BACKGROUND CONTEXT: Recent studies have demonstrated a close association between the development of ossification of the posterior longitudinal ligament (OPLL) and obesity. However, the association between OPLL and visceral fat obesity, which is prevalent in the Asian population, remains unexplored. PURPOSE: To examine the impact of visceral fat obesity on the development of asymptomatic OPLL. STUDY DESIGN: Single-institution cross-sectional study. PATIENT SAMPLE: Between 2020 and 2021, data were collected from 249 Japanese individuals (147 men and 102 women) who underwent computed tomography (CT) to assess both the visceral fat content and OPLL. OUTCOME MEASURES: We assessed patient background information, serum data, and CT images, including the abdominal circumference (cm), total fat area (cm(2)), visceral fat area (cm(2)), and subcutaneous fat area (cm(2)) at the umbilicus level. OPLL localization was assessed using whole-spine CT images. METHODS: The individuals were categorized into 4 groups based on obesity and visceral fat: nonobesity without visceral fat (n=85), obesity without visceral fat (n=18), nonobesity with visceral fat (n=44), and obesity with visceral fat (n=102). OPLL was classified as localized or diffuse when present in the cervical spine alone or in the cervical and thoracic spine, respectively. The prevalence of each type of OPLL was compared between the groups. Multivariable analysis was conducted to calculate the effect size of body mass index (BMI) on the prevalence of OPLL, comparing the high and low visceral fat groups. RESULTS: The obesity with visceral fat group exhibited a significantly higher proportion of diffuse OPLL than did the nonobesity without visceral fat group (27.5% vs 7.1%, p<.001). The effect size of BMI for the occurrence of diffuse OPLL was 2.1 times greater in the high visceral fat group (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.66-5.87) than in the low visceral fat group (OR, 1.44; 95% CI, 0.64-3.22). CONCLUSIONS: Our data show that visceral fat, in conjunction with BMI, influences the occurrence of OPLL in the Japanese population. This supports the hypothesis that systemic metabolic disorders share a disease mechanism with OPLL and indicates that the high prevalence of OPLL in Japan may be attributed to physical characteristics that promote visceral fat accumulation. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Introduction: To compare the clinical outcomes between a full-endoscopic transforaminal approach lumbar interbody fusion (TF-LIF) using the percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) system and a minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Methods: A total of 102 patients (80 females, 22 males; mean age: 70.0 years) with degenerative lumbar spine disorders who underwent PETLIF and were followed up for 2 years were assigned to the PETLIF group. Based on age, sex, and operated lumbar levels in the PETLIF group, 100 patients (71 women and 29 men; mean age: 68.9 years) who underwent MIS-TLIF were randomly selected and included in the MIS-TLIF group. This retrospective investigation included surgical data, radiographic assessment, and clinical outcomes. Results: The fusion rate was 95.1% and 96.0% in the PETLIF and MIS-TLIF groups, respectively (P=0.38). The decrease in hemoglobin levels from before surgery to 1 day after surgery was significantly lower in the PETLIF group than in the MIS-TLIF group (P<0.01). Five patients had detectable transient neurologic disorders after PETLIF that were resolved within 3 months. The increase in the local lordosis angle from before surgery to the final follow-up was significantly higher in the MIS-TLIF group than in the PETLIF group (P<0.01). Clinical scores were comparable between the two groups. Conclusions: Compared with MIS-TLIF, PETLIF showed excellent bone fusion rate and clinical outcomes. It was minimally invasive, resulting in less blood loss. However, exiting nerve root injury was a PETLIF-specific complication, and proper preventive management, including techniques to enlarge the Kambin's triangle, is required.

A four-dimensional (4D) anatomical spinal reconstruction (ASR) technique and anatomical notch-free, pre-bent rods have been developed for thoracic adolescent idiopathic scoliosis (AIS) surgery. We aimed to evaluate the outcomes of ASR using notch-free rods through multiple comparisons with conventional methods, including the simultaneous double-rod rotation technique (SDRRT) and ASR using manually bent notched rods. Three consecutive series of 126 patients who underwent surgery for Lenke 1 AIS curves were prospectively followed up for 2 years after surgery. The operative time was significantly shorter in the ASR using notch-free rods group than in the other two groups (P < 0.05). The correction rate of the main thoracic (MT) curve was higher in the ASR group than in the SDRRT group (P < 0.01). Thoracic kyphosis (TK) was greater in the ASR using notch-free rods group than in the other two groups at the final follow-up (P < 0.01). The percentage of patients with a T6–T8 location of the TK apex was greater in the ASR using notch-free rods group than in the SDRRT group at the final follow-up (P < 0.01). ASR using notch-free rods created an anatomical TK, contributing to a shorter operative time and standardization of the procedure.

PURPOSE:Lumbosacral nerve root anomalies are relatively rare but can be a risk factor for intraoperative nerve injury. However, it is often difficult to evaluate them with preoperative imaging. We developed a software that automatically generates three-dimensional (3D) nerve root images from magnetic resonance (MR) imaging using artificial intelligence (AI). This study aims to evaluate the accuracy and utility of this modality in clinical practice by conducting an epidemiological study of nerve root anomalies. METHODS:The incidence and morphology of nerve root anomalies were evaluated in the 3D images of 1,500 patients. The accuracy of the images was evaluated by comparing the images generated automatically using this AI software with those created manually by conventional methods. RESULTS:Of 1,500 cases, 53 (3.5%) had nerve root anomalies with total of 58 nerve root anomalies. With respect to the spinal level, 35 nerve root anomalies were found in the L5-S1 level, the most common (60.3%). As for morphology, 47 nerve roots (81.0%) were of the Neidre-MacNab classification Type 1. The images matched in 1,493 out of 1,500 cases (99.5%) between the two methods, and the remaining 7 cases all had nerve root abnormalities, which were detected as abnormal by the AI software. CONCLUSION:The MR nerve root 3D imaging provided a 3D visualization and understanding of nerve root morphology, including nerve root anomalies. The AI software enables easy and precise 3D nerve root imaging, which greatly aids in the preoperative evaluation for spinal surgery.

BACKGROUND:In full-endoscopic spine surgery via transforaminal approach (FESS-TF), the outside-in method facilitates treatment for various cases; however, the technique is difficult to perform. To facilitate this procedure, we developed a duckbill release technique. In this article, we aimed to introduce the details of this technique and investigate its effectiveness. METHODS:Fifty patients who underwent FESS-TF for intervertebral disc herniation were divided into 2 groups: the conventional technique and the duckbill release technique groups. The time from the initiation of surgery to exposure of the bone outside the superior articular process was measured in both groups. The visual analog scale score for leg pain and the Japanese Orthopaedic Association score before and after surgery were compared in terms of clinical outcomes. RESULTS:No significant differences were observed between the 2 groups in terms of patient background. The approach time was 252 ± 86 seconds in the conventional group, while it was 105 ± 26 seconds in the duckbill release group, which was significantly shorter (P < 0.001). In terms of clinical outcomes, the 2 groups did not significantly differ in all endpoints of the visual analog scale score for leg pain or the Japanese Orthopaedic Association score. CONCLUSIONS:The duckbill release technique for the outside-in method in FESS-TF could be efficient because it is a simple and time-saving approach.

BACKGROUND CONTEXT:Lumbar spinal canal stenosis (LSCS) is the most common spinal degenerative disorder in elderly people and usually first seen by primary care physicians or orthopedic surgeons who are not spine surgery specialists. Magnetic resonance imaging (MRI) is useful in the diagnosis of LSCS, but the equipment is often not available or difficult to read. LSCS patients with progressive neurologic deficits have difficulty with recovery if surgical treatment is delayed. So, early diagnosis and determination of appropriate surgical indications are crucial in the treatment of LSCS. Convolutional neural networks (CNNs), a type of deep learning, offers significant advantages for image recognition and classification, and work well with radiographs, which can be easily taken at any facility. PURPOSE:Our purpose was to develop an algorithm to diagnose the presence or absence of LSCS requiring surgery from plain radiographs using CNNs. STUDY DESIGN:Retrospective analysis of consecutive, nonrandomized series of patients at a single institution. PATIENT SAMPLE:Data of 150 patients who underwent surgery for LSCS, including degenerative spondylolisthesis, at a single institution from January 2022 to August 2022, were collected. Additionally, 25 patients who underwent surgery at 2 other hospitals were included for extra external validation. OUTCOME MEASURES:In annotation 1, the area under the curve (AUC) computed from the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In annotation 2, correlation coefficients were used. METHODS:Four intervertebral levels from L1/2 to L4/5 were extracted as region of interest from lateral plain lumbar spine radiographs totaling 600 images were obtained. Based on the date of surgery, 500 images derived from the first 125 cases were used for internal validation, and 100 images from the subsequent 25 cases used for external validation. Additionally, 100 images from other hospitals were used for extra external validation. In annotation 1, binary classification of operative and nonoperative levels was used, and in annotation 2, the spinal canal area measured on axial MRI was labeled as the output layer. For internal validation, the 500 images were divided into each 5 dataset on per-patient basis and 5-fold cross-validation was performed. Five trained models were registered in the external validation prediction performance. Grad-CAM was used to visualize area with the high features extracted by CNNs. RESULTS:In internal validation, the AUC and accuracy for annotation 1 ranged between 0.85-0.89 and 79-83%, respectively, and the correlation coefficients for annotation 2 ranged between 0.53 and 0.64 (all p<.01). In external validation, the AUC and accuracy for annotation 1 were 0.90 and 82%, respectively, and the correlation coefficient for annotation 2 was 0.69, using 5 trained CNN models. In the extra external validation, the AUC and accuracy for annotation 1 were 0.89 and 84%, respectively, and the correlation coefficient for annotation 2 was 0.56. Grad-CAM showed high feature density in the intervertebral joints and posterior intervertebral discs. CONCLUSIONS:This technology automatically detects LSCS from plain lumbar spine radiographs, making it possible for medical facilities without MRI or nonspecialists to diagnose LSCS, suggesting the possibility of eliminating delays in the diagnosis and treatment of LSCS that require early treatment.

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Case: A 42-year-old woman presented with lateral chest and back pain. She was referred to our hospital after magnetic resonance imaging revealed a thoracic spine lesion. The initial examination revealed no obvious neurological deficits. A biopsy was performed, and enzyme-linked immunosorbent assay and western blotting confirmed Echinococcus infection. Paralysis and paresthesia developed, and stabilization and albendazole treatment were initiated. Postoperatively, the paralysis improved, and 2 years later, there was no lesion progression or symptom recurrence. Conclusions: Lesion resection is ideal for spinal echinococcosis; however, when resection is difficult, posterior stabilization and antiparasitic drugs may be effective.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Early detection of deformity and timely intervention, such as brace treatment, can help inhibit progressive changes. A three-dimensional (3D) depth-sensor imaging system with a convolutional neural network was previously developed to predict the Cobb angle. The purpose of the present study was to (1) evaluate the performance of the deep learning algorithm (DLA) in predicting the Cobb angle and (2) assess the predictive ability depending on the presence or absence of clothing in a prospective analysis. We included 100 subjects with suspected AIS. The correlation coefficient between the actual and predicted Cobb angles was 0.87, and the mean absolute error and root mean square error were 4.7° and 6.0°, respectively, for Adam’s forward bending without underwear. There were no significant differences in the correlation coefficients between the groups with and without underwear in the forward-bending posture. The performance of the DLA with a 3D depth sensor was validated using an independent external validation dataset. Because the psychological burden of children and adolescents on naked body imaging is an unignorable problem, scoliosis examination with underwear is a valuable alternative in clinics or schools.

Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.

This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.

Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.

Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden.

Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Superscript/Subscript Available

Introduction:Despite perioperative risks in nonagenarian patients who undergo open spine surgery for degeneration disorder or spinal trauma being of great interest, the prevalence of complications in this group remains unclear. This study aims to examine the perioperative complications of open spine surgery in the elderly over 90 years of age.Methods:Preoperative and intraoperative characteristics including the American Society of Anesthesiologists Physical Status (ASA-PS) class, type of surgery, and complications within 30 postoperative days were retrospectively collected from the medical records of nonagenarians who underwent open spine surgery between April 2004 and July 2019 at our spine centers.Results:A total of 48 patients met the inclusion criteria of this study. All belong to ASA-PS class 2 (69%) or 3. Preoperative American Spinal Injury Association Impairment Scale grades in trauma group were grade A in 4 cases, B in 1 case, C in 5 cases, D in 11 cases, and E in 1 case. Major complications (deep surgical site infection, cardiac event, respiratory disorder, gastrointestinal hemorrhage, and renal failure) occurred in 13 cases, and the rate of overall perioperative complications was 45.8%. One patient who underwent cervical stabilization for cervical fracture dislocation died at postoperative 13 days due to respiratory disorder. The rates of major complications and overall perioperative complications were 3.6% and 14.3% in the degenerative group and 45.5% and 81.8% in the trauma group, respectively. Especially in the trauma group, respiratory disorder occurred in 7 cases, delirium in 11 cases, and urinary tract infection in 5 cases.Conclusions:Although the perioperative complication rate reached 81.8% in spinal trauma cases, the complication rate in degenerative disorders was relatively low as 14.3%. Open spine surgery for degenerative disorders can be relatively safe even in nonagenarians, whereas the risks of perioperative complications, including respiratory disorder and delirium, were high in spinal trauma cases.

Study Design Retrospective observational study. Objectives To evaluate the long-term recurrence rates and functional status of patients with thoracic ossification of the posterior longitudinal ligament (OPLL) after decompression and posterior fusion surgery. Methods Thirty-seven consecutive patients who underwent posterior thoracic spine surgery at a single institution were retrospectively reviewed. The long-term neurological and functional outcomes of 25 patients who were followed up for ≥10 years after surgery were assessed. Factors associated with the recurrence of myelopathy were also analyzed. Results The mean preoperative Japanese Orthopaedic Association score was 3.7, which improved to 6.5 at postoperative year 2 and declined to 6.0 at a mean follow-up of 18 years. No patient experienced a relapse of myelopathy due to OPLL within the instrumented spinal segments. However, 15 (60%) patients experienced late neurological deterioration, 10 of whom had a relapse of myelopathy due to OPLL or ossification of the ligamentum flavum (OLF) in the region outside the primary operative lesion, while 4 developed myelopathy due to traumatic vertebral fracture of the ankylosed spine. Young age, a high body mass index, and lumbar OPLL are likely associated with late neurological deterioration. Conclusions Decompression and posterior instrumented fusion surgery is a reliable surgical procedure with stable long-term clinical outcomes for thoracic OPLL. However, as OPLL may progress through the spine, attention should be paid to the recurrence of paralysis due to OPLL or OLF in regions other than the primary operative lesion and vertebral fractures of the ankylosed spine after surgery for thoracic OPLL.

BACKGROUND The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits. METHODS The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells. RESULTS There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis. CONCLUSIONS BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs. CLINICAL RELEVANCE Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.

Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.

BACKGROUND:Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs.METHODS:Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs.FINDINGS:Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs.INTERPRETATION:These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs.FUNDING:Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.