Intervertebral disc degeneration (IDD), a primary cause of low back pain, currently lacks therapeutic strategies capable of halting its progression or promoting disc regeneration. Vascular ingrowth is the hallmark pathological feature of IDD, which arises from annulus fibrosus (AF) injury and accelerates degenerative processes through intricate interactions with inflammation and extracellular matrix degradation. This review summarizes the characteristics of vascular ingrowth in IDD, including differential vascular distribution between normal and degenerative discs, spatiotemporal dynamics of progressive invasion, and its association with pain via neurovascular co-invasion. The key underlying mechanisms involve the activation of pro-angiogenic factors (e.g., vascular endothelial growth factor [VEGF]), regulation by miRNA networks (e.g., miR-140-5p), macrophage-mediated coupling of inflammation and angiogenesis, and the dual roles of stress pathways and hypoxia-inducible factor signaling in driving pathological vascularization. Current research employs in vivo models (e.g., puncture- or fixation-induced degeneration), in vitro vascular co-culture systems, as well as advanced imaging techniques to dissect the process of vascular ingrowth in IDD. Aimed at counteracting pathological angiogenesis and halting the progression of IDD, emerging therapeutic strategies have been developed, including VEGF interventions, miRNA-targeted therapies, modulation of the inflammatory microenvironment, and multi-target combinatorial regimens. Despite substantial advances in understanding vascular ingrowth, several critical unresolved issues remain, including the unclear causal relationship between vascular ingrowth and IDD progression, species-specific disparities in preclinical models, and challenges in optimizing therapeutic timing and target selection. Future research will focus on addressing these gaps, with key priorities including single-cell analysis of vascular heterogeneity, mechanobiological coupling with vascularization, biomaterial-based precision regulation, and the establishment of standardized clinical translation pathways. In summary, vascular ingrowth is a critical driver of IDD, and mechanistic insights gained herein support its potential as a therapeutic target. Addressing current challenges will accelerate the translation of novel strategies into clinical practice for effective IDD management.
Ossification of posterior longitudinal ligament (OPLL) is a complex multifactorial spinal disorder characterized by ectopic bone formation within the ligament, leading to progressive spinal canal stenosis and neurological deficits. While its epidemiological and clinical profiles are well-established, the precise molecular pathogenesis remains incompletely understood. This review systematically synthesizes recent advances in understanding the mechanistic underpinnings of OPLL, highlighting the interplay of genetic predisposition, epigenetic regulation, metabolic disorders, and biomechanical stress. Pathological manifestations, anatomical features, and the dual-origin hypothesis of OPLL are elaborated, alongside its phenotypic overlaps with ankylosing spondylitis and the contribution of inflammatory signaling cascades. Susceptibility loci identified via genome-wide association studies and their functional relevance to key regulatory pathways are summarized. Epigenetic regulation, encompassing pre and posttranscriptional modifications, is highlighted with particular attention to the roles of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Metabolic mechanisms implicated in OPLL, including diabetes, lipoprotein receptor-related protein 5 signaling, and lipid metabolism dysregulation, are discussed, as is the critical role of biomechanical stress in disease progression. By integrating insights across multiple disciplines, this review establishes a comprehensive pathophysiological framework for OPLL, with the goal of bridging basic science and clinical practice and identifying promising avenues for the development of targeted therapeutic strategies.
Abbreviations: AS = ankylosing spondylitis, BMP = bone morphogenetic proteins, BM-MSCs = bone marrow mesenchymal stem cells, COL6A1 = collagen type Ⅵ alpha 1, C-OPLL = cervical OPLL, 1,25(OH)2D = 1,25-dihydroxyvitamin D, ECM = extracellular matrix, FASL = factor-related Apoptosis Ligand, GWAS = genome-wide association studies, HLA = human leukocyte antigen, IL17RC = interleukin 17 receptor C, LDL = low-density lipoprotein, lncRNAs = long noncoding RNAs, LRP5 = lipoprotein receptor-related protein 5, MMPs = matrix metalloproteases, OPLL = ossification of posterior longitudinal ligament, PLL = posterior longitudinal ligament, ROR2 = receptor tyrosine kinase-like orphan receptor 2, RSPO2 = R-spondin 2, sEVs = small extracellular vesicles, SNPs = single-nucleotide polymorphisms, T-OPLL = thoracic OPLL, TIMPs = tissue inhibitor of metalloproteinases, UV = ultraviolet, VDR = vitamin D Receptor, YAP = yes1 associated transcriptional regulator
To analyze the correlation among subcutaneous lumbar spine index (SLSI), paraspinal muscle parameters, and lumbar bone mineral density (BMD), and to evaluate their predictive value on lumbar BMD for patients with lumbar spondylolisthesis. A total of 216 patients with lumbar spondylolisthesis were included. All of them were divided into groups of normal bone mass, osteopenia, and osteoporosis (OP) according to BMD of L1–4 measured by dual-energy X-ray absorptiometry (DXA). SLSI was obtained by computed tomography, and paraspinal muscle parameters were calculated by the Image J software. The differences between SLSI and paraspinal muscle parameters were compared in 3 groups. Correlation analysis and multiple linear regression were used to analyze the relationship between parameters and lumbar BMD. SLSI and paraspinal muscle parameters were analyzed among 3 groups. There was a significant difference in cross-sectional areas (CSAs) of psoas major (PS) and quadratus lumborum (QL), PS index, relative cross-sectional areas (rCSAs) of PS and QL, fatty infiltration (FI) of multifidus (MF) and erector spinae (ES) between normal bone mass group and osteopenia group, normal bone mass group and OP group (p < 0.05). Correlation analysis among body mass index (BMI), SLSI, paraspinal muscle parameters, and BMD was adopted for all included patients. There were positive correlations among BMI, CSAs of PS and QL, PS index, rCSAs of PS and QL, and lumbar BMD (p < 0.05). There were negative correlations among MF index, FI of PS, MF and ES, and lumbar BMD (p < 0.05). The regression equation of lumbar BMD: BMD = −3.461 + 0.063 × BMI + 0.943 × rCSA of PS − 3.871 × FI of ES (R2 = 0.111). For patients with lumbar spondylolisthesis, smaller CSAs of flexor muscle group and more FI of paraspinal muscles are related to less bone mass and lower lumbar BMD. Combined with BMI, rCSA of PS and FI of ES have predictive value on lumbar BMD. For patients with both lumbar spondylolisthesis and OP, those who have higher SLSI are estimated to have less bone mass. BMD = bone mineral density, BMI = body mass index, CSAs = cross-sectional areas, CT = computed tomography, DXA = dual energy X-ray absorptiometry, ES = erector spinae, FI = fatty infiltration, MF = multifidus, OP = osteoporosis, PS = psoas major, QL = quadratus lumborum, rCSAs = relative cross-sectional areas, SFT = subcutaneous fat thickness, SLSI = subcutaneous lumbar spine index, SPH = spinous process height
The C7-T1 segment poses challenges in spinal surgery due to its biomechanical transition from the mobile cervical spine to the rigid thoracic spine, with concerns about subsidence from stress-shielding of the T1 superior endplate by the first rib. The impact of fusing C7-T1 on outcomes remains unclear relative to other levels during anterior cervical discectomy and fusion (ACDF). In a cohort of patients undergoing ACDF, we sought to determine the impact of C7-T1 fusion on patient-reported outcome measures (PROMs) and clinical outcomes. A retrospective cohort study using the Quality Outcome Database was conducted for patients who underwent primary single- or 2-level ACDF. The primary exposure variable was fusion of C7-T1. The primary outcome was 3-month and 12-month PROMs, including numeric rating scale for neck and arm pain, neck disability index, quality-adjusted life year (QALY) score, and patient satisfaction. Secondary outcomes included 30-day complications and 3-month readmissions and reoperations. Multivariable regression models were fitted for each outcome, controlling for baseline variables. Of 12,240 patients (age 55.8 ± 11.6 years; 48.7% male) undergoing ACDF, 4736 (38.7%) had C7-T1 fusion. On multivariable regression, fusion of C7-T1 was associated with a greater 3-month QALY score (odds ratio [OR] = 1.142; 95% confidence interval [CI]: 1.055–1.237; p < 0.001) and lower rate of readmission (OR = 0.760; 95% CI: 0.625–0.924; p = 0.006), with no association to other PROMs, patient satisfaction, complications, and reoperation (p > 0.05). On subanalysis of 4103 myelopathic patients, C7-T1 fusion was only associated with lower odds of 3-month readmission (OR = 0.602; 95% CI: 0.420–0.864; p = 0.006). C7–T1 fusion was associated with a better 3-month QALY score and a lower rate of readmission. Myelopathy patients with C7-T1 fusion were also less likely to be readmitted within 3 months of surgery. C7-T1 fusion was not associated with any other outcome. Our results suggest comparable outcomes when fusing C7-T1, which may be useful when counseling patients facing surgery for pathology at this level. ACDF = anterior cervical discectomy and fusion, PROMs = patient-reported outcome measures, QALY = quality-adjusted life year, CTJ = cervicothoracic junction, PCF = posterior cervical fusion, QOD = quality outcomes database, BMI = body mass index, NRS = Numeric rating scale, mJOA = modified Japanese Orthopaedic Association, CAD = coronary artery disease, COPD = chronic obstructive pulmonary disease, NDI = neck disability index, OR = odds ratio, CI = confidence interval.
Artificial intervertebral discs (AIDs) aim to restore spinal kinematics, but few replicate the natural disc’s essential viscoelasticity for shock absorption and stress distribution. The internal mechanics of such biomimetic designs also lack thorough finite element analysis (FEA). Therefore, this study aimed to develop a mechanically biomimetic AID model using a 3D lamellar scaffold-strengthened hydrogel and evaluate its biomechanical performance through integrated experimental testing and FEA. The biomimetic AID model was evaluated through in vitro tests (axial compression, compression shear, axial torsion) and corresponding FEA. Mechanical tests demonstrated a compressive stress–strain curve with a J-shaped profile, with a linear modulus of 10MPa. The AID exhibited a compression-shear stiffness of 90N·mm-1 and axial torsion stiffness of 0.23 N·m·degree-1, with creep behavior comparable to a natural disc. FEA revealed that coherent load transfer through both the interconnections within the lamellar scaffold and the scaffold-hydrogel interface, and the entire AID showed a stress profilometry analogous to natural intervertebral disc. In conclusion, we developed an annulus-nucleus structure biomimetic AID that successfully emulates the viscoelastic and mechanical properties of a natural intervertebral disc, presenting a promising prototype for clinical application.
Epidural fibrosis, a major contributor to failed back surgery syndrome, involves post-operative scar adhesion and nerve compression leading to persistent pain and compromised outcomes. While neutrophil extracellular traps (NETs) are implicated in pathological scar formation, effective and sustained strategies to modulate their activity are lacking. This study aimed to leverage the anti-NETs potential of curcumin, overcoming its inherent limitations of poor bioavailability, for the active prevention of epidural fibrosis. Curcumin (Cur) was encapsulated within core–shell poly (L-lactic acid) micro-sol electrospun fibers (MS@Cur) to enable localized, sustained delivery. The release profile and physicochemical properties of the fabricated membranes were characterized. In vitro studies evaluated their cytocompatibility and their ability to inhibit NETs formation by neutrophils. Efficacy was further evaluated in a rat laminectomy model, where the impact of MS@Cur implantation on NETs markers (myeloperoxidase and citrullinated histone H3), collagen deposition, and myofibroblast activation was analyzed histologically. The MS@Cur membranes demonstrated successful curcumin encapsulation, mitigating burst release and achieving sustained release for over 28 days. They showed favorable cytocompatibility and effectively inhibited NETs formation in vitro. In vivo, implantation of MS@Cur led to a notable downregulation of NETs markers. Histological analyses confirmed a significant reduction in excessive collagen deposition and aberrant myofibroblast activation at the laminectomy site. The developed biomimetic dural patch enables sustained and efficient local delivery of curcumin, effectively modulating NETs formation after laminectomy. This strategy represents a novel and effective therapeutic approach for the active prevention of epidural scar formation following dural injury, with significant translational potential. α-SMA = α-smooth muscle actin, Cur = curcumin, FBSS = failed back surgery syndrome, H3cit = citrullinated histone H3, H&E = hematoxylin–eosin, MPO = myeloperoxidase, MRI = magnetic resonance imaging, NETs = neutrophil extracellular traps, PBS = phosphate buffered saline, PLLA = poly (L-lactic acid), ROS = reactive oxygen species, SEM = scanning electron microscopy
Here’s a report on bone cement leakage. Our review of the literature revealed that cases of bone cement leakage are commonly reported, but intradural leakage of bone cement is rare. Here, we present a delayed case of L2 and L3 radiculopathy secondary to bone cement leakage from percutaneous vertebroplasty (PVP). This case exhibited extensive intravertebral and intradural cement leakage, with only a slight decrease in lower extremity strength and lateral thigh pain in the immediate postoperative period. In this case, we describe a rare occurrence of substantial postoperative PVP with intradural leakage. In terms of treatment, early surgical decompression and cement removal should be performed in patients with significant symptomatic cement leakage.
Abbreviations: ODI = oswestry disability index, OVCFs = osteoporotic vertebral compression fractures, PVP = percutaneous vertebroplasty, PKP = percutaneous kyphoplasty, VCF = vertebral compression fracture.