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Impact of Habitual Flexion on Bone Formation After Spinal Fusion Surgery: An In Silico Study 习惯性屈曲对脊柱融合术后骨形成的影响：一项计算机研究
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70075
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.

背景腰椎融合术目前被认为是治疗脊柱畸形、退行性椎间盘疾病和退行性椎体滑脱最有效的手术方法之一。然而，该手术仍然面临着高发生率的不愈合。导致骨不愈合的一个关键因素是应力屏蔽效应，这与融合部位的不利机械信号有关。核聚变现场的机械条件是由日常活动产生的负荷条件决定的。最近的研究表明，人类一天中的大部分时间都处于脊椎弯曲的状态。屈曲载荷在骨融合进展中的作用仍然知之甚少。本研究探讨了习惯性屈曲载荷对脊柱融合过程的影响，使用了一个将有限元分析与骨愈合算法相结合的计算建模框架来模拟融合手术后的骨再生。方法建立健康人腰椎有限元模型，并用体外实验数据进行验证。之后，进行虚拟后路腰椎椎体间融合术，在L4-L5水平插入2个椎间笼并进行后路固定。研究了两种加载条件对预测融合过程的影响：(1)压缩加载；(2)模拟日常生活中遇到的习惯性屈曲的混合（压缩+屈曲）加载方案。结果术后14周可出现骨桥。在第14周，对于混合载荷，模型预测骨体积为70%，而对于压缩载荷，骨体积预测为59%。计算机模型预测表明，习惯性屈曲载荷可以通过诱导有利于骨形成的机械环境来促进前区和外周区的骨形成。结论屈曲载荷可通过促进有利的机械条件来促进骨愈合。计算框架可以指导优化康复方案的发展，以改善融合结果。
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引用次数: 0
Demographic and Biomedical Characteristics of an Observational Cohort With Chronic Low Back Pain: A Descriptive Analysis 慢性腰痛观察队列的人口统计学和生物医学特征：描述性分析
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70094
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

背景：关于慢性腰痛（cLBP）的文献很少包括对大样本个体的人口统计学和生物医学因素的全面描述。匹兹堡大学机械研究中心，题为“腰痛：生物学，生物力学，行为表型（LB3P）”，是美国国立卫生研究院帮助结束成瘾长期倡议的一部分。LB3P进行了一项前瞻性、观察性队列研究，以确定cLBP患者的表型。在这里，我们报告了一大批cLBP患者的人口统计学和生物医学特征，按性别和年龄分层，收集于现场登记访问中。方法主要入选标准为患有cLBP的成年人，英语使用者，并在本医疗中心的电子健康记录中确认。招募策略是通过临床合作伙伴邀请他们的患者加入研究和研究登记。参与者完成了人口和生物医学调查。对总体样本和亚组（男性/女性和年龄60岁/≥60岁）进行描述性统计。结果入组1007例，女性60%，平均年龄59±17岁。大多数参与者是非西班牙裔（90%），白人（75%），53%接受过大学或高等教育。54%的人已婚或有伴侣，43%的人有工作，38%的人退休，41%的人家庭年收入超过5万美元，20%的人因为腰痛（LBP）而离开工作超过30天，16%的人申请或接受残疾，6%的人领取工人补偿。大多数人肥胖（平均BMI为31.5 kg/m2）， 61%的人背痛5年，76%的人每天或几乎每天都有疼痛。参与者报告了高患病率的骨关节炎（58%）、焦虑（40%）、抑郁（40%）、视力障碍（35%）和平衡问题/跌倒（31%）。在慢性重叠疼痛疾病中，最常见的是偏头痛或头痛（29%），肠易激综合征（16%）和颞下颌关节功能障碍（12%）。有25%的患者曾做过腰背部手术。在前一个月，最常见的LBP治疗方法是自己进行常规运动（58%），物理治疗，职业治疗或脊椎按摩护理（33%），正念，冥想或放松（22%），饮食或营养咨询（21%）。上个月服用非甾体类抗炎药占43%，加巴喷丁占18%，阿片类药物占13%，抗抑郁药占10%。根据性别和年龄对cLBP患者进行全面的人口学和生物医学特征的描述，将为临床医生和研究计划提供参考，特别是在cLBP的合并症和治疗利用方面。这些数据将有助于未来对cLBP进行全面表型分析。
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引用次数: 0
Chondrodystrophic Dogs as a Preclinical Large Animal Model of Discogenic Back Pain 软骨营养不良犬作为椎间盘源性背痛的临床前大型动物模型
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-07-14 DOI: 10.1002/jsp2.70082
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
背景：椎间盘（IVD）退变是人类和犬腰痛（LBP）的主要原因。IVD变性影响椎间盘和支配背根神经节（DRG）神经元的结构和功能。临床前动物模型对于阐明椎间盘源性腰痛的机制和疼痛信号通路是必要的。软骨营养不良（CD）犬表现出与临床人群相似的特征，受ivdd相关的LBP影响。然而，在这种犬模型中，需要进一步研究翻译工具来研究这些条件和新治疗的疗效。本研究的目的是：(1)使用一套全面的结果测量方法评估损伤后IVD和DRG结构和功能的变化，包括疼痛行为；(2)评估潜在治疗方法在减轻CD犬模型损伤引起的这些病理变化方面的疗效。方法对接受脊柱手术的退休雌性研究小猎犬进行T11/T12、T12/T13和T13/L1 ivd鉴定，并用含有蛋白酶激活受体2拮抗剂（PAR2A）和色钼酸钠（CS）溶液（N = 3）或磷酸盐缓冲盐水（PBS） （N = 3）的针穿刺。通过DRG、von Frey分析、FitBark活性和c反应蛋白血浆水平的RNA-seq，纵向或在12周终点评估疼痛表型和相关结果。通过MRI、力学、二甲基亚甲基蓝（DMMB）、小天狼星红/阿利新蓝（PR/AB）和荧光染色及DRG神经元电生理观察观察IVD结构/功能的变化。我们评估了一系列综合的结局指标，以确定IVD损伤对犬IVD和DRG结构/功能的影响，以及IVD和背部疼痛的体内CD犬模型的疼痛。具体来说，我们建立了从犬DRGs中获得高质量信使RNA的方法来进行批量RNA测序。我们证明椎间盘损伤导致炎症和疼痛信号基因的显著上调，以及邻近支配DRG神经元的发育基因的下调。此外，我们从犬DRGs中分离培养活神经元，并通过全细胞膜片钳发现，与对照组相比，支配受损椎间盘的DRGs表现出改变的电压门控钠通道活性。通过t2加权MRI，我们证明，与内控椎间盘相比，6只狗中有4只狗被刺破椎间盘的松弛时间缩短，这表明这些受伤的ivd的潜在成分发生了变化。在这个小队列中没有观察到PAR2A和CS治疗的显著效果，需要进一步研究。结论：本研究评估了一系列严格的结果指标，以确定IVD损伤对CD犬背部疼痛模型的椎间盘关节和疼痛的影响。这是首次研究椎间盘损伤对犬DRG转录组的影响以及全细胞贴片夹紧对犬DRG神经元的影响。研究结果支持CD犬作为研究IVDD和LBP的临床相关转化模型，以及评估新疗法在缓解这些疾病相关变化方面的潜在疗效。
{"title":"Chondrodystrophic Dogs as a Preclinical Large Animal Model of Discogenic Back Pain","authors":"Mary K. Heimann,&nbsp;Shirley N. Tang,&nbsp;Gilian Gunsch,&nbsp;Kyle Kuchynsky,&nbsp;Brett Klamer,&nbsp;Fangli Zhao,&nbsp;Megan Co,&nbsp;Maciej Pietrzak,&nbsp;Justin Richards,&nbsp;Jake Klausner,&nbsp;Adam Smith,&nbsp;Kaitlyn Cimney,&nbsp;Sara McBride-Gagyi,&nbsp;Brad Youngblood,&nbsp;Kara Corps,&nbsp;Candice Askwith,&nbsp;Benjamin A. Walter,&nbsp;Sarah A. Moore,&nbsp;Devina Purmessur","doi":"10.1002/jsp2.70082","DOIUrl":"https://doi.org/10.1002/jsp2.70082","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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 (&lt;i&gt;N&lt;/i&gt; = 3) or phosphate-buffered saline (PBS) (&lt;i&gt;N&lt;/i&gt; = 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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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}
引用次数: 0
Mechanistic Interactions Driving Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration: A Multi-Axial Perspective of Mechanical, Immune, and Metabolic Pathways 椎间盘退变中驱动髓核细胞衰老的机制相互作用：机械、免疫和代谢途径的多轴视角
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-07-02 DOI: 10.1002/jsp2.70089
Yunbo Yang, Haoming Li, Junhui Zuo, Fei Lei

Background

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.

髓核细胞（NPCs）的衰老是导致腰痛的椎间盘退变（IVDD）发病机制的核心。异常机械应力通过激活压电型机械敏感离子通道组分1 （PIEZO1）通道导致细胞内Ca2+过载。通过诱导内质网应激和线粒体活性氧（ROS）爆发，以及直接激活NLRP3炎性小体/NF-кB轴，促进IL-1β等促炎因子的释放，形成氧化炎症损伤的正反馈循环。结果能量代谢崩溃是通过ROS-PINK1/Parkin通路导致线粒体自噬过度激活的机制原因，SIRT1功能抑制进一步损害线粒体质量控制。机械刺激引起的炎性髓核（NP）使巨噬细胞向M1型极化，释放的TNF-α/IL-1β激活了p38MAPK通路，从而增加了p16/p21等衰老标志物。值得注意的是，ROS既触发有丝分裂又激活p53通路。一方面，氧化损伤诱导的ATM/ATR激酶激活导致p53磷酸化，从而触发p21介导的细胞周期阻滞。另一方面，p53通过抑制SIRT1表达加剧线粒体功能障碍，形成p53- ros -mitophagy的三角形扩增环。此外，p53通过改变Bax/Bcl-2平衡刺激细胞凋亡，并与m1型巨噬细胞分泌的炎症物质协同作用，导致衰老相关分泌表型（SASP）的发展。结论该相互作用网络揭示了IVDD过程中机械-免疫-代谢途径的动态耦合，为开发多靶向干预策略提供了理论基础，如PIEZO1抑制剂联合m2型巨噬细胞极化调节，有望通过阻断关键节点来延缓疾病进展。
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引用次数: 0
Ultrafine-Grained Materials With Antibacterial Properties: A Novel Approach to Reducing Spinal Implant-Associated Infections 具有抗菌特性的超细颗粒材料：一种减少脊柱植入物相关感染的新方法
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-30 DOI: 10.1002/jsp2.70091
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。
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引用次数: 0
The Helical Compliance Vector: Utility for Quantifying Spinal Mechanics 螺旋顺应矢量：量化脊柱力学的实用工具
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-19 DOI: 10.1002/jsp2.70088
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.

本研究引入了螺旋柔度向量（HCV），这是一种新的测量参数，通过整合螺旋轴框架内的动力学和运动学数据来量化关节柔度（刚度逆）的方向和大小。HCV提供了高时间和空间分辨率，能够在整个运动过程中详细分析顺应性和刚度，超越了传统静态或末端测量的局限性，这些指标通常无法捕捉运动过程中发生的刚度瞬态变化和多平面相互作用。方法对8个尸体腰椎节段（L4-L5）进行横向弯曲、屈伸、轴向旋转和多平面（Kemp’s）试验。结果研究结果显示了明显的矩特异性顺应性趋势，低矩屈曲时的顺应性最高，轴向旋转时的顺应性最低。Kemp的测试证明了HCV能够捕捉复杂的耦合运动，结合横向弯曲和轴向旋转运动。在所有加载场景中，在接近运动末端范围时，顺应性显著下降，说明其在整个运动过程中的演变。通过同时表征顺应性的大小和方向，HCV框架为理解关节力学提供了全面、高分辨率的方法。该方法为研究多平面关节行为奠定了基础，并可通过先进的成像和肌肉骨骼建模技术扩展到体内应用。
{"title":"The Helical Compliance Vector: Utility for Quantifying Spinal Mechanics","authors":"Matthew R. MacEwen,&nbsp;Rebecca E. Abbott,&nbsp;Victor H. Barocas,&nbsp;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}
引用次数: 0
Human Placental Extract as a Promising Epidural Therapy for Lumbar Spinal Stenosis: Enhancing Axonal Plasticity and Mitigating Pain and Inflammation in a Rat Model 人胎盘提取物作为一种有前途的硬膜外治疗腰椎管狭窄：在大鼠模型中增强轴突可塑性和减轻疼痛和炎症
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-17 DOI: 10.1002/jsp2.70085
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.

背景硬膜外注射通过靶向局部炎症和组织损伤治疗腰椎管狭窄（LSS）。然而，目前的药物，如皮质类固醇和局部麻醉剂，往往是有限的疗效和显著的不良反应。方法利用过氧化氢（H2O2）处理的大鼠背根神经节神经元体外模型，研究具有再生和抗炎作用的人胎盘提取物（HPE）对轴突的促进作用和镇痛作用。结果应用不同剂量的HPE， 2.5或5 mg/mL均能增强细胞活力和神经突生长，同时减轻H2O2引起的疼痛相关标志物（IB4、CGRP、TRPV1）表达的增加，且呈剂量依赖性。随后，LSS大鼠接受10或20 mg/kg HPE硬膜外注射，每周5次，连续4周。体内实验结果显示，重复注射HPE可显著降低ED1+巨噬细胞，改变巨噬细胞标志物M1 （iNOS、TNF-α、COX-2）和M2 （Arg1、CD206）的表达。疼痛相关标志物（TRPV1、IB4、CGRP、NF200）和基因（Il1rn、Scn9a）在3D背根神经节组织中显著下调。此外，3D脊髓显示出5 -羟色胺能轴突增加，轴突生长和神经营养因子相关基因表达上调（Nefh, Ngf, Bdnf, Gap43）。结论反复硬膜外注射人胎盘提取物可改善LSS大鼠的运动功能。这强调了人胎盘提取物作为硬膜外药物的潜在益处，增强了恢复过程，并为LSS提供了一种新的微创治疗策略。
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引用次数: 0
Complex In Vivo Motion of the Bovine Tail Provides Unique Insights Into Intervertebral Disc Adaptation 牛尾巴复杂的体内运动为椎间盘适应提供了独特的见解
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-17 DOI: 10.1002/jsp2.70084
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.

牛尾椎间盘（IVD）是一种在器官、组织和细胞水平上常用的人类椎间盘的研究模拟物。虽然这些尾巴每天要经历数千次动态运动事件，但人们对这些运动如何诱导组织重塑知之甚少，特别是连接相邻椎骨的ivd的纤维外环（AF）。本研究假设，尽管牛尾部ivd的几何形状和生化组成相似，但重复体内运动的水平变化可能与组织水平的适应有关。方法通过在成年奶牛尾部放置惯性测量单元传感器，利用多段刚体模型计算水平屈伸角和侧向弯曲角，测量奶牛体内主动运动范围（RoM）。水平方向被动RoM测量从尸体成年牛尾巴在屈曲，延伸和侧屈，皮肤和肌肉去除。提取ivd用于测量高度、直径、AF径向厚度和AF纤维卷曲周期。结果体内关节RoM在不同水平下变化很大，主要是由于在第四个关节有明显的二阶模式。在这个拐点附近的关节水平被发现有最高的被动rom。在尾部近端，RoM的减少与AF外层纤维卷曲时间的增加有关，而在尾部远端，RoM的减少与AF厚度的增加有关。综上所述，这些研究结果表明，牛尾部的ivd通过中尺度（生长期间AF增厚）和微观尺度（成熟状态下残余应变积累）的适应过程来响应重复的复杂动态运动。因此，牛尾巴提供了一个强大的工具，用于模拟人类腰椎间盘如何在暴露于重复运动变化时进行重塑。
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引用次数: 0
Injection Volume Is a Better Predictor of Stiffness Restoration Than Injection Force in an In Vitro Study of Nucleus Augmentation of the Intervertebral Disc 在椎间盘核增强的体外研究中，注射体积比注射力更能预测刚度恢复
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-10 DOI: 10.1002/jsp2.70081
J. P. Warren, A. R. Dixon, M. P. Culbert, A. Khan, M. Mengoni, R. K. Wilcox

Purpose

Nucleus augmentation has been proposed as an early-stage intervention for intervertebral disc degeneration and involves the injection of a biomaterial into the nucleus to restore disc height and functionality. The aim of this work was to identify clinically relevant quantitative measures that indicate the mechanical performance of the disc following nucleus augmentation.

Method

Bovine tail bone-disc-bone units (n = 22) were mechanically tested under cyclic loading sequentially in native, artificially degenerated, and treated states. Treatment involved injection of a peptide-glycosaminoglycan mixture into the degenerated disc to a predetermined load using a syringe driver with an integrated force sensor. The stiffness restoration of the treatment was determined by comparing the biomechanical behavior of the native state to the treated state of each disc. The stiffness restoration was then compared against clinically quantifiable parameters.

Results

No significant biomechanical differences were observed between the native and treated states, but both were significantly different from the degenerated state. The force delivered during injection was found to ramp to a steady state, followed by a final rapid increase; however, all measures associated with injection force poorly correlated with the level of stiffness restoration. Volume injected and change in disc height from injection had the strongest relationship to stiffness restoration.

Conclusion

This work showed that measuring the injection force for injectable treatments of the disc can provide lower and upper limits for delivery, but direct measures are stronger indicators of disc stiffness restoration.

目的核增强术被认为是椎间盘退变的早期干预手段，包括向核内注射生物材料以恢复椎间盘高度和功能。这项工作的目的是确定临床相关的定量措施，表明核增强后椎间盘的力学性能。方法对22只牛尾骨-椎间盘-骨单元分别在自然状态、人工退化状态和处理状态下进行循环加载力学试验。治疗包括使用带集成力传感器的注射器驱动器将肽-糖胺聚糖混合物注射到退变的椎间盘到预定的负载。通过比较每个椎间盘的自然状态和治疗状态的生物力学行为来确定治疗后的刚度恢复。然后将刚度恢复与临床可量化参数进行比较。结果原始状态和治疗状态生物力学无明显差异，但与退变状态均有显著差异。在注入过程中，所施加的力逐渐达到稳定状态，随后最终迅速增加；然而，所有与注射力相关的措施与刚度恢复水平相关性较差。注射体积和注射后椎间盘高度的变化与刚度恢复的关系最强。结论在椎间盘注射治疗中，测量注射力可以提供给药的下限和上限，但直接测量是椎间盘刚度恢复的更强指标。
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引用次数: 0
The Role of Adipokines in Spinal Disease: A Narrative Review 脂肪因子在脊柱疾病中的作用：综述
IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-06-03 DOI: 10.1002/jsp2.70083
Jake M. McDonnell, Stacey Darwish, Joseph S. Butler, Conor T. Buckley

Background

Adipokines are bioactive molecules secreted by adipose tissue that influence both local and systemic physiological processes. Although adipokine dysregulation has been widely implicated in the pathogenesis of cardiovascular, gastrointestinal, nervous, immune, and musculoskeletal disorders- especially osteoarthritis, rheumatoid arthritis, and osteoporosis- their involvement in spinal pathology remains comparatively underinvestigated. Recent evidence indicates that certain adipokines may influence spinal disease progression by affecting bone, intervertebral discs, musculature, and neural structures.

Methods

A comprehensive literature review was conducted to evaluate preclinical and clinical studies investigating the role of adipokines in spinal pathology. PubMed and related databases were searched for studies reporting associations between adipokine expression and structural or functional changes in spinal tissues, including vertebral bone, intervertebral discs, paraspinal muscles, spinal ligaments, and the spinal cord. Particular attention was given to mechanistic insights and translational relevance.

Results

The review identified emerging evidence implicating several adipokines, including leptin, adiponectin, resistin, and visfatin, in degenerative and inflammatory changes across various spinal structures. Adipokines were found to influence matrix degradation, bone turnover, muscle atrophy, and neural inflammation through cytokine signaling, oxidative stress, and metabolic dysregulation. However, findings are often heterogeneous and context-dependent, with limited longitudinal or interventional data.

Conclusions

Adipokines represent a promising yet underexplored avenue in spinal disease research. Their diverse functions in both structural and metabolic regulation highlight their potential as both biomarkers and therapeutic targets. Further mechanistic and clinical studies are needed to elucidate causal relationships and therapeutic efficacy, particularly in degenerative spine disorders.

脂肪因子是由脂肪组织分泌的生物活性分子，影响局部和全身生理过程。尽管脂肪因子失调已广泛涉及心血管、胃肠、神经、免疫和肌肉骨骼疾病的发病机制，尤其是骨关节炎、风湿性关节炎和骨质疏松症，但它们在脊柱病理中的作用仍未得到充分研究。最近的证据表明，某些脂肪因子可能通过影响骨骼、椎间盘、肌肉组织和神经结构来影响脊柱疾病的进展。方法对研究脂肪因子在脊柱病理中的作用的临床前和临床研究进行综述。检索PubMed和相关数据库，寻找脂肪因子表达与脊柱组织（包括椎骨、椎间盘、棘旁肌、脊髓韧带和脊髓）结构或功能改变之间的相关研究。特别注意的是机械的见解和翻译的相关性。结果：该综述发现了一些新的证据表明，包括瘦素、脂联素、抵抗素和visfatin在内的几种脂肪因子与各种脊柱结构的退行性和炎症变化有关。脂肪因子通过细胞因子信号传导、氧化应激和代谢失调影响基质降解、骨转换、肌肉萎缩和神经炎症。然而，研究结果往往是异质的和环境相关的，纵向或介入性数据有限。结论脂肪因子在脊柱疾病研究中是一种有前景但尚未开发的途径。它们在结构和代谢调节中的多种功能突出了它们作为生物标志物和治疗靶点的潜力。需要进一步的机制和临床研究来阐明因果关系和治疗效果，特别是在退行性脊柱疾病中。
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