Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post‐operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze‐drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC‐injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10–12%) viscoelastic moduli after mild degeneration within goats, though the inter‐animal differences were relatively large (complex modulus ～12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ～75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 703–709, 2013     

CT扫描资料间接法建立股骨上段三维有限元模型

目的 建立正常人体股骨上段三维有限元模型，作为今后该部位进一步有限元分析的基础。方法 采用活体股骨上段为对象，应用CT扫描技术，图形数字化方法获取股骨上面三维坐标，输入有限元分析软件ANSYS5．6，通过确定材料特性参数和网格化，建立完整的股骨上段三维有限元模型。结果 建立的三维有限元模型几何形状与材料特性还原良好，网格大小可根据研究者的需要在一定范围内自行调整，可以满足有限元分析的需要。结论 采用CT扫描资料建立三维有限元模型切实可靠；间接法建立三维有限元模型比直接法更加简便，高效，可以更精确地模拟复杂几何形态的实体。     

Effects of aging and degeneration on the human intervertebral disc during the diurnal cycle: A finite element study

A significant biochemical change that takes place in intervertebral disc degeneration is the loss of proteoglycans in the nucleus pulposus. Proteoglycans attract fluid, which works to reduce mechanical stresses in the solid matrix of the nucleus and provide a hydrostatic pressure to the annulus fibrosus, whose fibrous nature accommodates this stress. Our goals are to develop an osmo‐poroelastic finite element model to study the relationship between proteoglycan content and the stress distribution within the disc and to analyze the effects of degeneration on the disc's diurnal mechanical response. Stress in the annulus increased with degeneration from ～0.2 to 0.4 MPa, and an increase occurred in the center of the nucleus from 1.2 to 1.6 MPa. The osmotic pressure in the central nucleus region decreased the most with degeneration, from ～0.42 to ～0.1 MPa in a severely dehydrated disc. A 3% decrease in diurnal fluid lost with degeneration equated to ～21% decrease in fluid exchange, and hence a decrease in nutrients that require convection to enter the disc. We quantified the increases in internal stresses in the nucleus and annulus throughout the various stages of degeneration, suggesting that these changes lead to further remodeling of the tissue. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:122–128, 2012     

组织工程化同种异体椎间盘移植的动物实验研究

目的观察组织工程技术的运用能否延缓椎间盘移植后的退行性改变。方法将髓中受细胞复合至同种异体椎间盘,体外培养后植入犬L4／k椎间隙作为实验组（A组）,对照组（B组）行同种异体椎间髓移植。使用影像学、生物力学及组织学分析评估植入椎间盘的转归并行组间比较。结果移植椎间盘可与宿主椎体实现骨性融合。对照组椎间盘术后退变明显,12周时其椎间盘高度及髓核信号比灰度值明显低于实验组,稳定性丧失明显;组织学观察发现实验组移植椎间盘结构保持较好,髓核细胞数量较多,排列规则;对照组髓核形态保持欠佳,结构紊乱,髓核细胞数量减少,退行性改变明显。结论通过复合种子细胞实现异体椎间盘的组织工程化可有效延缓椎间盘移植后的退行性改变。     

大鼠尾椎椎间盘退变静态压力模型的构建

目的采用静态压力构建稳定的大鼠尾椎椎间盘退变模型。方法将40只12周龄大鼠随机分为静态压力组和针刺组,每组20只。静态压力组:在尾椎C_(4~7)椎体上安装静态压力环形外固定支架,压缩的4根弹簧施加的压强均为10 kPa,维持8周。针刺组:采用16 G针头刺入尾椎C_4/C_5/C_6/C_7椎间盘,限制损伤深度5 mm、朝向椎间盘中心,损伤后留置10 s。分别于术后8周进行组织病理学切片观察,采用秩和检验比较2组Thompson椎间盘退变病理分级。结果对2组大鼠尾椎共120个椎间盘髓核组织标本进行病理分级,统计结果显示静态压力组退变级别明显高于针刺组,差异有统计学意义(P0.05)。结论采用静态压力构建的椎间盘退变模型稳定可靠,较传统针刺模型具有优势,可为临床椎间盘退变研究提供可靠的动物模型。     

Investigation of solute concentrations in a 3D model of intervertebral disc

As the disc is the largest avascular structure in the body, disc cells depend for their normal function on an adequate supply of nutrients (oxygen and glucose) and the removal of metabolic by-products (lactic acid) via blood vessels at the cartilaginous endplates and annulus periphery. Concentration gradients develop depending on the balance between the rates of transport and rates of cellular activity. Since consumption and production rates are coupled via extracellular pH, the gradients are interdependent. This is a novel model study which takes into account the realistic 3D geometry of a L5-S1 lumbar disc in solving the nonlinear coupled diffusion equations. Effects of perturbations (calcification, sclerosis) in endplates, increases in cell metabolic rates following growth factor injection and changes in lumbar posture (kyphotic or lordotic) on extreme values of nutrient and metabolite concentrations and their spatial locations are investigated. Solute concentrations, particularly those of glucose, substantially diminish as a consequence of disturbances in supply at the endplates, increases in cell metabolic rate and more lordotic postures. Results, when compared to those from simplified axisymmetric models, demonstrate the importance of consideration of realistic 3D disc geometry.     

坐位骶髂关节面应力分布的三维有限元研究

目的 模拟研究成人正常静态坐位骶髂关节面的应力分布。方法 建立骶髂关节与骨盆三维有限元模型,且骶骨上面加载,双侧坐骨结节为支撑点,分析骶髂关节面的应力分布特点。结果 坐位时骶髂关节面骶骨侧与髂骨侧的应力分布规律和应力水平相似,关节面上端与中下部的应力值较高,前缘高于后缘,前后向的“山谷”较平坦。结论 坐位时骶髂关节面的应力分布较均匀,有利于关节的稳定和减少关节周围结构的劳损。     

Novel human intervertebral disc strain template to quantify regional three‐dimensional strains in a population and compare to internal strains predicted by a finite element model

Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4–L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel‐wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group‐level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc‐level mechanical response. Depending on the strain component, 81–99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264–1273, 2016.     

正常双腿站立位股骨上段应力分布的三维有限元分析

目的 用三维有限元方法分析双腿站立位时正常人体股骨上段的应力分布，验证该部位应力与结构的对应关系。方法 在建立股骨上段三维有限元模型的基础上，确定边界条件，加载负荷，用三维有限元分析软件计算并图示股骨上段应力分布。结果 股骨上段应力分布结构合理，验证了结构与功能的对应关系。结论 三维有限元分析与方法是一种简便实用的生物力学研究方法，可作为实验生物力学研究的验证和补充方法。     

In vitro evaluation of a manganese chloride phantom-based MRI technique for quantitative determination of lumbar intervertebral disc composition and condition

The application of MRI as a non-invasive, quantitative tool for diagnosing lumbar intervertebral disc degeneration is currently an area of active research. The objective of this study was to examine, in vitro, the efficacy of a manganese chloride phantom-based MRI technique for quantitatively assessing lumbar disc composition and degenerative condition. Sixteen human lumbar discs were imaged ex vivo using T2-weighted MRI, and assigned a quantitative grade based on the relative signal intensities of nine phantoms containing serial concentrations of manganese chloride. Discs were then graded macroscopically for degenerative condition, and water and uronic acid (glycosaminoglycan) contents were determined. MRI ranking exhibited significant and strong negative correlation with nucleus pulposus uronic acid content (r = −0.78). MRI grades were significantly higher for degenerate discs. The technique described presents immediate potential for in vitro studies requiring robust, minimally invasive and quantitative determination of lumbar disc composition and condition. Additionally, the technique may have potential as a clinical tool for diagnosing lumbar disc degeneration as it provides a standardised series of reference phantoms facilitating cross-platform consistency, requires short scan times and simple T2-weighted signal intensity measurements.     

颅上颌复合体三维有限元模型的建立

目的:建立颅上颌复合体三维有限元模型,为分析其生物力学性质提供一个标准数学模型。方法:选择牙列完整、咬合关系正常,磨牙为中性关系,牙周组织健康,无颞颌关节病的成年健康男性志愿者一例做为建模素材,通过螺旋CT扫描技术,主要采用PRO/ENGINEER 2001和ANSYS8.0软件建立颅上颌复合体三维有限元模型。结果:探索出一条建立颅上颌复合体三维有限元模型的新方法,建立了三维坐标系下的可从任意视角观察的健康人颅上颌复合体三维重建生物医学模型和三维有限元模型,由129750个单元和207056个节点组成。结论:该模型有较好的力学和几何学相似性,为临床探索正畸正颌外科手术的生物力学机制提供了研究手段。     

L4/5关节突关节融合后椎间盘应力变化的三维有限元分析

目的 :建立正常人L3~L5三维非线性有限元模型,运用有限元分析方法模拟分析L4/5双侧关节突关节未融合与融合后L4/5椎间盘的应力分布情况和L4/5节段活动度。方法:选取1例健康成年男性志愿者,年龄27岁,身高175cm,体重70kg,既往无腰痛病史。采用64排螺旋CT对T12~S1行薄层平扫,得到Dicom格式数据,经Mimics软件选取L3~L5椎体二维图像数据,再经Geomagic软件简化、光滑处理,3-matic软件划分面网格和体网格,Mimics软件赋值,最终导入Ansys软件中重建腰椎关节突关节未融合和融合(融合L4/5双侧关节突关节)的三维有限元模型。利用Ansys软件约束L5椎体下表面各向活动度,给予L3椎体上表面垂直向下的面载荷500N,并给予7.5N·m的力矩模拟正常人体垂直压缩、前屈、后伸、左侧屈、右侧屈、左旋转、右旋转7种运动状态,对L4/5双侧关节突未融合与融合后L4/5椎间盘的应力分布情况和L4/5节段活动度进行分析。结果:成功建立了正常人L3~L5关节突关节未融合和融合的三维有限元模型,未融合模型L3/4、L4/5节段活动度与既往文献中腰椎活动度趋势一致。与未融合模型比较,关节突关节融合模型在各运动状态下L4/5椎间盘后方应力明显减小,差异有统计学意义(P0.05);前方应力未见明显改变。关节突关节融合模型L4/5节段活动度明显减小。结论:腰椎关节突关节融合可以降低融合节段椎间盘后方应力,减少融合节段的活动度,有利于维持节段的稳定性。     

不同入路经皮内窥镜下关节成形术对椎间盘生物力学影响的三维有限元分析

目的:通过三维有限元法分析经皮内窥镜下L4下关节突成形术与L5上关节突成形术对椎间盘生物力学的影响。方法:选取1例健康青年男性志愿者,对其进行薄层螺旋CT扫描,建立正常的L3～L5三维有限元模型,将上述有限元模型与经典文献数据进行验证。验证后,模拟腰椎经皮内窥镜技术分别于侧后方入路对L5上关节突与后方入路对L4下关节突做直径7.5mm的圆柱状骨切除以模拟椎间孔成形,从而获得正常模型、L5上关节突成形模型(A模型)和L4下关节突成形模型(B模型)3种模型。在L3椎体上表面向终板施加负荷为400N的垂直于水平面压力模拟正常人腰椎承载重力,在前屈、后伸、左右侧弯、左右旋转的方向上分别施加7.5N·m的纯扭矩,比较3种模型在前屈、后伸、左右侧曲、左右旋转状况下L3/4、L4/5椎间盘应力变化情况。结果:A模型前屈、后伸、左侧屈、右侧屈、左旋、右旋状态下L4/5椎间盘的最大应力分别为0.390MPa、0.520MPa、0.450MPa、0.430MPa、0.510MPa和0.498 MPa;B模型前屈、后伸、左侧屈、右侧屈、左旋、右旋状态下L4/5椎间盘的最大应力分别为0.375MPa、0.490MPa、0.440MPa、0.420MPa、0.482MPa和0.478MPa。A模型前屈、后伸、左侧屈、右侧屈、左旋、右旋状态下L3/4椎间盘的最大应力分别为0.369MPa、0.480MPa、0.442MPa、0.432MPa、0.468MPa和0.452MPa;B模型前屈、后伸、左侧屈、右侧屈、左旋、右旋状态下L3/4椎间盘的最大应力分别为0.368MPa、0.478MPa、0.436MPa、0.430MPa、0.465MPa和0.444MPa。结论:腰椎经皮内窥镜技术下,侧后入路L5上关节突成形较后方入路L4下关节突成形对L4/5椎间盘在后伸、旋转状态下的生物力学影响较大。两者对邻近节段L3/4椎间盘的应力变化的影响较小。     

Human intervertebral disc internal strain in compression: The effect of disc region,loading position,and degeneration

The primary function of the disc is mechanical; therefore, degenerative changes in disc mechanics and the interactions between the annulus fibrosus (AF) and nucleus pulposus (NP) in nondegenerate and degenerate discs are important to functional evaluation. The disc experiences complex loading conditions, including mechanical interactions between the pressurized NP and the surrounding fiber‐reinforced AF. Our objective was to noninvasively evaluate the internal deformations of nondegenerate and degenerate human discs under axial compression with flexion, neutral, and extension positions using magnetic resonance imaging and image correlation. The side of applied bending (e.g., anterior AF in flexion) had higher tensile radial and compressive axial strains, and the opposite side of bending exhibited tensile axial strains even though the disc was loaded under axial compression. Degenerated discs exhibited higher compressive axial and tensile radial strains, which suggest that load distribution through the disc subcomponents are altered with degeneration, likely due to the depressurized NP placing more of the applied load directly on the AF. The posterior AF exhibited higher compressive axial and higher tensile radial strains than the other AF regions, and the strains were not correlated with degeneration, suggesting this region undergoes high strains throughout life, which may predispose it to failure and tears. In addition to understanding internal disc mechanics, this study provides important new data into the changes in internal strain with degeneration, data for validation of finite element models, and provides a technique and baseline data for evaluating surgical treatments. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 547–555, 2011     

颈胸腰多发性椎间盘突出伴椎管狭窄症

目的 探讨同时发生在颈、胸、腰段的联合性多节段椎管狭窄的临床特点及治疗方法。方法 采用回顾性研究方法对手术治疗颈、胸、腰段的联合性多节段椎管狭窄的病例进行总结分析。结果 7例病人均同时患颈胸腰三处椎管狭窄。椎间盘突出、后纵韧带骨化、椎板及小关节增生肥大为造成颈胸腰椎管狭窄的主要病因。病人接受一处椎管减压3例，二处椎管减压3例，三处椎管减压1例。结论 同时发生在颈胸腰的椎管狭窄因各节段椎管狭窄致病原因复杂，脊髓受压迫时间较长，临床症状上多样化，易于相互影响。治疗上应先对各部位病情及影像学结果综合后作出轻重缓急的判断，以安排治疗上的先后次序。     

下颌骨髁突囊内骨折不同内固定方式下的应力分布

目的：研究小型钛板和拉力螺钉两种不同内固定方式治疗下颌骨髁突囊内骨折时局部的应力分布情况,从理论上探讨髁突囊内骨折最理想的内固定方式。方法：通过建立下颌骨囊内骨折三维有限元模型,并在此模型基础上模拟下颌骨囊内骨折,在同样的约束及载荷条件下分析小型钛板固定及拉力螺钉固定方式下各自的应力分布情况及骨折断端间相对位移情况。结果：小型钛板和拉力螺钉固定方式均可起到稳定骨折断端的作用,但小型钛板固定方式下其自身及固定螺钉均有着明显的应力集中,应力主要集中于骨折断端附近。结论：拉力螺钉内固定方式较小型钛板固定方式更有利于形成可靠的内固定环境,小型钛板内固定时在骨折愈合早期更应注意下颌制动并避免大的咀嚼力量。     

Degeneration and the chemical composition of the human lumbar intervertebral disc

Fifteen lumbar spines were collected postmortem. The intervertebral discs were assigned morphological grades and were analyzed for water, collagen, and proteoglycan. In order of increasing degeneration, five grade 0, four grade 1, 45 grade 2, 12 grade 3A, and nine grade 3B discs were identified. The proteoglycan concentration fell progressively with increasing grade, although the concentrations of each component overlapped extensively among the grades. Grade 2 discs showed no consistent differences from adjacent grade 3A or 3B discs in the same spine. All discs in seven of the eight spines with grade 3A or 3B discs and all discs in three spines with no grade 3A or 3B discs had proteoglycan concentrations below 52 mg/g fresh weight. Four of five spines with at least one disc of proteoglycan concentration above this value contained no grade 3A or 3B discs. These observations support the hypothesis that low proteoglycan concentrations in all the discs of a spine precede degeneration.