Structure Of Intervertebral Disc Research Articles

Сучасне розуміння етіопатогенезу дегенеративної хвороби дисків поперекового відділу у осіб дитячого віку. Освітлення ключових аспектів і перспектив

Low back pain is the most common complaint among people of any age, and degenerative disc disease (DHD) is the most common cause. Low back pain due to lumbar spondylolysis in adolescent athletes ranges from 8.8% to 47%. Features of the structure of intervertebral discs, a combination of genetic, mechanical, metabolic, and inflammatory factors create conditions for the development of degenerative changes in the vertebral motor segment, especially in intervertebral discs. The results of pathomorphological and magnetic resonance imaging studies show that degenerative changes in discs begin in childhood. Individual publications present data on the formation of a protrusion, even hernias occur in teenagers. Some publications have shown the effectiveness of drugs containing chondrocyte substitutes, indicating that early diagnosis of degenerative changes in the discs will allow timely treatment and secondary preventive measures. Further detailed research is needed to study the features of the development of degenerative changes in the discs in adolescents using imaging methods, taking into account the most common etiopathogenetic factors.

Evaluating the efficacy of a cost-effective, fully three-dimensional-printed vertebra model for endoscopic spine surgery training for neurosurgical residents.

A fused deposition modeling three-dimensional (3D)-printed model of the L4-5 vertebra for lumbar discectomy was designed. The model included separately printed dura mater, spinal cord, ligamentum flavum, intervertebral disc (from thermoplastic polyurethane), and bony structures (from polylactic acid), and the material cost approximately US$ 1 per model. A simple plumbing endoscope was used for visualization. Dura mater injury was assessed by painting two layers on the dura mater, which peeled off with trauma. Endoscopic spine surgery is a subject of high interest in neurosurgery given its minimally invasive nature; however, it has a steep learning curve. This study evaluated the effectiveness of a cost-efficient 3D-printed model when teaching this technique to neurosurgery residents. Only a few studies have investigated the efficacy of such a model. Eight residents with >2 years of training participated. Residents performed the procedure bilaterally and twice at 1-week intervals. From the 32 surgeries, four were excluded because of facet removal (as it widened the surgical corridor), leaving 28 surgeries for analysis. Initial surgeries demonstrated a mean operation time of 21 minutes 18 seconds (standard deviation [SD], 2 minutes 32 seconds), which improved to a mean of 6 minutes 45 seconds (SD, 37 seconds) in the fourth surgery (F(3, 17)=19.18, p <0.0001), demonstrating a significant reduction in surgical time over successive surgeries. The median area with the paint removed decreased, from 161.80 (85.55-217.83) to 95.13 mm2 (12.62-160.54), (F(2.072, Inf)=2.04, p =0.128); however, this was not significant. Resident feedback indicated high satisfaction with the educational value of the model. The developed fully 3D-printed model provides a viable and scalable option for neurosurgical training programs, enhancing the learning experience while maintaining low costs. This model may be an excellent stepping stone for learning lumbar spine endoscopy, acclimating to the two-dimensional view, progressing to cadaver models, and, eventually, independent surgery.

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

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

An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain

Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.

EZH2-H3K27me3-Mediated Epigenetic Silencing of DKK1 Induces Nucleus Pulposus Cell Pyroptosis in Intervertebral Disc Degeneration by Activating NLRP3 and NAIP/NLRC4.

Nucleus pulposus (NP) cell pyroptosis is crucial for intervertebral disc degeneration (IDD). However, the precise mechanisms underlying pyroptosis in IDD remain elusive. Therefore, this study aimed to investigate how dickkopf-1 (DKK1) influences NP cell pyroptosis and delineate the regulatory mechanisms of IDD. Behavioral tests and histological examinations were conducted in rat IDD models to assess the effect of DKK1 on the structure and function of intervertebral discs. Detected pyroptosis levels using Hoechst 33,342/propidium iodide (PI) double staining, and determined pyroptosis-related protein expression via western blotting. The cellular mechanisms of DKK1 in pyroptosis were explored in interleukin (IL)-1β-induced NP cells transfected with or without DKK1 overexpression plasmids (oe-DKK1). In addition, IL-1β-treated NP cells transfected with sh-EZH2 and/or sh-DKK1 were utilized to clarify the interplay between the enhancer of zeste homologue 2 (EZH2) and DKK1 in pyroptosis. Additionally, the epigenetic regulation of DKK1 by EZH2 was explored in NP cells treated with the EZH2 inhibitors GSK126/DZNep. DKK1 expression decreased in IDD rats. Transfection with oe-DKK1 reduced pro-inflammatory factors and extracellular matrix markers in IDD rats. In IL-1β-induced NP cells, DKK1 overexpression suppressed pyroptosis and inhibited the NLRP3 and NAIP/NLRC4 inflammasome activation. EZH2 knockdown increased DKK1 expression and reduced pyroptosis-related proteins. Conversely, DKK1 downregulation reversed the inhibitory effects of EZH2 knockdown on pyroptosis. Furthermore, EZH2 suppressed DKK1 expression via H3K27 methylation at the DKK1 promoter. EZH2 negatively regulates DKK1 expression via H3K27me3 methylation, promoting NP cell pyroptosis in IDD patients. This regulatory effect involves the activation of NLRP3 and NAIP/NLRC4 inflammasomes.

Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering.

Intervertebral disc degeneration (IVDD) stands as the foremost contributor to low back pain (LBP), imposing a substantial weight on the world economy. Traditional treatment modalities encompass both conservative approaches and surgical interventions; however, the former falls short in halting IVDD progression, while the latter carries inherent risks. Hence, the quest for an efficacious method to reverse IVDD onset is paramount. Biomaterial delivery systems, exemplified by hydrogels, microspheres, and microneedles, renowned for their exceptional biocompatibility, biodegradability, biological efficacy, and mechanical attributes, have found widespread application in bone, cartilage, and various tissue engineering endeavors. Consequently, IVD tissue engineering has emerged as a burgeoning field of interest. This paper succinctly introduces the intervertebral disc (IVD) structure and the pathophysiology of IVDD, meticulously classifies biomaterials for IVD repair, and reviews recent advances in the field. Particularly, the strengths and weaknesses of biomaterials in IVD tissue engineering are emphasized, and potential avenues for future research are suggested.

IL-1ra loaded chondroitin sulfate-functionalized microspheres for minimally invasive treatment of intervertebral disc degeneration

Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1β, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70 % in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. Statement of significanceThe strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1β. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility, good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo, they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD.

Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed “Discogenic back pain”, DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model. Injured IVDs treated with eEVs loaded with FOXF1 demonstrated robust sex-specific reductions in pain behaviors compared to control groups. Furthermore, significant restoration of IVD structure and function in animals treated with FOXF1 eEVs were observed, with significant increases in disc height, tissue hydration, proteoglycan content, and mechanical properties. This is the first study to successfully restore tissue function while modulating pain behaviors in an animal model of DBP using eEV-based non-viral delivery of transcription factor genes. Such a strategy can be readily translated to other painful musculoskeletal disorders.

Dynamics of structural transformations of intervertebral discs in humans in the fetal period

BACKGROUND:The process of formation of the intervertebral disc structure remains poorly understood. Therefore, evaluating the forecasts for the development of the disc’s fibrous component as the foundation of its strength and elastic properties in the postnatal period seems appropriate.&#x0D; AIM:To identify microstructural transformations of the annulus fibrosus and nucleus pulposus in the fetal period and compare them with the ontogenetic orientation of the spinal motion segment.&#x0D; MATERIAL AND METHODS:The study material included 150intervertebral discs obtained during autopsy of 50fetuses. The gestational age of 42fetuses was in the early fetal period, 8fetuses were in the late fetal period. Intervertebral discs СV–СVI, ThV–ThVI, LV–SIwere examined in each fetus. All histological preparations were stained with hematoxylin and eosin, silver impregnation method, PAS reaction, Alcian blue (pH=1.0), Van Gieson and Weigert stains. For intergroup comparisons, the Kruskal–Wallis, Mann–Whitney, and Newman–Keuls tests were used. Differences were considered statistically significant atp≤0.05.&#x0D; RESULTS:Elastic fibers in the late fetal period were found in the annulus fibrosus and the peripheral zone of the nucleus pulposus. The intensity of staining of collagen and elastic fibers was more pronounced in the outer layers of the annulus fibrosus. Analysis of the parameters of the vascular-connective tissue formations showed an increase in their number (p=0.0368) and an increase in the number of vessels in the vascular-connective tissue formations of the intervertebral disc (p=0.0449) in the direction of the lower levels of the spinal motion segments. Differences in these two indicators were obtained between the СV–СVIand LV–SIdiscs, as well as between the СV–СVIand ThV–ThVIdiscs. In relation to all the studied morphometric parameters of the vascular-connective tissue formations in the cervical and thoracic spine, no statistically significant differences were obtained between the early and late fetal periods.&#x0D; CONCLUSION:The development of the intervertebral disc occurs from the peripheral parts to the center; the source for its further development is the fibrous ring.

Therapeutic effect and mechanism of Yougui Wan in rats with intervertebral disk degeneration

ObjectiveTo explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats.MethodsThirty male Sprague–Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method.ResultsCompared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P < 0.05), the protein expression levels of collagen II were decreased, and the protein expression levels of Notch1 were increased. Compared with those in the model group, the levels of IL-10 in the TCM group were increased (P < 0.05), the levels of MIF and TNF-α were decreased (P < 0.05), the protein expression levels of collagen II were increased, and the protein expression levels of Notch1 were decreased.ConclusionYougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway.

Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues.

Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.

Influence of instrumentation type on outcomes after surgical management of spondylodiscitis: a systematic review and meta-analysis.

Spondylodiscitis refers to infection of the intervertebral disk and neighboring structures. Outcomes based on instrumentation type are not well reported in the literature, but are important in establishing guidelines for surgical management of spondylodiscitis. This study aims to clarify the effect of instrumentation material selection on clinical and radiographic outcomes in patients with spondylodiscitis. Studies that evaluated the use of polyetheretherketone (PEEK), titanium, allograft, and/or autologous bone grafts for spondylodiscitis were identified in the literature. Radiographic and clinical data were analyzed using a meta-analysis of proportions, with estimated risk and confidence intervals reported for our primary study outcomes. Thirty-two retrospective studies totaling 1088 patients undergoing surgical management of spondylodiscitis with PEEK, TTN, allograft, and autologous bone graft instrumentation were included. There were no differences in fusion rates (p-interaction = 0.55) with rates of fusion of 93.4% with TTN, 98.6% with allograft, 84.2% with autologous bone graft, and 93.9% with PEEK. There were no differences in screw loosening (p-interaction = 0.52) with rates of 0.33% with TTN, 0% with allograft, 1.3% with autologous bone graft, and 8.2% with PEEK. There were no differences in reoperation (p-interaction = 0.59) with rates of 2.64% with TTN, 0% with allograft, 1.69% with autologous bone graft, and 3.3% with PEEK. This meta-analysis demonstrates that the choice of instrumentation type in the surgical management of spondylodiscitis resulted in no significant differences in rate of radiographic fusion, screw loosening, or reoperation. Future comparative studies to optimize guidelines for the management of spondylodiscitis are needed.

Comparative effects of patient-specific 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy

BackgroundLow back pain (LBP) resides as a most common type of symptom pointing towards lumber radiculopathy. It is defined as burning sharp leg pain that originates from the back and goes all the way down your legs and extends into the toes and foot. Lumbosacral radiculopathy is caused by pathology of the intervertebral disk or associated structures. Different dimensional traction has been used to treat lumbar radiculopathy. This study aimed to compare the effects of 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy. The randomized clinical trial study of 4 weeks was carried out at the Lifeline Health Care Imaging and Pain Center and the Hamza Hospital Lahore. Twenty-six subjects were included in the clinical trial and divided into two groups after randomization. Group A received three-dimensional lumbar traction with traction force 50% of total body weight on Spine MT 3D traction machine, and group B received two-dimensional lumbar traction with traction force 50% of total body weight. Pre- and post-values of NPRS and ODI were noted.ResultsParametric tests were used during statistical analysis because data was normally distributed. NPRS pre- and posttreatment values showed significant results with p-value < 0.05. ODI pre- and post-values were also obvious with p-value < 0.05. Independent sample T-test was used to assess across the group comparison, suggesting that both groups showed significant improvements of NPRS and ODI post-treatment with p-value (< 0.001).ConclusionThe study concluded that 3D traction significantly reduced pain levels and improved functional impairment more effectively than 2D traction in patients with lumbar radiculopathy.Trial registrationTrial was registered with ClinicalTrials.gov: NCT05356689.

Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.

Intervertebral disc (IVD) degeneration is associated with chronic back pain. We previously demonstrated that the phosphatase pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1 was positively correlated with IVD degeneration and its deficiency decelerated IVD degeneration in both mouse IVDs and human nucleus pulposus (NP) cells. Small molecule PHLPP inhibitors may offer a translatable method to alleviate IVD degeneration. In this study, we tested the effectiveness of the two PHLPP inhibitors NSC117079 and NSC45586 in promoting a healthy NP phenotype. Tail IVDs of 5-month-old wildtype mice were collected and treated with NSC117079 or NSC45586 under low serum conditions ex vivo. Hematoxylin & eosin staining was performed to examine IVD structure and NP cell morphology. The expression of KRT19 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human NP cells were obtained from patients with IVD degeneration. The gene expression of KRT19, ACAN, SOX9, and MMP13 was analyzed via real time qPCR, and AKT phosphorylation and the protein expression of FOXO1 was analyzed via immunoblot. In a mouse IVD organ culture model, NSC45586, but not NSC117079, preserved vacuolated notochordal cell morphology and KRT19 expression while suppressing cell apoptosis, counteracting the degenerative changes induced by serum deprivation, especially in males. Likewise, in degenerated human NP cells, NSC45586 increased cell viability and the expression of KRT19, ACAN, and SOX9 and reducing the expression of MMP13, while NSC117079 treatment only increased KRT19 expression. Mechanistically, NSC45586 treatment increased FOXO1 protein expression in NP cells, and inhibiting FOXO1 offset NSC45586-induced regenerative potential, especially in males. Our study indicates that NSC45586 was effective in promoting NP cell health, especially in males, suggesting that PHLPP plays a key role in NP cell homeostasis and that NSC45586 might be a potential drug candidate in treating IVD degeneration.

Intervertebral disc generation tissue engineering treatment platform: gelatin-methacryloyl hydrogel composite system.

Intervertebral disc generation tissue engineering treatment platform: gelatin-methacryloyl hydrogel composite system.

Bioinspired Intervertebral Disc with Multidirectional Stiffness Prepared via Multimaterial Additive Manufacturing

AbstractDegenerative disc disease (DDD) has become a significant public health issue worldwide. This can result in loss of spinal function affecting patient health and quality of life. Artificial total disc replacement (A‐TDR) is an effective approach for treating symptomatic DDD that compensates for lost functionality and helps patients perform daily activities. However, because current A‐TDR devices lack the unique structure and material characteristics of natural intervertebral discs (IVDs), they fail to replicate the multidirectional stiffness needed to match physiological motions and characterize anisotropic behavior. It is still unclear how the multidirectional stiffness of the disc is affected by structural parameters and material characteristics. Herein, a bioinspired intervertebral disc (BIVD‐L) based on a representative human lumbar segment is developed. The proposed BIVD‐L reproduces the multidirectional stiffness needed for the most common physiological kinematic behaviors. The results demonstrate that the multidirectional stiffness of the BIVD‐L can be regulated by structural and material parameters. The results of this research deepen knowledge of the biomechanical behavior of the human lumbar disc and may provide new inspirations for the design and fabrication of A‐TDR devices for both engineering and functional applications.

Mechanical Signal-Tailored Hydrogel Microspheres Recruit and Train Stem Cells for Precise Differentiation.

The aberrant mechanical microenvironment in degenerated tissues induces misdirection of cell fate, making it challenging to achieve efficient endogenous regeneration. Herein, a hydrogel microsphere-based synthetic niche with integrated cell recruitment and targeted cell differentiation properties via mechanotransduction was constructed for enhanced endogenous regeneration. Through the incorporation of microfluidics and photo-polymerization strategies, we prepared fibronectin (Fn) modified methacrylated gelatin (GelMA) microspheres with the independently tunable elastic modulus(1-10Kpa) and ECM ligand density (2 and 10μg/ml), allowing a wide range of cytoskeleton modulation to trigger the corresponding mechanobiological signaling to direct cell fate. The combination of the soft matrix (2Kpa) and low ligand density (2μg/ml) could support the nucleus pulposus (NP)-like differentiation of intervertebral disc (IVD) progenitor/stem cells by translocating Yes-associated protein (YAP), without the addition of inducible biochemical factors. Meanwhile, platelet-derived growth factor-BB was loaded onto Fn-GelMA microspheres (PDGF@Fn-GelMA) via the heparin-binding domain of Fn and exhibited continuous release for over 28 days to initiate endogenous cell recruitment. In in vivo experiments, hydrogel microsphere-niche maintained the IVD structure and stimulated ECM synthesis, thereby enhancing the endogenous regeneration of NP. Overall, this synthetic niche with cell recruiting and mechanical training capabilities offered a promising novel strategy for endogenous tissue regeneration. This article is protected by copyright. All rights reserved.

Effect of acupotomy intervention on the expressions of proteoglycans in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration

To observe the effect of acupotomy intervention on the expressions of biglycan(BGN), decorin(DCN) and Caspase-3 in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration (LIDD), so as to explore its possible mechanism in relieving LIDD. Thirty male Japanese white rabbits were randomly divided into normal, model and acupotomy groups, with 10 rabbits in each group. The LIDD model was established by axial compression method, and magnetic resonance imaging (MRI) was used to judge whether the model was successful or not. After modeling, the acupotomy was applied to lumbar (L)4-L5 spinous process space and bilateral transverse processes for loosening, twice a week for 4 weeks. The structural changes of L4-L5 intervertebral disc were observed by MRI. The morphological changes of lumbar spine were observed by HE staining. The expression of Caspase-3 in nucleus pulposus was observed by immunohistochemistry, and the protein expressions of DCN and BGN in intervertebral disc were detected by Western blot, separatively. After mode-ling, the rabbits showed slow movement, stiff back muscles with cords or nodules, the fibrous ring structure of lumbar intervertebral disc was disordered, the number of nucleus pulposus cells was reduced, and the signal intensity of L4-L5 intervertebral disc was decreased in the model group relevant to the normal group. At the same time, the expression of Caspase-3 in nucleus pulposus was increased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were decreased significantly (P<0.05). After acupotomy treatment, the modeling induced slow movement, stiff back muscles and disordered structure of lumbar intervertebral disc were significantly improved. The number of nucleus pulposus cells was increased, the signal intensity of L4-L5 intervertebral disc was enhanced, the expression of Caspase-3 in nucleus pulposus was decreased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were increased significantly (P<0.05) compared with the model group. Acupotomy intervention can inhibit cell apoptosis, reduce the degradation of extracellular matrix in nucleus pulposus of intervertebral disc, and restore the normal force balance and dynamic balance of lumbar spine, which may be one of its mechanisms underlying improving LIDD.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

FOXO3-Activated circFGFBP1 Inhibits Extracellular Matrix Degradation and Nucleus Pulposus Cell Death via miR-9-5p/BMP2 Axis in Intervertebral Disc Degeneration In Vivo and In Vitro

(1) Background: intervertebral disc degeneration (IVDD) defined as the degenerative changes in intervertebral disc is characterized by extracellular matrix (ECM) degradation and death in nucleus pulposus (NP) cells. (2) Methods: The model of IVDD was established in male Sprague Dawley rats using a puncture of a 21-gauge needle at the endplates located in the L4/5 intervertebral disc. Primary NP cells were stimulated by 10 ng/mL IL-1β for 24 h to mimic IVDD impairment in vitro. (3) Results: circFGFBP1 was downregulated in the IVDD samples. circFGFBP1 upregulation inhibited apoptosis and extracellular matrix (ECM) degradation and promoted proliferation in IL-1β-stimulated NP cells. Additionally, circFGFBP1 upregulation mitigated the loss of NP tissue and the destruction of the intervertebral disc structure in vivo during IVDD. FOXO3 could bind to the circFGFBP1 promoter to enhance its expression. circFGFBP1 upregulated BMP2 expression in NP via sponging miR-9-5p. FOXO3 enhanced the protection of circFGFBP1 in IL-1β-stimulated NP cells, whereas a miR-9-5p increase partly reversed the protection. miR-9-5p downregulation contributed to the survival of IL-1β-stimulated NP cells, which was partially reversed by BMP2 silence. (4) Conclusions: FOXO3 could activate the transcription of circFGFBP1 via binding to its promoter, which resulted in the enhancement of BMP2 via sponging miR-9-5p and then inhibited apoptosis and ECM degradation in NP cells during IVDD.