneration. MSCs therapy has been particularly valuable in facilitating repair of damaged tissues and may benefit in mitigating inflammation' degenerative events. Therefore, this review article conducts comprehensive research to further understand the intertwine between the mechanisms of action of IVD components and therapeutic potential of MSCs, exploring their characteristics, how to optimize their use and establish them safely in distinct settings for LPB treatment.

Adult degenerative scoliosis (ADS) research lacks bibliometric analysis, despite numerous studies. This study aimed to systematically analyze the development, current status, hot topics, frontier areas, and trends in ADS research.

A systematic literature review was conducted in the Web of Science Core Collection database from January 1998 to June 2023. Information regarding the country, institution, author, journal, and keywords was collected for each article. Bibliometric analysis was performed using VOSviewer and Citespace software.

The final analysis covered 1695 publications, demonstrating a steady increase in ADS research. The United States was the most prolific and influential country with 684 publications, followed by China and Japan. The University of California System was the most productive institution with 113 publications. Shaffrey, CI (47 publications) and Lenke, LG (41 publications) were top authors. The analysis revealed seven main research clusters: "intervertebral disc", "adult spinal deformity", "lumbar fusion", "minimally invasive surgery", "navigation", "postoperative complications", and "mental retardation". Keywords with strong bursts of activity included degeneration, prevalence, imbalance, classification, lumbar spinal stenosis, and kyphosis.

In conclusion, in recent years, ADS research has undergone rapid development. This study analyzed its hot topics, advancements, and research directions, making it the latest bibliometric analysis in this field. The findings aim to provide a new perspective and guidance for clinical practitioners and researchers.

Background The human vertebral column generates movements under versatile, dynamic loads. Understanding how the spine reacts to these movements and loads is crucial for developing new spine implants and surgical treatments for intervertebral disc injuries. Mechanically uni-axial compression models have been extensively studied. However, the spine's daily loading is not limited to compression, so it is crucial to measure its behavior in all movements (flexion-extension, rotation, and axial compression). Methods This study utilized L1-L5 segments from 19 healthy adult sheep spines. The L2-L3 disc of the first spine underwent only histological evaluation without biomechanical testing to define basic histological parameters. The remaining 18 were divided into three groups of six and subjected to biomechanical tests. Different mechanisms for three groups of spinal segments were prepared, and tests were performed on Shimadzu AG-IS 10 KN (Universal Drawing Press, Kyoto, Japan). An axial load (800 N) was applied to the first group, an axial load with 15 degrees of flexion to the second group, and an axial load with 10 degrees of rotation plus 15 degrees of flexion to the third group. A biomechanical evaluation of the maximum elongation amounts (MEAs) was performed and compared between the groups. Then, the L2-L3 discs were removed from the sheep spines, and a histological examination of the discs was conducted using Hematoxylin-Eosin (HE), Alcian Blue (AB), and Masson's Trichrome (MT) staining. Results The mean MEA ± Standard Deviation (Range) was 1.39 ± 0.38 (0.91-1.94) for Group 1, 2.02 ± 0.75 (0.91-3.01) for Group 2, and 2.47 ± 1.09 (0.64-3.9) for Group 3. Biomechanically, although MEAs increased from Group 1 to Group 3 (meaning that the mean MEAs increased as the number of types of applied force increased), there was no statistically significant difference between the groups regarding the MEAs (P = 0.092). Histologically, no significant differences were observed between all groups after HE staining. In all groups, hypercellularity, edema in the connective tissue, separation between tissue layers, delamination, and signs of swelling and necrosis in the cells were observed similarly. For the AB staining, there was a decrease in the glycosaminoglycan (GAG) structure in the tissue samples compared to the control tissue, but no significant differences were observed between the groups. However, it was observed that the stratification in Group 3 was slightly more deteriorated than in the other groups. For the MT staining, collagen structure deterioration was observed in all groups. It was observed that the amount of collagen was significantly reduced compared to the control tissue. Conclusion As a result, when the axial load is applied biomechanically, there is more displacement of the vertebral discs in Group 3 with multidimensional movements. Furthermore, histological studies revealed deterioration between tissue layers when exposed to complex movements, and the degradation of stratification in group 3 compared to other loading combinations in groups 2 and 3 may indicate the role of complex loads in the formation of disc herniation.

New information on the results of scientific research may change the understanding of the etiology and pathogenesis of diseases, which makes adjustments in treatment approaches. Cyclic local traction therapywas created in USA by the group of scientists for NASA (Axiom Worldwide, Tampa, FL) and approved by FDA in 2003. The year 2023 is the 20th anniversary of its successful application in practical medicine. Evaluating the effectiveness of the method, it has been shown that after undergoing treatment in patients with chronic back pain, the height of the intervertebral discs increases, pain syndrome and frequency of taking pain medications decreases, daily activity and duration of walking without pain increases. It is assumed that the treatment effect was achieved due to the «vacuum» effect, which could contribute to the regeneration of the intervertebral disc. It is also known about the possibility of intervertebral disc herniation reduction after a course of traction therapy and it was believed that this was ensured by «retraction» of the hernia back into the intervertebral space under the influence of the longitudinal ligament. However, fundamental studies of the past century and the present indicate the presence of other mechanisms affecting the structures of the vertebral motor segment, especially the processes occurring inside the intervertebral disc and contributing to the regression of the intervertebral disc herniation.

Intervertebral disk (IVD) degeneration (IVDD) is a main factor in lower back pain, and immunomodulation plays a vital role in disease progression. The IVD is an immune privileged organ, and immunosuppressive molecules in tissues reduce immune cell (mainly monocytes/macrophages and mast cells) infiltration, and these cells can release proinflammatory cytokines and chemokines, disrupting the IVD microenvironment and leading to disease progression. Improving the inflammatory microenvironment in the IVD through immunomodulation during IVDD may be a promising therapeutic strategy. This article reviews the normal physiology of the IVD and its degenerative mechanisms, focusing on IVDD-related immunomodulation, including innate immune responses involving Toll-like receptors, NOD-like receptors and the complement system and adaptive immune responses that regulate cellular and humoral immunity, as well as IVDD-associated immunomodulatory therapies, which mainly include mesenchymal stem cell therapies, small molecule therapies, growth factor therapies, scaffolds, and gene therapy, to provide new strategies for the treatment of IVDD.

Low back pain (LBP) is a major public health problem worldwide and a significant health and economic burden. Intervertebral disc degeneration (IDD) is the reason for LBP. However, we have not identified effective therapeutic strategies to address this challenge. With accumulating knowledge on the role of circular RNAs in the pathogenesis of IDD, we realised that circular RNAs (circRNAs) may have tremendous therapeutic potential and clinical application prospects in this field. This review presents an overview of the current understanding of characteristics, classification, biogenesis, and function of circRNAs and summarises the protective and detrimental circRNAs involved in the intervertebral disc that have been studied thus far. This review is aimed to help researchers better understand the regulatory role of circRNAs in the progression of IDD, reveal their clinical therapeutic potential, and provide a theoretical basis for the prevention and targeted treatment of IDD.

This study aims to assess the clinical outcomes of three transpedicular dynamic systems in treating degenerative disc disease and evaluate their impact on both clinical and radiological aspects of the operated and adjacent segments.

A total of 111 patients who underwent posterior transpedicular short-segment dynamic system procedures for treatment of degenerative disc disease were included. The patients were categorized into three groups, namely, Group 1 (Dynesys system, n = 38), Group 2 (Safinaz screw + PEEK rod, n = 37), and Group 3 (Safinaz screw + titanium rod, n = 36). Disc regeneration in the operated segment and disc degeneration in the operated, upper, and lower adjacent segments were assessed using the Pfirrmann Classification.

Postoperatively, a statistically significant difference was observed in visual analog scale and Oswestry Disability Index scores (p < 0.001). However, no statistically significant difference was seen in disc degeneration/regeneration and degeneration scores of the upper and lower adjacent segments between the preoperative and postoperative groups (p = 0.763, p = 0.518, p = 0.201). Notably, a positive effect on disc regeneration at the operated level (32.4%) was observed. No significant differences were found between the groups in terms of operation rates, screw loosening, and screw breakage after adjacent segment disease (p > 0.05).

In patients without advanced degeneration, all three dynamic systems demonstrated the ability to prevent degeneration in the adjacent and operated segments while promoting regeneration in the operated segment. Beyond inhibiting abnormal movement in painful segments, maintaining physiological motion and providing axial distraction in the operated segment emerged as key mechanisms supporting regeneration.

Low back pain caused by disc herniation and spinal stenosis imposes an enormous medical burden on society due to its high prevalence and refractory nature. This is mainly due to the long-term inflammation and degradation of the extracellular matrix in the process of intervertebral disc degeneration (IVDD), which manifests as loss of water in the nucleus pulposus (NP) and the formation of fibrous disc fissures. Biomaterial repair strategies involving hydrogels play an important role in the treatment of intervertebral disc degeneration. Excellent biocompatibility, tunable mechanical properties, easy modification, injectability, and the ability to encapsulate drugs, cells, genes, etc. make hydrogels good candidates as scaffolds and cell/drug carriers for treating NP degeneration and other aspects of IVDD. This review first briefly describes the anatomy, pathology, and current treatments of IVDD, and then introduces different types of hydrogels and addresses "smart hydrogels". Finally, we discuss the feasibility and prospects of using hydrogels to treat IVDD.

The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments.

Intervertebral disc degeneration (IVDD) is widely recognized as the primary etiological factor underlying low back pain, often necessitating surgical intervention as the sole recourse in severe cases. The metabolic pathway of arachidonic acid (AA), a pivotal regulator of inflammatory responses, influences the development and progression of IVDD.

Initially, a comparative analysis was conducted to investigate the relationship between AA expression patterns and different stages of IVDD using single-cell sequencing (scRNA-seq) data. Additionally, three machine learning methods (LASSO, random forest, and support vector machine recursive feature elimination) were employed to identify hub genes associated with IVDD. Subsequently, a novel artificial intelligence prediction model was developed for IVDD based on an artificial neural network algorithm and validated using an independent dataset. The identified hub genes were further subjected to functional enrichment, immune infiltration, and Connectivity Map analysis. Moreover, external validation was performed using flow cytometry and real-time reverse transcription polymerase chain reaction analysis.

Both scRNA-seq and bulk RNA-seq data revealed a positive correlation between the severity of IVDD and the AA metabolic pathway. They also revealed increased AA metabolic activity in macrophages and neutrophils, as well as enhanced intercellular communication with nucleus pulposus cells. Utilizing advanced machine learning algorithms, five hub genes (AKR1C3, ALOX5, CYP2B6, EPHX2, and PLB1) were identified, and an incipient diagnostic model was developed with an AUC of 0.961 in the training cohort and 0.72 in the validation cohort. An in-depth exploration of the functionality of these hub genes revealed their notable association with inflammatory responses and immune cell infiltration. Lastly, AH6809 was found to delay IVDD by inhibiting AKR1C3.

This study offers comprehensive insights into potential biomarkers and small molecules associated with the early pathogenesis of IVDD. The identified biomarkers and the developed integrated diagnostic model hold great promise in predicting the onset of early IVDD. AH6809 was established as a therapeutic target for AKR1C3 in the treatment of IVDD, as evidenced by computer simulations and biological experiments.

This study is the first to report the enhancement of cell migration and proliferation induced by in vitro microsecond pulsed electric field (μsPEF) exposure of primary bovine annulus fibrosus (AF) fibroblast-like cells. AF primary cells isolated from fresh bovine intervertebral disks (IVDs) are exposed to 10 and 100 μsPEFs with different numbers of pulses and applied electric field strengths. The results indicate that 10 μs-duration pulses induce reversible electroporation, while 100 μs pulses induce irreversible electroporation of the cells. Additionally, μsPEF exposure increased AF cell proliferation up to 150% while increasing the average migration speed by 0.08 μm/min over 24 h. The findings suggest that the effects of PEF exposure on cells are multifactorial-depending on the duration, intensity, and number of pulses used in the stimulation. This highlights the importance of optimizing the μsPEF parameters for specific cell types and applications. For instance, if the goal is to induce cell death for cancer treatment, then high numbers of pulses can be used to maximize the lethal effects. On the other hand, if the goal is to enhance cell proliferation, a combination of the number of pulses and the applied electric field strength can be tuned to achieve the desired outcome. The information gleaned from this study can be applied in the future to in vitro cell culture expansion and tissue regeneration.

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients' quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology.

Degeneration of the lumbar intervertebral disc is the most common cause of lower back pain. It is directly related to daily activities, mechanical stress, and other biological factors. We use imaging modalities to assess the degree of disc degeneration, out of which magnetic resonance imaging (MRI) is the most popular non-invasive modality. It is believed that early changes in disc degeneration are due to the biochemical events in the disc and can be evaluated by sequences in MRI involving the diffusion of water molecules. The apparent diffusion coefficient (ADC) is one such sequence that captures the signals based on the diffusion of water molecules. Ten articles were chosen from PubMed and Google Scholar using the MeSH terms 'lumbar spine degeneration' and 'apparent diffusion coefficient'. This review article has summarized various studies intending to gain a better understanding of the biochemical events leading to the development of disc degeneration. This study has also gathered the role of various sequences in MRI that can quantitatively assess disc degeneration.

Myeloid-derived suppressor cells (MDSCs) expand when the body undergoes inflammatory diseases and chronic diseases. However, its role in intervertebral disc degeneration remains unclear. The present study aimed to characterize specific subsets of MDSCs as potential indicators of disease progression in patients with lumbar disc herniation (LDH). The Gene Expression Omnibus (GEO) database was used to analyze the changes in granulocyte MDSCs (G-MDSCs). Peripheral blood samples were collected from 40 patients with LDH and 15 healthy controls, and flow cytometry was used to characterize different subsets of MDSCs. All subjects underwent lumbar spine magnetic resonance imaging. Then, t-distributed stochastic neighborhood embedding and FlowSOM were used to analyze the data obtained by CytoFlex. The correlation between circulating MDSCs and the clinicopathological stage of LDH was then further analyzed. The GEO database predicted that G-MDSCs were highly expressed in patients with LDH. The frequency of circulating G-MDSCs increased with Pfirrmann stage III and IV, while the percentage of mononuclear MDSCs (M-MDSCs) only increased. Patient age and sex did not correlate with the frequency of circulating G-MDSCs and M-MDSCs. The results of the computer algorithm analysis were consistent with those of our manual gating. The present study showed that the occurrence of LDH led to changes in the MDSC subpopulation in the circulating peripheral blood of patients, and the frequency of circulating G-MDSCs in patients with clinical stage III and IV LDH increased with the degree of degeneration. The determination of G-MDSCs can be used as an auxiliary examination item for LDH.

To construct an injectable, sustained-release fibrin gel containing rhein to solve the problem of low bioavailability of rhein, and observe its efficacy in the treatment of intervertebral disc degeneration.

The fibrin gel containing rhein was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Secondly, the degenerative cell model was constructed by stimulating nucleus pulposus cells with lipopolysaccharide (LPS), and the corresponding intervention treatment was carried out to observe the effect in vitro. Finally, the rat tail intervertebral disc was acupunctured by needles to establish the intervertebral disc degeneration model, and the effect of the material was observed through intradiscal injection.

The fibrin glue containing rhein (rhein@FG) showed good injectability, sustained release and biocompatibility. Rhein@FG can improve the LPS-induced inflammatory microenvironment, regulate ECM metabolic disorders of nucleus pulposus cells and aggregation of the NLRP3 inflammasome in vitro, and inhibit cell pyroptosis. Furthermore, in vivo experiments, rhein@FG effectively prevented needle puncture-induced intervertebral disc degeneration in rats.

Rhein@FG has better efficacy than rhein or FG alone due to its slow release and mechanical properties, which can be used as a potential replacement therapy for intervertebral disc degeneration.

Low back pain is a major contributor to disability worldwide and generates a tremendous socioeconomic impact. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to discogenic pain by sensitizing nociceptive neurons innervating the disc to stimuli that is nonpainful in healthy patients. Previously, we demonstrated the ability of degenerative IVDs to sensitize neurons to mechanical stimuli; however, elucidation of degenerative IVDs discogenic pain mechanisms is required to develop therapeutic strategies that directly target these mechanisms.

In this study, we utilized CRISPR epigenome editing of nociceptive neurons to identify mechanisms of degenerative IVD-induced changes to mechanical nociception and demonstrated the ability of multiplex CRISPR epigenome editing of nociceptive neurons to modulate inflammation-induced mechanical nociception.

Utilizing an in vitro model, we demonstrated degenerative IVD-produced IL-6-induced increases in nociceptive neuron activity in response to mechanical stimuli, mediated by TRPA1, ASIC3, and Piezo2 ion channel activity. Once these ion channels were identified as mediators of degenerative IVD-induced mechanical nociception, we developed singleplex and multiplex CRISPR epigenome editing vectors that modulate endogenous expression of TRPA1, ASIC3, and Piezo2 via targeted gene promoter histone methylation. When delivered to nociceptive neurons, the multiplex CRISPR epigenome editing vectors abolished degenerative IVD-induced mechanical nociception while preserving nonpathologic neuron activity.

This work demonstrates the potential of multiplex CRISPR epigenome editing as a highly targeted gene-based neuromodulation strategy for the treatment of discogenic pain, specifically; and, for the treatment of inflammatory chronic pain conditions, more broadly.