Taylor J. Jackson, Craig Louer, Ron El-Hawary, Jennifer Hurry, Hui Nian, Christine Farnsworth, Carrie E. Bartley, Tracey P. Bryan, Michael P. Kelly, Peter O. Newton, Stefan Parent, Pediatric Spine Study Group, Vidyadhar V. Upasani
Background
The relationship between tether tension and spinal growth modulation following vertebral body tethering (VBT) has not been studied in growing children.
Aims
This study aims to explore the relationship between vertebral body growth modulation under varying tether tension.
Materials and Methods
A retrospective, multicenter pediatric registry was queried for idiopathic scoliosis patients treated with right-sided VBT, with recorded intraoperative tension (using an ordinal scale of 0–3), and 3D reconstructions from biplanar radiographs at the first erect (FE) and 2-year post-operative visits. Custom MATLAB code was used to calculate vertebral height (mm) on the untethered and tethered sides from T5-T12. Generalized linear mixed models were used to analyze the effect of tension on vertebral body growth.
Results
Fifty-two subjects (47 female) were included with a mean age of 12.5 ± 1 years. Patients were skeletally immature (triradiate cartilage open in 23 patients) with Proximal Femoral Maturity Index scores of 2 (nine patients), 3 (21 patients), 4 (20 patients), and 5 (two patients). A total of 330 vertebral bodies were analyzed. Mean height change of the vertebral bodies from FE to 2 years was 1.6 + 1.9 mm (untethered) and 1.2 + 1.8 mm (tethered). On the tethered side, greater tension resulted in less height change, with the greatest differential growth observed between maximal tension and no tension (0.8 mm vs. 0.2 mm, p = 0.02). Greater tension resulted in less vertebral body growth and greater differential growth. Future studies should quantify forces applied during VBT surgery, as well as the forces maintained in the post-operative period with spinal motion.
Conclusion
Intraoperative intervertebral tensioning significantly affects vertebral body growth over 2 years.
背景：尚未对正在发育的儿童进行椎体系留术（VBT）后系留张力与脊柱生长调节之间的关系进行研究。目的探讨不同系索张力下椎体生长调节的关系。材料和方法回顾性的、多中心的儿童登记查询了接受右侧VBT治疗的特发性脊柱侧凸患者，记录了术中张力（使用0-3的顺序量表）、首次勃起（FE）时双平面x线片的3D重建和术后2年的随访。使用自定义MATLAB代码从T5-T12计算未系缚侧和系缚侧的椎体高度（mm）。采用广义线性混合模型分析张力对椎体生长的影响。结果纳入52例患者，其中女性47例，平均年龄12.5±1岁。患者骨骼未成熟（23例患者为三放射软骨开放），股骨近端成熟度指数评分分别为2（9例）、3（21例）、4（20例）和5（2例）。共分析了330个椎体。从FE到2年，椎体平均高度变化为1.6 + 1.9 mm（未系留）和1.2 + 1.8 mm（系留）。在系绳一侧，较大的张力导致高度变化较小，最大张力和无张力之间的差异最大（0.8 mm vs. 0.2 mm, p = 0.02）。较大的张力导致椎体生长减少和差异生长增加。未来的研究应该量化VBT手术期间施加的力，以及术后脊柱运动期间保持的力。结论术中椎间张紧对2年内椎体生长有显著影响。
{"title":"Effect of Vertebral Body Tether Tensioning on Vertebral Body Growth Modulation","authors":"Taylor J. Jackson, Craig Louer, Ron El-Hawary, Jennifer Hurry, Hui Nian, Christine Farnsworth, Carrie E. Bartley, Tracey P. Bryan, Michael P. Kelly, Peter O. Newton, Stefan Parent, Pediatric Spine Study Group, Vidyadhar V. Upasani","doi":"10.1002/jsp2.70098","DOIUrl":"https://doi.org/10.1002/jsp2.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The relationship between tether tension and spinal growth modulation following vertebral body tethering (VBT) has not been studied in growing children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to explore the relationship between vertebral body growth modulation under varying tether tension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A retrospective, multicenter pediatric registry was queried for idiopathic scoliosis patients treated with right-sided VBT, with recorded intraoperative tension (using an ordinal scale of 0–3), and 3D reconstructions from biplanar radiographs at the first erect (FE) and 2-year post-operative visits. Custom MATLAB code was used to calculate vertebral height (mm) on the untethered and tethered sides from T5-T12. Generalized linear mixed models were used to analyze the effect of tension on vertebral body growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-two subjects (47 female) were included with a mean age of 12.5 ± 1 years. Patients were skeletally immature (triradiate cartilage open in 23 patients) with Proximal Femoral Maturity Index scores of 2 (nine patients), 3 (21 patients), 4 (20 patients), and 5 (two patients). A total of 330 vertebral bodies were analyzed. Mean height change of the vertebral bodies from FE to 2 years was 1.6 + 1.9 mm (untethered) and 1.2 + 1.8 mm (tethered). On the tethered side, greater tension resulted in less height change, with the greatest differential growth observed between maximal tension and no tension (0.8 mm vs. 0.2 mm, <i>p</i> = 0.02). Greater tension resulted in less vertebral body growth and greater differential growth. Future studies should quantify forces applied during VBT surgery, as well as the forces maintained in the post-operative period with spinal motion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Intraoperative intervertebral tensioning significantly affects vertebral body growth over 2 years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Astrid Soubrier, Hermann Kasper, Nadja Vonlanthen, Ilse Jonkers, Sibylle Grad
Introduction
Intervertebral disc (IVD) degeneration is driven by a vicious circle of interrelated biological and biomechanical factors. Dynamic unloading, defined as dynamic partial decompression, promotes water and metabolite flow, which is essential for IVD homeostasis. However, the mechanobiological effects of unloading remain poorly understood. IVD organ cultures offer a valuable model for studying IVD degeneration and regeneration at the molecular level. This study investigated the biological and biomechanical effects of induced degeneration and the subsequent short-term dynamic unloading of bovine tail IVDs in a bioreactor culture system.
Methods
We applied a one-strike degenerative trigger on Day 0 and assessed its immediate effects after 1 day of culture under bioreactor loading (Timepoint 1). The impact of dynamic unloading for three additional days (Timepoint 2) was evaluated in comparison to continued loading. We evaluated biological outcomes, namely cell viability, gene expression, water/sulfated glycosaminoglycan (sGAG) ratio, and sGAG release. Mechanical readouts included disc height, slope of the elastic zone, area under the curve, and neutral zone characteristics.
Results
On Timepoint 1, we demonstrated degeneration in the nucleus pulposus with altered viability, increased inflammatory and catabolic gene expression, elevated sGAG release, a decreased slope of the elastic zone, and an increased area under the curve. On Timepoint 2, we noticed a sustained degenerative cascade in both degeneration groups. However, unloading showed a trend towards partial mitigation of the induced degeneration with decreased iNOS and TRPV4 expression, an increased water/sGAG ratio, reduced sGAG release, and recovery of the disc height.
Conclusion
This first ex vivo study on unloading mechanobiology of bovine degenerated IVDs unveils encouraging preliminary insights. The findings suggest potential benefits of unloading and, more broadly, therapeutic movement as regenerative strategies for degenerated IVDs. These results underscore the need for further studies and encourage research combining mechanical and biological approaches in organ culture models.
{"title":"Short-Term Dynamic Unloading of Bovine Tail Discs in Culture Partially Mitigates Induced Degeneration After One-Strike Trigger","authors":"Astrid Soubrier, Hermann Kasper, Nadja Vonlanthen, Ilse Jonkers, Sibylle Grad","doi":"10.1002/jsp2.70092","DOIUrl":"https://doi.org/10.1002/jsp2.70092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is driven by a vicious circle of interrelated biological and biomechanical factors. Dynamic unloading, defined as dynamic partial decompression, promotes water and metabolite flow, which is essential for IVD homeostasis. However, the mechanobiological effects of unloading remain poorly understood. IVD organ cultures offer a valuable model for studying IVD degeneration and regeneration at the molecular level. This study investigated the biological and biomechanical effects of induced degeneration and the subsequent short-term dynamic unloading of bovine tail IVDs in a bioreactor culture system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We applied a one-strike degenerative trigger on Day 0 and assessed its immediate effects after 1 day of culture under bioreactor loading (Timepoint 1). The impact of dynamic unloading for three additional days (Timepoint 2) was evaluated in comparison to continued loading. We evaluated biological outcomes, namely cell viability, gene expression, water/sulfated glycosaminoglycan (sGAG) ratio, and sGAG release. Mechanical readouts included disc height, slope of the elastic zone, area under the curve, and neutral zone characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>On Timepoint 1, we demonstrated degeneration in the nucleus pulposus with altered viability, increased inflammatory and catabolic gene expression, elevated sGAG release, a decreased slope of the elastic zone, and an increased area under the curve. On Timepoint 2, we noticed a sustained degenerative cascade in both degeneration groups. However, unloading showed a trend towards partial mitigation of the induced degeneration with decreased iNOS and TRPV4 expression, an increased water/sGAG ratio, reduced sGAG release, and recovery of the disc height.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This first ex vivo study on unloading mechanobiology of bovine degenerated IVDs unveils encouraging preliminary insights. The findings suggest potential benefits of unloading and, more broadly, therapeutic movement as regenerative strategies for degenerated IVDs. These results underscore the need for further studies and encourage research combining mechanical and biological approaches in organ culture models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Siddarth Ananth Swaminathan, Nima Taheri, Luis Becker, Matthias Pumberger, Hendrik Schmidt, Sara Checa
Background
Lumbar spinal fusion is currently regarded as one of the most effective surgical treatments for patients with spinal deformities, degenerative disc disease, and degenerative spondylolisthesis. However, the procedure still faces a high incidence of non-unions. A key factor contributing to non-union is stress shielding effects related to unfavorable mechanical signals at the fusion site. Mechanical conditions at the fusion site are determined by the loading conditions that result from daily activities. Recent studies have reported that humans spend most of the day with their spine in a flexed position. The role of flexion loading in the progression of bone fusion remains poorly understood. This study explores the influence of habitual flexion loading on the spinal fusion process using a computational modeling framework that integrates finite element analysis with bone healing algorithms to simulate bone regeneration following fusion surgery.
Methods
A finite element model of the lumbar spine based on a healthy subject was developed and validated with in vitro experimental data. Thereafter, a virtual posterior lumbar interbody fusion was performed where 2 intervertebral cages were inserted at the L4-L5 level together with posterior fixation. The influence of two loading conditions on the predicted fusion process were investigated: (1) A compression load (2) A hybrid (compression + flexion) loading protocol simulating habitual flexion encountered during daily living.
Results
Bone bridging was predicted to occur 14 weeks after surgery. At week 14, for the hybrid loading, the model predicted a bone volume of 70%, whereas for compression load, the bone volume prediction was 59%. Computer model predictions showed that habitual flexion loading can promote bone formation in the anterior and peripheral regions by inducing a mechanical environment favorable for bone formation.
Conclusion
Flexion loading may enhance bone healing by promoting mechanically advantageous conditions. The computational framework could guide the development of optimized rehabilitation protocols to improve fusion outcomes.
{"title":"Impact of Habitual Flexion on Bone Formation After Spinal Fusion Surgery: An In Silico Study","authors":"Siddarth Ananth Swaminathan, Nima Taheri, Luis Becker, Matthias Pumberger, Hendrik Schmidt, Sara Checa","doi":"10.1002/jsp2.70075","DOIUrl":"https://doi.org/10.1002/jsp2.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar spinal fusion is currently regarded as one of the most effective surgical treatments for patients with spinal deformities, degenerative disc disease, and degenerative spondylolisthesis. However, the procedure still faces a high incidence of non-unions. A key factor contributing to non-union is stress shielding effects related to unfavorable mechanical signals at the fusion site. Mechanical conditions at the fusion site are determined by the loading conditions that result from daily activities. Recent studies have reported that humans spend most of the day with their spine in a flexed position. The role of flexion loading in the progression of bone fusion remains poorly understood. This study explores the influence of habitual flexion loading on the spinal fusion process using a computational modeling framework that integrates finite element analysis with bone healing algorithms to simulate bone regeneration following fusion surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A finite element model of the lumbar spine based on a healthy subject was developed and validated with in vitro experimental data. Thereafter, a virtual posterior lumbar interbody fusion was performed where 2 intervertebral cages were inserted at the L4-L5 level together with posterior fixation. The influence of two loading conditions on the predicted fusion process were investigated: (1) A compression load (2) A hybrid (compression + flexion) loading protocol simulating habitual flexion encountered during daily living.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bone bridging was predicted to occur 14 weeks after surgery. At week 14, for the hybrid loading, the model predicted a bone volume of 70%, whereas for compression load, the bone volume prediction was 59%. Computer model predictions showed that habitual flexion loading can promote bone formation in the anterior and peripheral regions by inducing a mechanical environment favorable for bone formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Flexion loading may enhance bone healing by promoting mechanically advantageous conditions. The computational framework could guide the development of optimized rehabilitation protocols to improve fusion outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara R. Piva, Clair Smith, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Corey Flynn, Carol M. Greco, Gina P. McKernan, Michael J. Schneider, Gwendolyn A. Sowa, Meenakshi Sundaram, Nam V. Vo, Leming Zhou, Charity G. Patterson
Background
The chronic low back pain (cLBP) literature rarely includes comprehensive characterization of demographic and biomedical factors in a large sample of individuals. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. The LB3P conducted a prospective, observational cohort study to identify phenotypes of people with cLBP. Here, we report demographic and biomedical characteristics of a large cohort of individuals with cLBP, stratified by sex and age, collected at the in-person enrollment visit.
Methods
The key eligibility criteria were adults with cLBP, English speakers, and identified in the electronic health record of our medical center. Recruitment strategies were through clinical partners who invited their patients to join the study and research registries. Participants completed demographic and biomedical surveys. Descriptive statistics were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60).
Results
N = 1007 individuals (60% female) were enrolled, with an average age of 59 ± 17 years. Most participants were non-Hispanic (90%), White (75%), and 53% attained college or higher education. 54% were married or had a partner, 43% were employed, 38% retired, 41% had an annual household income < $50 000, 20% had been off work for more than 30 days due to low back pain (LBP), 16% had applied for or received disability, and 6% were on worker's compensation. The majority were obese (average BMI of 31.5 kg/m2), 61% had back pain for > 5 years, and pain had been ongoing every or nearly every day in 76% of the sample. The participants reported a high prevalence of osteoarthritis (58%), anxiety (40%), depression (40%), vision impairment (35%), and balance problems/falls (31%). Among the chronic overlapping pain conditions, the most common were migraine or headache (29%), irritable bowel syndrome (16%), and temporomandibular joint dysfunction (12%). Previous low back surgery was reported by 25%. The most frequently reported LBP treatments during the previous month were exercise routine done on their own (58%), physical therapy, occupational therapy, or chiropractic care (33%), mindfulness, meditation, or relaxation (22%), and diet or nutrition counseling (21%). Medication intake during the last month was 43% for nonsteroidal anti-inflammatory drugs, 18% for gabapentin, 13% for opioid, a
{"title":"Demographic and Biomedical Characteristics of an Observational Cohort With Chronic Low Back Pain: A Descriptive Analysis","authors":"Sara R. Piva, Clair Smith, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Corey Flynn, Carol M. Greco, Gina P. McKernan, Michael J. Schneider, Gwendolyn A. Sowa, Meenakshi Sundaram, Nam V. Vo, Leming Zhou, Charity G. Patterson","doi":"10.1002/jsp2.70094","DOIUrl":"https://doi.org/10.1002/jsp2.70094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The chronic low back pain (cLBP) literature rarely includes comprehensive characterization of demographic and biomedical factors in a large sample of individuals. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. The LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes of people with cLBP. Here, we report demographic and biomedical characteristics of a large cohort of individuals with cLBP, stratified by sex and age, collected at the in-person enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The key eligibility criteria were adults with cLBP, English speakers, and identified in the electronic health record of our medical center. Recruitment strategies were through clinical partners who invited their patients to join the study and research registries. Participants completed demographic and biomedical surveys. Descriptive statistics were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>N</i> = 1007 individuals (60% female) were enrolled, with an average age of 59 ± 17 years. Most participants were non-Hispanic (90%), White (75%), and 53% attained college or higher education. 54% were married or had a partner, 43% were employed, 38% retired, 41% had an annual household income < $50 000, 20% had been off work for more than 30 days due to low back pain (LBP), 16% had applied for or received disability, and 6% were on worker's compensation. The majority were obese (average BMI of 31.5 kg/m<sup>2</sup>), 61% had back pain for > 5 years, and pain had been ongoing every or nearly every day in 76% of the sample. The participants reported a high prevalence of osteoarthritis (58%), anxiety (40%), depression (40%), vision impairment (35%), and balance problems/falls (31%). Among the chronic overlapping pain conditions, the most common were migraine or headache (29%), irritable bowel syndrome (16%), and temporomandibular joint dysfunction (12%). Previous low back surgery was reported by 25%. The most frequently reported LBP treatments during the previous month were exercise routine done on their own (58%), physical therapy, occupational therapy, or chiropractic care (33%), mindfulness, meditation, or relaxation (22%), and diet or nutrition counseling (21%). Medication intake during the last month was 43% for nonsteroidal anti-inflammatory drugs, 18% for gabapentin, 13% for opioid, a","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary K. Heimann, Shirley N. Tang, Gilian Gunsch, Kyle Kuchynsky, Brett Klamer, Fangli Zhao, Megan Co, Maciej Pietrzak, Justin Richards, Jake Klausner, Adam Smith, Kaitlyn Cimney, Sara McBride-Gagyi, Brad Youngblood, Kara Corps, Candice Askwith, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur
<div> <section> <h3> Background</h3> <p>Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in humans and canines. IVD degeneration affects the structure and function of both the disc and the innervating dorsal root ganglion (DRG) neurons. Preclinical animal models are necessary for elucidating the mechanisms of IVD degeneration (IVDD) and the pain signaling pathways involved in discogenic back pain. The chondrodystrophic (CD) dog exhibits similar characteristics to the clinical population affected by IVDD-associated LBP. However, further investigation of the translational tools to study these conditions and the efficacy of novel treatments is needed in this canine model. The objectives of the present study are to: (1) assess the changes in the structure and function of the IVD and DRG, including pain behaviors, in response to injury using a comprehensive set of outcome measures and (2) evaluate the efficacy of potential therapeutics in mitigating these pathologic changes due to injury in the CD canine model.</p> </section> <section> <h3> Methods</h3> <p>Retired female research beagles underwent spinal surgery where T11/T12, T12/T13, and T13/L1 IVDs were identified and punctured with a needle containing either a protease-activated receptor 2 antagonist (PAR2A) and cromolyn sodium (CS) solution (<i>N</i> = 3) or phosphate-buffered saline (PBS) (<i>N</i> = 3). Pain phenotyping and related outcomes were assessed longitudinally or at the 12-week endpoint via RNA-seq on the DRG, von Frey analysis, FitBark activity, and C-reactive protein plasma levels. Changes in the structure/function of the IVD were assessed via MRI, mechanics, dimethylmethylene blue assay (DMMB), histological staining using picrosirius red/alcian blue (PR/AB) and fluoroscopy, and electrophysiology on the DRG neurons.</p> </section> <section> <h3> Results</h3> <p>We evaluated a comprehensive series of outcome measures to determine the effects of IVD injury on the structure/function of the canine IVD and DRG, and pain in the in vivo CD dog model of IVDD and back pain. Specifically, we established methods to obtain high-quality messenger RNA from canine DRGs to perform bulk RNA-seq. We demonstrated that injury to the disc resulted in significant upregulation of inflammatory and pain-signaling genes, and downregulation of developmental genes in the adjacent innervating DRG neurons. Additionally, we isolated and cultured viable neurons from canine DRGs and found through whole-cell patch-clamp that DRGs innervating the injured disc demonstrated altered voltage-gated sodium channel activity compared to controls. Using T2-weighted MRI, we demonstrated that relaxati
{"title":"Chondrodystrophic Dogs as a Preclinical Large Animal Model of Discogenic Back Pain","authors":"Mary K. Heimann, Shirley N. Tang, Gilian Gunsch, Kyle Kuchynsky, Brett Klamer, Fangli Zhao, Megan Co, Maciej Pietrzak, Justin Richards, Jake Klausner, Adam Smith, Kaitlyn Cimney, Sara McBride-Gagyi, Brad Youngblood, Kara Corps, Candice Askwith, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur","doi":"10.1002/jsp2.70082","DOIUrl":"https://doi.org/10.1002/jsp2.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in humans and canines. IVD degeneration affects the structure and function of both the disc and the innervating dorsal root ganglion (DRG) neurons. Preclinical animal models are necessary for elucidating the mechanisms of IVD degeneration (IVDD) and the pain signaling pathways involved in discogenic back pain. The chondrodystrophic (CD) dog exhibits similar characteristics to the clinical population affected by IVDD-associated LBP. However, further investigation of the translational tools to study these conditions and the efficacy of novel treatments is needed in this canine model. The objectives of the present study are to: (1) assess the changes in the structure and function of the IVD and DRG, including pain behaviors, in response to injury using a comprehensive set of outcome measures and (2) evaluate the efficacy of potential therapeutics in mitigating these pathologic changes due to injury in the CD canine model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retired female research beagles underwent spinal surgery where T11/T12, T12/T13, and T13/L1 IVDs were identified and punctured with a needle containing either a protease-activated receptor 2 antagonist (PAR2A) and cromolyn sodium (CS) solution (<i>N</i> = 3) or phosphate-buffered saline (PBS) (<i>N</i> = 3). Pain phenotyping and related outcomes were assessed longitudinally or at the 12-week endpoint via RNA-seq on the DRG, von Frey analysis, FitBark activity, and C-reactive protein plasma levels. Changes in the structure/function of the IVD were assessed via MRI, mechanics, dimethylmethylene blue assay (DMMB), histological staining using picrosirius red/alcian blue (PR/AB) and fluoroscopy, and electrophysiology on the DRG neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We evaluated a comprehensive series of outcome measures to determine the effects of IVD injury on the structure/function of the canine IVD and DRG, and pain in the in vivo CD dog model of IVDD and back pain. Specifically, we established methods to obtain high-quality messenger RNA from canine DRGs to perform bulk RNA-seq. We demonstrated that injury to the disc resulted in significant upregulation of inflammatory and pain-signaling genes, and downregulation of developmental genes in the adjacent innervating DRG neurons. Additionally, we isolated and cultured viable neurons from canine DRGs and found through whole-cell patch-clamp that DRGs innervating the injured disc demonstrated altered voltage-gated sodium channel activity compared to controls. Using T2-weighted MRI, we demonstrated that relaxati","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The senescence of nucleus pulposus cells (NPCs) at the heart of the pathogenesis of intervertebral disc degeneration (IVDD), which causes low back pain. Abnormal mechanical stress causes intracellular Ca2+ overload by activating the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) channel.
Aims
This creates a positive feedback loop of oxidative-inflammatory damage by inducing endoplasmic reticulum stress and mitochondrial reactive oxygen species (ROS) bursts, as well as directly activating the NLRP3 inflammasome/NF-кB axis to promote the release of pro-inflammatory factors like IL-1β.
Results
Energy metabolism collapsed as a result of mechanistic cause that caused excessive activation of mitophagy via the ROS-PINK1/Parkin pathway, and SIRT1 functional suppression further compromised mitochondrial quality control. The inflammatory nucleus pulposus (NP) brought on by mechanical stimulation caused macrophages to polarize toward the M1 type, and the p38MAPK pathway was activated by the TNF-α/IL-1β released, which in turn increased senescence markers like p16/p21. Notably, ROS both triggers mitophagy and activates the p53 pathway. On the one hand, oxidative damage-induced ATM/ATR kinase activation leads to p53 phosphorylation, which triggers p21-mediated cell-cycle block. On the other hand, p53 exacerbates mitochondrial dysfunction by inhibiting SIRT1 expression, creating a triangular amplification loop of p53-ROS-mitophagy. Furthermore, p53 stimulates apoptosis by altering the Bax/Bcl-2 balance and works in concert with inflammatory substances secreted by M1-type macrophages to cause the development of senescence-associated secretory phenotype (SASP).
Conclusion
This interaction network reveals the dynamic coupling of mechano-immune-metabolic pathways in the course of IVDD, providing a theoretical basis for the development of multi-targeted intervention strategies, such as PIEZO1 inhibitors combined with M2-type macrophage polarization modulation, which are expected to delay disease progression by blocking key nodes.
{"title":"Mechanistic Interactions Driving Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration: A Multi-Axial Perspective of Mechanical, Immune, and Metabolic Pathways","authors":"Yunbo Yang, Haoming Li, Junhui Zuo, Fei Lei","doi":"10.1002/jsp2.70089","DOIUrl":"https://doi.org/10.1002/jsp2.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The senescence of nucleus pulposus cells (NPCs) at the heart of the pathogenesis of intervertebral disc degeneration (IVDD), which causes low back pain. Abnormal mechanical stress causes intracellular Ca<sup>2+</sup> overload by activating the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) channel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This creates a positive feedback loop of oxidative-inflammatory damage by inducing endoplasmic reticulum stress and mitochondrial reactive oxygen species (ROS) bursts, as well as directly activating the NLRP3 inflammasome/NF-кB axis to promote the release of pro-inflammatory factors like IL-1β.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Energy metabolism collapsed as a result of mechanistic cause that caused excessive activation of mitophagy via the ROS-PINK1/Parkin pathway, and SIRT1 functional suppression further compromised mitochondrial quality control. The inflammatory nucleus pulposus (NP) brought on by mechanical stimulation caused macrophages to polarize toward the M1 type, and the p38MAPK pathway was activated by the TNF-α/IL-1β released, which in turn increased senescence markers like p16/p21. Notably, ROS both triggers mitophagy and activates the p53 pathway. On the one hand, oxidative damage-induced ATM/ATR kinase activation leads to p53 phosphorylation, which triggers p21-mediated cell-cycle block. On the other hand, p53 exacerbates mitochondrial dysfunction by inhibiting SIRT1 expression, creating a triangular amplification loop of p53-ROS-mitophagy. Furthermore, p53 stimulates apoptosis by altering the Bax/Bcl-2 balance and works in concert with inflammatory substances secreted by M1-type macrophages to cause the development of senescence-associated secretory phenotype (SASP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This interaction network reveals the dynamic coupling of mechano-immune-metabolic pathways in the course of IVDD, providing a theoretical basis for the development of multi-targeted intervention strategies, such as PIEZO1 inhibitors combined with M2-type macrophage polarization modulation, which are expected to delay disease progression by blocking key nodes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitsuhiro Nishizawa, Diane Hu, Hassan Serhan, Bahram Saleh, Ralph S. Marcucio, Kazuhito Morioka
Background
Implant-associated infection remains a serious complication of instrumented spinal surgery. Since biofilm formation on the implant surface is a key factor in the pathogenesis of such infections, current preventive strategies include the use of implants with antibiotic coatings. However, these approaches raise concerns related to antibiotic resistance and cytotoxicity. Ultrafine-grained (UFG) stainless steel, characterized by nanoscale grain sizes, has demonstrated superior mechanical properties and potential antimicrobial effects. This study aimed to evaluate the antibacterial properties of UFG stainless steel implants against Staphylococcus aureus biofilm formation in both in vitro and in vivo models.
Methods
UFG and conventional SUS316L stainless steel wires were incubated with bioluminescent Staphylococcus aureus Xen36 for up to 7 days in vitro. Biofilm formation was assessed using crystal violet (CV) staining, colony-forming unit (CFU) counting, and quantitative PCR (qPCR) for 16S rRNA and luxA genes. In vivo antibacterial effects were evaluated using two mouse models: a subcutaneous pouch model and a postoperative spinal implant infection model. Wires were harvested at 1, 3, and 7 days post-infection and analyzed using the same assays.
Results
In vitro, UFG wires had significantly lower CFU counts than standard wires at 4 h (p = 0.0005), 1 day (p = 0.0001), and 3 days (p = 0.0314). In the subcutaneous pouch model, UFG wires showed significantly reduced bacterial load at Day 1 by CFU (p = 0.011). In the spinal implant model, CFU counts were significantly lower on UFG wires at Day 3 (p = 0.015).
Conclusions
UFG stainless steel implants demonstrated a significant reduction in early biofilm formation by Staphylococcus aureus in both in vitro and in vivo, suggesting a delay in the biofilm formation process. These findings support the potential of UFG materials as promising candidates for infection-resistant spinal implants.
背景：植入物相关感染仍然是脊柱固定手术的一个严重并发症。由于种植体表面的生物膜形成是此类感染发病机制的关键因素，目前的预防策略包括使用抗生素涂层的种植体。然而，这些方法引起了对抗生素耐药性和细胞毒性的担忧。超细晶（UFG）不锈钢具有纳米级的晶粒尺寸，具有优异的机械性能和潜在的抗菌效果。本研究旨在通过体外和体内模型评价UFG不锈钢植入物对金黄色葡萄球菌生物膜形成的抑菌性能。方法UFG与普通SUS316L不锈钢丝与金黄色葡萄球菌Xen36体外培养7 d。采用结晶紫（CV）染色、菌落形成单位（CFU）计数和16S rRNA和luxA基因的定量PCR （qPCR）评估生物膜的形成。采用两种小鼠模型：皮下袋模型和术后脊柱植入物感染模型来评估体内抗菌效果。在感染后1、3和7天采集金属丝，使用相同的方法进行分析。结果UFG丝在体外4 h （p = 0.0005）、1 d （p = 0.0001）和3 d （p = 0.0314）时CFU计数明显低于标准丝。在皮下袋模型中，CFU在第1天显著降低了UFG丝的细菌负荷（p = 0.011）。在脊柱植入物模型中，第3天UFG丝上的CFU计数明显降低（p = 0.015）。结论UFG不锈钢植入物在体外和体内均能显著减少金黄色葡萄球菌的早期生物膜形成，提示生物膜形成过程延迟。这些发现支持了UFG材料作为抗感染脊柱植入物的潜力。
{"title":"Ultrafine-Grained Materials With Antibacterial Properties: A Novel Approach to Reducing Spinal Implant-Associated Infections","authors":"Mitsuhiro Nishizawa, Diane Hu, Hassan Serhan, Bahram Saleh, Ralph S. Marcucio, Kazuhito Morioka","doi":"10.1002/jsp2.70091","DOIUrl":"https://doi.org/10.1002/jsp2.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Implant-associated infection remains a serious complication of instrumented spinal surgery. Since biofilm formation on the implant surface is a key factor in the pathogenesis of such infections, current preventive strategies include the use of implants with antibiotic coatings. However, these approaches raise concerns related to antibiotic resistance and cytotoxicity. Ultrafine-grained (UFG) stainless steel, characterized by nanoscale grain sizes, has demonstrated superior mechanical properties and potential antimicrobial effects. This study aimed to evaluate the antibacterial properties of UFG stainless steel implants against <i>Staphylococcus aureus</i> biofilm formation in both in vitro and in vivo models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UFG and conventional SUS316L stainless steel wires were incubated with bioluminescent <i>Staphylococcus aureus</i> Xen36 for up to 7 days in vitro. Biofilm formation was assessed using crystal violet (CV) staining, colony-forming unit (CFU) counting, and quantitative PCR (qPCR) for <i>16S rRNA</i> and <i>luxA</i> genes. In vivo antibacterial effects were evaluated using two mouse models: a subcutaneous pouch model and a postoperative spinal implant infection model. Wires were harvested at 1, 3, and 7 days post-infection and analyzed using the same assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro, UFG wires had significantly lower CFU counts than standard wires at 4 h (<i>p</i> = 0.0005), 1 day (<i>p</i> = 0.0001), and 3 days (<i>p</i> = 0.0314). In the subcutaneous pouch model, UFG wires showed significantly reduced bacterial load at Day 1 by CFU (<i>p</i> = 0.011). In the spinal implant model, CFU counts were significantly lower on UFG wires at Day 3 (<i>p</i> = 0.015).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>UFG stainless steel implants demonstrated a significant reduction in early biofilm formation by <i>Staphylococcus aureus</i> in both in vitro and in vivo, suggesting a delay in the biofilm formation process. These findings support the potential of UFG materials as promising candidates for infection-resistant spinal implants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew R. MacEwen, Rebecca E. Abbott, Victor H. Barocas, Arin M. Ellingson
Background
This study introduces the helical compliance vector (HCV), a novel measuring parameter that quantifies the orientation and magnitude of joint compliance (inverse of stiffness) by integrating kinetic and kinematic data within the helical axis framework. The HCV provides high temporal and spatial resolution, enabling detailed analysis of compliance and stiffness throughout motion, surpassing the limitations of traditional static or end-range metrics, which often fail to capture transient variations in stiffness and multiplanar interactions that occur during movement.
Methods
Eight cadaveric lumbar segments (L4–L5) were tested under pure moment loading (up to 7 Nm) in lateral bending, flexion/extension, axial rotation, and a multiplanar (Kemp's) test.
Results
The findings revealed distinct moment-specific compliance trends, with the highest compliance during low-moment flexion and the lowest during axial rotation. The Kemp's test demonstrated the HCV's ability to capture complex coupled motions, combining lateral bending and axial rotation motion. Across all loading scenarios, compliance decreased significantly near the end range of motion, illustrating its evolution throughout motion.
Conclusion
By simultaneously characterizing the magnitude and directionality of compliance, the HCV framework offers a comprehensive, high-resolution approach to understanding joint mechanics. This method establishes a foundation for investigating multiplanar joint behaviors and can be extended to in vivo applications using advanced imaging and musculoskeletal modeling technologies.
{"title":"The Helical Compliance Vector: Utility for Quantifying Spinal Mechanics","authors":"Matthew R. MacEwen, Rebecca E. Abbott, Victor H. Barocas, Arin M. Ellingson","doi":"10.1002/jsp2.70088","DOIUrl":"https://doi.org/10.1002/jsp2.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study introduces the helical compliance vector (HCV), a novel measuring parameter that quantifies the orientation and magnitude of joint compliance (inverse of stiffness) by integrating kinetic and kinematic data within the helical axis framework. The HCV provides high temporal and spatial resolution, enabling detailed analysis of compliance and stiffness throughout motion, surpassing the limitations of traditional static or end-range metrics, which often fail to capture transient variations in stiffness and multiplanar interactions that occur during movement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eight cadaveric lumbar segments (L4–L5) were tested under pure moment loading (up to 7 Nm) in lateral bending, flexion/extension, axial rotation, and a multiplanar (Kemp's) test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings revealed distinct moment-specific compliance trends, with the highest compliance during low-moment flexion and the lowest during axial rotation. The Kemp's test demonstrated the HCV's ability to capture complex coupled motions, combining lateral bending and axial rotation motion. Across all loading scenarios, compliance decreased significantly near the end range of motion, illustrating its evolution throughout motion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By simultaneously characterizing the magnitude and directionality of compliance, the HCV framework offers a comprehensive, high-resolution approach to understanding joint mechanics. This method establishes a foundation for investigating multiplanar joint behaviors and can be extended to in vivo applications using advanced imaging and musculoskeletal modeling technologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Young Hong, Hyun Kim, Wan-Jin Jeon, Changhwan Yeo, Junseon Lee, Hyunseong Kim, Yoon Jae Lee, In-Hyuk Ha
Background
Epidural injections treat lumbar spinal stenosis (LSS) by targeting localized inflammation and tissue damage. However, current medications such as corticosteroids and local anesthetics often have limited efficacy and significant adverse effects.
Methods
Human placental extract (HPE), with regenerative and anti-inflammatory properties, was tested for its axon-promoting and pain-relieving effects in an in vitro model using dorsal root ganglion neurons exposed to hydrogen peroxide (H2O2).
Results
Various HPE doses were applied, and 2.5 or 5 mg/mL enhanced cell viability and neurite outgrowth while alleviating the increased expression of pain-related markers (IB4, CGRP, TRPV1) caused by H2O2 in a dose-dependent manner. Subsequently, rats with LSS received epidural injections of 10 or 20 mg/kg HPE five times weekly for four weeks. In vivo results showed that repeated HPE injections significantly reduced ED1+ macrophages and altered the expression of M1 (iNOS, TNF-α, COX-2) and M2 (Arg1, CD206) macrophage markers. Pain-related markers (TRPV1, IB4, CGRP, NF200) and genes (Il1rn, Scn9a) were significantly downregulated in 3D dorsal root ganglion tissues. Additionally, the 3D spinal cord exhibited increased serotonergic axons and upregulated expression of genes related to axonal growth and neurotrophic factors (Nefh, Ngf, Bdnf, Gap43).
Conclusions
Our findings suggest that repeated epidural injections of human placental extract in LSS rats can improve locomotor function. This underscores the potential benefits of human placental extract as an epidural agent, enhancing the recovery process and offering a new and minimally invasive treatment strategy for LSS.
{"title":"Human Placental Extract as a Promising Epidural Therapy for Lumbar Spinal Stenosis: Enhancing Axonal Plasticity and Mitigating Pain and Inflammation in a Rat Model","authors":"Jin Young Hong, Hyun Kim, Wan-Jin Jeon, Changhwan Yeo, Junseon Lee, Hyunseong Kim, Yoon Jae Lee, In-Hyuk Ha","doi":"10.1002/jsp2.70085","DOIUrl":"https://doi.org/10.1002/jsp2.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epidural injections treat lumbar spinal stenosis (LSS) by targeting localized inflammation and tissue damage. However, current medications such as corticosteroids and local anesthetics often have limited efficacy and significant adverse effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human placental extract (HPE), with regenerative and anti-inflammatory properties, was tested for its axon-promoting and pain-relieving effects in an in vitro model using dorsal root ganglion neurons exposed to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Various HPE doses were applied, and 2.5 or 5 mg/mL enhanced cell viability and neurite outgrowth while alleviating the increased expression of pain-related markers (IB4, CGRP, TRPV1) caused by H<sub>2</sub>O<sub>2</sub> in a dose-dependent manner. Subsequently, rats with LSS received epidural injections of 10 or 20 mg/kg HPE five times weekly for four weeks. In vivo results showed that repeated HPE injections significantly reduced ED1<sup>+</sup> macrophages and altered the expression of M1 (iNOS, TNF-α, COX-2) and M2 (Arg1, CD206) macrophage markers. Pain-related markers (TRPV1, IB4, CGRP, NF200) and genes (<i>Il1rn</i>, <i>Scn9a</i>) were significantly downregulated in 3D dorsal root ganglion tissues. Additionally, the 3D spinal cord exhibited increased serotonergic axons and upregulated expression of genes related to axonal growth and neurotrophic factors (<i>Nefh, Ngf, Bdnf, Gap43</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that repeated epidural injections of human placental extract in LSS rats can improve locomotor function. This underscores the potential benefits of human placental extract as an epidural agent, enhancing the recovery process and offering a new and minimally invasive treatment strategy for LSS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur J. Michalek, Isabelle M. Wood, Daniela Gonzalez Carranza, Lindsay Ferlito
Introduction
The intervertebral disc (IVD) of the bovine tail is a commonly used research analogue for the human disc at the organ, tissue, and cellular levels. While these tails are subjected to thousands of dynamic motion events daily, little is known about how these motions might induce tissue remodeling, particularly in the outer annulus fibrosus (AF) of IVDs connecting adjacent vertebrae. This study hypothesized that despite the similarities in geometry and biochemical composition of IVDs in the bovine tail, level-wise variations in repetitive in-vivo motion would be associated with tissue level adaptations.
Methods
In-vivo active range of motion (RoM) was measured by placing inertial measurement unit sensors on the tails of adult cows and using a multi-segment rigid body model to calculate level-wise flexion-extension and lateral bending angles. Level-wise passive RoM was measured from cadaveric adult bovine tails in flexion, extension, and lateral bending with skin and muscles removed. IVDs were extracted for measurement of height, diameters, AF radial thicknesses, and AF fiber crimp periods.
Results
In-vivo joint RoM was found to vary drastically by level, largely due to a prominent second order mode with inflection point at the fourth joint. Joint levels near this inflection point were found to have the highest passive RoMs. In the proximal tail, decreased RoM was associated with an increased fiber crimp period in the outer AF, while in the distal tail it was associated with increased AF thickness.
Discussion
Taken together, these findings suggest that IVDs in the bovine tail respond to repeated complex dynamic motions through a process of adaptation at the mesoscale (AF thickening during growth) and microscale (residual strain accumulation in the mature state). The bovine tail thus provides a powerful tool for modeling how the human lumbar intervertebral disc may remodel in response to changes in exposure to repetitive motions.
{"title":"Complex In Vivo Motion of the Bovine Tail Provides Unique Insights Into Intervertebral Disc Adaptation","authors":"Arthur J. Michalek, Isabelle M. Wood, Daniela Gonzalez Carranza, Lindsay Ferlito","doi":"10.1002/jsp2.70084","DOIUrl":"https://doi.org/10.1002/jsp2.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The intervertebral disc (IVD) of the bovine tail is a commonly used research analogue for the human disc at the organ, tissue, and cellular levels. While these tails are subjected to thousands of dynamic motion events daily, little is known about how these motions might induce tissue remodeling, particularly in the outer annulus fibrosus (AF) of IVDs connecting adjacent vertebrae. This study hypothesized that despite the similarities in geometry and biochemical composition of IVDs in the bovine tail, level-wise variations in repetitive in-vivo motion would be associated with tissue level adaptations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In-vivo active range of motion (RoM) was measured by placing inertial measurement unit sensors on the tails of adult cows and using a multi-segment rigid body model to calculate level-wise flexion-extension and lateral bending angles. Level-wise passive RoM was measured from cadaveric adult bovine tails in flexion, extension, and lateral bending with skin and muscles removed. IVDs were extracted for measurement of height, diameters, AF radial thicknesses, and AF fiber crimp periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In-vivo joint RoM was found to vary drastically by level, largely due to a prominent second order mode with inflection point at the fourth joint. Joint levels near this inflection point were found to have the highest passive RoMs. In the proximal tail, decreased RoM was associated with an increased fiber crimp period in the outer AF, while in the distal tail it was associated with increased AF thickness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Taken together, these findings suggest that IVDs in the bovine tail respond to repeated complex dynamic motions through a process of adaptation at the mesoscale (AF thickening during growth) and microscale (residual strain accumulation in the mature state). The bovine tail thus provides a powerful tool for modeling how the human lumbar intervertebral disc may remodel in response to changes in exposure to repetitive motions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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