Intervertebral Disc Research Articles

Computed tomography of the equine caudal spine and pelvis. Pathological findings in 56 clinical cases (2018-2023).

Computed tomography (CT) of the axial skeleton is increasing across many equine hospitals. CT of the pelvis and caudal spine in a large group of clinical cases has not been reported previously. To describe the pathological lesions identified in the caudal spine/pelvis in horses and ponies undergoing CT spine of this region. A retrospective case series. Horses with CT imaging of the caudal spine/pelvis were included. Horses aged under 6 months and those with CT examinations performed post-mortem were excluded. Fifty-six horses met the inclusion criteria. Ages ranged from 8 months to 20 years and bodyweights from 85 to 680 kg (mean 488 kg). Horses presented predominantly for lameness (30/56) and poor performance (18/56). Osseous pathology was identified in 41/56 horses; including osteoarthritis of the sacroiliac joint(s) (n: 28), pathology of the intervertebral disc joint(s) (n: 12), pelvic fractures (n: 9), osteoarthritis of the coxofemoral joint(s) (n: 8), ventral spondylosis (n: 6), acetabular rim fracture (n: 2), dislocation of coxofemoral joint(s) (n: 2), and dorsal dermal sinus of the sacrum (n: 1). The relationship between CT imaging findings and clinical signs in horses remains unclear. Further work is required to describe the relationship between congenital, developmental, and acquired changes in the caudal spine and pelvis, and clinical signs. CT of the caudal spine and pelvis can be utilised in horses and ponies for diagnosing a range of clinical disorders that may be causing 'lumbosacroiliac pain', poor performance, hindlimb lameness, and stiffness. The pathologies we observed were diverse and many patients had multiple lesions.

Development of a spinopelvic complex finite element model for quantitative analysis of the biomechanical response of patients with degenerative spondylolisthesis.

Research on degenerative spondylolisthesis (DS) has focused primarily on the biomechanical responses of pathological segments, with few studies involving muscle modelling in simulated analysis, leading to an emphasis on the back muscles in physical therapy, neglecting the ventral muscles. The purpose of this study was to quantitatively analyse the biomechanical response of the spinopelvic complex and surrounding muscle groups in DS patients using integrative modelling. The findings may aid in the development of more comprehensive rehabilitation strategies for DS patients. Two new finite element spinopelvic complex models with detailed muscles for normal spine and DS spine (L4 forwards slippage) modelling were established and validated at multiple levels. Then, the spinopelvic position parameters including peak stress of the lumbar isthmic-cortical bone, intervertebral discs, and facet joints; peak strain of the ligaments; peak force of the muscles; and percentage difference in the range of motion were analysed and compared under flexion-extension (F-E), lateral bending (LB), and axial rotation (AR) loading conditions between the two models. Compared with the normal spine model, the DS spine model exhibited greater stress and strain in adjacent biological tissues. Stress at the L4/5 disc and facet joints under AR and LB conditions was approximately 6.6 times greater in the DS spine model than in the normal model, the posterior longitudinal ligament peak strain in the normal model was 1/10 of that in the DS model, and more high-stress areas were found in the DS model, with stress notably transferring forwards. Additionally, compared with the normal spine model, the DS model exhibited greater muscle tensile forces in the lumbosacral muscle groups during F-E and LB motions. The psoas muscle in the DS model was subjected to 23.2% greater tensile force than that in the normal model. These findings indicated that L4 anterior slippage and changes in lumbosacral-pelvic alignment affect the biomechanical response of muscles. In summary, the present work demonstrated a certain level of accuracy and validity of our models as well as the differences between the models. Alterations in spondylolisthesis and the accompanying overall imbalance in the spinopelvic complex result in increased loading response levels of the functional spinal units in DS patients, creating a vicious cycle that exacerbates the imbalance in the lumbosacral region. Therefore, clinicians are encouraged to propose specific exercises for the ventral muscles, such as the psoas group, to address spinopelvic imbalance and halt the progression of DS.

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

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

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

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

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

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

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

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

Risk and clinical characteristics of spinal cord compression across different mucopolysaccharidosis types: A retrospective cohort study.

In patients with mucopolysaccharidosis (MPS), the accumulation of glycosaminoglycans leads to various complications, including spinal cord compression (SCC). Although SCC is a well-known complication in MPS, data comparing its clinical features across different MPS types remain limited. This study aimed to investigate the timing, location, and underlying causes of SCC in MPS, as well as to compare the risk and clinical characteristics by MPS type. We conducted a retrospective cohort study, reviewing the medical records of 183 patients with all types of MPS who were followed at Samsung Medical Center from January 1995 to March 2024. The distribution of patients diagnosed with SCC by MPS type was 33.3% for type I, 10.5% for type II, 55.0% for type IV, and 100% for type VI. The median age at SCC diagnosis was 16.3 years. Compared to type II, the risk of SCC was higher for type I (2.4 times, 95% confidence interval [CI]: 0.9-6.2), type IV (3.5 times; 95% CI: 1.5-8.1), and type VI (4.5 times, 95% CI: 1.2-16.4). Enzyme replacement therapy did not reduce the risk of SCC (P = .70). Moreover, SCC most frequently occurred at the C0 to C4 and T11 to L2 spinal levels. In the cervical spine, ligament thickening, and skeletal deformities were the predominant causes, whereas in the thoracolumbar spine, kyphoscoliosis and intervertebral disc issues were the main contributors. Although there was no significant difference in the location of SCC (P = .99), the underlying causes varied significantly by MPS type (P < .001). SCC is a common complication in MPS, but its risk and pathophysiology vary by MPS type. Therefore, an individualized approach is needed for early detection and appropriate intervention.

Apical stress redistribution during anterior vertebral body tethering for thoracic adolescent idiopathic scoliosis: a finite element analysis of a novel surgical technique.

Apical stress redistribution (ASR) is proposed to mitigate failure risks after anterior vertebral body tethering for adolescent idiopathic scoliosis. It consists in releasing set-screws at peri-apical levels following curve tensioning to redistribute stresses within the construct. This study determines the biomechanical impact and curve correction obtained with ASR. Finite element models of anterior vertebral body tethering were constructed for three typical scoliotic patients with Lenke 1 curves. ASR was simulated by releasing tension on the cable at the level of the three apical set screws (i.e. untightening three consecutive periapical set screws), followed by retightening of the set screws without further tensioning. Cable tension, implant forces and spine geometry were compared before and after performing ASR. Periapical cable tension decreased post-ASR, and ASR alsoreduced the maximum tensions proximally and distally. Postoperative disc height was similar between conventional and ASR approaches. Apical intervertebral disc stresses were shifted from concave to convex compression intra and postoperatively, with a similar pattern between the conventional and ASR techniques. The ASR technique achieved scoliotic curve corrections of 54%, 68%, and 79%, while the conventional technique resulted in corresponding corrections (54%, 68%, and 80%) for subjects 1, 2, and 3. The periapical coronal curves exhibited similar patterns. ASR demonstrated promising apical cable and implant forces re-equilibrium compared to the conventional approach. This novel technique did not impair immediate and postoperative curve correction, while maintaining similar apical intervertebral stress distribution. ASR shows potential to modulate growth while reducing maximum cable tension infra- and supra-apical.

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

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

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

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

Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.

Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. 370 (31%) of 1197 participants, had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with versus without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, P<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, body mass index, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, P=.054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99 to 6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend P=.005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.

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

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

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

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

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

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

Biomechanical significance of intervertebral discs on growthplate stresses in scoliotic trunks following unilateral muscle weakening: A hybrid approach of finite element and musculoskeletal modeling.

This study aimed to ascertain the relevance of intervertebral discs (IVD) in the stress distribution on growthplates (GPs) of a trunk model with adolescent idiopathic scoliosis (AIS) following a unilateral weakening of muscles. A thoracolumbar spine finite element (FE) model of a young female healthy and an AIS spine comprising GPs linked to the T12 through sacrum vertebrae. Two scenarios of including (FEI) and excluding (FEE) IVDs were considered. Then, using optimization-driven musculoskeletal models of the AIS and healthy trunks, the FE models were examined under subject-specific muscle forces and gravity loads. Results of this study demonstrate that when IVDs included in the FE model, an increase, ranging from 0.2 to 1.7 MPa, with the highest value occurring at the apex of the AIS model, in the von Mises stresses in the GPs. The ratio of 1.5 was found for the maximum von-Mises stress value on the most tilted GP in the FEI over the FEE model. Unilateral paralysis of muscles caused a reduction of 50% and 63% in the von Mises stress ratio of the concave-over-convex side of the most tilted GP in the FEI and FEE models of the AIS spine with healthy muscles, respectively. The intradiscal pressures, found for FEE and FEI models, assented to recent in-vivo investigations. Nonetheless, employing IVDs in the simulations provides an indispensable tool to anticipate the effects of neuromuscular disorders on GP stresses in an AIS spine and predict deformity progression during growth.

Effect of Therapeutic Exercise and Activities of Daily Living Instructions on Prolapsed Lumbar Intervertebral Disc

Background: Clinically significant sciatica due to disc prolapse occurs in 4-6% of the population. Among various options for the treatment of Prolapsed Lumber Intervertebral Disc (PLID) Pharmacotherapy, thermotherapy and exercise therapy are commonly used. Therapeutic exercises and ADL instruction can enable greater return of neurological function and improves long term outcome and quality of life. Objective: To see the effects of therapeutic exercises and ADL instructions on the treatment of PLID and their outcome. Materials and Methods: This prospective randomized clinical trial was performed over a period of six months on the patients of PLID. Evaluation was made at initial visit and follow up was done at third and sixth week by same investigator. In each visit pain intensity was seen by using straight leg raising test (SLR), Visual Analogue scale (VAS) respectively. Post intervention result was compared with baseline result. Results: The pain was mild in 11.4% cases of group A and 17.1% cases of group B (p=0.587). LBP was intermittent in most of the cases in both groups which was 71.4% cases and 80.0% cases in group A and group B respectively. Pain aggravates in most of the patient by walking (28.6%) and bending (21.3%) in both groups. However significant difference between group A and group B was found at week 6 follow up (p=&lt;.005). During the study the SLR was improved significantly on week 6 follow up. The significant difference between group A and group B was found at week 6 follow up (p=&lt;.005) regarding straight leg raising test (SLR) score. Conclusions: This study demonstrates the superiority of therapeutic exercises and activities of daily living in reduction of pain in management of patients with PLID. KYAMC Journal Volume: 15, No: 01, April 2024: 08-15.

Exosome-Laden Hydrogels as Promising Carriers for Oral and Bone Tissue Engineering: Insight into Cell-Free Drug Delivery.

Mineralization is a key biological process that is required for the development and repair of tissues such as teeth, bone and cartilage. Exosomes (Exo) are a subset of extracellular vesicles (~50-150 nm) that are secreted by cells and contain genetic material, proteins, lipids, nucleic acids, and other biological substances that have been extensively researched for bone and oral tissue regeneration. However, Exo-free biomaterials or exosome treatments exhibit poor bioavailability and lack controlled release mechanisms at the target site during tissue regeneration. By encapsulating the Exos into biomaterials like hydrogels, these disadvantages can be mitigated. Several tissue engineering approaches, such as those for wound healing processes in diabetes mellitus, treatment of osteoarthritis (OA) and cartilage degeneration, repair of intervertebral disc degeneration, and cardiovascular diseases, etc., have been exploited to deliver exosomes containing a variety of therapeutic and diagnostic cargos to target tissues. Despite the significant efficacy of Exo-laden hydrogels, their use in mineralized tissues, such as oral and bone tissue, is very sparse. This review aims to explore and summarize the literature related to the therapeutic potential of hydrogel-encapsulated exosomes for bone and oral tissue engineering and provides insight and practical procedures for the development of future clinical techniques.

Biomimetic Microstructural Materials for Intervertebral Disk Degeneration Repair

The intervertebral disks (IVD) serve as shock absorbers in the spine. As the largest avascular tissue in the human body, it has a limited capacity for regeneration. To address this issue, various innovative biomimetic materials have been explored to facilitate IVD regeneration at both microscopic and macroscopic levels. Techniques such as electrostatic spinning and fiber‐winding machines have been employed to prepare biomimetic materials. In this review, the physiological structure of the IVD is described, and advanced studies on its microstructure are summarized. The techniques used in biomimetic biomaterial development are further investigated, and biomimetic materials that facilitate IVD regeneration are systematically explored. Specifically, this article provides a detailed description and summary of the key features of biomimetic materials, including the types of loads they can withstand and their regenerative effects. Finally, a prospective outlook for the development and application of biomimetic materials in IVD regeneration is presented.

Protective effects of PDGF-AB/BB against cellular senescence in human intervertebral disc.

Cellular senescence, characterized by a permanent state of cell cycle arrest and a secretory phenotype contributing to inflammation and tissue deterioration, has emerged as a target for age-related interventions. Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. Previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptosis, anti-inflammation, and pro-anabolism. However, its impact on IVD cell senescence remains elusive. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for 5 days and changes of transcriptome profiling were examined through mRNA sequencing. NP and AF cells demonstrated similar but distinct responses to the treatment. However, the effects of PDGF-AB and BB on human IVD cells were comparable. Specifically, PDGF-AB/BB treatment resulted in downregulation of gene clusters related to neurogenesis and response to mechanical stimulus in AF cells while the downregulated genes in NP cells were mainly associated with metabolic pathways. In both NP and AF cells, PDGF-AB and BB treatment upregulated the expression of genes involved in cell cycle regulation, mesenchymal cell differentiation, and response to reduced oxygen levels, while downregulating the expression of genes related to senescence associated phenotype, including oxidative stress, reactive oxygen species (ROS), and mitochondria dysfunction. Network analysis revealed that PDGFRA and IL6 were the top hub genes in treated NP cells. Furthermore, in irradiation-induced senescent NP cells, PDGFRA gene expression was significantly reduced compared to non-irradiated cells. However, rhPDGF-AB/BB treatment increased PDGFRA expression and mitigated the senescence progression through increased cell population in the S phase, reduced SA-β-Gal activity, and decreased expression of senescence related regulators including P21, P16, IL6, and NF-κB. Our findings reveal a novel anti-senescence role of PDGF in the IVD, demonstrating its ability to alleviate the senescent phenotype and protect against the progression of senescence. This makes it a promising candidate for preventing or treating IVD degeneration by targeting cellular senescence.

Correlation Between Quantitative Cage Pressure Measurements and Surgeons' Qualitative Tactile Assessments During Extraction in Lumbar Lateral Interbody Fusion: A Cadaveric Study.

A cadaveric study. Measuring the pressure exerted on lumbar lateral interbody fusion (LLIF) cages and examining its correlation with qualitative assessment of tactile feedback related to pullout strength during cage extraction to determine the optimal cage height. No data exists on the relationship between the surgeon's tactile feedback related to pullout strength during the LLIF cage extraction and the cage pressures measured during surgery. We used four cadavers to insert the original stress-measuring cages at the L2/3 to L4/5 levels (12 intervertebral spaces) using the oblique lumbar lateral approach. The intervertebral disc height (IDH) was measured before cage insertion. These stainless-steel stress-measuring cages were designed with the same shape as standard cages and included a built-in load cell to measure the stress applied. The cage heights were set at 8, 10, and 12 mm and they were inserted sequentially from 8mm, with stress measurements taken at each step. Four spine surgeons qualitatively evaluated the extraction strength using three rating categories ("loose," "appropriate," and "hard to extract"). After cage removal, endplate damage (ED) and anterior longitudinal ligament injury (ALLI) were checked. The anterior part of the vertebral body was dissected to expose the ALL and it is checked for obvious injuries. Additionally, a surgical probe is used to check for ED and ALLI. The measured cage pressures were 45, 120, and 191 N for the "loose," "appropriate," and "hard to extract" ratings, respectively (P < 0.001). ED was observed in five intervertebral spaces, whereas no ALLI was noted. The average maximum pressure when ED occurred was 127 N. The primary risk factor for ED was identified as the difference between the height of the inserted cage and IDH, with a cut-off value of 4.5mm. The appropriate extraction strength corresponded to a cage pressure of 120 N. A cage pressure ≥127 N posed a risk for ED. ED incidence was high when the difference between the IDH and the height of the inserted cage exceeded 4.5mm. Level Three.