Vibration stimuli and the differentiation of musculoskeletal progenitor cells: Review of results in vitro and in vivo

Due to the increasing burden on healthcare budgets of musculoskeletal system disease and injury, there is a growing need for safe, effective and simple therapies. Conditions such as osteoporosis severely impact onquality of life and result in hundreds of hours of hospital time and resources. There is growing interest in the use of low magnitude, high frequency vibration(LMHFV) to improve bone structure and muscle performance in a variety of different patient groups. The technique has shown promise in a number of different diseases, but is poorly understood in terms of the mechanism of action. Scientific papers concerning both the in vivo and in vitro use of LMHFV are growing fast, but they cover a wide range of study types, outcomes measured and regimens tested. This paper aims to provide an overview of some effects of LMHFV found during in vivo studies. Furthermore we will review research concerning the effects of vibration on the cellular responses, in particular for cells within the musculoskeletal system. This includes both osteogenesis and adipogenesis, as well as the interaction between MSCs and other cell types within bone tissue.

Harnessing the HDAC–histone deacetylase enzymes,inhibitors and how these can be utilised in tissue engineering

There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of alternatives.We explore here how a cell’s epigenome influences determination of cell type,and potential applications in tissue engineering.A prevalent epigenetic modification is the acetylation of DNA core histone proteins.Acetylation levels heavily influence gene transcription.Histone deacetylase (HDAC) enzymes can remove these acetyl groups,leading to the formation of a condensed and more transcriptionally silenced chromatin.Histone deacetylase inhibitors (HDACis) can inhibit these enzymes,resulting in the increased acetylation of histones,thereby affecting gene expression.There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering,potentially providing novel tools to control stem cell fate.This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone,cardiac,neural tissues),including the history,current status and future perspectives of using HDACis for stem cell research and tissue engineering,with particular attention paid to how different HDAC isoforms may be integral to this field.

Methods of predicting vertebral body fractures of the lumbar spine

Lumbar vertebral body(VB) fractures are increasingly common in an ageing population that is at greater risk of osteoporosis and metastasis. This review aims to identify different models, as alternatives to bone mineral density(BMD), which may be applied in order to predict VB failure load and fracture risk. The most representative models are those that take account of normal spinal kinetics and assess the contribution of the cortical shell to vertebral strength. Overall, predictive models for VB fracture risk should encompass a range of important parameters including BMD, geometric measures and patient-specific factors. As interventions like vertebroplasty increase in popularity for VB fracture treatment and prevention, such models are likely to play a significant role in the clinical decision-making process. More biomechanical research is required, however, to reduce the risks of post-operative adjacent VB fractures.

Study on the Microstructure of Human Articular Cartilage/Bone Interface

For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure and model the micro- structure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified car- tilage and subchondral bone are in the manner of＂protrusion-pore＂ with average diameter of 17.0 gm and 34.1 lam respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

基于有限元方法的柔性钛下颌骨替代物的结构设计准则

目的:探讨具有柔性的定制化钛下颌骨替代物的可行性,旨在兼顾支架整体强度的基础上,向患者自体骨提供有益于骨改建的应力刺激,促进患者自体骨与受骨的融合、改建。方法:结合骨改建理论提出一种通过改变钛下颌骨体部结构以增加骨替代物柔性的优化设计方案,制定一套以最佳应变体积比和最大许用应力为评价指标的评价体系。运用有限元优化分析法分析五种骨替代物结构,并对计算结果进行比较。结果:判断最易促进骨改建的柔性结构为直回形槽结构,并获得最佳直槽结构尺寸。结论:基于有限元方法的结构设计准则有效保证了骨替代物的植入安全性,并在此前提下最大限度的消减应力屏蔽现象,有利于促进植骨的改建。

γ射线辐照交联PVA水凝胶关节软骨修复材料的结构与性能研究

目的研究制备工艺对γ射线辐照交联PVA水凝胶关节软骨修复材料的结构与摩擦学性能的影响,为其在关节软骨损伤修复领域的应用提供理论基础。方法采用冷冻解冻和辐照交联相结合的方法制备聚乙烯醇(PVA)水凝胶,研究其微观形貌、含水量及与自然软骨配副的摩擦学性能。结果(1)微观结构的观察表明,制备的PVA水凝胶具有三维多孔网络结构,辐照交联使得网络结构更加致密和完善;(2)水凝胶的含水量随着辐照剂量和PVA浓度的增加而减小;(3)在往复式销-盘摩擦磨损试验机上,研究本水凝胶材料与自然关节软骨配副时的摩擦学性能,结果表明,摩擦的起始阶段,双相润滑机制其主导作用,载荷主要由水凝胶中的液体相所承担,摩擦系数较小,随着载荷作用时间的延长,固体相所承受载荷的比例相对增高,摩擦系数渐渐增大且趋于稳定,润滑机制转为边界润滑。摩擦系数随着辐照剂量和PVA浓度的增加而减小。

全膝关节置换个体化患者右转步态的骨肌多体动力学仿真

目的构建个体化患者全膝关节置换(total knee replacement,TKR)的骨肌多体力学模型,模拟患者下肢右转步态时体内膝关节的生物力学行为。方法以1位具体患者的相关数据为材料,基于骨肌动力学仿真软件Any Body及其依赖于力的运动学建模方法,建立与患者相对应的TKR下肢骨肌多体动力学模型,并对患者的右转步态进行模拟。通过逆动力学分析右转步态,同时预测患者膝关节接触力、关节运动、肌肉活性和韧带力。结果模型预测的胫骨-股骨关节内、外侧接触力的均值均方根误差分别为285、164 N,相关系数分别为0.95和0.61,预测的髌骨接触力均值最大值为250 N。模型预测的接触力和肌肉活性与患者实验测量结果基本一致。此外,模型预测的胫骨-股骨的伸展弯曲、内外旋和内外翻运动的均值分布范围分别为3°~47°、-3.4°~1.5°、0.2°^-1.5°,胫骨-股骨的前后、上下和内外侧平移的运动范围分别为2.6~9.0 mm、1.6~3.2 mm、4.2~5.2 mm。模型还预测了内、外侧旁系韧带力和后交叉韧带力,其最大值分别为190、108、108 N。结论所开发的模型能够预测人工膝关节体内生物力学行为,为后续研究膝关节假体临床失效问题提供强有力的计算平台。

Patient-Specific Design and Biomechanical Evaluation of a Novel Bipolar Femoral Hemi-Knee Prosthesis

While total knee replacement is successful, hemiarthroplasty is necessary for some young, obese and active patients who are especially not suitable for unicompartmental or total knee prostheses. Hemiarthroplasty also provides an opportunity for children with bone tumors. The design ofhemiarthroplasty should be patient-specific to reduce contact stress and friction as well as instability, compared to conventional hemi-knee prosthesis. A novel bipolar hemi-knee prosthesis with two flexion stages was developed according to a healthy male＇s knee morphological profile. The motion mode of the bipolar hemi-knee prosthesis was observed through roentgenoscopy in vitro experiment. The biomechanical properties in one gait cycle were evaluated though finite element simulation. The bipolar hemi-knee prosthesis was found to produce knee flexion at two stages through X-ray images. The first stage is the motion from upright posture to a specified 60~ flexion, followed by the second stage of motion subsequently to deep flexion. The finite element simulation results also show that the designed hemi-knee prosthesis has the ability to reduce stresses on the joint contact surfaces. Therefore, it is possible for the bipolar hemi-knee prosthesis to provide better biotribological performances because it can reduce stresses and potentially wear on the opposing contacting surface during a gait cycle, orovidin~ a t^romisin~ treatment strate^v in future Joint renair znd renlneement

Numerical wear study of metal-on-ultrahigh molecular weight polyethylene-based cervical total disc arthroplasty by coupling finite element analysis and multi-body dynamics

In this study,the effects of in vivo(head flexion-extension,lateral bending,and axial rotation)and in vitro(ISO 18192-1)working conditions on the wear of ultrahigh mo-lecular weight polyethylene(UHWMPE)-based cervical disc prosthesis were studied via numerical simulation.A finite-element-based wear prediction framework was built by using a sliding distance and contact area dependent Archard wear law.Moreover,a pre-developed cervical spine multi-body dynamics model was incorporated to obtain the in vivo conditions.Contact mechanic analysis stated that in vitro conditions normally led to a higher contact stress and a longer sliding distance,with oval or crossing-path-typed sliding track.In contrast,in vivo conditions led to a curvilinear-typed sliding track.In general,the predicted in vivo wear rate was one order of magnitude smaller than that of in vitro.According to the yearly occurrence of head movement,the estimated total in vivo wear rate was 0.595 mg/annual.While,the wear rate given by the ISO standard test condition was 3.32 mg/annual.There is a significant impact of loading and kinematic condition on the wear of UHMWPE prosthesis.The work conducted in the present study provided a feasible way for quantitatively assessing the wear of joint prosthesis.

The influence of lubricant temperature on the wear of total knee replacements

Experimental in vitro simulation can be used to predict the wear performance of total knee replacements.The in vitro simulation should aim to replicate the in vivo loading,motion and environment experienced by the joint,predicting wear and potential failure whilst minimising test artefacts.Experimental wear simulation can be sensitive to envi-ronmental conditions;the environment temperature is one variable which should be controlled and was the focus of this investigation.In this study,the wear of an all‐polymer(PEEK‐OPTIMA™polymer‐on‐UHMWPE)total knee replacement and a conventional cobalt chrome‐on‐UHMWPE implant of similar initial surface topography and geometry were investigated under elevated temperature conditions.The wear was compared to a previous study of the same implants under simulator running temperature(i.e.without heating the test environment).Under elevated temperature conditions,the wear rate of the UHMWPE tibial inserts was low against both femoral component materials(mean<2 mm3/million cycles)and significantly lower(p<0.05)than for investigations at simulator running temperature.Protein precipitation from the lubricant onto the component articulating surfaces is a possible explanation for the lower wear.This study highlights the need to understand the influence of different variables including envi-ronmental temperature to minimise the test artefacts during wear simulation which may affect the wear rates.

Numerical surface characterization of wear debris from artificial joints using atomic force microscopy

Study on surface features of wear particles generated in wear process provides an insight into the progress of material failure of artificial joints. It is very important to quantify the surface features of wear particles in three dimensions. In this study, a new approach using atomic force microscopy was proposed to carry out 3D numerical surface characterization of wear debris generated from artificial joints. Atomic force microscopy combined with image processing techniques was used to acquire appropriate 3D images of wear debris. Computerized image analysis techniques were then used to quantify surface texture features of wear debris such as surface roughness parameters and surface texture index. The method developed from the present study was found to be feasible to quantity the surface characterization of nanoand micro-sized wear debris generated from artificial joints.

Biphasic Mechanical Properties of in vivo Repaired Cartilage

In the fast growing field of scaffold-based tissue engineering, improvement on the mechanical properties of newly formed tissues, e.g. the repaired cartilage, has always been one of the core issues. Studies on the correlations among scaffold composition, in vivo morphological changes of the construct, and the finite deformation behaviors of new tissues （e.g. creep and stress-relaxation, and equilibrium response）, have attracted increasing interests. In this paper, the correlations between the compressive biphasic mechanical properties （i.e., equilibrium elastic modulus E and permeability coefficient k） of 3D printing scaffold （consisting of collagen and fl-tricalcium phosphate） and the proteoglycans （PGs） concentration of the repaired carti- lages after 24 weeks, 36 weeks and 52 weeks of scaffold implantation were investigated. Results indicated that the repaired cartilage covered the entire cartilage surface of large cylindrical osteochondral defects （10 mm in diameter ~ 15 mm in depth） on the canine trochlea grooves after 24 weeks. The equilibrium elastic modulus of the repaired cartilage reached 22.4% at 24 weeks, 70.3% at 36 weeks, and 93.4% at 52 weeks of the native cartilage, respectively. Meanwhile, the permeability coefficient decreased with time and at 52 weeks was still inferior to that of the native cartilage in one order of magnitude. In addition, the amount of glycosaminoglycans （GAGs） of repaired cartilage increased constantly with time, which at 52 weeks approached to nearly 60% of that of native cartilage. 3D printed scaffolds have potential applications in repairing large-scale cartilage defects.

Bio-tribological characterisation of ultra-high molecular weight polyethylene against different metal counterparts

Excessive wear is a key issue affecting the performance of ultra-high molecular weight polyethylene(UHMWPE)-based artificial prosthesis.This work is focussed on the biotribology behaviours of UHMWPE when mating with different metal counterparts(iron-based 316L,Co-based Stellite-S21 and Stellite-S22).According to the ASTM F732 standard,two million cycles comparative wear tests were carried out under bovine serum lubrication.When coupled with S21,S22,and 316L metal counterparts,the obtained average wear factors of UHMWPE were 1.333±0.192,1.360±0.160,and 1.190±0.177×10^(−6)mm^(3)/N·m,respectively.Initial surface roughness of the metal counterpart has shown an important role in controlling the volume of UHMWPE wear,especially the first one million cycles.Compared with 316L,CoCrMo-based counterparts possessed relative higher hardness and exhibited less rise in surface roughness caused by wear.For UHMWPE-on-metal bearings,random scratch,surface pit,and wear debris attachment were commonly seen,which suggested the coexistence of abrasion,thirdbody abrasion,and adhesion-based wear.In contrast,the metal counterpart was slightly scratched with no polymer transfer film formation.The work conducted in the present study gives useful knowledge regarding the UHMWPE-on-metal bearing design.With an intention to minimise wear,surface roughness of metal counterpart should be carefully controlled.

大尺寸关节支架的3D打印及应用

人工关节假体的置换与长期植入后的失效问题将造成关节组织不可恢复的损失,小块可降解骨软骨关节支架具有恢复病变关节的力学环境和诱导新生组织生长的能力,为大尺寸关节病变缺损修复提供了新的治疗策略.大面积深层病变软骨关节病变位置的生理结构与力学环境的分析,以及多材料复合关节支架的仿生制造与手术方案是治疗方案开发的难点.本文提出一种新型多材料关节支架的仿生设计与制造技术和植入方法.以诱导组织生长为导向,选择聚乙二醇凝胶(polyethyleneglyco,PEG)、β-磷酸三钙陶瓷(β-tricalcium phosphate,β-TCP)、聚乳酸(polylactide,PLA)等生物材料开发新型支架;以羊膝关节为研究对象,通过反求工程、有限元分析和3D打印技术,利用有限的影像学数据信息,建立膝关节模型和易病变软骨区域;基于支架生理结构特征与关节缺损区机械承载能力的映射关系,建立大块仿生骨软骨支架的结构与稳定性固定结构.实验证明该支架在置换初期较好地恢复了缺损关节的力学环境.所提出的方法和支架有望为大面积骨软骨缺损的修复提供一种新的治疗方案.