Optimal Mass Distribution Prediction for Human Proximal Femur with Bi-modulus Property

Simulation of the mass distribution in a human proximal femur is important to provide a reasonable therapy scheme for a patient with osteoporosis. An algorithm is developed for prediction of optimal mass distribution in a human proximal femur under a given loading environment. In this algorithm, the bone material is assumed to be bi-modulus, i.e., the tension modulus is not identical to the compression modulus in the same direction. With this bi-modulus bone material, a topology optimization method, i.e., modified SIMP approach, is employed to determine the optimal mass distribution in a proximal femur. The effects of the difference between two moduli on the final material distribution are numerically investigated. Numerical results obtained show that the mass distribution in bi-modular bone materials is different from that in traditional isotropic material. As the tension modulus is less than the compression modulus for bone tissues, the amount of mass required to support tension loads is greater than that required by isotropic material for the same daily activities including one-leg stance, abduction and adduction.     

To reduce the maximum stress and the stress shielding effect around a dental implant–bone interface using radial functionally graded biomaterials

In a dental implant system, the value of stress and its distribution plays a pivotal role on the strength, durability and life of the implant–bone system. A typical implant consists of a Titanium core and a thin layer of biocompatible material such as the hydroxyapatite. This coating has a wide range of clinical applications in orthopedics and dentistry due to its biocompatibility and bioactivity characteristics. Low bonding strength and sudden variation of mechanical properties between the coating and the metallic layers are the main disadvantages of such common implants. To overcome these problems, a radial distributed functionally graded biomaterial (FGBM) was proposed in this paper and the effect of material property on the stress distribution around the dental implant–bone interface was studied. A three-dimensional finite element simulation was used to illustrate how the use of radial FGBM dental implant can reduce the maximum von Mises stress and, also the stress shielding effect in both the cortical and cancellous bones. The results, of course, give anybody an idea about optimized behaviors that can be achieved using such materials. The finite element solver was validated by familiar methods and the results were compared to previous works in the literature.     

A Computational Model for Cortical Endosteal Surface Remodeling Induced by Mechanical Disuse

In mechanical disuse conditions associated with immobilization and microgravity in spaceflight, cortical endosteal surface moved outward with periosteal surface moving slightly or unchanged, resulting in reduction of cortical thickness. Reduced thickness of the shaft cortex of long bone can be considered as an independent predictor of fractures. Accordingly, it is important to study the remodeling process at cortical endosteal surface. This paper presents a computer simulation of cortical endosteal remodeling induced by mechanical disuse at the Basic Multicellular Units level with cortical thickness as controlling variables. The remodeling analysis was performed on a representative rectangular slice of the cross section of cortical bone volume. The pQCT data showing the relationship between the duration of paralysis and bone structure of spinal cord injured patients by Eser et al. (2004) were used as an example of mechanical disuse to validate the model. Cortical thickness, BMU activation frequency, mechanical load and principal compressive strain for tibia and femur cortical models were simulated. The effects of varying the mechanical load and maximum BMU activation frequency were also investigated. The cortical thicknesses of femur and tibia models were both consistent with the clinical data. Varying the decreasing coefficient in mechanical load equation had little effect on the steady state values of cortical thickness and BMU activation frequency. However, it had much effect on the time to reach steady state. The maximum BMU activation frequency had effects on both the steady state value and the time to reach steady state for cortical thickness and BMU activation frequency. The computational model for cortical endosteal surface remodeling developed in this paper can be further used to quantify and predict the effects of mechanical factors and biological factors on cortical thickness and help us to better understand the relationship between bone morphology and mechanical as well as biological environment.     

Changes in the Fabric and Compliance Tensors of Cancellous Bone due to Trabecular Surface Remodeling,Predicted by a Digital Image-based Model

Fabric and compliance tensors of a cube of cancellous bone with a complicated three-dimensional trabecular structure were obtained for trabecular surface remodeling by using a digital image-based model combined with a large-scale finite element method. Using mean intercept length and a homogenization method, the fabric and compliance tensors were determined for the trabecular structure obtained in the computer remodeling simulation. The tensorial quantities obtained indicated that anisotropic structural changes occur in cancellous bone adapting to the compressive loading condition. There were good correlations between the fabric tensor, bone volume fraction, and compliance tensor in the remodeling process. The result demonstrates that changes in the structural and mechanical properties of cancellous bone are essentially anisotropic and should be expressed by tensorial quantities.     

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.     

软骨细胞上清液诱导冻存复苏后人骨髓间充质干细胞的研究

目的:探讨人软骨细胞培养上清诱导冻存人骨髓充质干细胞向软骨细胞分化的可行性.方法:取进行全髋关节置换术老年患者的骨髓和软骨组织,利用密度梯度离心法、全骨髓培养法分别培养骨髓间充质干细胞,冻存备用.培养软骨细胞,观察细胞生长,收集软骨细胞培养上清.复苏冻存的人骨髓间充质干细胞,观察复苏后细胞生长状态.利用收集的软骨细胞培养上清对复苏间充质干细胞进行定向诱导,诱导培养2周,观察细胞外观表型变化,Ⅱ型胶原免疫组化检测诱导后人骨髓间充质干细胞Ⅱ型胶原的表达.结果:密度梯度离心法与全骨髓培养法均可分离获得人骨髓间充质干细胞,原代生长前者优于后者.复苏细胞仍进行可传代,与正常生长骨髓间充质细胞无明显差异,均可传至第8代.软骨细胞培养上清诱导2周后,细胞形状向圆形,多角形转变,冻存骨髓间充质干细胞Ⅱ型胶原免疫组化检测Ⅱ型胶原表达阳性.结论:老年人骨髓间充质干细胞仍具有向软骨细胞转化的能力,冻存不影响其转化能力.     

Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders.     

A Comparative Analysis of Different Treatments for Distal Femur Fractures using the Finite Element Method

The main objective of this work is the evaluation, by means of the finite element method (FEM) of the mechanical stability and long-term microstructural modifications in bone induced to three different kinds of fractures of the distal femur by three types of implants: the Condyle Plate, the less invasive stabilization system plate (LISS) and the distal femur nail (DFN). The displacement and the stress distributions both in bone and implants and the internal bone remodelling process after fracture and fixation are obtained and analysed by computational simulation. The main conclusions of this work are that distal femoral fractures can be treated correctly with the Condyle Plate, the LISS plate and the DFN. The stresses both in LISS and DFN implant are high especially around the screws. When respect to remodelling, the LISS produces an important resorption in the fractured region, while the other two implants do not strongly modify bone tissue microstructure.     

Characteristics of the Cells-Producents of Thymic Chemotactic Factor for Bone Marrow Stem Elements

It was shown using complement-dependent cytolysis and monoclonal antibodies against CD4, CD8, and NK1.1 antigens that the cortisone-resistant CD3⁺4^–8^–NK1.1^–-thymocytes spontaneously secreted a chemotactic transmitter inducing the release and directed migration of bone marrow cells. When estimating the general profile of the cytokines of these thymocytes by PCR with revertase, it was demonstrated the cells in question did not express cytokines with colony stimulating activities (SCF, IL-3, or GM-CSF) or cytokines affecting the migration of bone marrow stem elements (IL-2, 4, or 7). In addition, an active expression of gene bcl-2 was detected. Thus, the chemotactic cytokine inducing the release of bone marrow stem elements is a product of the cortisone-resistant long-living CD3⁺4^–8^–NK1.1^–-T-cells of the thymus.     

A Three-Dimensional Histological Method for Direct Determination of the Number of Trabecular Termini in Cancellous Bone

Osteoporotic fractures occur frequently in aging populations. Established methods for analyzing microarchitecture indicate that cancellous bone loss in the elderly is associated with progressive reduction in the connectivity of the trabecular network. This disconnection may explain the increased skeletal fragility that is sometimes out of proportion to the amount of bone lost. Connectivity, however, is difficult to measure and usually requires indirect methods. We describe development of a simple, inexpensive and direct procedure for counting sites of trabecular disconnection. The method is based upon preparation of 300-500 fjim thick slices of methylmethacrylate embedded material rather than the more usual thin 8 μm. histological sections. The marrow tissue is retained within the thick slice; this is essential for conservation of any detached bone fragments. In such preparations differential superficial staining of the upper and lower surfaces with alizarin red and light green, respectively, allows the two-dimensional image to be viewed at the same time as its three-dimensional counterpart. In this way, “real” (i. e., unstained) trabecular termini can be distinguished from “apparent” (i. e., stained red or green) termini that are artifacts of the plane of section. Partly polarized light enhances the microscope image. The method does not destroy the material for subsequent bone histomorphom-etry and, therefore, may be a useful adjunct to iliac bone biopsy analysis in studies of metabolic bone disease.     

A functionally graded material model for the transmural stress distribution of the aortic valve leaflet

Heterogeneities in structure and stress within heart valve leaflets are of significant concern to their functional physiology, as they affect how the tissue constituents remodel in response to pathological and non-pathological (e.g. exercise, pregnancy) alterations in cardiac function. Indeed, valve interstitial cells (VICs) are known to synthesize and degrade leaflet extracellular matrix (ECM) components in a manner specific to their local micromechanical environment. Quantifying local variations in ECM structure and stress is thus necessary to understand homeostatic valve maintenance as well as to develop predictive models of disease progression and post-surgical outcomes. In the aortic valve (AV), transmural variations in stress have previously been investigated by modeling the leaflet as a composite of contiguous but mechanically distinct layers. Based on previous findings about the bonded nature of these layers (Buchanan and Sacks, BMMB, 2014), we developed a more generalized structural constitutive model by treating the leaflet as a functionally graded material (FGM), whose properties vary continuously over the thickness. We informed the FGM model using high-resolution morphological measurements, which demonstrated that the composition and fiber structure change gradually over the thickness of the AV leaflet. For validation, we fit the model against an extensive database of whole-leaflet and individual-layer mechanical responses. The FGM model predicted large stress variations both between and within the leaflet layers at end-diastole, with low-collagen regions bearing significant radial stress. These novel results suggest that the continually varying structure of the AV leaflet has an important purpose with regard to valve function and tissue homeostasis.     

IL-10在人骨髓间充质干细胞移植治疗食蟹猴脑缺血中的作用

目的探讨食蟹猴脑缺血模型在人骨髓间充质干细胞（human bone marrow-derived mesenchymal stem cells,hBMSCs）移植后IL-10的表达及其对脑缺血损伤的保护作用。方法食蟹猴8只,在脑定位仪定位下,应用光化学法构建食蟹猴脑缺血模型,并将其随机分为高剂量治疗组、低剂量治疗组和模型组,分别在脑缺血部位附近注射高、低密度的hBMSCs和生理盐水。手术后,通过影像学、神经功能评分及组织病理学观察对hBMSC的治疗效果进行评价。并应用原位细胞凋亡检测的方法观察脑缺血周围神经细胞的凋亡情况。应用免疫组织化学、RT-PCR以及real-time PCR法检测检测脑损伤周围IL-10的表达水平。结果与模型组相比,hBMSC治疗组损伤部位周围细胞凋亡明显减少,免疫组织化学显示[L-IO阳性细胞的数量及染色强度均较模型组明显升高,IL-10在mRNA水平表达也明显升高。结论hBMSCs对食蟹猴脑缺血模型具有修复作用,其治疗机制可能与促进炎症抑制因子IL-10的表达有关。     

直接重整细胞核程序的诱导性多能干细胞研究进展

诱导性多能干细胞（induced pluripotent stem cells, iPS）是分化细胞在外源性因子作用下,经直接细胞核程序重整而重新获得分化潜能的干细胞,具有很重要的应用前景。介绍了iPS诱导方法从转录因子、RNA结合蛋白、小分子化合物、到信号传导通路的发展过程,以及在提高生物安全性方面的改进。iPS的生成在细胞学上表现为渐进的、时间依赖的过程,同细胞的分化状态密切相关;然而,iPS同胚胎干细胞表遗传特征并非完全相同。iPS的进展结合基因治疗和细胞治疗的成果已应用到动物疾病模型的治疗。     

A Symbolic Model for the Regulation by Bone Metabolism of the Blood Calcium Level in Rats

The control by bone metabolism of the blood calcium level in young rats may be described in terms of a regulator-type system. The model presented here comprises a feedback loop involving only a proportional control in thyroparathyroidectomized, and a combination of proportional and integral controls in normal animals. It accounts for the variations observed when the system was subjected to a variety of experimental constraints. The implications, limitations, and possible extensions of the model are discussed.     

Influence of Different Abutment Designs on the Biomechanical Behavior of One-Piece Zirconia Dental Implants and Their Surrounding Bone: A 3D-FEA

BackgroundIn a dental implant/bone system, the design factors affect the value and distributions of stress and deformations that plays a pivotal role on the stability, durability and lifespan of the implant/bone system.ObjectiveThe aim of this study was to compare the influence of different abutment designs on the biomechanical behavior of one-piece zirconia dental implants and their surrounding bone tissues using three-dimensional finite element analysis.MethodsA three-dimensional geometrical model of a zirconia dental implant and its surrounding bone tissue were created. The occlusal loading force applied to the prosthetic abutments was a combination of 114.6 N in the axial direction, 17.1 N in the lingual direction and 23.4 N toward the mesial direction where these components represent masticatory force of 118.2 N in the angle of approximately 75° to the occlusal plane.ResultsThe system included implant abutment Model 01 showed a decrease of 9.58%, 9.92% and 3.62% at least in the average value of maximum von Mises stress compared to Model 02, Model 03 and Model 04 respectively. The results also showed that the system included implant abutment Model 01 decreases the average value of maximum deformation of 16.96%, 7.17% and 9.47% at least compared to Model 02, Model 03 and Model 04 respectively.ConclusionThe one-piece zirconia dental implant abutment Model 01 presents a better biomechanical behavior in the peri-implant bone than others. It can efficiently distribute the applied load and present more homogeneous behavior of stress distribution and has less deformation than others, which will enhance the stability of implant/bone system and prolong its lifespan.     

Snail基因修饰对骨髓基质干细胞骨架结构稳定作用及促迁移和对无血清培养诱导细胞凋亡的保护作用研究

转录因子Snail是调控肿瘤细胞迁徙转移的重要调控分子,基于干细胞与肿瘤细胞分子机制的重叠性,提出通过借鉴肿瘤细胞迁移的相关机制以用于提高骨髓基质干细胞向缺氧受损组织迁移能力的假设和研究思路,探讨Snail基因在人骨髓基质干细胞(MSCs)中的转染和表达情况,及转染后对基质干细胞促迁移作用、骨架结构的稳定作用及对无血清培养诱导细胞凋亡的保护作用。密度梯度离心法及细胞体外培养分离纯化人骨髓MSCs,脂质体法将重组表达载体pCAGGSneo-Snail-HA转染MSCs,G418筛选稳定表达,流式细胞仪检测MSCs表面抗原,采用免疫荧光染色技术检测转染后MSCs报告基因HA及目的基因Snail表达,Transwell细胞迁移实验和Western-blot评估细胞迁移能力和检测有关细胞信号转导通路分子水平变化,荧光染色分析细胞骨架,Sub-G1凋亡峰流式细胞仪检测细胞凋亡率并评估细胞抗凋亡能力。经流式细胞仪选择检测分离纯化扩增MSCs表面分子特点为CD34(-)/CD29( ),Snail及报告基因在转染后MSCs呈阳性表达,Snail质粒转染MSCs(MSCs-Sna)较对照空质粒转染MSCs(MSCs-neo)细胞迁移率增加(P<0.05),PI-3K信号通路特异性抑制剂Wortmannin能显著抑制此迁移率的增加,无血清培养72h后,MSCs-Sna凋亡率较MSCs-neo低(P<0.05)。经Snail基因转染,MSCs迁移能力、骨架结构的稳定性及在无血清培养环境中抗凋亡能力增加。     

The Structural Basis for Specific Recognition of H3K14 Acetylation by Sth1 in the RSC Chromatin Remodeling Complex

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