人膝关节软骨与聚乙烯醇水凝胶人工软骨压缩实验比较研究

目的 比较人膝关节软骨和聚乙烯醇水凝胶（PVA-H）人工软骨的生物力学性能 方法 使用人膝关节软骨和PVA-H人工软骨进行轴向压缩试验,分别进行压缩应力应变、应力松弛和蠕变实验,得到关节软骨和PVA-H人工软骨的应力应变关系。结果 实验中人关节软骨和PVA-H的力学性能有差异,人关节软骨压缩模量大于PVA-H人工软骨,人关节软骨的压缩模量为（3.6492±0.6199）Mpa,PVA-H的压缩模量为（1.5951±0.1469）Mpa。结论 软骨和PVA-H人工软骨的生物力学性能具有一定差异,试验结果对人工软骨的进一步改进具有指导意义。     

关节软骨体外构建力学环境的研究进展

很多物理因素都影响软骨组织的生长和发育,其中力学因素起主要作用。软骨的生长、发育是力学调控的适应过程。当前采用多种力学条件应用于软骨生物反应器,如流体剪应力、液体压力、直接压缩等,或其中部分组合,但这些条件还没有构建出与活体软骨结构-功能相匹配的人工软骨。如果一种载荷能适合构建软骨,那么这种载荷首先能保证培养物内部信号分子、营养和废物的有效运输;其次,能对支架内种子细胞特定的力学刺激;第三,能促进培养物结构-功能的发展。本文回顾、分析当前多种力学条件的作用效果,其中流体剪应力、液体压力、拉伸、直接压缩或变形剪应力都是软骨受力状态的部分体现。作者认为滚压载荷是软骨培养的合适力学环境,它是当前多种力学条件的一个综合指标,对软骨培养物可以形成纵向的动态压缩和横向的动态变形剪应力,并且有利于细胞新陈代谢物质的运输,因此,滚压环境可能是人工软骨结构-功能构建的发展方向。     

力学参数随深度变化的关节软骨数值模拟

目的在软骨数值模拟中,对由于设置均匀和随深度变化的力学参数而导致的结果差异进行评估。方法利用COMSOL多孔介质模块建立软骨非线性两相多孔介质模型。在静载荷下,分别用均匀和随深度变化的两种软骨力学参数对模型进行了计算,并对两者的计算结果差异进行了分析。结果对于软骨总应力,两种参数设置的结果之间差异很小。但在分析软骨的固相应力、液体压力和流动等较深入细致的问题时,两种参数设置结果之间的差异不能忽略。结论不同的软骨力学参数设置对软骨总应力的结果几乎没有影响,但对软骨内流速场则影响很大。所以均匀的力学参数设置可用来简化计算软骨总应力的问题,而其他一些更细致的分析需要立足于随深度变化的软骨力学参数。这些结论可以为今后的软骨建模和数值计算提供参考,为人工关节的设计和计算奠定基础。     

软骨组织无约束压缩的有限元分析

目的采用有限元仿真和实验对比分析关节软骨的承载机理和应力松弛效应。方法考虑关节软骨基质固相、孔隙液相和胶原纤维增强相,并综合考虑软骨分层结构以及关节软骨渗透率随固体基质膨胀率变化特性,建立关节软骨纤维增强多孔弹性有限元模型。基于该模型,应用ABAQUS软件和FORTRAN语言编程嵌套,对关节软骨无约束阶梯压缩进行有限元仿真。应用自行研制的生物力学性能测试系统,通过阶梯加载实验对生猪软骨有限元分析结果进行了实测对比。结果试件以0.45%/s应变速率阶梯加载时,在试件中心,液相可维持承载80 s左右,最大可承担近90%的总应力。结论基于纤维增强多孔弹性有限元模型的无约束阶梯压缩有限元分析可定量评价关节软骨的固、液两相承载能力随应变和时间的变化特性。结合软骨无约束压缩实验的仿真分析有助于更准确地评价软骨的力学性能。     

关节软骨不同层区的率相关性能研究

目的 采用不同加载速率对关节软骨进行非围限压缩试验,探究其不同层区的率相关性能。方法 采用新鲜猪关节软骨作为研究对象,结合非接触式数字图像相关技术,测试不同加载率下软骨不同层区的力学性能。结果 在恒定加载率作用下,取相同压缩应力时,软骨浅表层的压缩应变最大,深层区压缩应变最小,中间层压缩应变鉴于表层与深层之间;沿软骨厚度方向,从浅表层到深层,软骨的泊松比逐渐增大;不同加载率作用下,软骨的压缩应力 应变曲线不重合,说明关节软骨的压缩力学性能具有率相关性;随着加载速率的增大,软骨的弹性模量呈增大的趋势;取相同压缩应力时,加载率越大,不同层区的压缩应变都减小。结论 关节软骨沿厚度方向,从浅表层到深层的压缩应变逐渐减小,泊松比逐渐增大,软骨不同层区的力学性能具有率相关性。实验研究可为临床软骨疾病预防、治疗提供理论依据,同时对人工软骨力学评价具有重要意义。     

生长因子在关节软骨损伤修复中的应用进展

关节是人体重要的运动器官,其组织结构特殊,成熟关节软骨组织没有血供,一旦损伤难以自愈.临床上常用的关节软骨损伤修复手段有微骨裂术、关节软骨移植、关节置换术、软骨组织工程等,但这些方法的修复效果都不理想.生长因子是体内组织分泌的一种具有生物活性的物质,可促进细胞生长、增殖、迁移和分化.软骨发育过程中有许多生长因子参与,如成纤维细胞生长因子(FGF)、骨形态发生蛋白(BMP)、胰岛素样生长因子(IGF)等.研究显示,在关节软骨修复过程中加入外源性生长因子可有效促进关节软骨损伤的修复.对目前应用于关节软骨损伤修复研究中的生长因子进行综述,讨论这些生长因子在关节软骨发育及其在关节软骨修复中的作用,分析生长因子在关节软骨修复应用中存在的问题.     

The mechanical and material properties of elderly human articular cartilage subject to impact and slow loading

The mechanical properties of articular cartilage vary enormously with loading rate, and how these properties derive from the composition and structure of the tissue is still unclear. This study investigates the mechanical properties of human articular cartilage at rapid rates of loading, compares these with measurements at slow rates of loading and explores how they relate to the gross composition of the tissue. Full-depth femoral head cartilage biopsies were subjected to a slow, unconfined compression test followed by an impact at an energy of 78.5 mJ and velocity 1.25 m s⁻¹. The modulus was calculated from the slope of the loading curve and the coefficient of restitution from the areas under the loading and unloading curves.Tissue composition was measured as water, collagen and glycosaminoglycan contents. The maximum dynamic modulus ranged from 25 to 150 MPa. These values compared with 1–3 MPa measured during quasi-static loading. The coefficient of restitution was 0.502 (0.066) (mean (standard deviation)) and showed no site variation. Water loss was not detectable. Composition was not strongly associated with modulus; water and collagen contents together predicted about 25% of the variance in modulus.     

Load partitioning influences the mechanical response of articular cartilage

The role of the fluid within articular cartilage as affected by the load-sharing mechanism and its potential, beneficial effects were assessed with the u-p finite element method. The mechanical behavior of cartilage as it covers the surface of a diarthrodial joint was evaluated when the partitioning of an applied stress to the solid and fluid phases of the tissue was varied. Comparisons were made in the response of the cartilage when 0%, 25%, 50%, or 75% of the applied stress was supported by the fluid at the surface. Substantial changes in the behavior of the tissue were observed for each load case. As the fluid sustained a larger portion of the applied stress, several parameters were affected; the fluid pressure within the cartilage layer remained at a higher value, the stress and strain generated in the solid matrix decreased while the compression of the cartilage layer decreased. These findings indicate that an increased loadpartitioning to the fluid phase in cartilage may perform the function of shielding the solid matrix from excessive stresses. This could also potentially alter the mechanical environment around the chondrocytes, influencing metabolic activity and homeostasis.     

循环加载下关节软骨的棘轮应变及理论预测

目的获得不同加载条件下关节软骨的棘轮应变,建立预测棘轮应变的理论模型,并对软骨的棘轮应变进行预测。方法将猪股骨远端滑车部的新鲜关节软骨作为研究对象,采用非接触式数字图像技术,测试循环压缩载荷下关节软骨的棘轮应变;建立预测棘轮应变的理论模型,对不同应力幅值和加载率下软骨的棘轮应变进行预测,并比较预测结果与实验结果。结果随循环圈数的增加,软骨的棘轮应变先快速增长然后趋于稳定;定加载率下,软骨的棘轮应变随应力幅值的增大而增大;定应力幅值下,棘轮应变随加载率的增大而减小。实验结果与建立的理论模型预测结果吻合良好。结论关节软骨的棘轮应变与应力幅值成正比,与加载率成反比。建立的理论模型可以预测软骨的棘轮行为,同时为组织工程软骨的构造提供指导。     

miR-564在关节软骨损伤修复中作用机制的研究进展

关节软骨损伤修复一直是关节外科的热点和难点,最新研究表明,miR-564可能在关节软骨损伤修复中起着至关重要的作用。miR-564是位于第3号染色体上的非编码RNA,其功能主要是通过影响mRNA的稳定性和翻译进而参与基因表达的转录后调节,因此未来有望通过调控miR-564实现关节软骨损伤的原位修复。本文就miR-564的结构、功能及在关节软骨损伤修复中的作用机制作一综述。     

Uncertainties in indentation testing of articular cartilage: a fibril-reinforced poroviscoelastic study

Indentation testing provides a quantitative technique to evaluate mechanical characteristics of articular cartilage in situ and in vivo. Traditionally, analytical solutions proposed by Hayes et al. [Hayes WC, Keer LM, Herrmann G, Mockros LF. A mathematical analysis for indentation tests of articular cartilage. J Biomech 1972;5(5):541–51] have been applied for the analysis of indentation measurements, and due to their practicality, they have been used for clinical diagnostics. Using this approach, the elastic modulus is derived based on scaling factors which depend on cartilage thickness, indenter radius and Poisson's ratio, and the cartilage model is assumed isotropic and homogeneous, thereby greatly simplifying the true tissue characteristics. The aim was to investigate the validity of previous model assumptions for indentation testing. Fibril-reinforced poroviscoelastic cartilage (FRPVE) model including realistic tissue characteristics was used to simulate indentation tests. The effects of cartilage inhomogeneity, anisotropy, and indentation velocity on the indentation response were evaluated, and scaling factors from the FRPVE analysis were derived. Subsequently, the validity of scaling factors obtained using the traditional and the FRPVE analyses was studied by calculating indentation moduli for bovine cartilage samples, and comparing these values to those obtained experimentally in unconfined compression testing. Collagen architecture and compression velocity had significant effects on the indentation response. Isotropic elastic analysis gave significantly higher (30–107%) Young's moduli for indentation compared to unconfined compression testing. Modification of Hayes’ scaling factors by accounting for cartilage inhomogeneity and anisotropy improved the agreement of Young's moduli obtained for the two test configurations by 14–28%. These results emphasize the importance of realistic cartilage structure and mechanical properties in the indentation analysis. Although it is not possible to fully describe tissue inhomogeneity and anisotropy with just the Young's modulus and Poisson's ratio, accounting for inhomogeneity and anisotropy in these two parameters may help to improve the in vivo characterization of tissue using arthroscopic indentation testing.     

基因芯片技术在关节软骨研究中的应用进展

基因芯片通常指DNA芯片,其基本原理是将指大量寡核苷酸分子嗣定于支持物上,然后与标记的样品进行杂交,通过芯片扫描检测杂交信号的强弱进而判断样品中靶分子的数量。基因芯片能对微量样品中的核苷酸序列进行检测和分析,其高通量、快速、并行化采集生物信息的特点均优于其他传统基因检测技术,故已广泛应用于医学各领域研究。将近年来基因芯片技术在关节软骨生物学特性、形成及发育、损伤与修复、退变及再生等领域的应用进行综述：     

Repair of articular cartilage defect by cell transplantation

Full-thickness articular cartilage defects are a major clinical problem; however, at present there is no treatment that is widely accepted to regeneratively repair these lesions. The current therapeutic approach is to drill or abrade the base of the defect to expose the bone marrow with its cells and growth factors. This usually results in a repaired tissue of fibrocartilage that functions poorly in the loaded joint environment. Recently, autologous cultured chondrocyte transplantation and mosaic plasty were explored. We can repair small articular cartilage defects using these methods, although their effectiveness is still controversial. We have reported that transplantation of allogeneic chondrocytes embedded in collagen gels or allogeneic chondrocytes cultured in collagen gels could repair articular cartilage defect in a rabbit model. We also reported that autologous culture-expanded bone marrow mesenchymal cell transplantation could repair articular cartilage defect in a rabbit model. This procedure offers expedient clinical use, given that autologous bone marrow cells are easily obtained and can be culture-expanded. We transplanted autologous culture-expanded bone marrow cells into the cartilage defect of the osteoarthritic knee joint on 11 patients at the time of high tibial osteotomy. As early as 6.8 weeks after transplantation, the defect was covered with white soft tissue, in which slight metachromasia was histologically observed. Thirty-three weeks after transplantation, the repaired tissue had hardened. Histologically, repaired tissues showed stronger metachromasia and a partial hyaline cartilage-like appearance. This procedure may prove a promising method by which to repair articular cartilage defects.     

半月板切除对急性关节软骨损伤愈合影响的实验研究

目的　探讨半月板切除对急性关节软骨损伤 (缺损 )愈合的影响。方法　分离收集 5月龄新西兰兔 35只。,将新西兰兔的股骨内髁行钻孔术造成深达软骨下骨的全层关节软骨缺损模型 ,右膝为实验组 ,切除半月板 ;左膝为对照组 ,保留半月板 ,于 10周取材行大体、组织学、透射电镜观察。结果　大体观察 :10周时对照组关节软骨缺损已由泛白色的类似于正常关节软骨的组织修复 ,而实验组修复组织表面有裂隙、剥脱等迹象。组织学观察 :10周时对照组的关节软骨缺损已基本由软骨下骨的软骨细胞层修复 ,而实验组修复组织表层软骨结构存在裂隙 (纤维性变 )、剥脱等不良改变。透射电镜观察显示 :10周时实验组修复组织表层软骨细胞很多发生凋亡 ,而对照组软骨细胞结构基本正常。结论　表明半月板切除诱发了全层关节软骨缺损修复组织表层软骨结构中的软骨细胞发生凋亡 ,导致裂隙、剥脱等不良改变。半月板是不可缺的生理结构 ,它有极其重要生物学功能 ,即通过维持正常的生物力学环境 ,保证急性关节软骨损伤修复     

关节软骨胶原纤维增强特性

目的在COMSOL关节软骨计算中引入胶原纤维增强特性,并分析引入前后模型结果的差异。方法以软骨中胶原纤维的走向为基础,对胶原纤维的应力单独建模,将胶原纤维的应力写入到原来软骨多孔弹性模型中。为避免应变2次项的出现采用了函数调用方式,同时提高求解器的迭代次数以更好收敛。结果胶原纤维增强模型表面的Y方向初始位移仅为15μm,是非增强模型的17.6%。增强模型的X方向正应变仅为非增强模型的10%,而近表面的X方向正应力超过非增强模型的10倍。结论在COMSOL关节软骨计算中实现了胶原纤维增强特性的引入,为软骨胶原纤维损伤提供了计算模型和理论分析。胶原纤维通过横向增强约束了竖直方向的应变,提高了软骨承载能力,改善了软骨的力学性能。     

Chondrocytes synthesize type I collagen and accumulate the protein in the matrix during development of rat tibial articular cartilage

The present study was designed to investigate whether or not chondrocytes in articular cartilage express type I collagen in vivo under physiological conditions. Expressions of the gene and the phenotype of type I collagen were examined in rat tibial articular cartilage in the knee joint during development. Knee joints of Wistar rats at 1, 5, and 11 weeks postnatal were fixed in 4% paraformaldehyde with or without 0.5% glutaraldehyde and decalcified in 10% EDTA. After the specimens were embedded in paraffin and serial sections made, adjacent sections were processed for immunohistochemistry and in situ hybridization for type I collagen. The epiphysis of the tibia was composed of cartilage in week-1 rats. Formation of articular cartilage was in progress in week 5 as endochondral ossification proceeded and was completed in week 11. Anti-type I collagen antibody stained only the superficial area of the epiphysis in week 1, but the immunoreactivity was expanded into the deeper region of the articular cartilage with development in weeks 5 and 11. Hybridization signals for pro-alpha 1 (I) collagen were seen in some of chondrocytes in the epiphysis of the week-1 tibia. The most intense signals were identified in chondrocytes in week 5 and the signals appeared weaker in week 11. The present study demonstrated that chondrocytes synthesize type I collagen and accumulate the protein in the matrix during development of the articular cartilage.     

基于纳米压痕法的关节软骨保湿测量技术

目的 在保持关节软骨表面湿润的情况下,进行纳米压痕实验,研究具有一定生物活性的关节软骨微结构的力学性能。方法 通过实验的方法,评估冷镶嵌法和保湿法对保持软骨在体力学性能的优劣,并应用保湿法得到不同保护液下软骨微结构的力学性能。结果 冷镶嵌法测得的软骨表层的弹性模量远大于保湿法测得的数值,蒸馏水保护下的软骨表层和深层的弹性模量明显高于壳多糖溶液和生理盐水保护下的软骨的弹性模量。结论 保湿法更有利于保持生物材料在体时的力学性能和保持生物材料的生物活性,通过保湿法也可以证明壳多糖溶液及生理盐水均可有效保持软骨的力学性能。     

Comparison of medial and lateral posterior femoral condyle articular cartilage wear patterns

Background

While degenerative changes to the articular cartilage of the anterior and distal portions of the femoral condyles have been well studied in the literature, the changes that occur on the posterior femoral condyle are not as clear. The purpose of this study was to assess the difference in articular cartilage thickness between the medial and lateral posterior femoral condyles in knees undergoing unicompartmental knee arthroplasty.

On the ultrastructure of softened cartilage: a possible model for structural transformation

The fibrillar architecture in the general matrix of softened cartilage has been compared with that of the normal matrix using both Nomarski light microscopy and transmission electron microscopy with combined stereoscopic reconstruction. A pseudorandom network developed from an overall radial arrangement of collagen fibrils is the most fundamental ultrastructural characteristic of the normal general matrix. This, in turn, provides an efficient entrapment system for the swelling proteoglycans. Conversely, the most distinctive feature of the softened matrix is the presence of parallel and relatively unentwined fibrils, strongly aligned in the radial direction. The presence of an optically resolvable fibrous texture in the softened cartilage matrix indicates the presence of discrete bundles of closely packed and aligned fibrils at the ultrastructural level of organisation. The general absence of such texture in the normal cartilage general matrix is consistent with the much greater degree of interconnectedness and related short-range obliquity in the fibrillar architecture, hence the importance of the term pseudorandom network. A mechanism of structural transformation is proposed based on the important property of lateral interconnectivity in the fibrils which involves both entwinement and nonentwinement based interactions. The previously reported difference in intrinsic mechanical strength between the normal and softened matrices is consistent with the transformation model proposed in this study.     

Poroelastic response of articular cartilage by nanoindentation creep tests at different characteristic lengths

Nanoindentation is an experimental technique which is attracting increasing interests for the mechanical characterization of articular cartilage. In particular, time dependent mechanical responses due to fluid flow through the porous matrix can be quantitatively investigated by nanoindentation experiments at different penetration depths and/or by using different probe sizes. The aim of this paper is to provide a framework for the quantitative interpretation of the poroelastic response of articular cartilage subjected to creep nanoindentation tests. To this purpose, multiload creep tests using spherical indenters have been carried out on saturated samples of mature bovine articular cartilage achieving two main quantitative results. First, the dependence of indentation modulus in the drained state (at equilibrium) on the tip radius: a value of 500 kPa has been found using the large tip (400 μm radius) and of 1.7 MPa using the smaller one (25 μm). Secon, the permeability at microscopic scale was estimated at values ranging from 4.5 × 10⁻¹⁶ m⁴/N s to 0.1 × 10⁻¹⁶ m⁴/N s, from low to high equivalent deformation. Consistently with a poroelastic behavior, the size-dependent response of the indenter displacement disappears when characteristic size and permeability are accounted for. For comparison purposes, the same protocol was applied to intrinsically viscoelastic homogeneous samples of polydimethylsiloxane (PDMS): both indentation modulus and time response have been found size-independent.