Modic changes (MCs), characterized by magnetic resonance imaging signal alterations at vertebral endplates and adjacent bone marrow, are increasingly recognized as immune-driven lesions rather than mere structural degeneration. This review focuses on the pivotal roles of immune system and key immunological signaling in the initiation and progression of MCs. Within the Modic microenvironment, diverse immune cell populations—including monocytes, macrophages, mast cells, neutrophils, and lymphocytes—exhibit stage-specific infiltration patterns. In parallel, MCs are governed by a complex network of innate and adaptive immune signals. Endplate disruption and nucleus pulposus exposure break local immune privilege, activating inflammatory cascades that sustain cytokine and chemokine production, amplify immune cell recruitment, and promote chronic low-grade inflammation. Oxidative stress, metabolic disturbances, and potential microbial triggers such as Cutibacterium acnes further modulate these immune landscapes. The interplay of these mechanisms underscores MCs as dynamic immunoinflammatory processes, with distinct cellular and molecular profiles corresponding to their radiologic stages. Recognizing the immunological complexity of MCs underscores the need for future studies to delineate molecular signatures that could guide personalized treatment strategies and improve clinical outcomes.
Abbreviations: C. acnes = cutibacterium acnes, MCs = modic changes, MRI = magnetic resonance imaging, NP = nucleus pulposus.
Intervertebral disc degeneration (IDD) is the primary pathological driver of debilitating low back pain, representing a massive global socioeconomic burden. Current clinical management relies on palliative analgesia or destructive surgical fusion, which fails to halt degeneration and risks adjacent segment disease. The irreconcilable conflict between palliative clinical management and escalating degenerative burden underscores the imperative for biologically rational reconstruction strategies. This review synthesizes recent advances in regenerative approaches for IDD, progressing from targeted tissue engineering towards the emerging paradigm of organoid and assembloid construction. Conventional tissue engineering strategies focus on mitigating the pathological microenvironment (inflammation, oxidative stress, hypoxia, and acidosis) and restoring the structural integrity of degenerated disc components. For the nucleus pulposus, injectable biomaterials deliver anti-inflammatory/antioxidant agents, modulate immune cell infiltration, enhance hypoxia tolerance, and serve as biomechanical surrogates. Annulus fibrosus repair employs suturing techniques, biomimetic angle-ply patches, adhesive hydrogels, and scaffolds modulating the local niche to promote endogenous repair and extracellular matrix integration. Cartilaginous endplate strategies aim to enhance nutrient transport and combat degeneration via matrix modification or stem cell-derived exosome delivery. While promising, these approaches often face limitations in achieving native-equivalent biomechanics, seamless interfacial integration, and replicating the disc's complex heterocellular composition. Organoid technology, recapitulating developmental processes, offers a transformative solution. Significant progress has been made in generating nucleus pulposus-like cells from induced pluripotent stem cells via defined signaling pathways, differentiating induced pluripotent stem cells towards annulus fibrosus-like fates, and constructing cartilage organoids for cartilaginous endplate modeling. These self-organizing 3D structures better mimic native tissue microarchitecture, cellular diversity, and matrix composition than traditional scaffolds. Furthermore, "assembloid" strategies, involving the fusion of distinct organoids or their combination with specialized scaffolds, present a revolutionary framework for holistic disc reconstruction, overcoming the limitations of ad hoc component assembly. Despite the immense potential of organoid/assembloid platforms for creating developmentally inspired, functional disc replacements, key challenges remain: standardization of protocols, biomimetic engineering of critical disc-vertebral interfaces, and achieving physiological biomechanical competence. Future translation necessitates GMP-compliant biomanufacturing, advanced material integration, and optimized maturation protocols. The evolution from palliative care and reductionist tissue engineering towards organoid/assembloid-based reconstruction heralds a new era in biologically rational IDD therapy.
This study aimed to investigate the role and underlying mechanism of miR-146a-5p in inflammationinduced intervertebral disc degeneration (IDD). We performed miRNA sequencing and bioinformatic analysis on IL-1β-treated rat primary nucleus pulposus cells (RPNPCs). The function of miR-146a-5p was validated using mimics and inhibitors in vitro, and its therapeutic effect was assessed in a needle-punctured rat disc organotypic explant model. Target gene prediction and validation, along with loss- and gain-of-function experiments for Sod2, were conducted. miR-146a-5p was significantly upregulated in degenerative human discs and IL-1β-treated RPNPCs. Its overexpression promoted extracellular matrix catabolism and inhibited anabolism, and induced apoptosis in RPNPCs, while its inhibition exerted protective effects. Mechanistically, miR-146a-5p directly targeted and downregulated superoxide dismutase 2 (SOD2). Knockdown of Sod2 exacerbated degenerative phenotypes, whereas its overexpression mitigated IL-1β-induced damage. In the explant model, inhibition of miR-146a-5p restored Sod2 expression and ameliorated disc degeneration. miR-146a-5p drives inflammation-induced IDD by suppressing Sod2, leading to mitochondrial oxidative stress and NP cell dysfunction. Targeting the miR-146a-5p/Sod2 axis represents a novel potential therapeutic strategy for IDD.
Social media platforms have become increasingly valuable tools for medical collaboration, allowing healthcare professionals to share knowledge and seek real-time guidance. The Spinal Implants Identification Facebook group is a specialized community where spine surgeons, providers, and industry representatives collaborate to identify spinal hardware, particularly in preparation for revision surgeries. Given the challenges of identifying implants from imaging alone, especially in complex cases, this group offers a unique avenue for peer consultation. This study aimed to characterize engagement patterns, assess response reliability, and explore clinical trends among spinal instrumentation cases posted in the group. A retrospective observational review of 100 consecutive posts from the Spinal Implants Identification Facebook group was conducted. Posts were included if they contained adequate imaging and context for spinal implant discussion. Metrics recorded included time to first response, total number of responses, and whether responses were confirmed by the original author. Clinical data such as levels of fusion, instrumentation components, spinal alignment, pelvic parameters, and reported complications (e.g., pseudarthrosis and rod fractures) were analyzed. The mean response time was 278.7 ± 25.5 minutes, with 81.0% of posts receiving at least one response. Commonly involved levels were L4–L5 and L4–S1 (23.0% each), and the mean number of instrumented levels was 2.3 ± 2.5. Pseudarthrosis was observed in 34.0% of cases and rod fractures in 5.0%. Interbody devices were used in 31.0% of cases. The mean lumbar lordosis was 48.2° ± 12.0°. The mean L4–S1 lordosis was 27.3° ± 9.3°, and the mean lumbar distribution index was 0.6 ± 0.15. Pelvic parameters demonstrated a mean sacral slope of 35.0° ± 9.9°, pelvic tilt of 29.3° ± 9.7°, and pelvic incidence of 77.5° ± 10.3°. Social media groups can serve as supplemental resources in spine care, supporting rapid implant identification and professional collaboration. However, variability in response reliability and limited clinical context underscore the need for cautious interpretation when applying these insights to patient care.
Vertebral burst fractures can lead to a multitude of clinical issues, including pain, spinal deformity, neurological deficits, and a decreased quality of life. While current literature extensively covers risk factors associated with the failure of conservative treatment for burst fractures, there exists a relative paucity of data regarding risk factors for surgical treatment failures. This study aimed to determine the predictors of reoperation among patients with vertebral burst fractures. A retrospective cohort study was undertaken of patients undergoing surgical treatment of thoracic and lumbar vertebrae burst fractures from a single institution between 2010 and 2021. The primary outcome was reoperation within 12 months. Patients with less than 12 months of follow-up and without revision surgery were excluded. Multivariable regression models were performed controlling for age, body mass index, American Society of Anesthesiology (ASA) grade, and smoking status. Of 91 burst fracture patients included in this study, the mean age was 43.0 ± 17.9 and 60 (65.9%) were male. There were 27 (29.7%) patients who underwent reoperation within 12 months. Patients requiring reoperation had higher proportions of active smokers (44.4% vs. 23.4%, p = 0.045) and ASA grades 3 or 4 (81.5% vs. 50%, p = 0.005) than patients without reoperation. There was no difference in perioperative variables between the 2 cohorts. On multivariable regression, ASA grade of 3 or 4 (odds ratio = 3.934, 95% confidence interval = 1.169–13.235, p = 0.027) and smoking (odds ratio = 3.208, 95% confidence interval = 1.100–9.355, p = 0.033), with no impact of age or body mass index on the reoperation rate. In our cohort of patients with vertebral burst fractures, smoking and ASA grades of 3 or 4 independently increased the odds of requiring reoperation. Smoking disrupts blood flow and oxygenation at the surgical site, impairing bone regeneration and wound healing. Higher ASA grades reflect more severe systemic health conditions, which can compromise postoperative recovery, leading to a higher likelihood of reoperation. These results can support surgeons in determining which burst fracture patients are at higher risk for reoperation and allow surgeons to provide more appropriate counseling and risk mitigation strategies. ASA = American Society of Anesthesiology, BMI = body mass index, OR = odds ratio.
Spinal endoscopic surgery has been the most rapidly developing subspecialty in the field of spinal surgery in the past decade, with explosive growth in the number of operations. The learning curve of spinal endoscopic surgery is steep, and the issues of concern at the beginning of training are not clear. This study utilized an exploratory sequential mixed-methods design in 2 stages. In phase 1, concerns were collected by openly and qualitatively listing questions from their stance among 110 novices in endoscopic spinal surgery and were analyzed by using the content analysis approach with the assistance of Nvivo software. In phase 2, qualitative results were sequentially transformed into constructs and items for the Delphi survey questionnaire. Two rounds of e-Delphi were conducted among Chinese experts in endoscopic spinal surgery to identify the 20 most important core concerns of novices. The 20 most important core questions were mainly focused on facet arthroplasty (2 items), structural identification under a microscope (2 items), lateral treatment of spinal stenosis (6 items), and judgment of nucleus pulposus removal (4 items). The average score of the importance of each question ranged from 8.57 to 8.93 points. The 20 most important core questions in the early stage of endoscopic spinal surgery were identified by a panel of spinal endoscopic surgery doctors with rich surgical experience and a stellar reputation in China, including surgical procedures and details, as well as the indications of spinal endoscopy, perioperative management, retreatment of postoperative symptoms, and even the treatment of cervical spondylosis and degenerative spinal diseases such as lumbar spinal stenosis. CV = coefficient of variation.
Chronic low back pain, primarily caused by intervertebral disc degeneration (IVDD), significantly impairs quality of life and imposes a substantial economic burden on society. Research on IVDD and tissue repair relies heavily on high-quality primary cell cultures, including nucleus pulposus cells, annulus fibrosus cells, and mesenchymal stem cells. However, refractory bacterial contamination during cell extraction and culture poses a major challenge, hindering experimental progress and compromising the safety of cell-based therapies. This study aims to develop a simple and effective method to combat bacterial contamination in rat intervertebral disc and mesenchymal cell cultures, particularly cases resistant to conventional antibiotics like penicillin-streptomycin. We employed commercially available levofloxacin eye drops as an intervention agent. Through quantitative intervention, we assessed the drug’s cytotoxic effects and therapeutic efficacy, establishing an optimized treatment protocol for refractory bacterial contamination. Our findings demonstrate that levofloxacin eye drops effectively eliminate bacterial contamination without significant cytotoxicity, providing a feasible solution for contaminated cell cultures. A standardized treatment process was developed to ensure reliable outcomes. This study presents a simple, efficient, and practical approach to managing refractory bacterial contamination in musculoskeletal cell research. The method enhances experimental reliability and supports advancements in IVDD studies and cell-based therapies.
This case report describes the use of bovine testicular hyaluronidase (BTH) for managing lower limb spasticity in a 40-year-old spinal cord injury (SCI) patient in Peru. The patient, who sustained an ASIA B T7 traumatic SCI, developed severe spastic paraplegia. Traditional interventions and phenol chemodenervation failed to sustain prolonged improvement. Evidence supports the efficacy of human recombinant hyaluronidase for spasticity management, though not for BTH; with it unavailable, BTH was chosen as a more accessible and cost-effective option. About 1500 units were injected into 14 lower limb muscles under ultrasound guidance. The intervention improved the patient’s passive range of motion and muscle tone over a 3-week period, with no adverse effects observed. However, further follow-up was limited due to patient transfer. This case suggests that BTH could be a promising, affordable option for post-SCI spasticity management in resource-limited settings. Future studies should evaluate BTH efficacy compared with other interventions.