Search Results (584)

Background and Objectives: Low back pain (LBP) is a leading cause of disability worldwide and is frequently associated with intervertebral disc degeneration (IVDD). Current therapeutic strategies are primarily symptomatic and do not restore native disc biology, largely due to the avascular nature of the intervertebral disc and the hostile inflammatory and mechanical microenvironment that characterizes degeneration. The aim of this study is to provide an updated and clinically oriented overview of the pathophysiology of IVDD and to evaluate the current evidence on mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP)-based therapies. Materials and Methods: A focused narrative literature review was performed to evaluate current evidence on MSC- and PRP-based therapies for intervertebral disc degeneration (IVDD). The search was conducted in PubMed. Only studies in English were considered eligible. Results: Mesenchymal stem cells (MSCs) demonstrated regenerative and immunomodulatory effects primarily through paracrine mechanisms, enhancing extracellular matrix synthesis and reducing inflammation and apoptosis. MSC-derived extracellular vesicles emerged as a promising cell-free alternative, potentially overcoming limitations related to cell survival and safety. Platelet-rich plasma (PRP) showed anabolic and anti-inflammatory properties, promoting disc cell proliferation and matrix production, particularly in early-stage degeneration. Clinical studies, including randomized trials, reported significant improvements in pain and function for both MSC and PRP therapies, with favourable safety profiles. However, heterogeneity in treatment protocols and limited long-term data remain significant limitations. Orthobiologic therapies represent a minimally invasive option for patients with discogenic low back pain refractory to conservative treatment. Patient selection is crucial and should consider degeneration stage, disc viability, and clinical presentation. PRP is primarily indicated in early-stage degeneration (Pfirrmann II–III), whereas MSC-based therapies may be considered in selected patients with more advanced but still viable discs. Based on current evidence, a stepwise approach is proposed, progressing from conservative management to PRP, MSCs, and ultimately surgery. Orthobiologics should be integrated within a multimodal strategy including rehabilitation. Conclusions: MSCs and PRP represent a promising and, eventually, complementary orthobiologic therapies for IVDD. PRP is primarily effective in early degenerative stages as a biologic stimulator, whereas MSCs may provide regenerative benefits in more advanced but still viable discs. Further studies are necessary to standardize protocols and confirm long-term efficacy and safety. Full article

Intervertebral disc degeneration is the most recognized cause of low back pain, characterized by the decline in tissue structure and mechanics. Image-based mechanical parameters (e.g., strain, stiffness) may provide an ideal assessment of disc function that is lost with degeneration, but unfortunately, these remain underdeveloped. Moreover, it is unknown whether strain or stiffness of the disc may be predicted by MRI relaxometry (e.g., T₁ or T₂), an increasingly accepted quantitative measure of disc structure. In this study, we quantified T₁ and T₂ relaxation times and compared to in-plane strains measured with displacement-encoded MRI within human cadaveric discs under physiological levels of compression and bending. Using a novel inverse approach, we then estimated shear modulus in orthogonal image planes and regionally compared these values to relaxation times and 2D strains. Intratissue strain depended on the loading mode, and shear modulus in the nucleus pulposus was typically an order of magnitude lower than the annulus fibrosus. Relative shear moduli estimated from strain data derived under compression generally did not correspond with those from bending experiments. Only one anatomical region showed a significant correlation between relative shear modulus and relaxometry (T₁ vs. µ_rel, coronal plane under bending). Together, these results suggest that future inverse analyses may be improved by incorporating multiple loading conditions into the same model and that image-based elastography and relaxometry should be viewed as complementary measures of disc structure and function to assess degeneration in future studies. Full article

Background: Sciatic scoliosis is a nonstructural, compensatory spinal deformity secondary to lumbar disc herniation. In adolescents and young adults, sciatic scoliosis is frequently misdiagnosed as adolescent idiopathic scoliosis due to the low prevalence of lumbar disc herniation in this demographic. Early clinical suspicion is essential, as radiographic features, particularly minimal or absent vertebral rotation on standing radiographs, help distinguish sciatic scoliosis from structural curves such as adolescent idiopathic scoliosis. Key differentiating features include painful scoliosis, a highly positive straight leg raise test, and minimal or absent vertebral rotation on standing radiographs. Delayed diagnosis or inappropriate management may result in residual deformity, highlighting the importance of early surgical decompression. Despite recognition for decades, the literature is fragmented, largely composed of case reports, small series, and retrospective studies, with heterogeneous definitions, radiological assessments, and outcome measures. Objective: Provide a comprehensive, up-to-date systematic synthesis of the clinical presentation, radiological characteristics, management strategies, and outcomes of lumbar disc herniation-associated sciatic scoliosis. Methods: Thirteen studies evaluating conventional open discectomy and minimally invasive endoscopic procedures (FEID/PELD) were included. Data on demographics, surgical approach, clinical improvement (VAS, ODI, Macnab), and radiographic correction (Cobb angle, trunk list, sagittal alignment) were extracted and synthesized. Results: Surgical decompression consistently leads to clinical improvement. Trunk list and coronal deformity were rapidly corrected, with resolution rates ≥ 85% within 6 months across most series. Both open and endoscopic approaches were effective, with minimally invasive techniques offering advantages in tissue preservation and recovery. Conclusions: Sciatic Scoliosis is a reversible, nonstructural deformity that responds reliably to surgical decompression. Accurate recognition, particularly in adolescents and young adults, and timely intervention targeting the underlying nerve root compression are critical for optimal outcomes. This review consolidates fragmented evidence, providing a comprehensive synthesis of current knowledge. Full article

Musculoskeletal disorders and injuries are highly prevalent and encompass a broad range of conditions, including bone fractures and segmental defects, tendinopathies and tendon injury, and cartilage disorders such as osteoarthritis, cartilage defects, and intervertebral disc disease. These conditions can arise from diverse causes including trauma and injury, tumor resection, congenital abnormalities, and age-related degeneration. In the past decades, administration of chemically modified mRNA (cmRNA) encoding growth factors and transcriptional regulators has demonstrated effectiveness in repairing musculoskeletal tissues in preclinical studies. This review summarizes recent advancements in bone, tendon, cartilage, intervertebral disc, and muscle regeneration achieved through the localized delivery of protein-encoding mRNAs to express therapeutic target proteins. Delivery of cmRNA encoding growth factors such as BMP-2, BMP-9, VEGF, FGF-18, and IGF-1, or transcriptional regulators including Runx1, to various animal models has shown beneficial effects on bone, tendon, cartilage, and muscle injury repair in preclinical models. Alongside these progresses, the advantages and disadvantages of applying chemically modified mRNA for musculoskeletal tissue regeneration are also discussed. While studies show the promise of cmRNA for therapeutic applications in orthopedic tissue regeneration, more research is required to optimize growth factors and delivery methods, as well as validate long-term safety and efficacy prior to successful translation into new therapies to benefit patients. Full article

Cervical spondylosis is a common cause of spinal cord dysfunction, and anterior cervical discectomy and fusion (ACDF) is widely employed when conservative treatment fails. Conventional implant systems such as the cervical cage with plate (CCP) and zero-profile stand-alone cage (ZPSC) are commonly used to enhance spinal stability and promote fusion, but they are associated with complications including dysphagia and adjacent segment degeneration. To address these limitations, a novel flexible plate cage system (FPCS) has been developed to optimize biomechanical performance while minimizing surgical risk. In this study, a finite element model of the C3–T1 cervical spine was constructed to simulate ACDF at the C5–C6 level using CCP, ZPSC, and FPCS implants. Under standardized loading conditions, von Mises stress was analyzed in the bone, intervertebral disc, endplates, cage, and screws, using the mean of the top 5% stress values to ensure accuracy. All surgical models showed increased stress compared to the intact reference spine. The ZPSC model exhibited the highest stress in the cage and screws, suggesting a more concentrated load path. The CCP model showed a more evenly distributed stress profile, particularly affecting the inferior adjacent segment. The FPCS model demonstrated moderate cage stress, reduced screw stress, and the highest plate stress, indicating a design that effectively redirects mechanical load from the screw-bone interface toward the anterior plate. This may be related to the unique structural configuration of the FPCS, which secures screws horizontally into the anterior vertebral body without penetrating the endplates. These findings suggest that the FPCS may offer a biomechanically favorable alternative to existing ACDF implants. Full article

In the body, mast cells are found in the circulation and located in tissues. These immune cells arise in the bone marrow and are often associated with conditions such as allergies and asthma. However, these cells also play roles in other inflammatory reactions, dysregulated wound healing and chronic conditions. Regarding their presence in tissues of the intervertebral disc (IVD), mast cells have been located in the normal nucleus pulposus, and reports indicate mast cell numbers are elevated in IVD degenerative conditions. As the integrity of the IVD is reported to decline with ageing as well as in sciatica and clinically defined degenerative conditions, targeting mast cell function may be a viable conservative treatment option for the ageing IVD in health and disease. This review discusses the possible involvement of mast cells in IVD health and disease, and the rationale for the use of mast cell stabilizers such as ketotifen as potential treatment options for conditions affecting IVD integrity. Such mast cell targeting treatments may be considered alone or in combination with other molecules such as specific proteinase inhibitors impacting proteinases known to be present in the affected tissues, such as MMP-3 and HTRA1. Thus, a multicomponent approach in such treatments may provide effectiveness in inhibiting progressive loss of IVD integrity and function in chronic degenerative conditions or adverse outcomes due to non-resorption of extruded nucleus pulposus in sciatica. Full article

Cervical Intervertebral Disc Degeneration (CIVDD) involves significant microenvironmental physical stiffening, forcing nucleus pulposus cells (NPCs) into a rigid phenotype via F-actin over-assembly. It remains unclear if cyclic tensile strain (CTS) can reverse this physical stiffening, particularly in severe degeneration. This study stratified 18 patients into Mild, Moderate, and Severe cohorts based on MRI. Primary NPCs were subjected to physiological 5% CTS (1 Hz, 24 h). Atomic Force Microscopy (AFM) and immunofluorescence were utilized to evaluate Young’s modulus and cytoskeletal remodeling. Results demonstrated that baseline cellular stiffness increased significantly with degeneration severity. Following CTS, all groups exhibited universal de-stiffening and F-actin depolymerization. Crucially, a “Degeneration Paradox” emerged: the Severe group displayed the highest relative elastic modulus recovery rate, significantly surpassing the Mild group. This microscopic recovery correlated inversely with preoperative disc height loss and range of motion. We conclude that severely degenerated cells are not metabolically quiescent but “physically locked” by a rigid cytoskeleton. Physiological CTS restores compliance via mechanical unloading, confirming that severe cells retain superior relative mechanoplasticity and may benefit from mechanotherapy-based “unlocking” strategies. Full article

Intervertebral disc degeneration is characterized by inflammation, extracellular matrix breakdown, and neurovascular ingrowth, processes that contribute to discogenic, chronic back pain. The transient receptor potential canonical 6 (TRPC6) channel is a calcium-permeable ion channel implicated in inflammation and pain signaling in multiple tissues; however, its functional role in human disc cells remain unknown. Here, we investigated the expression, activation, and downstream consequences of TRPC6 activation using Hyp9, a pharmacological activator of TRPC6. TRPC6 transcripts were consistently detected across all donors examined (n = 17). Functional TRPC6 activation induced a rapid, dose-dependent calcium (Ca²⁺) influx across 0.5–100 µM Hyp9. TRPC6 activation did not reduce metabolic activity or increase cytotoxicity at concentrations commonly used for in vitro TRPC6 activation. Mechanistically, TRPC6 activation induced mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways, as demonstrated by increased phosphorylation of p38 and extracellular signal-regulated kinase (ERK), degradation of the inhibitor of κB-alpha (IκB-α), and increased nuclear translocation of the NF-κB p65 subunit. Downstream of these early signaling events, TRPC6 activation elicited a robust inflammatory and catabolic response with upregulation of IL-6, IL-8, COX-2, MMP-1, MMP-3, NGF, and VEGF, with corresponding increases in protein secretion. These findings identify TRPC6 as an important signaling node linking calcium influx to inflammatory, catabolic, and neuro- and angiogenesis-associated pathways in disc cells, highlighting TRPC6 as a potential therapeutic target in degenerative disc disease. Full article

It is widely accepted that modern humans display distinctive vertebral and intervertebral disc (IVD) morphologies that evolved to meet the biomechanical demands of habitual terrestrial bipedalism. This study synthesizes macro- and microstructural differences in the lumbar spine to clarify how human specializations compare with those of extant apes. The skeletal sample consisted of 240 humans, 20 chimpanzees, and 25 gorillas. The CT scan sample comprised 180 humans and eight chimpanzees. Histological analysis of the IVD was performed on 10 humans and four ape specimens. Vertebral bodies and discs were measured. Histological analyses employed hematoxylin–eosin, Von Kossa, and Van Gieson staining. Statistical analyses included ANOVA with Bonferroni-corrected t-tests or Welch’s ANOVA and Games–Howell post hoc tests. Regression analyses were performed using ordinary least-squares estimation, and differences between regression lines were assessed using ANCOVA. Humans and chimpanzees differed significantly in vertebral body proportions, bone volume fraction, IVD thickness, apophyseal ring thickness, annulus fibrosus lamellar organization, endplate and subchondral bone thickness, and vascularization at the bone–endplate interface. These results indicate substantial evolutionary modification of the human vertebral body and IVD, enhancing rotational mobility and resistance to axial loading, key functional requirements for maintaining upright posture and efficient bipedal locomotion. Full article

Intervertebral disk pathology, including disk herniation and degeneration, is a major contributor to chronic low back pain, and when conservative treatment fails, surgical management often involves discectomy-based procedures that leave residual annulus fibrosus (AF) defects associated with reherniation and progressive degeneration. These limitations have motivated interest in regenerative strategies using biomaterial scaffolds; however, reproducing the hierarchical, angle-ply architecture of the AF remains challenging. Here, we present a single-step extrusion-based 3D-printing approach to fabricate polycaprolactone (PCL) scaffolds with aligned microscale surface grooves that promote AF-like organization. Patterned nozzles with circumferential peaks generated uniaxial concave microgrooves (10–17 µm wide) directly during printing, enabling formation of multilamellar angle-ply constructs. Human bone marrow-derived mesenchymal stem cells cultured on patterned scaffolds aligned longitudinally within concave grooves, forming end-to-end arrays that guided extracellular matrix deposition. Gene expression analysis showed that topographical cues governed cellular organization without significantly altering gene expression profiles, while TGF-β3 supplementation upregulated outer AF-associated markers, including COL1, COL12, SFRP2, MKX, MCAM, and SCX. TAGLN expression increased specifically on patterned scaffolds in the absence of TGF-β3, indicating an association between microgroove-guided cellular organization and TAGLN expression, warranting further investigation into potential tension-related mechanisms. This novel single-step extrusion-printing approach leverages custom nozzle geometry to impart concave microgrooves, facilitating scalable fabrication of multilamellar angle-ply scaffolds that induce aligned cellular organization and support potential applications in annulus fibrosus repair, as well as mechanobiological studies of anisotropic musculoskeletal tissues. Full article

Intervertebral disc (IVD) viscoelasticity is governed primarily by fluid transport driven by coupled osmotic and mechanical pressure gradients. Disc degeneration disrupts this balance through glycosaminoglycan loss and reduced cartilage endplate permeability. However, how degeneration interacts with compressive loading to regulate fluid-driven viscoelastic behavior at the whole-disc level remains unclear. To address this gap, a probabilistic biphasic swelling finite element framework was employed to simulate fluid-driven viscoelastic behavior of the IVD. Fifty discs were generated by varying anterior–posterior length, lateral width, nucleus pulposus volume ratio, wedge angle, and disc height. These discs were subjected to swelling, creep, and relaxation protocols under multiple compressive magnitudes for both healthy and degenerated conditions. Time-dependent responses were quantified using rheological models comprising two viscoelastic elements and one elastic element. Predicted intradiscal pressure, disc height, and viscoelastic responses fell within reported experimental ranges. Degeneration primarily governed fluid-dependent behavior. It reduced osmotic pressure, limited fluid mobility, and delayed axial equilibration. These changes decreased swelling displacement, increased creep deformation, and prolonged characteristic time constants, while minimally affecting instantaneous elastic response. In contrast, loading magnitude modulated the extent of viscoelastic deformation and progressively reduced degeneration-related differences in long-term creep displacement and long-term relaxation time constant. Collectively, degeneration governs fluid-dependent viscoelastic mechanisms, whereas loading magnitude modulates their expression. This study systematically examines how degeneration and load magnitude interact to regulate fluid-driven viscoelastic behavior of the IVD. By combining probabilistic geometry with biphasic swelling mechanics, it addresses a critical gap in understanding load–degeneration interactions in disc hydration-dependent mechanics. Full article

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis. Full article

Diagnosing cervical spine instability with flexion-extension radiographs is challenging, as current guidelines are based on limited cadaver studies and do not adequately account for level, vertebral size, or patient effort. There is a need for automated cervical instability metrics anchored to normative reference data, accompanied by evidence on how often abnormal findings occur in real clinical populations and which soft-tissue injury patterns they can detect. We developed and evaluated fully automated, radiographic-based cervical intervertebral motion (IVM) metrics—adapted from prior lumbar methods—using an FDA-cleared analysis pipeline that segments C2–C7 and derives rotation, translation, disc heights, and regression-based instability indices. Normative reference data were first established from flexion-extension radiographs of 341 asymptomatic volunteers after excluding radiographically degenerated levels. Abnormality prevalence was then estimated in two symptomatic cohorts: pooled preoperative clinical-trial radiographs and 881 patients with symptoms attributed to motor-vehicle accidents, excluding levels with <5° rotation to reduce unreliable data due to insufficiently stressed spines. Finally, potential diagnostic performance was assessed in a controlled cadaveric ligament-sectioning model (12 cadavers) using ROC analysis and Youden’s J thresholds. Across clinical cohorts, objective IVM abnormalities were uncommon. Prevalence increased when studies demonstrated adequate total C2–C7 motion, emphasizing the importance of patient effort. In cadavers, vertical instability metrics were most discriminative (AUC 0.96–0.97) with high sensitivity (0.89) and perfect specificity at optimal thresholds, whereas translation changed minimally with sectioning. These results support regression-based instability indices as promising candidates for standardized, physiology-guided cervical instability assessment. Full article

Background/Objectives: The L5–S1 segment presents unique characteristics that make surgical access challenging in minimally invasive spine surgery (MISS) procedures. Variability in bony and neural anatomy may restrict transforaminal and extraforaminal approaches, yet few studies have combined cadaveric dissection with radiologic analysis to define relevant morphology in L5–S1 approaches. The purpose of the study is to characterize anatomical and radiological features of the lumbosacral region relevant to MISS planning and execution. Methods: Twelve Thiel-embalmed donor bodies underwent CT imaging (lumbopelvic region) followed by posterior dissection. Bony landmarks were used to obtain bilateral anatomical measurements. Qualitative anatomical analysis included iliolumbar ligament morphology and extraforaminal access feasibility. CT-based morphometrics included L5 transverse process (TP) length; maximal and minimal distances between L5 TP and sacral ala; extraforaminal area bounded by L5 TP, L5–S1 facet (zygapophyseal) joint, and sacral ala; iliac crest-based approach angle to the L5–S1 intervertebral disc (IVD); minimal distance between this approach vector and the ventral ramus of the fifth lumbar spinal nerve (VRL5); facet angulation; and iliac crest height. Results: No left–right asymmetry was detected. Except for L5 TP length, all anatomical measurements obtained directly in the donor bodies differed significantly between sexes. A direct IVD access with a uniportal endoscopic working tube was feasible in 25% of cases. On CT analysis, the maximal and minimal distances between the L5 TP and sacral ala were 11.1 (4.0) mm and 5.6 ± 2.9 mm, with a mean extraforaminal area of 202.0 ± 45.9 mm². The mean approach angle was 35.2 ± 5.0°, and an extraforaminal corridor to L5–S1 IVD was feasible in 75% of donated bodies. The median minimal distance between the approach vector and the VRL5 was 5.0 (7.1) mm, with frequent overlap. Conclusions: The results of this study reveal that the L5–S1 segment shows substantial interindividual morphologic variability, compromising the feasibility of transforaminal and extraforaminal MISS approaches, and highlight the need for individualized preoperative planning, neural identification and/or bony resection to create a safe working corridor. Full article