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Sample records for modeling bone structure

  1. Animal models of maternal nutrition and altered offspring bone structureBone development across the lifecourse

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    SA Lanham

    2011-11-01

    Full Text Available It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.

  2. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

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    Yao, Xiaomei; Carleton, Stephanie M; Kettle, Arin D; Melander, Jennifer; Phillips, Charlotte L; Wang, Yong

    2013-06-01

    Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

  3. Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

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    Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

    2013-04-01

    Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

  4. Accurate Fabrication of Hydroxyapatite Bone Models with Porous Scaffold Structures by Using Stereolithography

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    Maeda, Chiaki; Tasaki, Satoko; Kirihara, Soshu, E-mail: c-maeda@jwri.osaka-u.ac.jp [Joining and Welding Research Institute, Osaka University, 11-1 Mihogaoka, Ibaraki City, Osaka 567-0047 (Japan)

    2011-05-15

    Computer graphic models of bioscaffolds with four-coordinate lattice structures of solid rods in artificial bones were designed by using a computer aided design. The scaffold models composed of acryl resin with hydroxyapatite particles at 45vol. % were fabricated by using stereolithography of a computer aided manufacturing. After dewaxing and sintering heat treatment processes, the ceramics scaffold models with four-coordinate lattices and fine hydroxyapatite microstructures were obtained successfully. By using a computer aided analysis, it was found that bio-fluids could flow extensively inside the sintered scaffolds. This result shows that the lattice structures will realize appropriate bio-fluid circulations and promote regenerations of new bones.

  5. Numerical damage models using a structural approach: application in bones and ligaments

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    Arnoux, P. J.; Bonnoit, J.; Chabrand, P.; Jean, M.; Pithioux, M.

    2002-01-01

    The purpose of the present study was to apply knowledge of structural properties to perform numerical simulations with models of bones and knee ligaments exposed to dynamic tensile loading leading to tissue damage. Compact bones and knee ligaments exhibit the same geometrical pattern in their different levels of structural hierarchy from the tropocollagen molecule to the fibre. Nevertheless, their mechanical behaviours differ considerably at the fibril level. These differences are due to the contribution of the joints in the microfibril-fibril-fibre assembly and to the mechanical properties of the structural components. Two finite element models of the fibrous bone and ligament structure were used to describe damage in terms of elastoplastic laws or joint decohesion processes.

  6. Effects of Eurycoma longifolia on Testosterone Level and Bone Structure in an Aged Orchidectomised Rat Model

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    Abdul Shukor Tajul Ariff

    2012-01-01

    Full Text Available Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.

  7. Structure model index does not measure rods and plates in trabecular bone

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    Phil L Salmon

    2015-10-01

    Full Text Available Structure model index (SMI is widely used to measure rods and plates in trabecular bone. It exploits the change in surface curvature that occurs as a structure varies from spherical (SMI = 4, to cylindrical (SMI = 3 to planar (SMI = 0. The most important assumption underlying SMI is that the entire bone surface is convex and that the curvature differential is positive at all points on the surface. The intricate connections within the trabecular continuum suggest that a high proportion of the surface could be concave, violating the assumption of convexity and producing regions of negative differential. We implemented SMI in the BoneJ plugin and included the ability to measure the amounts of surface that increased or decreased in area after surface mesh dilation, and the ability to visualize concave and convex regions. We measured SMI and its positive (SMI+ and negative (SMI- components, bone volume fraction (BV/TV, the fraction of the surface that is concave (CF, and mean ellipsoid factor (EF in trabecular bone using 38 X-ray microtomography (XMT images from a rat ovariectomy model of sex steroid rescue of bone loss, and 169 XMT images from a broad selection of 87 species' femora (mammals, birds, and a crocodile. We simulated bone resorption by eroding an image of elephant trabeculae and recording SMI and BV/TV at each erosion step. Up to 70%, and rarely less than 20%, of the trabecular surface is concave (CF 0.155 – 0.700. SMI is unavoidably influenced by aberrations from SMI-, which is strongly correlated with BV/TV and CF. The plate-to-rod transition in bone loss is an erroneous observation resulting from SMI's close and artefactual relationship with BV/TV. SMI cannot discern between the distinctive trabecular geometries typical of mammalian and avian bone, whereas EF clearly detects birds' more plate-like trabeculae. EF is free from confounding relationships with BV/TV and CF. SMI results reported in the literature should be treated with

  8. Three dimensional stereolithography models of cancellous bone structures from muCT data: testing and validation of finite element results.

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    Dobson, C A; Sisias, G; Phillips, R; Fagan, M J; Langton, C M

    2006-04-01

    Stereolithography (STL) models of complex cancellous bone structures have been produced from three-dimensional micro-computed tomography data sets of human cancellous bone histological samples from four skeletal sites. The STL models have been mechanically tested and the derived stiffness compared with that predicted by finite element analysis. The results show a strong correlation (R2 = 0.941) between the predicted and calculated stiffnesses of the structures and show promise for the use of STL as an additional technique to complement the use of finite element models, for the assessment of the mechanical properties of complex cancellous bone structures.

  9. Inducible models of bone loss.

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    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions. Copyright © 2014 John Wiley & Sons, Inc.

  10. A 3D Multiscale Modelling of Cortical Bone Structure, Using the Inverse Identification Method: Microfibril Scale Study

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    Barkaoui, Abdelwahed

    2011-01-01

    Complexity and heterogeneity of bone tissue require a multiscale modelling to understand their mechanical behaviour and their remodelling mechanism. Human cortical bone structure consists of six structural scale levels which are the (macroscopic) cortical bone, osteonal, lamellar, fibrous, fibril and microfibril. In this paper, a 3D model based on finite elements method was achieved to study the nanomechanical behaviour of collagen Microfibril. The mechanical properties and the geometry (gap, overlap and diameter) of both tropocollagen and mineral were taken into consideration as well as the effects of cross-links. An inverse identification method has been applied to determine equivalent averaged properties in order to link up these nanoscopic characteristics to the macroscopic mechanical behaviour of bone tissue. Results of nanostructure modelling of the nanomechanical properties of strain deformation under varying cross-links were investigated in this work.

  11. New bio-ceramization processes applied to vegetable hierarchical structures for bone regeneration: an experimental model in sheep.

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    Filardo, Giuseppe; Kon, Elizaveta; Tampieri, Anna; Cabezas-Rodríguez, Rafael; Di Martino, Alessandro; Fini, Milena; Giavaresi, Gianluca; Lelli, Marco; Martínez-Fernández, Julian; Martini, Lucia; Ramírez-Rico, Joaquin; Salamanna, Francesca; Sandri, Monica; Sprio, Simone; Marcacci, Maurilio

    2014-02-01

    Bone loss is still a major problem in orthopedics. The purpose of this experimental study is to evaluate the safety and regenerative potential of a new scaffold based on a bio-ceramization process for bone regeneration in long diaphyseal defects in a sheep model. The scaffold was obtained by transformation of wood pieces into porous biomorphic silicon carbide (BioSiC®). The process enabled the maintenance of the original wood microstructure, thus exhibiting hierarchically organized porosity and high mechanical strength. To improve cell adhesion and osseointegration, the external surface of the hollow cylinder was made more bioactive by electrodeposition of a uniform layer of collagen fibers that were mineralized with biomimetic hydroxyapatite, whereas the internal part was filled with a bio-hybrid HA/collagen composite. The final scaffold was then implanted in the metatarsus of 15 crossbred (Merinos-Sarda) adult sheep, divided into 3 groups: scaffold alone, scaffold with platelet-rich plasma (PRP) augmentation, and scaffold with bone marrow stromal cells (BMSCs) added during implantation. Radiological analysis was performed at 4, 8, 12 weeks, and 4 months, when animals were sacrificed for the final radiological, histological, and histomorphometric evaluation. In all tested treatments, these analyses highlighted the presence of newly formed bone at the bone scaffolds' interface. Although a lack of substantial effect of PRP was demonstrated, the scaffold+BMSC augmentation showed the highest value of bone-to-implant contact and new bone growth inside the scaffold. The findings of this study suggest the potential of bio-ceramization processes applied to vegetable hierarchical structures for the production of wood-derived bone scaffolds, and document a suitable augmentation procedure in enhancing bone regeneration, particularly when combined with BMSCs.

  12. Photogrammetry in 3d Modelling of Human Bone Structures from Radiographs

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    Hosseinian, S.; Arefi, H.

    2017-05-01

    Photogrammetry can have great impact on the success of medical processes for diagnosis, treatment and surgeries. Precise 3D models which can be achieved by photogrammetry improve considerably the results of orthopedic surgeries and processes. Usual 3D imaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI), have some limitations such as being used only in non-weight-bearing positions, costs and high radiation dose(for CT) and limitations of MRI for patients with ferromagnetic implants or objects in their bodies. 3D reconstruction of bony structures from biplanar X-ray images is a reliable and accepted alternative for achieving accurate 3D information with low dose radiation in weight-bearing positions. The information can be obtained from multi-view radiographs by using photogrammetry. The primary step for 3D reconstruction of human bone structure from medical X-ray images is calibration which is done by applying principles of photogrammetry. After the calibration step, 3D reconstruction can be done using efficient methods with different levels of automation. Because of the different nature of X-ray images from optical images, there are distinct challenges in medical applications for calibration step of stereoradiography. In this paper, after demonstrating the general steps and principles of 3D reconstruction from X-ray images, a comparison will be done on calibration methods for 3D reconstruction from radiographs and they are assessed from photogrammetry point of view by considering various metrics such as their camera models, calibration objects, accuracy, availability, patient-friendly and cost.

  13. Understanding the Structure of Bones

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    ... structure of bone is very similar to reinforced concrete that is used to make a building or ... a defective blueprint is produced that tells the cell to produce deformed collagen, resulting in bad collagen ...

  14. 3D Modelling and monitoring of denervated muscle under Functional Electrical Stimulation treatment and associated bone structural changes

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    Paolo Gargiulo

    2011-03-01

    Full Text Available A novel clinical rehabilitation method for patients who have permanent and non recoverable muscle denervation in the legs was developed in the frame of the European Project RISE. The technique is based on FES and the project results shows, in these severely disabled patients, restoration of muscle tissue and function. This study propose novel methods based on image processing technique and medical modelling to monitor growth in denervated muscle treated with FES. Geometrical and structural changes in muscle and bone are studied and modelled. Secondary effects on the bone mineral density produced by the stimulation treatment and due the elicited muscle contraction are also investigated. The restoration process in DDM is an important object of discussion since there isn’t yet a complete understanding of the mechanisms regulating growth in denervated muscle. This study approaches the problem from a macroscopic point of view, developing 3-dimensional models of the whole stimulated muscles and following changes in volume, geometry and density very accurately. The method is based on the acquisition of high resolution Spiral CT scans from patients who have long-term flaccid paraplegia and the use of special image processing tools allowing tissue discriminations and muscle segmentation. Three patients were measured at different points of time during 4 years of electrical stimulation treatment. In this study is quantitatively demonstrated the influences of FES treatment on the different quadriceps bellies. The rectus femoris muscle is positioned in the middle of the quadriceps and responds (in general better to stimulation. In a patient with abundant adipose tissue surrounding the quadriceps, rectus femoris almost doubled the volume during the FES treatment while in the other bellies the changes measured were minimal. The analysis of the density shows clearly a restoration of the muscular structure in the growing muscle. The remarkable increase of

  15. Erythropoietin modulates the structure of bone morphogenetic protein 2-engineered cranial bone.

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    Sun, Hongli; Jung, Younghun; Shiozawa, Yusuke; Taichman, Russell S; Krebsbach, Paul H

    2012-10-01

    The ideally engineered bone should have similar structural and functional properties to the native tissue. Although structural integrity is critical for functional bone regeneration, we know less about modulating the structural properties of the engineered bone elicited by bone morphogenetic protein (BMP) than efficacy and safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used to augment blood transfusion in orthopedic surgery. However, the effects of Epo on bone regeneration are not well known. Here, we determined the role of Epo in BMP2-induced bone regeneration using a cranial defect model. Epo administration improved the quality of BMP2-induced bone and more closely resembled natural cranial bone with a higher bone volume (BV) fraction and lower marrow fraction when compared with BMP2 treatment alone. Epo increased red blood cells (RBCs) in peripheral blood and also increased hematopoietic and mesenchymal stem cell (MSC) populations in bone marrow. Consistent with our previous work, Epo increased osteoclastogenesis both in vitro and in vivo. Results from a metatarsal organ culture assay suggested that Epo-promoted osteoclastogenesis contributed to angiogenesis because angiogenesis was blunted when osteoclastogenesis was blocked by alendronate (ALN) or osteoprotegerin (OPG). Earlier calcification of BMP2-induced temporary chondroid tissue was observed in the Epo+BMP group compared to BMP2 alone. We conclude that Epo significantly enhanced the outcomes of BMP2-induced cranial bone regeneration in part through its actions on osteoclastogenesis and angiogenesis.

  16. Characteristic anatomical structures of rat temporal bone

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    Peng Li; Kelei Gao; Dalian Ding; Richard Salvi

    2015-01-01

    As most gene sequences and functional structures of internal organs in rats have been well studied, rat models are widely used in experi-mental medical studies. A large number of descriptions and atlas of the rat temporal bone have been published, but some detailed anatomy of its surface and inside structures remains to be studied. By focusing on some unique characteristics of the rat temporal bone, the current paper aims to provide more accurate and detailed information on rat temporal bone anatomy in an attempt to complete missing or unclear areas in the existed knowledge. We also hope this paper can lay a solid foundation for experimental rat temporal bone surgeries, and promote information exchange among colleagues, as well as providing useful guidance for novice researchers in the field of hearing research involving rats. Copyright © 2015 The Authors. Production & hosting by Elsevier (Singapore) Pte Ltd On behalf of PLA General Hospital Department of Otolaryngology Head and Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  17. Three-dimensional virtual bone bank system workflow for structural bone allograft selection: a technical report.

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    Ritacco, Lucas Eduardo; Farfalli, German Luis; Milano, Federico Edgardo; Ayerza, Miguel Angel; Muscolo, Domingo Luis; Aponte-Tinao, Luis

    2013-01-01

    Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor.

  18. Mathematical model for bone mineralization

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    Svetlana V Komarova

    2015-08-01

    Full Text Available Defective bone mineralization has serious clinical manifestations, including deformities and fractures, but the regulation of this extracellular process is not fully understood. We have developed a mathematical model consisting of ordinary differential equations that describe collagen maturation, production and degradation of inhibitors, and mineral nucleation and growth. We examined the roles of individual processes in generating normal and abnormal mineralization patterns characterized using two outcome measures: mineralization lag time and degree of mineralization. Model parameters describing the formation of hydroxyapatite mineral on the nucleating centers most potently affected the degree of mineralization, while the parameters describing inhibitor homeostasis most effectively changed the mineralization lag time. Of interest, a parameter describing the rate of matrix maturation emerged as being capable of counter-intuitively increasing both the mineralization lag time and the degree of mineralization. We validated the accuracy of model predictions using known diseases of bone mineralization such as osteogenesis imperfecta and X-linked hypophosphatemia. The model successfully describes the highly non-linear mineralization dynamics, which includes an initial lag phase when osteoid is present but no mineralization is evident, then fast primary mineralization, followed by secondary mineralization characterized by a continuous slow increase in bone mineral content. The developed model can potentially predict the function for a mutated protein based on the histology of pathologic bone samples from mineralization disorders of unknown etiology.

  19. An adaptation model for trabecular bone at different mechanical levels

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    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  20. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    stiffnesses are in GPa. Location Femm Tibia Femur Femur Method illtrasound Mechanical illtrasound illtrasound Preferential Model Testing 95%EFM...0.2654 Femoral Neck [103] 0.2067 0.172 Femoral Head [104] 0.27 0.2 Distal Femm [105] 0.27 0.19 Proximal Femur [105] 0.105 Greater Trochanter [103...stiffer in compression than tension for all models. Additionally, the distal and proximal femm is stiffer than both the femoral neck and head. This is

  1. The dynamics of bone structure development during pubertal growth.

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    Rauch, F

    2012-03-01

    The pubertal growth spurt is a time of rapid changes in bone length, mass and structure, followed by the cessation of longitudinal growth. The two best studied anatomical areas in this respect are the metaphyses and the diaphyses of peripheral long bones. A model is presented here in which the speed of longitudinal growth and the resulting age gradient in metaphyseal bone are key factors in explaining the high incidence of distal radius fractures during puberty. As growth in length accelerates, the age of the bone structural elements at a given distance to the growth plate decreases, leaving less time for cortical thickening through trabecular coalescence. This leads to a discrepancy between stagnant metaphyseal bone strength and increasing mechanical requirements in the case of accidents. In comparison to the metaphysis, diaphyseal bone develops more in line with the increasing mechanical requirements, presumably because the bone formation rates needed for diaphyseal growth in width are only a fraction of the apposition rates in the metaphysis. It remains largely unexplored how local and systemic signals are integrated to achieve site-specific changes in bone structure.

  2. Tubular open-porous β-tricalcium phosphate polycaprolactone scaffolds as guiding structure for segmental bone defect regeneration in a novel sheep model.

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    Pobloth, Anne-Marie; Schell, Hanna; Petersen, Ansgar; Beierlein, Katleen; Kleber, Christian; Schmidt-Bleek, Katharina; Duda, Georg N

    2017-05-08

    Large segmental bone defect reconstruction with sufficient functional restoration is one of the most demanding challenges in orthopaedic surgery. Available regenerative treatment options, as the vascularized bone graft transfer, the Masquelet technique or the Ilizarov distraction osteogenesis, are associated with specific indications and distinct limitations. As an alternative, a hollow cylindrical ceramic-polymer composite scaffold (β-tricalcium phosphate and poly-lactid co-ε- caprolactone), facilitating a strong surface guiding effect for tissue ingrowth (group 1; n = 6) was investigated here. In combination with an additional autologous, cancellous bone graft filling, the scaffold's ability to work as an open-porous membrane to improve the defect healing process was analysed (group 2; n = 6). A novel model of a critical size (40 mm) tibia osteotomy defect stabilized with an external hybrid-ring fixator, was established in sheep. Segmental defect regeneration and tissue organization in relation to the scaffold were analysed radiologically, (immune-) histologically, and with second-harmonic generation imaging 12 weeks after surgery. The scaffold's tubular shape and open-porous structure controlled the collagen fibre orientation within the bone defect and guided the following mineralization process along the scaffold surface. In combination with the osteoinductive stimulus, a unilateral bony bridging of the critically sized defect was achieved in one third of the animals. The external hybrid-ring fixator was appropriate for large segmental defect stabilization in sheep. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Three-scale model of single bone osteon modelled as double-porous fluid saturated body: Study of influence of micro/meso-structure

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    Turjanicová J.

    2014-12-01

    Full Text Available This paper deals with the multiscale description of a single osteon of cortical bones. The cortical bone tissue is modeled as a double-porous medium decomposed into the solid matrix and the fluid saturated canals. The resulting homogenized model describes deformation of such medium in response to a static loading by external forces and to an injection of slightly compressible fluid. Three numerical examples are presented, showing the influence of selected lower-scales geometrical features on the macroscopic body behavior.

  4. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

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    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  5. Computer-simulated bone architecture in a simple bone-remodeling model based on a reaction-diffusion system.

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    Tezuka, Ken-ichi; Wada, Yoshitaka; Takahashi, Akiyuki; Kikuchi, Masanori

    2005-01-01

    Bone is a complex system with functions including those of adaptation and repair. To understand how bone cells can create a structure adapted to the mechanical environment, we propose a simple bone remodeling model based on a reaction-diffusion system influenced by mechanical stress. Two-dimensional bone models were created and subjected to mechanical loads. The conventional finite element method (FEM) was used to calculate stress distribution. A stress-reactive reaction-diffusion model was constructed and used to simulate bone remodeling under mechanical loads. When an external mechanical stress was applied, stimulated bone formation and subsequent activation of bone resorption produced an efficient adaptation of the internal shape of the model bone to a given stress, and demonstrated major structures of trabecular bone seen in the human femoral neck. The degree of adaptation could be controlled by modulating the diffusion constants of hypothetical local factors. We also tried to demonstrate the deformation of bone structure during osteoporosis by the modulation of a parameter affecting the balance between formation and resorption. This simple model gives us an insight into how bone cells can create an architecture adapted to environmental stress, and will serve as a useful tool to understand both physiological and pathological states of bone based on structural information.

  6. Erythropoietin Modulates the Structure of Bone Morphogenetic Protein 2–Engineered Cranial Bone

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    Sun, Hongli; Jung, Younghun; Shiozawa, Yusuke; Taichman, Russell S.; Krebsbach, Paul H.

    2012-01-01

    The ideally engineered bone should have similar structural and functional properties to the native tissue. Although structural integrity is critical for functional bone regeneration, we know less about modulating the structural properties of the engineered bone elicited by bone morphogenetic protein (BMP) than efficacy and safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used to augment blood transfusion in orthopedic surgery. However, the effects of Epo on bone regene...

  7. Trabecular bone structure analysis of the spine using clinical MDCT: can it predict vertebral bone strength?

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    Baum, Thomas; Gräbeldinger, Martin; Räth, Christoph; Garcia, Eduardo Grande; Burgkart, Rainer; Patsch, Janina M; Rummeny, Ernst J; Link, Thomas M; Bauer, Jan S

    2014-01-01

    Recent technical improvements have made it possible to determine trabecular bone structure parameters of the spine using clinical multi-detector computed tomography (MDCT). Therefore, the purpose of this study was to analyze trabecular bone structure parameters obtained from clinical MDCT in relation to high resolution peripheral quantitative computed tomography (HR-pQCT) as a standard of reference and to investigate whether clinical MDCT can predict vertebral bone strength. Fourteen functional spinal segment units between T7 and L3 were harvested from 14 formalin-fixed human cadavers (11 women and 3 men; age 84 ± 10 years). All functional spinal segment units were examined using HR-pQCT (isotropic voxel size of 41 μm(3)) and a clinical whole-body MDCT (interpolated voxel size of 146 × 146 × 300 μm(3)). Trabecular bone structure analyses (histomorphometric and texture measures) were performed in the HR-pQCT as well as MDCT images. Vertebral failure load (FL) of the functional spinal segment units was determined in an uniaxial biomechanical test. The HR-pQCT and MDCT derived trabecular bone structure parameters showed correlations ranging from r = 0.60 to r = 0.90 (p parameters and FL amounted up to r = 0.86 (p parameters obtained with HR-pQCT and MDCT were not significantly different (p > 0.05). In this cadaver model, the spatial resolution of clinically available whole-body MDCT scanners was suitable for trabecular bone structure analysis of the spine and to predict vertebral bone strength.

  8. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

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    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  9. Quantification of spatial structure of human proximal tibial bone biopsies using 3D measures of complexity

    DEFF Research Database (Denmark)

    Saparin, Peter I.; Thomsen, Jesper Skovhus; Prohaska, Steffen

    2005-01-01

    Changes in trabecular bone composition during development of osteoporosis are used as a model for bone loss in microgravity conditions during a space flight. Symbolic dynamics and measures of complexity are proposed and applied to assess quantitatively the structural composition of bone tissue fr...

  10. Statistical shape and appearance models of bones.

    Science.gov (United States)

    Sarkalkan, Nazli; Weinans, Harrie; Zadpoor, Amir A

    2014-03-01

    When applied to bones, statistical shape models (SSM) and statistical appearance models (SAM) respectively describe the mean shape and mean density distribution of bones within a certain population as well as the main modes of variations of shape and density distribution from their mean values. The availability of this quantitative information regarding the detailed anatomy of bones provides new opportunities for diagnosis, evaluation, and treatment of skeletal diseases. The potential of SSM and SAM has been recently recognized within the bone research community. For example, these models have been applied for studying the effects of bone shape on the etiology of osteoarthritis, improving the accuracy of clinical osteoporotic fracture prediction techniques, design of orthopedic implants, and surgery planning. This paper reviews the main concepts, methods, and applications of SSM and SAM as applied to bone.

  11. Trabecular bone structure in the primate wrist.

    Science.gov (United States)

    Schilling, Ann-Marie; Tofanelli, Sergio; Hublin, Jean-Jacques; Kivell, Tracy L

    2014-05-01

    Trabecular (or cancellous) bone has been shown to respond to mechanical loading throughout ontogeny and thus can provide unique insight into skeletal function and locomotion in comparative studies of living and fossil mammalian morphology. Trabecular bone of the hand may be particularly functionally informative because the hand has more direct contact with the substrate compared with the remainder of the forelimb during locomotion in quadrupedal mammals. This study investigates the trabecular structure within the wrist across a sample of haplorhine primates that vary in locomotor behaviour (and thus hand use) and body size. High-resolution microtomographic scans were collected of the lunate, scaphoid, and capitate in 41 individuals and eight genera (Homo, Gorilla, Pan, Papio, Pongo, Symphalangus, Hylobates, and Ateles). We predicted that particular trabecular parameters would 1) vary across suspensory, quadrupedal, and bipedal primates based on differences in hand use and load, and 2) scale with carpal size following similar allometric patterns found previously in other skeletal elements across a larger sample of mammals and primates. Analyses of variance (trabecular parameters analysed separately) and principal component analyses (trabecular parameters analysed together) revealed no clear functional signal in the trabecular structure of any of the three wrist bones. Instead, there was a large degree of variation within suspensory and quadrupedal locomotor groups, as well as high intrageneric variation within some taxa, particularly Pongo and Gorilla. However, as predicted, Homo sapiens, which rarely use their hands for locomotion and weight support, were unique in showing lower relative bone volume (BV/TV) compared with all other taxa. Furthermore, parameters used to quantify trabecular structure within the wrist scale with size generally following similar allometric patterns found in trabeculae of other mammalian skeletal elements. We discuss the challenges

  12. Effects of Tai Ji Exercise on Bone Structure and Function

    Institute of Scientific and Technical Information of China (English)

    Xu Hong; David Lawson

    2005-01-01

    To evaluated the effects of the 24 movements Tai Ji exercise on bone structure and function. Broadband Ultrsonic Attenuation (BUA) and velocity of sound (VOS), bone formation marker Osteocalcin (OSTN) and bone resorption markers urinary Pyridum crosslinks (PYR and D-PYR) were studied before and after four months of Tai Ji exercise. Improved bone structure and increased bone density in menopausal women were reflected by BUA results. The increased BUA appears to be associated with increased bone formation rather than decreased bone resorption.

  13. A new zebrafish bone crush injury model

    Directory of Open Access Journals (Sweden)

    Sara Sousa

    2012-07-01

    While mammals have a limited capacity to repair bone fractures, zebrafish can completely regenerate amputated bony fin rays. Fin regeneration in teleosts has been studied after partial amputation of the caudal fin, which is not ideal to model human bone fractures because it involves substantial tissue removal, rather than local tissue injury. In this work, we have established a bone crush injury model in zebrafish adult caudal fin, which consists of the precise crush of bony rays with no tissue amputation. Comparing these two injury models, we show that the initial stages of injury response are the same regarding the activation of wound healing molecular markers. However, in the crush assay the expression of the blastema marker msxb appears later than during regeneration after amputation. Following the same trend, bone cells deposition and expression of genes involved in skeletogenesis are also delayed. We further show that bone and blood vessel patterning is also affected. Moreover, analysis of osteopontin and Tenascin-C reveals that they are expressed at later stages in crushed tissue, suggesting that in this case bone repair is prolonged for longer than in the case of regeneration after amputation. Due to the nature of the trauma inflicted, the crush injury model seems more similar to fracture bone repair in mammals than bony ray amputation. Therefore, the new model that we present here may help to identify the key processes that regulate bone fracture and contribute to improve bone repair in humans.

  14. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  15. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  16. The complex channel networks of bone structure

    CERN Document Server

    Costa, Luciano da Fontoura; Beletti, Marcelo E

    2006-01-01

    Bone structure in mammals involves a complex network of channels (Havers and Volkmann channels) required to nourish the bone marrow cells. This work describes how three-dimensional reconstructions of such systems can be obtained and represented in terms of complex networks. Three important findings are reported: (i) the fact that the channel branching density resembles a power law implies the existence of distribution hubs; (ii) the conditional node degree density indicates a clear tendency of connection between nodes with degrees 2 and 4; and (iii) the application of the recently introduced concept of hierarchical clustering coefficient allows the identification of typical scales of channel redistribution. A series of important biological insights is drawn and discussed

  17. Quantifying Changes in the Spatial Structure of Trabecular Bone

    CERN Document Server

    Marwan, Norbert; Felsenberg, Dieter; Saparin, Peter; Kurths, Jürgen

    2010-01-01

    We apply recently introduced measures of complexity for the structural quantfication of distal tibial bone. For the first time, we are able to investigate the temporal structural alteration of trabecular bone. Based on four patients, we show how bone may alter due to temporal immobilisation.

  18. Structural orientation dependent sub-lamellar bone mechanics.

    Science.gov (United States)

    Jimenez-Palomar, Ines; Shipov, Anna; Shahar, Ron; Barber, Asa H

    2015-12-01

    The lamellar unit is a critical component in defining the overall mechanical properties of bone. In this paper, micro-beams of bone with dimensions comparable to the lamellar unit were fabricated using focused ion beam (FIB) microscopy and mechanically tested in bending to failure using atomic force microscopy (AFM). A variation in the mechanical properties, including elastic modulus, strength and work to fracture of the micro-beams was observed and related to the collagen fibril orientation inferred from back-scattered scanning electron microscopy (SEM) imaging. Established mechanical models were further applied to describe the relationship between collagen fibril orientation and mechanical behaviour of the lamellar unit. Our results highlight the ability to measure mechanical properties of discrete bone volumes directly and correlate with structural orientation of collagen fibrils.

  19. Growth hormone stimulates bone healing in a critical-sized bone defect model

    NARCIS (Netherlands)

    Theyse, L. F. H.; Oosterlaken-Dijksterhuis, M. A.; van Doorn, J.; Dhert, W. J. A.; Hazewinkel, H. A. W.

    2006-01-01

    Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was qu

  20. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K; Parker, Valorie A; Matthews, Ryan R; Barreto, Rafael; Puppa, Melissa J; Kang, Kyung S; Carson, James A; Guise, Theresa A; Mohammad, Khalid S; Robling, Alexander G; Couch, Marion E; Koniaris, Leonidas G; Zimmers, Teresa A

    2016-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and Apc(Min/+). The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the Apc(Min/+) mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.

  1. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia

    Science.gov (United States)

    Bonetto, Andrea; Kays, Joshua K.; Parker, Valorie A.; Matthews, Ryan R.; Barreto, Rafael; Puppa, Melissa J.; Kang, Kyung S.; Carson, James A.; Guise, Theresa A.; Mohammad, Khalid S.; Robling, Alexander G.; Couch, Marion E.; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2017-01-01

    Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia. PMID:28123369

  2. Structural and mechanical properties of mandibular condylar bone.

    Science.gov (United States)

    van Eijden, T M G J; van der Helm, P N; van Ruijven, L J; Mulder, L

    2006-01-01

    The trabecular bone of the mandibular condyle is structurally anisotropic and heterogeneous. We hypothesized that its apparent elastic moduli are also anisotropic and heterogeneous, and depend on trabecular density and orientation. Eleven condyles were scanned with a micro-CT system. Volumes of interest were selected for the construction of finite element models. We simulated compressive and shear tests to determine the principal mechanical directions and the apparent elastic moduli. Compressive moduli were relatively large in directions acting in the sagittal plane, and small in the mediolateral direction. The degree of mechanical anisotropy ranged from 4.7 to 10.8. Shear moduli were largest in the sagittal plane and smallest in the transverse plane. The magnitudes of the moduli varied with the condylar region and were proportional to the bone volume fraction. Furthermore, principal mechanical direction correlated significantly with principal structural direction. It was concluded that variation in trabecular structure coincides with variation in apparent mechanical properties.

  3. Modelling and simulation of acrylic bone cement injection and curing within the framework of vertebroplasty

    CERN Document Server

    Landgraf, Ralf; Kolmeder, Sebastian; Lion, Alexander; Lebsack, Helena; Kober, Cornelia

    2013-01-01

    The minimal invasive procedure of vertebroplasty is a surgical technique to treat compression fractures of vertebral bodies. During the treatment liquid bone cement gets injected into the affected vertebral body and therein cures to a solid. In order to investigate the treatment and the impact of injected bone cement on the vertebra, an integrated modelling and simulation framework has been developed. The framework includes (i) the generation of computer models based on microCT images of human cancellous bone, (ii) CFD simulations of bone cement injection into the trabecular structure of a vertebral body as well as (iii) non-linear FEM simulations of the bone cement curing. Thereby, microstructural models of trabecular bone structures are employed. Furthermore, a detailed description of the material behaviour of acrylic bone cements is provided. More precisely, a non-linear fluid flow model is chosen for the representation of the bone cement behaviour during injection and a non-linear viscoelastic material mo...

  4. The Digital Astronaut Project Bone Remodeling Model

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

    2014-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

  5. Stress Distribution on Short Implants at Maxillary Posterior Alveolar Bone Model With Different Bone-to-Implant Contact Ratio: Finite Element Analysis.

    Science.gov (United States)

    Yazicioglu, Duygu; Bayram, Burak; Oguz, Yener; Cinar, Duygu; Uckan, Sina

    2016-02-01

    The aim of this study was to evaluate the stress distribution of the short dental implants and bone-to-implant contact ratios in the posterior maxilla using 3-dimensional (3D) finite element models. Two different 3D maxillary posterior bone segments were modeled. Group 1 was composed of a bone segment consisting of cortical bone and type IV cancellous bone with 100% bone-to-implant contact. Group 2 was composed of a bone segment consisting of cortical bone and type IV cancellous bone including spherical bone design and homogenous tubular hollow spaced structures with 30% spherical porosities and 70% bone-to-implant contact ratio. Four-millimeter-diameter and 5-mm-height dental implants were assumed to be osseointegrated and placed at the center of the segments. Lateral occlusal bite force (300 N) was applied at a 25° inclination to the implants long axis. The maximum von Mises stresses in cortical and cancellous bones and implant-abutment complex were calculated. The von Mises stress values on the implants and the cancellous bone around the implants of the 70% bone-to-implant contact group were almost 3 times higher compared with the values of the 100% bone-to-implant contact group. For clinical reality, use of the 70% model for finite element analysis simulation of the posterior maxilla region better represents real alveolar bone and the increased stress and strain distributions evaluated on the cortical and cancellous bone around the dental implants.

  6. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Atul Kumar [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Gajiwala, Astrid Lobo [Tissue Bank, Tata Memorial Hospital, Parel, Mumbai 400012 (India); Rai, Ratan Kumar [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Khan, Mohd Parvez [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Singh, Chandan [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Barbhuyan, Tarun [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Vijayalakshmi, S. [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Chattopadhyay, Naibedya [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Sinha, Neeraj, E-mail: neerajcbmr@gmail.com [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Kumar, Ashutosh, E-mail: ashutoshk@iitb.ac.in [Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076 (India); Bellare, Jayesh R., E-mail: jb@iitb.ac.in [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076 (India)

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS® (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  7. Modeling and experimentation of bone drilling forces.

    Science.gov (United States)

    Lee, JuEun; Gozen, B Arda; Ozdoganlar, O Burak

    2012-04-05

    Prediction and control of bone drilling forces are critical to the success of many orthopaedic operations. Uncontrolled and large forces can cause drill-bit breakage, drill breakthrough, excessive heat generation, and mechanical damage to the bone. This paper presents a mechanistic model for prediction of thrust forces and torques experienced during bone drilling. The model incorporates the radially varying drill-bit geometry and cutting conditions analytically, while capturing the material and friction properties empirically through a specific energy formulation. The forces from the chisel edge are modeled by considering the indentation process that occurs in the vicinity of the drill-bit axis. A procedure is outlined to calibrate the specific energies, where only a small number of calibration experiments are required for a wide range of drilling conditions and drill-bit geometry. The calibration parameters for the cortical portions of bovine tibia are identified through drilling tests. Subsequently, a series of validation tests are conducted under different feed rates and spindle speeds. The thrust forces and torques were observed to vary considerably between bones from different animals. The forces from the model were seen to match well with those from the experimentation within the inherent variations from the bone characteristics. The model can be used to select favorable drilling conditions, to assist in robotic surgeries, and to design optimal orthopaedic drill bits. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Residual stress in bone structure and tissue of rabbit's tibiofibula.

    Science.gov (United States)

    Tadano, Shigeru; Okoshi, Taro

    2006-01-01

    This paper presents an X-ray diffraction method of measuring the residual stress/strain in bone tissue of rabbit's tibia. To derive the residual stress, bone powder of the diameter less than 40 micrometers was used as a control specimen at non-stressed state. From the X-ray measurements, it was clear that the distribution of residual stress existed in the bone tissue. The tensile residual stress at bone axial direction occurred in the proximal-medial region of rabbit's tibia. The compressive stress occurred in the other regions. In addition, the mechanism to generate the residual stress was investigated by sequential cutting of the tibiofibula system from bone structure scale to bone tissue scale. The remodeling is a phenomenon that the bone structure adapts functionally to mechanical environment. The residual stress will become a mechanical trigger to induce the remodeling.

  9. Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents

    Energy Technology Data Exchange (ETDEWEB)

    Hamed, Elham [University of Illinois at Urbana-Champaign, Department of Mechanical Science and Engineering, 1206 West Green Street, Urbana, IL 61801 (United States); Novitskaya, Ekaterina, E-mail: eevdokim@ucsd.edu [University of California, San Diego, Department of Mechanical and Aerospace Engineering, Materials Science and Engineering Program, 9500 Gilman Dr., La Jolla, CA 92093 (United States); Li, Jun; Jasiuk, Iwona [University of Illinois at Urbana-Champaign, Department of Mechanical Science and Engineering, 1206 West Green Street, Urbana, IL 61801 (United States); McKittrick, Joanna [University of California, San Diego, Department of Mechanical and Aerospace Engineering, Materials Science and Engineering Program, 9500 Gilman Dr., La Jolla, CA 92093 (United States)

    2015-09-01

    The elastic moduli of trabecular bone were modeled using an analytical multiscale approach. Trabecular bone was represented as a porous nanocomposite material with a hierarchical structure spanning from the collagen–mineral level to the trabecular architecture level. In parallel, compression testing was done on bovine femoral trabecular bone samples in two anatomical directions, parallel to the femoral neck axis and perpendicular to it, and the measured elastic moduli were compared with the corresponding theoretical results. To gain insights on the interaction of collagen and minerals at the nanoscale, bone samples were deproteinized or demineralized. After such processing, the treated samples remained as self-standing structures and were tested in compression. Micro-computed tomography was used to characterize the hierarchical structure of these three bone types and to quantify the amount of bone porosity. The obtained experimental data served as inputs to the multiscale model and guided us to represent bone as an interpenetrating composite material. Good agreement was found between the theory and experiments for the elastic moduli of the untreated, deproteinized, and demineralized trabecular bone. - Highlights: • A multiscale model was used to predict the elastic moduli of trabecular bone. • Samples included demineralized, deproteinized and untreated bone. • The model portrays bone as a porous, interpenetrating two phase composite. • The experimental elastic moduli for trabecular bone fell between theoretical bounds.

  10. Augmented mandibular bone structurally adapts to functional loading

    NARCIS (Netherlands)

    Verhoeven, J. W.; Ruijter, J. M.; Koole, R.; de Putter, C.; Terlou, M.; Cune, M. S.

    2013-01-01

    Long-term changes in trabecular bone structure during the 10 years following onlay grafting with simultaneous mandibular implant placement were studied. Extraoral radiographs of both mandibular sides in eight patients were taken regularly. Bone structure was analysed using a custom-written image

  11. Biomechanical Stability of Juvidur and Bone Models on Osteosyntesic Materials

    Science.gov (United States)

    Grubor, Predrag; Mitković, Milorad; Grubor, Milan; Mitković, Milan; Meccariello, Luigi; Falzarano, Gabriele

    2016-01-01

    Introduction: Artificial models can be useful at approximate and qualitative research, which should give the preliminary results. Artificial models are usually made of photo-elastic plastic e.g.. juvidur, araldite in the three-dimensional contour shape of the bone. Anatomical preparations consist of the same heterogeneous, structural materials with extremely anisotropic and unequal highly elastic characteristics, which are embedded in a complex organic structure. The aim of the study: Examine the budget voltage and deformation of: dynamic compression plate (DCP), locking compression plate (LCP), Mitkovic internal fixator (MIF), Locked intramedullary nailing (LIN) on the compressive and bending forces on juvidur and veal bone models and compared the results of these two methods (juvidur, veal bone). Material and Methods: For the experimental study were used geometrically identical, anatomically shaped models of Juvidur and veal bones diameter of 30 mm and a length of 100 mm. Static tests were performed with SHIMADZU AGS-X testing machine, where the force of pressure (compression) increased from 0 N to 500 N, and then conducted relief. Bending forces grew from 0 N to 250 N, after which came into sharp relief. Results: On models of juvidur and veal bones studies have confirmed that uniform stability at the site of the fracture MIF with a coefficient ranking KMIF=0,1971, KLIN=0,2704, KDCP=0,2727 i KLCP=0,5821. Conclusion: On models of juvidur and veal bones working with Shimadzu AGS-X testing machine is best demonstrated MIF with a coefficient of 0.1971. PMID:27708489

  12. Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

    Science.gov (United States)

    Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

    2016-01-01

    The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

  13. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  14. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  15. Pinealectomy affects bone mineral density and structure - an experimental study in sheep

    Directory of Open Access Journals (Sweden)

    Egermann Marcus

    2011-11-01

    Full Text Available Abstract Background Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model. Methods Female sheep were arranged into four groups: Control, surgically ovariectomized (Ovx, surgically pinealectomized (Px and Ovx+Px. Before and 6 months after surgery, iliac crest biopsies were harvested and structural parameters were measured using μCT. Markers of bone formation and resorption were determined. To evaluate long term changes after pinealectomy, bone mineral density (BMD was analyzed at the distal radius at 0, 3, 9, 18 and 30 months. Results Cancellous bone volume (BV/TV declined after 6 months by -13.3% Px and -21.5% OvxPx. The bone loss was due to increased trabecular separation as well as decreased thickness. The histomorphometric quantification and determination of collagen degradation products showed increased bone resorption following pinealectomy. Ovariectomy alone results in a transient bone loss at the distal radius followed by continuous increase to baseline levels. The bone resorption activity after pinealectomy causes a bone loss which was not transient, since a continuous decrease in BMD was observed until 30 months. Conclusions The changes after pinealectomy in sheep are indicative of bone loss. Overall, these findings suggest that the pineal gland may influence bone metabolism and that pinealectomy can be used to induce bone loss in sheep.

  16. Constitutive Laws and Failure Models for Compact Bones Subjected to Dynamic Loading

    CERN Document Server

    Pithioux, M; Jean, M

    2002-01-01

    Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra-structure and macro-structure. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0 degrees, 45 degrees and 90 degrees to the longitudinal axis of the bone, and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.

  17. Muscle, tendons, and bone: structural changes during denervation and FES treatment.

    Science.gov (United States)

    Gargiulo, Paolo; Reynisson, Páll Jens; Helgason, Benedikt; Kern, Helmut; Mayr, Winfried; Ingvarsson, Páll; Helgason, Thordur; Carraro, Ugo

    2011-09-01

    This paper describes a novel approach to determine structural changes in bone, muscle, and tendons using medical imaging, finite element models, and processing techniques to evaluate and quantify: (1) progression of atrophy in permanently lower motor neuron (LMN) denervated human muscles, and tendons; (2) their recovery as induced by functional electrical stimulation (FES); and (3) changes in bone mineral density and bone strength as effect of FES treatment. Briefly, we used three-dimensional reconstruction of muscle belly, tendons, and bone images to study the structural changes occurring in these tissues in paralysed subjects after complete lumbar-ischiadic spinal cord injury (SCI). These subjects were recruited through the European project RISE, an endeavour designed to establish a novel clinical rehabilitation method for patients who have permanent and non-recoverable muscle LMN denervation in the lower extremities. This paper describes the use of segmentation techniques to study muscles, tendons, and bone in several states: healthy, LMN denervated-degenerated but not stimulated, and LMN denervated-stimulated. Here, we have used medical images to develop three-dimensional models and advanced imaging, including computational tools to display tissue density. Different tissues are visualized associating proper Hounsfield intervals defined experimentally to fat, connective tissue, and muscle. Finite element techniques are used to calculate Young's modulus on the patella bone and to analyse correlation between muscle contraction and bone strength changes. These analyses show restoration of muscular structures, tendons, and bone after FES as well as decline of the same tissues when treatment is not performed. This study suggests also a correlation between muscle growth due to FES treatment and increase in density and strength in patella bone. Segmentation techniques and finite element analysis allow the study of the structural changes of human skeletal muscle

  18. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  19. Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

    Science.gov (United States)

    Hambli, Ridha

    2014-01-01

    Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

  20. Imaging technologies for preclinical models of bone and joint disorders.

    Science.gov (United States)

    Tremoleda, Jordi L; Khalil, Magdy; Gompels, Luke L; Wylezinska-Arridge, Marzena; Vincent, Tonia; Gsell, Willy

    2011-07-29

    Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy.

  1. Mathematical Model for the Mineralization of Bone

    Science.gov (United States)

    Martin, Bruce

    1994-01-01

    A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification 'halos,' in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. ne model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

  2. A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone.

    Science.gov (United States)

    Lin, Yanping; Chen, Huajiang; Yu, Dedong; Zhang, Ying; Yuan, Wen

    2017-01-01

    Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. The presented bone drilling force model can be used for haptic rendering in surgical simulators.

  3. In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation.

    Science.gov (United States)

    Wittkowske, Claudia; Reilly, Gwendolen C; Lacroix, Damien; Perrault, Cecile M

    2016-01-01

    This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  4. In vitro bone cell models: Impact of fluid shear stress on bone formation

    Directory of Open Access Journals (Sweden)

    Claudia Wittkowske

    2016-11-01

    Full Text Available This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodelling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g. due to extended periods of bed rest or microgravity in space are associated with altered bone remodelling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signalling factors such as nitric oxide and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signalling, collagen deposition and matrix mineralization. Particular attention is given to in vitro set-ups which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibres which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  5. 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

    Science.gov (United States)

    Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

    2014-09-10

    The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

  6. Composites structures for bone tissue reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Neto, W.; Santos, João [Universidade Federal de São Carlos, Departament of Materials Engineering - Rd. Washington Luis, Km 235, 13565-905, São Carlos-SP (Brazil); Avérous, L.; Schlatter, G.; Bretas, Rosario, E-mail: bretas@ufscar.br [Université de Strasbourg, ECPM-LIPHT - 25 rue Becquerel, 67087, Strasbourg (France)

    2015-05-22

    The search for new biomaterials in the bone reconstitution field is growing continuously as humane life expectation and bone fractures increase. For this purpose, composite materials with biodegradable polymers and hydroxyapatite (HA) have been used. A composite material formed by a film, nanofibers and HA has been made. Both, the films and the non-woven mats of nanofibers were formed by nanocomposites made of butylene adipate-co-terephthalate (PBAT) and HA. The techniques used to produce the films and nanofibers were spin coating and electrospinning, respectively. The composite production and morphology were evaluated. The composite showed an adequate morphology and fibers size to be used as scaffold for cell growth.

  7. Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone

    Directory of Open Access Journals (Sweden)

    Kathryn Thrailkill

    2014-01-01

    Full Text Available Type 1 diabetes mellitus (T1D is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre ablation of the insulin receptor (IR, designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.

  8. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    Science.gov (United States)

    2008-08-01

    Injuries: Developing an animal model for standarizing the bone reparative potential of emerging progenitor cell therapies PRINCIPAL...osteogenesis in the surrounding host bone. Helos is a collagen fiber, hydroxyapatite composite that has sufficient structure to make inoculation with donor...adjacent to tubular green structures (muscular vessels). Although myofibroblastic like green cells are also present, they do not appear to

  9. A structural approach in the study of bones: fossil and burnt bones at nanosize scale

    Science.gov (United States)

    Piga, Giampaolo; Baró, Maria Dolors; Escobal, Irati Golvano; Gonçalves, David; Makhoul, Calil; Amarante, Ana; Malgosa, Assumpció; Enzo, Stefano; Garroni, Sebastiano

    2016-12-01

    We review the different factors affecting significantly mineral structure and composition of bones. Particularly, it is assessed that micro-nanostructural and chemical properties of skeleton bones change drastically during burning; the micro- and nanostructural changes attending those phases manifest themselves, amongst others, in observable alterations to the bones colour, morphology, microstructure, mechanical strength and crystallinity. Intense changes involving the structure and chemical composition of bones also occur during the fossilization process. Bioapatite material is contaminated by an heavy fluorination process which, on a long-time scale reduces sensibly the volume of the original unit cell, mainly the a-axis of the hexagonal P63/m space group. Moreover, the bioapatite suffers to a varying degree of extent by phase contamination from the nearby environment, to the point that rarely a fluorapatite single phase may be found in fossil bones here examined. TEM images supply precise and localized information, on apatite crystal shape and dimension, and on different processes that occur during thermal processes or fossilization of ancient bone, complementary to that given by X-ray diffraction and Attenuated Total Reflection Infrared spectroscopy. We are presenting a synthesis of XRD, ATR-IR and TEM results on the nanostructure of various modern, burned and palaeontological bones.

  10. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  11. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    Science.gov (United States)

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  12. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice☆

    Science.gov (United States)

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra

    2012-01-01

    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. PMID:22449447

  13. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Warmington, Kelly S; Morony, Sean; Gong, Jianhua; Cao, Jin; Gao, Yongming; Shalhoub, Victoria; Tipton, Barbara; Haldankar, Raj; Chen, Qing; Winters, Aaron; Boone, Tom; Geng, Zhaopo; Niu, Qing-Tian; Ke, Hua Zhu; Kostenuik, Paul J; Simonet, W Scott; Lacey, David L; Paszty, Chris

    2009-04-01

    The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

  14. A nonlocal constitutive model for trabecular bone softening in compression.

    Science.gov (United States)

    Charlebois, Mathieu; Jirásek, Milan; Zysset, Philippe K

    2010-10-01

    Using the three-dimensional morphological data provided by computed tomography, finite element (FE) models can be generated and used to compute the stiffness and strength of whole bones. Three-dimensional constitutive laws capturing the main features of bone mechanical behavior can be developed and implemented into FE software to enable simulations on complex bone structures. For this purpose, a constitutive law is proposed, which captures the compressive behavior of trabecular bone as a porous material with accumulation of irreversible strain and loss of stiffness beyond its yield point and softening beyond its ultimate point. To account for these features, a constitutive law based on damage coupled with hardening anisotropic elastoplasticity is formulated using density and fabric-based tensors. To prevent mesh dependence of the solution, a nonlocal averaging technique is adopted. The law has been implemented into a FE software and some simple simulations are first presented to illustrate its behavior. Finally, examples dealing with compression of vertebral bodies clearly show the impact of softening on the localization of the inelastic process.

  15. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    Science.gov (United States)

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  16. Material model of pelvic bone based on modal analysis: a study on the composite bone.

    Science.gov (United States)

    Henyš, Petr; Čapek, Lukáš

    2017-02-01

    Digital models based on finite element (FE) analysis are widely used in orthopaedics to predict the stress or strain in the bone due to bone-implant interaction. The usability of the model depends strongly on the bone material description. The material model that is most commonly used is based on a constant Young's modulus or on the apparent density of bone obtained from computer tomography (CT) data. The Young's modulus of bone is described in many experimental works with large variations in the results. The concept of measuring and validating the material model of the pelvic bone based on modal analysis is introduced in this pilot study. The modal frequencies, damping, and shapes of the composite bone were measured precisely by an impact hammer at 239 points. An FE model was built using the data pertaining to the geometry and apparent density obtained from the CT of the composite bone. The isotropic homogeneous Young's modulus and Poisson's ratio of the cortical and trabecular bone were estimated from the optimisation procedure including Gaussian statistical properties. The performance of the updated model was investigated through the sensitivity analysis of the natural frequencies with respect to the material parameters. The maximal error between the numerical and experimental natural frequencies of the bone reached 1.74 % in the first modal shape. Finally, the optimised parameters were matched with the data sheets of the composite bone. The maximal difference between the calibrated material properties and that obtained from the data sheet was 34 %. The optimisation scheme of the FE model based on the modal analysis data provides extremely useful calibration of the FE models with the uncertainty bounds and without the influence of the boundary conditions.

  17. The Structure and Function of Non-Collagenous Bone Proteins

    Science.gov (United States)

    Hook, Magnus; McQuillan, David J.

    1997-01-01

    The research done under the cooperative research agreement for the project titled 'The structure and function of non-collagenous bone proteins' represented the first phase of an ongoing program to define the structural and functional relationships of the principal noncollagenous proteins in bone. An ultimate goal of this research is to enable design and execution of useful pharmacological compounds that will have a beneficial effect in treatment of osteoporosis, both land-based and induced by long-duration space travel. The goals of the now complete first phase were as follows: 1. Establish and/or develop powerful recombinant protein expression systems; 2. Develop and refine isolation and purification of recombinant proteins; 3. Express wild-type non-collagenous bone proteins; 4. Express site-specific mutant proteins and domains of wild-type proteins to enhance likelihood of crystal formation for subsequent solution of structure.

  18. Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats.

    Science.gov (United States)

    Kido, Hueliton Wilian; Bossini, Paulo Sérgio; Tim, Carla Roberta; Parizotto, Nivaldo Antônio; da Cunha, Anderson Ferreira; Malavazi, Iran; Renno, Ana Claudia Muniz

    2014-10-01

    The aim of this study was to evaluate the influence of postmenopausal bone loss (induced by ovariectomy) in the process of bone healing in a tibial bone defect model in rats by means of histological evaluation of bone defects and the analysis of the expression of genes and proteins involved in bone consolidation. Twenty female Wistar rats (12 weeks old, weighing ±250 g) were randomly divided into two groups: control group (CG) and ovariectomized group (OG). Rats of OG were submitted to ovariectomy and after 8 weeks post-surgery, all animals were submitted to the tibial bone defect model. The main histological finding analysis revealed that ovariectomized animals showed a higher amount of granulation tissue and immature newly formed bone compared to CG. Furthermore, quantitative histological analysis showed that OG presented a significant decrease in the amount of newly formed bone (p = 0.0351). RT-PCR analysis showed no difference in Runx2, ALP, RANK, RANKL and Osterix gene expression 14-day post-surgery. Interestingly, immunohistochemical evaluation showed that Runx2 was down expressed (p = 0.0001) and RANKL was up expressed (p = 0.0022) in the OG. In conclusion, these data highlight that bone loss induced by ovariectomy causes an impairment in the capacity of bone to heal mainly probably because of alterations in the imbalance of osteoblasts and osteoclasts activities.

  19. Strength through structure: visualization and local assessment of the trabecular bone structure

    Energy Technology Data Exchange (ETDEWEB)

    Raeth, C; Monetti, R; Bauer, J; Sidorenko, I [Max-Planck Institut fuer Extraterrestrische Physik, Giessenbachstrasse 1, 85748 Garching (Germany); Mueller, D [Department of Radiology, Technische Universitaet Muenchen, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich (Germany); Matsuura, M [Institute of Anatomy, Ludwig Maximilians Universitaet Muenchen, Pettenkoferstrasse 11, 80336 Muenchen (Germany); Lochmueller, E-M [Department of Gynaecology I, Ludwig Maximilians Universitaet Muenchen, Maistrasse 11, 80337 Muenchen (Germany); Zysset, P [Institute for Lightweight Design and Structural Biomechanics, Vienna University of Technology (TU-Wien), Gusshausstrasse 27-29, 1040 Wien (Austria); Eckstein, F [Paracelsus Medical University Salzburg, Strubergasse 21, 5020 Salzburg (Austria)], E-mail: cwr@mpe.mpg.de

    2008-12-15

    The visualization and subsequent assessment of the inner human bone structures play an important role for better understanding the disease- or drug-induced changes of bone in the context of osteoporosis giving prospect for better predictions of bone strength and thus of the fracture risk of osteoporotic patients. In this work, we show how the complex trabecular bone structure can be visualized using {mu}CT imaging techniques at an isotropic resolution of 26 {mu}m. We quantify these structures by calculating global and local topological and morphological measures, namely Minkowski functionals (MFs) and utilizing the (an-)isotropic scaling index method (SIM) and by deriving suitable texture measures based on MF and SIM. Using a sample of 151 specimens taken from human vertebrae in vitro, we correlate the texture measures with the mechanically measured maximum compressive strength (MCS), which quantifies the strength of the bone probe, by using Pearson's correlation coefficient. The structure parameters derived from the local measures yield good correlations with the bone strength as measured in mechanical tests. We investigate whether the performance of the texture measures depends on the MCS value by selecting different subsamples according to MCS. Considering the whole sample the results for the newly defined parameters are better than those obtained for the standard global histomorphometric parameters except for bone volume/total volume (BV/TV). If a subsample consisting only of weak bones is analysed, the local structural analysis leads to similar and even better correlations with MCS as compared to BV/TV. Thus, the MF and SIM yield additional information about the stability of the bone especially in the case of weak bones, which corroborates the hypothesis that the bone structure (and not only its mineral mass) constitutes an important component of bone stability.

  20. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Directory of Open Access Journals (Sweden)

    Bruno Vidal

    Full Text Available We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.Twenty eight Wistar adjuvant-induced arthritis (AIA rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046. Histomorphometry showed a lower trabecular thickness (p = 0.0002 and bone volume (p = 0.0003 and higher trabecular sepa-ration (p = 0.0009 in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively in the arthritic group.We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  1. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Science.gov (United States)

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  2. The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

    Science.gov (United States)

    Pennline, James; Mulugeta, Lealem

    2013-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of

  3. DNA and bone structure preservation in medieval human skeletons.

    Science.gov (United States)

    Coulson-Thomas, Yvette M; Norton, Andrew L; Coulson-Thomas, Vivien J; Florencio-Silva, Rinaldo; Ali, Nadir; Elmrghni, Samir; Gil, Cristiane D; Sasso, Gisela R S; Dixon, Ronald A; Nader, Helena B

    2015-06-01

    Morphological and ultrastructural data from archaeological human bones are scarce, particularly data that have been correlated with information on the preservation of molecules such as DNA. Here we examine the bone structure of macroscopically well-preserved medieval human skeletons by transmission electron microscopy and immunohistochemistry, and the quantity and quality of DNA extracted from these skeletons. DNA technology has been increasingly used for analyzing physical evidence in archaeological forensics; however, the isolation of ancient DNA is difficult since it is highly degraded, extraction yields are low and the co-extraction of PCR inhibitors is a problem. We adapted and optimised a method that is frequently used for isolating DNA from modern samples, Chelex(®) 100 (Bio-Rad) extraction, for isolating DNA from archaeological human bones and teeth. The isolated DNA was analysed by real-time PCR using primers targeting the sex determining region on the Y chromosome (SRY) and STR typing using the AmpFlSTR(®) Identifiler PCR Amplification kit. Our results clearly show the preservation of bone matrix in medieval bones and the presence of intact osteocytes with well preserved encapsulated nuclei. In addition, we show how effective Chelex(®) 100 is for isolating ancient DNA from archaeological bones and teeth. This optimised method is suitable for STR typing using kits aimed specifically at degraded and difficult DNA templates since amplicons of up to 250bp were successfully amplified.

  4. Elastic moduli of untreated, demineralized and deproteinized cortical bone: validation of a theoretical model of bone as an interpenetrating composite material.

    Science.gov (United States)

    Hamed, E; Novitskaya, E; Li, J; Chen, P-Y; Jasiuk, I; McKittrick, J

    2012-03-01

    A theoretical experimentally based multi-scale model of the elastic response of cortical bone is presented. It portrays the hierarchical structure of bone as a composite with interpenetrating biopolymers (collagen and non-collagenous proteins) and minerals (hydroxyapatite), together with void spaces (porosity). The model involves a bottom-up approach and employs micromechanics and classical lamination theories of composite materials. Experiments on cortical bone samples from bovine femur include completely demineralized and deproteinized bones as well as untreated bone samples. Porosity and microstructure are characterized using optical and scanning electron microscopy, and micro-computed tomography. Compression testing is used to measure longitudinal and transverse elastic moduli of all three bone types. The characterization of structure and properties of these three bone states provides a deeper understanding of the contributions of the individual components of bone to its elastic response and allows fine tuning of modeling assumptions. Very good agreement is found between theoretical modeling and compression testing results, confirming the validity of the interpretation of bone as an interpenetrating composite material.

  5. Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

    Science.gov (United States)

    We conducted a study to examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. This was a 36-week study of sedentary, hyperphag...

  6. A MULTI-SITE SHEEP MODEL FOR CANCELLOUS BONE HEALING

    Directory of Open Access Journals (Sweden)

    Angad eMalhotra

    2014-09-01

    Full Text Available Appropriate, well characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14mm of fixed depth (25mm were compared in both skeletally immature (18 month old and aged sheep (5 year old. In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at four weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using µCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects, with woven bone normally forming near the periphery of the defect. Bone volume fraction (BV/TV significantly decreased with an increasing defect diameter. Actual bone volume (BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal, and encourages a reduction in animal numbers required for preclinical research.

  7. Repairing rabbit radial defects by combining bone marrow stroma stem cells with bone scaffold material comprising a core-cladding structure.

    Science.gov (United States)

    Wu, H; Liu, G H; Wu, Q; Yu, B

    2015-10-05

    We prepared a bone scaffold material comprising a PLGA/β-TCP core and a Type I collagen cladding, and recombined it with bone marrow stroma stem cells (BMSCs) to evaluate its potential for use in bone tissue engineering by in vivo and in vitro experiments. PLGA/β-TCP without a cladding was used for comparison. The adherence rate of the BMSCs to the scaffold was determined by cell counting. Cell proliferation rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The osteogenic capability was evaluated by alkaline phosphatase activity. The scaffold materials were recombined with the BMSCs and implanted into a large segmental rabbit radial defect model to evaluate defect repair. Osteogenesis was assessed in the scaffold materials by histological and double immunofluorescence labeling, etc. The adherence number, proliferation number, and alkaline phosphatase expression of the cells on the bone scaffold material with core-cladding structure were significantly higher than the corresponding values in the PLGA/β-TCP composite scaffold material (P cladding structure completely degraded at the bone defect site and bone formation was completed. The rabbit large sentimental radial defect was successfully repaired. The degradation and osteogenesis rates matched well. The bone scaffold with core-cladding structure exhibited better osteogenic activity and capacity to repair a large segmental bone defect compared to the PLGA/β-TCP composite scaffold. The bone scaffold with core-cladding structure has excellent physical properties and biocompatibility. It is an ideal scaffold material for bone tissue engineering.

  8. Automatic analysis of trabecular bone structure from knee MRI

    DEFF Research Database (Denmark)

    Marques, Joselene; Granlund, Rabia; Lillholm, Martin

    2012-01-01

    We investigated the feasibility of quantifying osteoarthritis (OA) by analysis of the trabecular bone structure in low-field knee MRI. Generic texture features were extracted from the images and subsequently selected by sequential floating forward selection (SFFS), following a fully automatic, un...

  9. Radiographic features of mandibular trabecular bone structure in hypodontia

    NARCIS (Netherlands)

    Créton, M.; Geraets, W.; Verhoeven, J.W.; van der Stelt, P.F.; Verhey, H.; Cune, M.

    2012-01-01

    Purpose: Radiographic parameters of mandibular trabecular bone structure between 67 subjects having hypodontia and those without were studied on digital panoramic radiographs. Materials and Methods: Three regions of interest (ROI) were defined: the ascending ramus, apical of the mandibular molar and

  10. Augmented mandibular bone structurally adapts to functional loading.

    Science.gov (United States)

    Verhoeven, J W; Ruijter, J M; Koole, R; de Putter, C; Terlou, M; Cune, M S

    2013-12-01

    Long-term changes in trabecular bone structure during the 10 years following onlay grafting with simultaneous mandibular implant placement were studied. Extraoral radiographs of both mandibular sides in eight patients were taken regularly. Bone structure was analysed using a custom-written image analysis program. Parameters studied were trabecular area and perimeter and marrow cavity area and perimeter. After skeletonisation of the trabecular network, the number of end points and branching points, skeleton length, and branch angle were determined. The observed structural changes agree with the development of a more complex and more delicate or fine osseous structure. The bone shows more trabecular branching. All changes are most pronounced in the graft spongiosa, but are also found in the graft cortex and in the original mandible. The mean trabecular branch angle becomes more horizontal. The applied technique can be used to analyse long-term changes in the architecture of bone grafts. Changes found in the graft architecture correspond to changes expected after functional adaptation to loading. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Radiographic features of mandibular trabecular bone structure in hypodontia

    NARCIS (Netherlands)

    M. Créton; W. Geraets; J.W. Verhoeven; P.F. van der Stelt; H. Verhey; M. Cune

    2012-01-01

    Purpose: Radiographic parameters of mandibular trabecular bone structure between 67 subjects having hypodontia and those without were studied on digital panoramic radiographs. Materials and Methods: Three regions of interest (ROI) were defined: the ascending ramus, apical of the mandibular molar and

  12. Radiographic Features of Mandibular Trabecular Bone Structure in Hypodontia

    NARCIS (Netherlands)

    Creton, Marijn; Geraets, Wil; Verhoeven, Jan Willem; van der Stelt, Paul F.; Verhey, Hans; Cune, Marco

    2012-01-01

    Purpose: Radiographic parameters of mandibular trabecular bone structure between 67 subjects having hypodontia and those without were studied on digital panoramic radiographs. Materials and Methods: Three regions of interest (ROI) were defined: the ascending ramus, apical of the mandibular molar and

  13. Bone malformations in Proteus syndrome: an analysis of bone structural changes and their evolution during growth

    Energy Technology Data Exchange (ETDEWEB)

    Pazzaglia, Ugo E.; Bonaspetti, Giovanni; Ranchetti, Federico [University of Brescia Spedali Civili di Brescia, Orthopaedic Clinic, Brescia (Italy); Beluffi, Giampiero [Fondazione I.R.C.C.S. Policlinico San Matteo, Pediatric Radiology Department, Pavia (Italy)

    2007-08-15

    The radiographic follow-up of a patient with Proteus syndrome is presented. Review of radiographs obtained at 3 years 10 months, 10 years, and 17 years 8 months indicated that the rate of growth in length of the oversized tubular bones of the hands was similar to that of the normal bones of the same hand. This observation supports the view that the primary lesion occurs in the early embryonic period, when the limb bud mesenchyme cells condense and cartilage differentiates producing oversized cartilage anlages, rather than being a defect of bone cell-mediated apposition and modelling processes of bone. Additional radiographs of the pelvis and spine were obtained at age 4 years 10 months and head CT at 8 years 10 months. This pathogenetic mechanism fits well with the hypothesis of somatic mosaicism, which is at present the most credible explanation for the aetiology of Proteus syndrome. Other skeletal malformations recognized as typical of the syndrome can be interpreted as secondary adaptations to the altered mechanical conditions induced by overgrowth of bones. (orig.)

  14. Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

    Science.gov (United States)

    Rendina, Elizabeth; Hembree, Kelsey D; Davis, McKale R; Marlow, Denver; Clarke, Stephen L; Halloran, Bernard P; Lucas, Edralin A; Smith, Brenda J

    2013-01-01

    Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

  15. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  16. Structure and Phase State of Bone Apatite of Calcified Aortic Fragments with Osteoporosis

    Directory of Open Access Journals (Sweden)

    Ya.V. Khyzhnya

    2013-10-01

    Full Text Available The paper represents the results of the study on the structure and phase composition of bone apatite and fragments of calcified aorta of the same experimental animal with model osteoporosis. Examination by the X-ray and electron diffraction, electron microscopy and infrared spectroscopy reveals that pathological calcification of rabbit aorta with model osteoporosis in crystal-chemical terms is the imperfect calcium apatite Ca10(PO46(OH2. Temperature growth of ectopic apatite crystals during annealing at 900C is similar to bioapatite of bone.

  17. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  18. The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Norazlina Mohamed

    2012-01-01

    Full Text Available Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja, a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV, decreased trabecular number (Tb.N, and increased trabecular separation (Tb.Sp. Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N and trabecular separation (Tb.Sp. Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

  19. The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats.

    Science.gov (United States)

    Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

    2012-01-01

    Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

  20. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model

    Directory of Open Access Journals (Sweden)

    Zil Hayatullina

    2012-01-01

    Full Text Available Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx, and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO. Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  1. Virgin coconut oil supplementation prevents bone loss in osteoporosis rat model.

    Science.gov (United States)

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  2. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  3. The Effect of Bone Loss Pattern on the Structural Capacity of the Proximal Femur

    Institute of Scientific and Technical Information of China (English)

    FAN Li-xia; Eric Wang

    2006-01-01

    The effect of age-related bone loss on the structural capacity of the proximal femur were investigated by Finite Element Analysis(FEA). Four bone loss patterns were considered. These were "uniform cortical bone loss", "neck cortical bone loss", "intertrochanteric cortical bone loss" and "uniform trabecular bone loss". The results show that the two "non-uniform cortical bone loss" patterns are more dangerous than the "uniform cortical bone loss" pattern, and that the cortical bone loss in intertrochanteric region is associated with a greater reduction in cortical failure load than the cortical bone loss in the femoral neck. The trabecular bone loss causes a limited decrease in both cortical failure and trabecular failure loads. This research should be helpful to the clinical assessment of femur fracture risk due to age-related bone loss.

  4. A Femur-Implant Model for the Prediction of Bone Remodeling Behavior Induced by Cementless Stem

    Institute of Scientific and Technical Information of China (English)

    He Gong; Lingyan Kong; Rui Zhang; Juan Fang; Meisheng Zhao

    2013-01-01

    Bone remodeling simulation is an effective tool for the prediction of long-term effect of implant on the bone tissue,as well as the selection of an appropriate implant in terms of architecture and material.In this paper,a finite element model of proximal femur was develop.ed to simulate the structures of internal trabecular and cortical bones by incorporating quantitative bone functional adaptation theory with finite element analysis.Cementless stems made of titanium,two types of Functionally Graded Material (FGM) and flexible 'iso-elastic' material as comparison were implanted in the structure of proximal femur respectively to simulate the bone remodeling behaviors of host bone.The distributions of bone density,von Mises stress,and interface shear stress were obtained.All the prosthetic stems had effects on the bone remodeling behaviors of proximal femur,but the degrees of stress shielding were different.The amount of bone loss caused by titanium implant was in agreement with the clinical observation.The FGM stems caused less bone loss than that of the titanium stem,in which FGM I stem (titanium richer at the top to more HAP/Col towards the bottom) could relieve stress shielding effectively,and the interface shear stresses were more evenly distributed in the model with FGM I stem in comparison with those in the models with FGM II (titanium and bioglass) and titanium stems.The numerical simulations in the present study provided theoretical basis for FGM as an appropriate material of femoral implant from a biomechanical point of view.The next steps are to fabricate FGM stem and to conduct animal experiments to investigate the effects of FGM stem on the remodeling behaviors using animal model.

  5. Structural bone allografts with intramedullary vascularized fibular autografts for the treatment of massive bone defects in extremities

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To report the clinical outcome of repairing massive bone defects biologically in limbs by homeochronous using structural bone allografts with intramedullary vascularized fibular auto-grafts. Methods: From January 2001 to December 2005. large bone defects in 19 patients (11 men and 8 women, aged 6 to 35 years) were repaired by structural bone allografts with intramedullary vascularized fibular autografts in the homeochronous period. The range of the length of bone defects was 11 to 25 cm (mean 17. 6 cm), length of vascularized free fibular was 15 to 29 cm (mean 19. 2 cm), length of massive bone allografts was 11 to 24 cm (mean 17. 1 cm). Location of massive bone defects was in humerus(n = 1), in femur(n = 9) and in tibia(n = 9), respectively. Results: After 9 to 69 months (mean 38. 2 months) follow-up, wounds of donor and recipient sites were healed in Ⅰ stage, monitoring-flaps were alive, eject reaction of massive bone allografts were slight, no complications in donor limbs. Fifteen patients had the evidence of radiographic union 3 to 6 months after surgery, 3 cases united 8 months later, and the remained one case of malignant synovioma in distal femur recurred and amputated the leg 2. 5 months, post-operatively. Five patients had been removed internal fixation, complete bone unions were found one year postoperatively. None of massive bone allografts were absorbed or collapsed at last follow-up. Conclusion: The homeochronous usage of structural bone allograft with an intramedullary vascularized fibular au-tograft can biologically obtain a structure with the immediate mechanical strength of the allograft, a potential result of revascularization through the vascularized fibula, and accelerate bone union not only between fibular autograft and the host but also between massive bone allograft and the host.

  6. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Bryan D. Johnston

    2015-01-01

    Full Text Available In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed.

  7. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Science.gov (United States)

    Johnston, Bryan D.; Ward, Wendy E.

    2015-01-01

    In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed. PMID:26060817

  8. Bone morphogenetic proteins: from structure to clinical use

    Directory of Open Access Journals (Sweden)

    Granjeiro J.M.

    2005-01-01

    Full Text Available Bone morphogenetic proteins (BMPs are multi-functional growth factors belonging to the transforming growth factor ß superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases.

  9. Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

    Science.gov (United States)

    Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

    2016-02-17

    Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Animal models for implant biomaterial research in bone: A review

    Directory of Open Access Journals (Sweden)

    A I Pearce

    2007-03-01

    Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.

  11. Structural study of octacalcium phosphate bone cement conversion in vitro.

    Science.gov (United States)

    Fosca, Marco; Komlev, Vladimir S; Fedotov, Alexander Yu; Caminiti, Ruggero; Rau, Julietta V

    2012-11-01

    The nature of precursor phase during the biomineralization process of bone tissue formation is still controversial. Several phases were hypothesized, among them octacalcium phosphate. In this study, an in situ monitoring of structural changes, taking place upon the octacalcium phosphate bone cement hardening, was carried out in the presence of biopolymer chitosan and simulated body fluid (SBF). Several systems with different combinations of components were studied. The energy dispersive X-ray diffraction was applied to study the structural changes in real time, while morphological properties of the systems were investigated by the scanning electron microscopy. The obtained results evidence that final hydroxyapatite phase is formed only in the presence of chitosan and/or SBF, providing new insights into the in vivo biomineralization mechanism and, consequently, favoring the development of new approaches in biomaterials technology.

  12. Tooth and bone deformation: structure and material properties by ESPI

    Science.gov (United States)

    Zaslansky, Paul; Shahar, Ron; Barak, Meir M.; Friesem, Asher A.; Weiner, Steve

    2006-08-01

    In order to understand complex-hierarchical biomaterials such as bones and teeth, it is necessary to relate their structure and mechanical-properties. We have adapted electronic speckle pattern-correlation interferometry (ESPI) to make measurements of deformation of small water-immersed specimens of teeth and bones. By combining full-field ESPI with precision mechanical loading we mapped sub-micron displacements and determined material-properties of the samples. By gradually and elastically compressing the samples, we compensate for poor S/N-ratios and displacement differences of about 100nm were reliably determined along samples just 2~3mm long. We produced stress-strain curves well within the elastic performance range of these materials under biologically relevant conditions. For human tooth-dentin, Young's modulus in inter-dental areas of the root is 40% higher than on the outer sides. For cubic equine bone samples the compression modulus of axial orientations is about double the modulus of radial and tangential orientations (20 GPa versus 10 GPa respectively). Furthermore, we measured and reproduced a surprisingly low Poisson's ratio, which averaged about 0.1. Thus the non-contact and non-destructive measurements by ESPI produce high sensitivity analyses of mechanical properties of mineralized tissues. This paves the way for mapping deformation-differences of various regions of bones, teeth and other biomaterials.

  13. The effect of naturally occurring chronic kidney disease on the micro-structural and mechanical properties of bone.

    Directory of Open Access Journals (Sweden)

    Anna Shipov

    Full Text Available Chronic kidney disease (CKD is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD. Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD.

  14. Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects.

    Science.gov (United States)

    Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V

    2015-09-01

    The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as

  15. Non-rigid image registration using bone growth model

    DEFF Research Database (Denmark)

    Bro-Nielsen, Morten; Gramkow, Claus; Kreiborg, Sven

    1997-01-01

    Non-rigid registration has traditionally used physical models like elasticity and fluids. These models are very seldom valid models of the difference between the registered images. This paper presents a non-rigid registration algorithm, which uses a model of bone growth as a model of the change b...

  16. A multiscale modelling of bone ultrastructure elastic proprieties using finite elements simulation and neural network method.

    Science.gov (United States)

    Barkaoui, Abdelwahed; Tlili, Brahim; Vercher-Martínez, Ana; Hambli, Ridha

    2016-10-01

    Bone is a living material with a complex hierarchical structure which entails exceptional mechanical properties, including high fracture toughness, specific stiffness and strength. Bone tissue is essentially composed by two phases distributed in approximately 30-70%: an organic phase (mainly type I collagen and cells) and an inorganic phase (hydroxyapatite-HA-and water). The nanostructure of bone can be represented throughout three scale levels where different repetitive structural units or building blocks are found: at the first level, collagen molecules are arranged in a pentameric structure where mineral crystals grow in specific sites. This primary bone structure constitutes the mineralized collagen microfibril. A structural organization of inter-digitating microfibrils forms the mineralized collagen fibril which represents the second scale level. The third scale level corresponds to the mineralized collagen fibre which is composed by the binding of fibrils. The hierarchical nature of the bone tissue is largely responsible of their significant mechanical properties; consequently, this is a current outstanding research topic. Scarce works in literature correlates the elastic properties in the three scale levels at the bone nanoscale. The main goal of this work is to estimate the elastic properties of the bone tissue in a multiscale approach including a sensitivity analysis of the elastic behaviour at each length scale. This proposal is achieved by means of a novel hybrid multiscale modelling that involves neural network (NN) computations and finite elements method (FEM) analysis. The elastic properties are estimated using a neural network simulation that previously has been trained with the database results of the finite element models. In the results of this work, parametric analysis and averaged elastic constants for each length scale are provided. Likewise, the influence of the elastic constants of the tissue constituents is also depicted. Results highlight

  17. Regularized Structural Equation Modeling.

    Science.gov (United States)

    Jacobucci, Ross; Grimm, Kevin J; McArdle, John J

    A new method is proposed that extends the use of regularization in both lasso and ridge regression to structural equation models. The method is termed regularized structural equation modeling (RegSEM). RegSEM penalizes specific parameters in structural equation models, with the goal of creating easier to understand and simpler models. Although regularization has gained wide adoption in regression, very little has transferred to models with latent variables. By adding penalties to specific parameters in a structural equation model, researchers have a high level of flexibility in reducing model complexity, overcoming poor fitting models, and the creation of models that are more likely to generalize to new samples. The proposed method was evaluated through a simulation study, two illustrative examples involving a measurement model, and one empirical example involving the structural part of the model to demonstrate RegSEM's utility.

  18. Preparation and characterization of bionic bone structure chitosan/hydroxyapatite scaffold for bone tissue engineering.

    Science.gov (United States)

    Zhang, Jiazhen; Nie, Jingyi; Zhang, Qirong; Li, Youliang; Wang, Zhengke; Hu, Qiaoling

    2014-01-01

    Three-dimensional oriented chitosan (CS)/hydroxyapatite (HA) scaffolds were prepared via in situ precipitation method in this research. Scanning electron microscopy (SEM) images indicated that the scaffolds with acicular nano-HA had the spoke-like, multilayer and porous structure. The SEM of osteoblasts which were polygonal or spindle-shaped on the composite scaffolds after seven-day cell culture showed that the cells grew, adhered, and spread well. The results of X-ray powder diffractometer and Fourier transform infrared spectrometer showed that the mineral particles deposited in the scaffold had phase structure similar to natural bone and confirmed that particles were exactly HA. In vitro biocompatibility evaluation indicated the composite scaffolds showed a higher degree of proliferation of MC3T3-E1 cell compared with the pure CS scaffolds and the CS/HA10 scaffold was the highest one. The CS/HA scaffold also had a higher ratio of adhesion and alkaline phosphate activity value of osteoblasts compared with the pure CS scaffold, and the ratio increased with the increase of HA content. The ALP activity value of composite scaffolds was at least six times of the pure CS scaffolds. The results suggested that the composite scaffolds possessed good biocompatibility. The compressive strength of CS/HA15 increased by 33.07% compared with the pure CS scaffold. This novel porous scaffold with three-dimensional oriented structure might have a potential application in bone tissue engineering.

  19. IL-1RI participates in normal growth plate development and bone modeling.

    Science.gov (United States)

    Simsa-Maziel, Stav; Zaretsky, Janna; Reich, Adi; Koren, Yoav; Shahar, Ron; Monsonego-Ornan, Efrat

    2013-07-01

    The proinflammatory cytokine interleukin-1 (IL-1) signals through IL-1 receptor type I (IL-1RI) and induces osteoclastogenesis and bone resorption mainly during pathological conditions. Little is known about the effect of excess or absence of IL-1 signaling on the physiological development of the growth plate and bone. In this study, we examine growth plate morphology, bone structure, and mechanical properties as well as osteoclast number in IL-1RI knockout mice to evaluate the role of IL-1RI in the normal development of the growth plate and bone. We show for the first time that IL-1RI knockout mice have narrower growth plates due to a smaller hypertrophic zone, suggesting a role for this cytokine in hypertrophic differentiation, together with higher proteoglycan content. The bones of theses mice exhibit higher trabecular and cortical mass, increased mineral density, and superior mechanical properties. In addition, IL-1RI knockout mice have significantly reduced osteoclast numbers in the chondro-osseous junction, trabecular bone, and cortical bone. These results suggest that IL-1RI is involved in normal growth plate development and ECM homeostasis and that it is significant in the physiological process of bone modeling.

  20. Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Nobuhiro Kobayashi

    2016-10-01

    Full Text Available The effect of porous alpha-tricalcium phosphate (α-TCP with immobilized basic fibroblast growth factor (bFGF on bone regeneration was evaluated in a canine mandibular bone defect model. Identical bone defects were made in the canine mandible; six defects in each animal were filled with porous α-TCP with bFGF bound via heparin (bFGF group, whereas the other was filled with unmodified porous α-TCP (control group. Micro-computed tomography and histological evaluation were performed two, four and eight weeks after implantation. The bone mineral density of the bFGF group was higher than that of the control group at each time point (p < 0.05, and the bone mineral content of the bFGF group was higher than that of the control group at four and eight weeks (p < 0.05. Histological evaluation two weeks after implantation revealed that the porous α-TCP had degraded and bone had formed on the surface of α-TCP particles in the bFGF group. At eight weeks, continuous cortical bone with a Haversian structure covered the top of bone defects in the bFGF group. These findings demonstrate that porous α-TCP with immobilized bFGF can promote bone regeneration.

  1. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

    Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig

    2000-01-01

    relationship is based on the fact that trabecular bone is a porous material. To date, it has not been possible to determine or quantify the influence other factors may have in determining the strength of a loadbearing trabecular network. However, it is known that with age: 1) There is a loss of connectivity...... through osteoclastic perforations of horizontal struts. 2) There is an increase in anisotropy - again due to loss of horizontal struts, and perhaps also due to micro-modelling drift or to thickening of some vertical trabeculae. 3) The changes in the network can lead to the slenderness ratio between...... can never be isolated in vivo, other factors need to be investigated: The interplay between the cortical shell and the trabecular network; transmission of load; the interplay between soft tissues (cartilage, connective tissue, muscle) and bone; the shock absorbing capacity of the discs...

  2. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  3. Vibration acceleration promotes bone formation in rodent models

    Science.gov (United States)

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  4. A method to establish a mouse model of bone marrow microenvironment injury.

    Science.gov (United States)

    Cheng, Wenzhe; Ge, Quanhu; Wan, Longfei; Wang, Xiaoyi; Chen, Xueling; Wu, Xiangwei

    2017-06-13

    A normal bone marrow microenvironment plays a very important role in the normal functioning of hematopoietic stem cells. Once disturbed, this microenvironment can become favorable for the occurrence of blood disorders, cancers, and other diseases. Therefore, further studies on the bone marrow microenvironment should be performed to reveal regulatory and stem cell fate determination mechanisms and promote the development of bone marrow transplantation, tissue repair and regenerative medicine, and other fields. A small animal model for further research is also urgently needed. In this study, an electric shock device was designed to elicit a femur bone marrow microenvironment injury in mice. A wire was inserted into the distal femur but not into the proximal femur, and the bone marrow microenvironment was evidently damaged by application of 100 ± 10 V for 1.5 ± 0.5 min; mortality, however, was low in the mice. Gross observation, hematoxylin and eosin staining, immunohistochemistry, bright-field microscopy, and micro-CT scanning were also conducted. A large number of new blood capillaries and sinusoids appeared in the injured distal femur after 2 weeks. The capillaries in the injured femur disappeared after 4 weeks, and mature blood vessels were scattered throughout the injured area. Red blood cells disappeared, and the cellular structure and trabecular bone were better than those observed 2 weeks previously. Thus, we developed a simply operated, accurate, reliable, and easily controlled small animal model as a good technical platform to examine angiogenesis and segmentation damage in the bone marrow microenvironment.

  5. Dynamic term structure models

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Meldrum, Andrew

    This paper studies whether dynamic term structure models for US nominal bond yields should enforce the zero lower bound by a quadratic policy rate or a shadow rate specification. We address the question by estimating quadratic term structure models (QTSMs) and shadow rate models with at most four...

  6. A model of trabecular bone and an application to osteoporosis

    Science.gov (United States)

    Gunaratne, Gemunu H.; Mohanty, Kishore K.; Wimalawansa, Sunil J.

    2002-11-01

    Large bones consists of an outer compact shaft and an inner porous segment, known as the trabecular architecture (TA). The TA is the principal load carrier in bones from older adults, and the aim of therapeutic interventions is to preserve their strength. It is argued that forms for broad-based diagnostic tools for osteoporosis can be identified through an analysis of simple model systems. A model based on elastic networks is introduced, and shows that weak networks can only utilize a small fraction of themselves for stress transmission. This observation is used to argue that the ratio of linear response of a network to DC and AC strain can be used as a surrogate for bone strength. We discuss the possibility of using this measure to identify osteoporotic bone and to monitor the efficacy of therapy.

  7. Modeling of biological doses and mechanical effects on bone transduction

    CERN Document Server

    Rieger, Romain; Jennane, Rachid; 10.1016/j.jtbi.2011.01.003

    2012-01-01

    Shear stress, hormones like parathyroid and mineral elements like calcium mediate the amplitude of stimulus signal which affects the rate of bone remodeling. The current study investigates the theoretical effects of different metabolic doses in stimulus signal level on bone. The model was built considering the osteocyte as the sensing center mediated by coupled mechanical shear stress and some biological factors. The proposed enhanced model was developed based on previously published works dealing with different aspects of bone transduction. It describes the effects of physiological doses variations of Calcium, Parathyroid Hormone, Nitric Oxide and Prostaglandin E2 on the stimulus level sensed by osteocytes in response to applied shear stress generated by interstitial fluid flow. We retained the metabolic factors (Parathyroid Hormone, Nitric Oxide, and Prostaglandin E2) as parameters of bone cell mechanosensitivity because stimulation/inhibition of induced pathways stimulates osteogenic response in vivo. We t...

  8. Sensitivity Analysis of the Bone Fracture Risk Model

    Science.gov (United States)

    Lewandowski, Beth; Myers, Jerry; Sibonga, Jean Diane

    2017-01-01

    Introduction: The probability of bone fracture during and after spaceflight is quantified to aid in mission planning, to determine required astronaut fitness standards and training requirements and to inform countermeasure research and design. Probability is quantified with a probabilistic modeling approach where distributions of model parameter values, instead of single deterministic values, capture the parameter variability within the astronaut population and fracture predictions are probability distributions with a mean value and an associated uncertainty. Because of this uncertainty, the model in its current state cannot discern an effect of countermeasures on fracture probability, for example between use and non-use of bisphosphonates or between spaceflight exercise performed with the Advanced Resistive Exercise Device (ARED) or on devices prior to installation of ARED on the International Space Station. This is thought to be due to the inability to measure key contributors to bone strength, for example, geometry and volumetric distributions of bone mass, with areal bone mineral density (BMD) measurement techniques. To further the applicability of model, we performed a parameter sensitivity study aimed at identifying those parameter uncertainties that most effect the model forecasts in order to determine what areas of the model needed enhancements for reducing uncertainty. Methods: The bone fracture risk model (BFxRM), originally published in (Nelson et al) is a probabilistic model that can assess the risk of astronaut bone fracture. This is accomplished by utilizing biomechanical models to assess the applied loads; utilizing models of spaceflight BMD loss in at-risk skeletal locations; quantifying bone strength through a relationship between areal BMD and bone failure load; and relating fracture risk index (FRI), the ratio of applied load to bone strength, to fracture probability. There are many factors associated with these calculations including

  9. Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

    Science.gov (United States)

    Werner, Christopher R.; Mulugeta, Lealem; Myers, J. G.; Pennline, J. A.

    2015-01-01

    NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

  10. Empirical angle-dependent Biot and MBA models for acoustic anisotropy in cancellous bone.

    Science.gov (United States)

    Lee, Kang Il; Hughes, E R; Humphrey, V F; Leighton, T G; Choi, Min Joo

    2007-01-01

    The Biot and the modified Biot-Attenborough (MBA) models have been found useful to understand ultrasonic wave propagation in cancellous bone. However, neither of the models, as previously applied to cancellous bone, allows for the angular dependence of acoustic properties with direction. The present study aims to account for the acoustic anisotropy in cancellous bone, by introducing empirical angle-dependent input parameters, as defined for a highly oriented structure, into the Biot and the MBA models. The anisotropy of the angle-dependent Biot model is attributed to the variation in the elastic moduli of the skeletal frame with respect to the trabecular alignment. The angle-dependent MBA model employs a simple empirical way of using the parametric fit for the fast and the slow wave speeds. The angle-dependent models were used to predict both the fast and slow wave velocities as a function of propagation angle with respect to the trabecular alignment of cancellous bone. The predictions were compared with those of the Schoenberg model for anisotropy in cancellous bone and in vitro experimental measurements from the literature. The angle-dependent models successfully predicted the angular dependence of phase velocity of the fast wave with direction. The root-mean-square errors of the measured versus predicted fast wave velocities were 79.2 m s(-1) (angle-dependent Biot model) and 36.1 m s(-1) (angle-dependent MBA model). They also predicted the fact that the slow wave is nearly independent of propagation angle for angles about 50 degrees , but consistently underestimated the slow wave velocity with the root-mean-square errors of 187.2 m s(-1) (angle-dependent Biot model) and 240.8 m s(-1) (angle-dependent MBA model). The study indicates that the angle-dependent models reasonably replicate the acoustic anisotropy in cancellous bone.

  11. Bone Loss During Spaceflight: Available Models and Counter-Measures

    Science.gov (United States)

    Morris, Jonathan; Bach, David; Geller, David

    2015-01-01

    There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground

  12. Enhanced bone structural analysis through pQCT image preprocessing.

    Science.gov (United States)

    Cervinka, T; Hyttinen, J; Sievanen, H

    2010-05-01

    Several factors, including preprocessing of the image, can affect the reliability of pQCT-measured bone traits, such as cortical area and trabecular density. Using repeated scans of four different liquid phantoms and repeated in vivo scans of distal tibiae from 25 subjects, the performance of two novel preprocessing methods, based on the down-sampling of grayscale intensity histogram and the statistical approximation of image data, was compared to 3 x 3 and 5 x 5 median filtering. According to phantom measurements, the signal to noise ratio in the raw pQCT images (XCT 3000) was low ( approximately 20dB) which posed a challenge for preprocessing. Concerning the cortical analysis, the reliability coefficient (R) was 67% for the raw image and increased to 94-97% after preprocessing without apparent preference for any method. Concerning the trabecular density, the R-values were already high ( approximately 99%) in the raw images leaving virtually no room for improvement. However, some coarse structural patterns could be seen in the preprocessed images in contrast to a disperse distribution of density levels in the raw image. In conclusion, preprocessing cannot suppress the high noise level to the extent that the analysis of mean trabecular density is essentially improved, whereas preprocessing can enhance cortical bone analysis and also facilitate coarse structural analyses of the trabecular region.

  13. Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

    Science.gov (United States)

    Tromp, A M; Bravenboer, N; Tanck, E; Oostlander, A; Holzmann, P J; Kostense, P J; Roos, J C; Burger, E H; Huiskes, R; Lips, P

    2006-12-01

    Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone

  14. Collagen modifications in postmenopausal osteoporosis: advanced glycation endproducts may affect bone volume, structure and quality.

    Science.gov (United States)

    Willett, Thomas L; Pasquale, Julia; Grynpas, Marc D

    2014-09-01

    The classic model of postmenopausal osteoporosis (PM-OP) starts with the depletion of estrogen, which in turn stimulates imbalanced bone remodeling, resulting in loss of bone mass/volume. Clinically, this leads to fractures because of structural weakness. Recent work has begun to provide a more complete picture of the mechanisms of PM-OP involving oxidative stress and collagen modifications known as advanced glycation endproducts (AGEs). On one hand, AGEs may drive imbalanced bone remodeling through signaling mediated by the receptor for AGEs (RAGE), stimulating resorption and inhibiting formation. On the other hand, AGEs are associated with degraded bone material quality. Oxidative stress promotes the formation of AGEs, inhibits normal enzymatically derived crosslinking and can degrade collagen structure, thereby reducing fracture resistance. Notably, there are multiple positive feedback loops that can exacerbate the mechanisms of PM-OP associated with oxidative stress and AGEs. Anti-oxidant therapies may have the potential to inhibit the oxidative stress based mechanisms of this disease.

  15. Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure.

    Science.gov (United States)

    Scholz-Ahrens, Katharina E; Ade, Peter; Marten, Berit; Weber, Petra; Timm, Wolfram; Açil, Yahya; Glüer, Claus-C; Schrezenmeir, Jürgen

    2007-03-01

    Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of probiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics

  16. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles

    Directory of Open Access Journals (Sweden)

    Chen Kun-Wan

    2011-10-01

    Full Text Available Abstract Background The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport. Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species before proliferating (invasive spread. Proliferation in the new site has an impact on the target organ microenvironment (ecological impact and eventually the human host (biosphere impact. Results Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells. Conclusions The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.

  17. [Sutural physical model building in the three-dimensional finite-element model of maxillofacial bones].

    Science.gov (United States)

    Liu, Chang; Zhu, Xian-chun; Zhang, Xing; Tai, Yin-xia; Yan, Sen

    2011-02-01

    To build the physical model of four suturae which are related to the growth of maxilla in the three-dimensional finite-element model of maxillofacial bones. A 16 years old volunteer with individual normal occlusion, good periodontium health condition and without diseases of temporomandibular joint was chosen to be the material of modeling. The three-dimensional finite-element model of the volunteer's maxillofacial bones was built using the CT scan and the finite-element modeling method. Finally we built the physical model of four suturae which were related to the growth of maxilla in the model of maxillofacial bones. The model of maxillofacial bones with 86,575 nodes and 485,915 elements was generated. This model contained four suturae including sutura frontomaxillaris, sutura zygomaticomaxillaris, sutura temporozygomatica and sutura pterygopalatine. A three-dimensional finite-element model of maxillofacial bones with good biological similarity was developed.

  18. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    Science.gov (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  19. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  20. Hierarchy effect on electronic structure and core-to-valence transitions in bone tissue: perspectives in medical nanodiagnostics of mineralized bone

    Science.gov (United States)

    Samoilenko, Dmitrii O.; Avrunin, Alexander S.; Pavlychev, Andrey A.

    2017-06-01

    Electronic structure and core-to-valence transitions in bone tissue are examined in the framework of the morphological 3DSL model that takes into account (i) structural and functional organization of the skeleton in the normal and pathological conditions and (ii) peculiarities of electron wave propagation in a three-dimensional superlattice of "black-nanocrystallites-in-muddy-waters". Our focus is on the HAP-to-bone red shifts of core-to-valence transitions near Ca and P 2p and O 1s edges in single-crystal hydroxyapatite (HAP) Ca10(PO4)6(OH)2. The origin of the HAP-to-bone shift is discussed and the extended comparative analysis of the experimental data is performed. The detected spectral shift is assigned with the effect of hierarchical organization of bone tissue. This hierarchy effect on the core-to-valence transition energies is regarded as a promising tool for medical imaging and perspective pathway for nanodiagnostics of mineralized bone. Contribution to the Topical Issue "Dynamics of Systems at the Nanoscale", edited by Andrey Solov'yov and Andrei Korol.

  1. A non-linear homogeneous model for bone-like materials under compressive load.

    Science.gov (United States)

    Mengoni, M; Voide, R; de Bien, C; Freichels, H; Jérôme, C; Léonard, A; Toye, D; Müller, R; van Lenthe, G H; Ponthot, J P

    2012-02-01

    Finite element (FE) models accurately compute the mechanical response of bone and bone-like materials when the models include their detailed microstructure. In order to simulate non-linear behavior, which currently is only feasible at the expense of extremely high computational costs, coarser models can be used if the local morphology has been linked to the apparent mechanical behavior. The aim of this paper is to implement and validate such a constitutive law. This law is able to capture the non-linear structural behavior of bone-like materials through the use of fabric tensors. It also allows for irreversible strains using an elastoplastic material model incorporating hardening. These features are expressed in a constitutive law based on the anisotropic continuum damage theory coupled with isotropic elastoplasticity in a finite strain framework. This material model was implemented into metafor (LTAS-MNNL, University of Liège, Belgium), a non-linear FE software. The implementation was validated against experimental data of cylindrical samples subjected to compression. Three materials with bone-like microstructure were tested: aluminum foams of variable density (ERG, Oakland, CA, USA), polylactic acid foam (CERM, University of Liège, Liège, Belgium), and cancellous bone tissue of a deer antler (Faculty of Veterinary Medicine, University of Liège, Liège, Belgium).

  2. Permeability of rapid prototyped artificial bone scaffold structures.

    Science.gov (United States)

    Lipowiecki, Marcin; Ryvolová, Markéta; Töttösi, Ákos; Kolmer, Niels; Naher, Sumsun; Brennan, Stephen A; Vázquez, Mercedes; Brabazon, Dermot

    2014-11-01

    In this work, various three-dimensional (3D) scaffolds were produced via micro-stereolithography (µ-SLA) and 3D printing (3DP) techniques. This work demonstrates the advantages and disadvantages of these two different rapid prototyping methods for production of bone scaffolds. Compared to 3DP, SLA provides for smaller feature production with better dimensional resolution and accuracy. The permeability of these structures was evaluated experimentally and via numerical simulation utilizing a newly derived Kozeny-Carman based equation for intrinsic permeability. Both experimental and simulation studies took account of porosity percentage, pore size, and pore geometry. Porosity content was varied from 30% to 70%, pore size from 0.34 mm to 3 mm, and pore geometries of cubic and hexagonal closed packed were examined. Two different fluid viscosity levels of 1 mPa · s and 3.6 mPa · s were used. The experimental and theoretical results indicated that permeability increased when larger pore size, increased fluid viscosity, and higher percentage porosity were utilized, with highest to lowest degree of significance following the same order. Higher viscosity was found to result in permeabilities 2.2 to 3.3 times higher than for water. This latter result was found to be independent of pore morphology type. As well as demonstrating method for determining design parameters most beneficial for scaffold structure design, the results also illustrate how the variations in patient's blood viscosity can be extremely important in allowing for permeability through the bone and scaffold structures.

  3. Validation of model-based pelvis bone segmentation from MR images for PET/MR attenuation correction

    Science.gov (United States)

    Renisch, S.; Blaffert, T.; Tang, J.; Hu, Z.

    2012-02-01

    With the recent introduction of combined Magnetic Resonance Imaging (MRI) / Positron Emission Tomography (PET) systems, the generation of attenuation maps for PET based on MR images gained substantial attention. One approach for this problem is the segmentation of structures on the MR images with subsequent filling of the segments with respective attenuation values. Structures of particular interest for the segmentation are the pelvis bones, since those are among the most heavily absorbing structures for many applications, and they can serve at the same time as valuable landmarks for further structure identification. In this work the model-based segmentation of the pelvis bones on gradient-echo MR images is investigated. A processing chain for the detection and segmentation of the pelvic bones is introduced, and the results are evaluated using CT-generated "ground truth" data. The results indicate that a model based segmentation of the pelvis bone is feasible with moderate requirements to the pre- and postprocessing steps of the segmentation.

  4. Clinical Application of Solid Model Based on Trabecular Tibia Bone CT Images Created by 3D Printer.

    Science.gov (United States)

    Cho, Jaemo; Park, Chan-Soo; Kim, Yeoun-Jae; Kim, Kwang Gi

    2015-07-01

    The aim of this work is to use a 3D solid model to predict the mechanical loads of human bone fracture risk associated with bone disease conditions according to biomechanical engineering parameters. We used special image processing tools for image segmentation and three-dimensional (3D) reconstruction to generate meshes, which are necessary for the production of a solid model with a 3D printer from computed tomography (CT) images of the human tibia's trabecular and cortical bones. We examined the defects of the mechanism for the tibia's trabecular bones. Image processing tools and segmentation techniques were used to analyze bone structures and produce a solid model with a 3D printer. These days, bio-imaging (CT and magnetic resonance imaging) devices are able to display and reconstruct 3D anatomical details, and diagnostics are becoming increasingly vital to the quality of patient treatment planning and clinical treatment. Furthermore, radiographic images are being used to study biomechanical systems with several aims, namely, to describe and simulate the mechanical behavior of certain anatomical systems, to analyze pathological bone conditions, to study tissues structure and properties, and to create a solid model using a 3D printer to support surgical planning and reduce experimental costs. These days, research using image processing tools and segmentation techniques to analyze bone structures to produce a solid model with a 3D printer is rapidly becoming very important.

  5. Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

    Science.gov (United States)

    Liu, Xi Ling; Li, Chun Lei; Lu, Weijia William; Cai, Wei Xin; Zheng, Li Wu

    2015-04-01

    Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. From histology to micro-CT: Measuring and modeling resorption cavities and their relation to bone competence.

    Science.gov (United States)

    Vanderoost, Jef; van Lenthe, G Harry

    2014-09-28

    The process of bone remodelling plays an essential role in the emergence and maintenance of bone geometry and its internal structure. Osteoclasts are one of the three main bone cell types that play a crucial role in the bone remodelling cycle. At the microstructural level, osteoclasts create bone deficits by eroding resorption cavities. Understanding how these cavities impair the mechanical quality of the bone is not only relevant in quantifying the impact of resorption cavities in healthy bone and normal aging, but maybe even more so in quantifying their role in metabolic bone diseases. Metabolic bone diseases and their treatment are both known to affect the bone remodelling cycle; hence, the bone mechanical competence can and will be affected. However, the current knowledge of the precise dimensions of these cavities and their effect on bone competence is rather limited. This is not surprising considering the difficulties in deriving three-dimensional (3D) properties from two-dimensional (2D) histological sections. The measurement difficulties are reflected in the evaluation of how resorption cavities affect bone competence. Although detailed 3D models are generally being used to quantify the mechanical impact of the cavities, the representation of the cavities themselves has basically been limited to simplified shapes and averaged cavity properties. Qualitatively, these models indicate that cavity size and location are important, and that the effect of cavities is larger than can be expected from simple bone loss. In summary, the dimensions of osteoclast resorption cavities were until recently estimated from 2D measures; hence, a careful interpretation of resorption cavity dimensions is necessary. More effort needs to go into correctly quantifying resorption cavities using modern 3D imaging techniques like micro-computed tomography (micro-CT) and synchrotron radiation CT. Osteoclast resorption cavities affect bone competence. The structure-function relationships

  7. A study on the changes of bone structure and properties in female rats under simulated weightlessness as osteoporosis models%模拟失重状态下雌性大鼠骨质疏松模型骨结构及性能变化研究

    Institute of Scientific and Technical Information of China (English)

    张恒; 任宁涛; 李洁; 雷伟; 刘宁; 张永刚; 张然; 杨彦玲; 崔赓

    2015-01-01

    Objective To study the changes of bone mineral density ( BMD ) of cancellous bone, trabecular bone structure, bone tissue morphology, bone metabolic biochemical markers and mechanical properties in tail-suspended female rats under simulated weightlessness, so as to provide certain theoretical support for the research on bone mass changes in female astronauts after the lfight and aerospace medicine.Methods Twenty 3-month-old female Sprague-Dawley ( SD ) rats were randomly divided into 2 groups. The tails of the rats in group A (n=10 ) were suspended for 4 weeks, and the other rates were taken as blank control group (n=10 ). All the rates were continuously fed for 4 weeks, and their general conditions were recorded, including activities, eating and drinking,defecation, weight, unhairing or not, death and tail falling off. All the rats were sacrificed at predetermined time points. The BMD of the L4 vertebral body and femoral condyle was evaluated by dual-energy X-ray absorption ( DEXA ). Micro computed tomography ( Micro-CT ) was applied to analyze the trabecular bone. Bone tissue slice staining was conducted by using ponceau. Serum bone metabolic biochemical markers were detected by Enzyme-linked immunosorbent assay ( ELISA ), and biochemical properties were investigated.Results At 4 weeks after the establishment of osteoporosis models, the activities, eating and drinking and defecation of the rats in group A were normal, and the differences in weight gain were not statistically significant between the 2 groups (P>0.05 ). No unhairing, death or tail falling off was noticed in either group. When compared with that in blank control group, the BMD of the L4 vertebral body and femoral condyle in group A was reduced by 29% and 30% (P<0.05 ). The bone volume / total volume ( BV/TV ), bone surface/bone volume ( BS/BV ), trabecular thickness ( Tb.Th ) and trabecular number ( Tb.N ) of the L4 vertebral body in group A was reduced by 40%, 15%, 30% and 33% when compared with

  8. Roles of Zinc and Iron on Bone Health in a Rat Model of Osteoporosis

    Science.gov (United States)

    Yan, Danhua

    Bone is one of the most vital organs in animals, serving as both structural and protective functions. Remodeling of bone is an important indicator of bone health, and disorders in bone remodeling may lead to bone diseases such as osteoporosis. Osteoporosis increases risk of bone fracture and even death, and much more preferable to be happened in postmenopausal women due to great changes in hormones. Micronutrients, such as Zinc (Zn) and Iron (Fe), would as well influence bone health in different manners. That Zn would promote bone health is widely accepted, for the reasons Zn increases osteoblast cell proliferation and differentiation, inhibits osteoclast cell activities, and forms alkaline phosphatase that does help to maintain bone metabolism. Diseases caused by Fe overload is usually related to osteoporosis. Ferric ion could facilitate osteoclast differentiation, inhibit osteoblast and alkaline phosphatase activities, and interfere with hydroxyapatite crystal growth and depositions. However, changes of concentrations and distributions for Zn and Fe in osteoporotic bones are seldom studied. In this thesis, ovariectomized rat femur bones are used as a model of postmenopausal osteoporosis. Rats from different ages and health conditions are categorized as 6 AM (6-month age matched control), 6 OVX (6-month ovariectomized control), 12 AM (12-month age matched control), 12 OVX (12-month ovariectomized control). The trace elements Zn and Fe is studied through Synchrotron Radiation X-Ray Fluorescence (SRXRF). Elemental maps are used to observe changes in distribution, and further quantitative analysis is used to discover changes in concentration among different animal groups. Both the decrease of Zn and the increase of Fe are significant from healthy to osteoporotic bones (p0.1) is also observed over age in healthy groups. Both elements show changes in distribution, that healthy animals present a more even distribution while in OVX groups the tendency of aggregation is

  9. Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

    2015-02-01

    Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased

  10. Bioactive glasses: Importance of structure and properties in bone regeneration

    Science.gov (United States)

    Hench, Larry L.; Roki, Niksa; Fenn, Michael B.

    2014-09-01

    This review provides a brief background on the applications, mechanisms and genetics involved with use of bioactive glass to stimulate regeneration of bone. The emphasis is on the role of structural changes of the bioactive glasses, in particular Bioglass, which result in controlled release of osteostimulative ions. The review also summarizes the use of Raman spectroscopy, referred to hereto forward as bio-Raman spectroscopy, to obtain rapid, real time in vitro analysis of human cells in contact with bioactive glasses, and the osteostimulative dissolution ions that lead to osteogenesis. The bio-Raman studies support the results obtained from in vivo studies of bioactive glasses, as well as extensive cell and molecular biology studies, and thus offers an innovative means for rapid screening of new bioactive materials while reducing the need for animal testing.

  11. Optimizing finite element predictions of local subchondral bone structural stiffness using neural network-derived density-modulus relationships for proximal tibial subchondral cortical and trabecular bone.

    Science.gov (United States)

    Nazemi, S Majid; Amini, Morteza; Kontulainen, Saija A; Milner, Jaques S; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

    2017-01-01

    Quantitative computed tomography based subject-specific finite element modeling has potential to clarify the role of subchondral bone alterations in knee osteoarthritis initiation, progression, and pain. However, it is unclear what density-modulus equation(s) should be applied with subchondral cortical and subchondral trabecular bone when constructing finite element models of the tibia. Using a novel approach applying neural networks, optimization, and back-calculation against in situ experimental testing results, the objective of this study was to identify subchondral-specific equations that optimized finite element predictions of local structural stiffness at the proximal tibial subchondral surface. Thirteen proximal tibial compartments were imaged via quantitative computed tomography. Imaged bone mineral density was converted to elastic moduli using multiple density-modulus equations (93 total variations) then mapped to corresponding finite element models. For each variation, root mean squared error was calculated between finite element prediction and in situ measured stiffness at 47 indentation sites. Resulting errors were used to train an artificial neural network, which provided an unlimited number of model variations, with corresponding error, for predicting stiffness at the subchondral bone surface. Nelder-Mead optimization was used to identify optimum density-modulus equations for predicting stiffness. Finite element modeling predicted 81% of experimental stiffness variance (with 10.5% error) using optimized equations for subchondral cortical and trabecular bone differentiated with a 0.5g/cm(3) density. In comparison with published density-modulus relationships, optimized equations offered improved predictions of local subchondral structural stiffness. Further research is needed with anisotropy inclusion, a smaller voxel size and de-blurring algorithms to improve predictions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    Science.gov (United States)

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-05

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.

  13. The Tarsometatarsus of the Ostrich Struthio camelus: Anatomy, Bone Densities, and Structural Mechanics.

    Directory of Open Access Journals (Sweden)

    Meagan M Gilbert

    Full Text Available The ostrich Struthio camelus reaches the highest speeds of any extant biped, and has been an extraordinary subject for studies of soft-tissue anatomy and dynamics of locomotion. An elongate tarsometatarsus in adult ostriches contributes to their speed. The internal osteology of the tarsometatarsus, and its mechanical response to forces of running, are potentially revealing about ostrich foot function.Computed tomography (CT reveals anatomy and bone densities in tarsometatarsi of an adult and a young juvenile ostrich. A finite element (FE model for the adult was constructed with properties of compact and cancellous bone where these respective tissues predominate in the original specimen. The model was subjected to a quasi-static analysis under the midstance ground reaction and muscular forces of a fast run. Anatomy-Metatarsals are divided proximally and distally and unify around a single internal cavity in most adult tarsometatarsus shafts, but the juvenile retains an internal three-part division of metatarsals throughout the element. The juvenile has a sparsely ossified hypotarsus for insertion of the m. fibularis longus, as part of a proximally separate third metatarsal. Bone is denser in all regions of the adult tarsometatarsus, with cancellous bone concentrated at proximal and distal articulations, and highly dense compact bone throughout the shaft. Biomechanics-FE simulations show stress and strain are much greater at midshaft than at force applications, suggesting that shaft bending is the most important stressor of the tarsometatarsus. Contraction of digital flexors, inducing a posterior force at the TMT distal condyles, likely reduces buildup of tensile stresses in the bone by inducing compression at these locations, and counteracts bending loads. Safety factors are high for von Mises stress, consistent with faster running speeds known for ostriches.High safety factors suggest that bone densities and anatomy of the ostrich tarsometatarsus

  14. Structural model integrity

    Science.gov (United States)

    Wallerstein, D. V.; Lahey, R. S.; Haggenmacher, G. W.

    1977-01-01

    Many of the practical aspects and problems of ensuring the integrity of a structural model are discussed, as well as the steps which have been taken in the NASTRAN system to assure that these checks can be routinely performed. Model integrity as used applies not only to the structural model but also to the loads applied to the model. Emphasis is also placed on the fact that when dealing with substructure analysis, all of the checking procedures discussed should be applied at the lowest level of substructure prior to any coupling.

  15. Effects of ionizing radiation on bone cell differentiation in an experimental murine bone cell model

    Science.gov (United States)

    Baumstark-Khan, Christa; Lau, Patrick; Hellweg, Christine; Reitz, Guenther

    During long-term space travel astronauts are exposed to a complex mixture of different radiation types under conditions of dramatically reduced weight-bearing activity. It has been validated that astronauts loose a considerable amount of bone mass at a rate up to one to two percent each month in space. Therapeutic doses of ionizing radiation cause bone damage and increase fracture risks after treatment for head-and-neck cancer and in pelvic irradiation. For low radiation doses, the possibility of a disturbed healing potential of bone was described. Radiation induced damage has been discussed to inflict mainly on immature and healing bone. Little is known about radiation effects on bone remodelling and even less on the combined action of microgravity and radiation. Bone remodelling is a life-long process performed by balanced action of cells from the osteoblast and osteoclast lineages. While osteoblasts differentiate either into bone-lining cells or into osteocytes and play a crucial role in bone matrix synthesis, osteoclasts are responsible for bone resorption. We hypothesize that the balance between bone matrix assembly by osteocytes and bone degradation by osteoclasts is modulated by microgravity as well as by ionizing radiation. To address this, a cell model consisting of murine cell lines with the potential to differentiate into bone-forming osteoblasts (OCT-1, MC3T3-E1 S24, and MC3T3-E1 S4) was used for studying radiation response after exposure to simulated components of cosmic radiation. Cells were exposed to graded doses of 150 kV X-rays, α particles (0.525 MeV/u, 160 keV/µm; PTB, Braunschweig, Germany) and accelerated heavy ions (75 MeV/u carbon, 29 keV/µm; 95 MeV/u argon, 230 keV/µm; GANIL, Caen, France). Cell survival was measured as colony forming ability; cell cycle progression was analyzed via fluorescence-activated cell scanning (FACS) by measurement of the content of propidium iodide-stained DNA, DNA damage was visualized by γH2AX

  16. Differential effects of calorie restriction and involuntary wheel running on body composition and bone structure in diet-induced obese rats

    Science.gov (United States)

    Weight reduction is recommended to reduce obesity-related health disorders. This study investigated the differential effects of weight reduction through caloric restriction and/or physical activity on bone structure and molecular characteristics of bone metabolism in an obese rat model. We tested th...

  17. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    Science.gov (United States)

    Schreurs, A.-S.; Torres, S.; Truong, T.; Kumar, A.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2014-01-01

    parameters. Taken together, this typically catabolic treatment (disuse and irradiation) appeared to stimulate cortical expansion in MCAT mice but not WT mice. In conclusion, these results reveal the importance of mitochondrial ROS generation in skeletal remodeling and show that MCAT mice provide a useful animal model for bone studies.

  18. Scaling relations between bone volume and bone structure as found using 3D µCT images of the trabecular bone taken from different skeletal sites

    Science.gov (United States)

    Raeth, Christoph; Müller, Dirk; Sidorenko, Irina; Monetti, Roberto; Eckstein, Felix; Matsuura, Maiko; Lochmüller, Eva-Maria; Zysset, Philippe K.; Bauer, Jan

    2010-03-01

    According to Wolff's law bone remodels in response to the mechanical stresses it experiences so as to produce a minimal-weight structure that is adapted to its applied stresses. Here, we investigate the relations between bone volume and structure for the trabecular bone using 3D μCT images taken from different skeletal sites in vitro, namely from the distal radii (96 specimens), thoracic (73 specimens) and lumbar vertebrae (78 specimens). We determine the local structure of the trabecular network by calculating isotropic and anisotropic scaling indices (α, αz). These measures have been proven to be able to discriminate rod- from sheet-like structures and to quantify the alignment of structures with respect to a preferential direction as given by the direction of the external force. Comparing global structure measures derived from the scaling indices (mean, standard deviation) with the bone mass (BV/TV) we find that all correlations obey very accurately power laws with scaling exponents of 0.14, 0.12, 0.15 (~), -0.2, -017, -0.17 (σ(αz)), 0.09, 0.05, 0.07 (~) and -0.20, -0.11 ,-0.13 (σ(αz)) distal radius, thoracic vertebra and lumbar vertebra respectively. Thus, these relations turn out to be site-independent, albeit the mechanical stresses to which the bones of the forearm and the spine are exposed, are quite different. The similar alignment might not be in agreement with a universal validity of Wolff's law. On the other hand, such universal power law relations may allow to develop additional diagnostic means to better assess healthy and osteoporotic bone.

  19. PERCEPTION OF MEDICAL STUDENTS TOWARDS ARTIFICIAL BONES AND POP MODELS OF VISCERA

    OpenAIRE

    Sumit Tulshidas Patil; Nazia Quadir; Rashmi Deopujari; Vivekanand Gajbhiye

    2015-01-01

    Background: In learning of anatomy, bones and viscera are very important. Now days, artificial bones are replacing the original bones for study purpose due to unavailability. Original viscera are available for students only at dissection hours. So we have tried to find out perception of medical students towards artificial bones and POP models of viscera. Materials and Methods: We had prepared a questionnaire consisting of 20 questions, 10 related to bones and 10 related to the POP models o...

  20. Structural Equation Model Trees

    Science.gov (United States)

    Brandmaier, Andreas M.; von Oertzen, Timo; McArdle, John J.; Lindenberger, Ulman

    2013-01-01

    In the behavioral and social sciences, structural equation models (SEMs) have become widely accepted as a modeling tool for the relation between latent and observed variables. SEMs can be seen as a unification of several multivariate analysis techniques. SEM Trees combine the strengths of SEMs and the decision tree paradigm by building tree…

  1. Bone compaction enhances implant fixation in a canine gap model

    DEFF Research Database (Denmark)

    Kold, Søren; Rahbek, Ole; Toft, Marianne;

    2005-01-01

    implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm......) were bilaterally inserted into cavities initially expanded to 8 mm diameters in the proximal humeri. Each dog served as its own control; thus, one humerus had the implant cavity prepared with compaction, the other with drilling. Eight dogs were euthanized after 2 weeks, and 7 dogs after 4 weeks. Humeri...... from additional 7 dogs represented time 0. At time 0 a spring-back effect of compacted bone was demonstrated as cavities, initially expanded to 8 mm by compaction, were reduced to a median cavity diameter of 6.6 mm. In contrast, cavities initially expanded to 8 mm by drilling, had a median cavity...

  2. Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model.

    Science.gov (United States)

    Napimoga, Marcelo H; Clemente-Napimoga, Juliana T; Macedo, Cristina G; Freitas, Fabiana F; Stipp, Rafael N; Pinho-Ribeiro, Felipe A; Casagrande, Rubia; Verri, Waldiceu A

    2013-12-27

    Periodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1β, TNF-α, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production.

  3. A Novel Temporal Bone Simulation Model Using 3D Printing Techniques.

    Science.gov (United States)

    Mowry, Sarah E; Jammal, Hachem; Myer, Charles; Solares, Clementino Arturo; Weinberger, Paul

    2015-09-01

    An inexpensive temporal bone model for use in a temporal bone dissection laboratory setting can be made using a commercially available, consumer-grade 3D printer. Several models for a simulated temporal bone have been described but use commercial-grade printers and materials to produce these models. The goal of this project was to produce a plastic simulated temporal bone on an inexpensive 3D printer that recreates the visual and haptic experience associated with drilling a human temporal bone. Images from a high-resolution CT of a normal temporal bone were converted into stereolithography files via commercially available software, with image conversion and print settings adjusted to achieve optimal print quality. The temporal bone model was printed using acrylonitrile butadiene styrene (ABS) plastic filament on a MakerBot 2x 3D printer. Simulated temporal bones were drilled by seven expert temporal bone surgeons, assessing the fidelity of the model as compared with a human cadaveric temporal bone. Using a four-point scale, the simulated bones were assessed for haptic experience and recreation of the temporal bone anatomy. The created model was felt to be an accurate representation of a human temporal bone. All raters felt strongly this would be a good training model for junior residents or to simulate difficult surgical anatomy. Material cost for each model was $1.92. A realistic, inexpensive, and easily reproducible temporal bone model can be created on a consumer-grade desktop 3D printer.

  4. Characterization and three-dimensional reconstruction of synthetic bone model foams

    Energy Technology Data Exchange (ETDEWEB)

    Gómez, S. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Vlad, M.D. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Faculty of Medical Bioengineering, “Gr. T. Popa” University of Medicine and Pharmacy, Str. Kogalniceanu 9-13, 700454 Iasi (Romania); López, J. [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain); Navarro, M. [Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG), Departament de Sanitat i d' Anatomia Animals, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Cerdanyola del Vallès (Spain); Fernández, E., E-mail: enrique.fernandez@upc.edu [Interdepartment Research Group for the Applied Scientific Collaboration (IRGASC), Division of Biomaterials and Bioengineering, Technical University of Catalonia (UPC), Avda. Diagonal 647, E-08028 Barcelona (Spain)

    2013-08-01

    Sawbones© open-cell foams with different porosity grades are being used as synthetic bone-like models for in vitro mechanical and infiltration experiments. However, a comprehensive characterization of these foams is not available and there is a lack of reliable information about them. For this reason two of these foams (Refs. 1522-505 and -507) have been characterized at the micro architectural level by scanning electron microscopy, computed tomography and image data analysis. BoneJ open software and ImageJ open software were used to obtain the characteristic histomorphometric parameters and the three dimensional virtual models of the foams. The results showed that both foams, while having different macro porosities, appeared undistinguishable at the micro scale. Moreover, the micro structural features resembled those of osteoporotic rather than healthy trabecular bone. It is concluded that Sawbones© foams behave reasonably as synthetic bone-like models. Consequently, their use is recommended for in vitro comparison purposes of both mechanical and infiltration testing performed in real vertebra. Finally, the virtual models obtained, which are available under request, can favour comparisons between future self-similar in vitro experiments and computer simulations. - Highlights: • Sawbones© model foams have been scanned by μ-CT. • Histomorphometric indices and 3D virtual models have been obtained. • The results will be of use to understand biocement vertebra infiltration studies.

  5. Numerical simulation of load-induced bone structural remodelling using stress-limit criterion.

    Science.gov (United States)

    Marzban, Ali; Nayeb-Hashemi, Hamid; Vaziri, Ashkan

    2015-01-01

    A simple and efficient numerical method for predicting the remodelling of adaptive materials and structures under applied loading was presented and implemented within a finite element framework. The model uses the trajectorial architecture theory of optimisation to predict the remodelling of material microstructure and structural organisation under mechanical loading. We used the proposed model to calculate the density distribution of proximal femur in the frontal plane. The loading considered was the hip joint contact forces and muscular forces at the attachment sites of the muscles to the bone. These forces were estimated from a separate finite element calculation using a heterogeneous three-dimensional model of the proximal femur. The density distributions obtained by this procedure has a qualitative similarity with in vivo observations. Solutions displayed the characteristic high-density channels that are evident in the Dual X-ray Absorptiometry scan. There is also evidence of the intramedullary canal, as well as low-density regions in the femoral neck. Several parametric studies were carried out to highlight the advantages of the proposed method, which includes fast convergence and low-computational cost. The potential applications of the proposed method in predicting bone structural remodelling in cancer are also briefly discussed.

  6. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    Directory of Open Access Journals (Sweden)

    Quarto Rodolfo

    2010-01-01

    Full Text Available Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

  7. Mathematical Model of Bone Regeneration in a Porous Implant

    Science.gov (United States)

    Maslov, L. B.

    2017-07-01

    A mathematical model of the reparative regeneration of bone tissue governed by the law of cell differentiation and action of an external periodic mechanical loading is presented. The model allows one to study the recovery processes of injured human locomotor system elements under a dynamic loading and to theoretically substantiate the choice of an optimum periodic impact on the defective tissues for their fastest and steady healing.

  8. Engineered bone from bone marrow stromal cells: a structural study by an advanced x-ray microdiffraction technique

    Energy Technology Data Exchange (ETDEWEB)

    Cedola, A [Istituto di Fotonica e Nanotecnologie-CNR, V Cineto Romano 42, 00156 Rome (Italy); Medical Physics Specialisation School, University of Milan (Italy); Mastrogiacomo, M [Dipartimento di Oncologia, Biologia e Genetica, Universita' di Genova, Istituto Nazionale per la Ricerca sul Cancro-Genova, Largo R. Benzi 10, 16132 Genova (Italy); Burghammer, M [ESRF, BP 220, F-38043 Grenoble Cedex (France); Komlev, V [INFM, Department of Sciences Applied to Complex Systems, Polytechnic University of Marche, Via Ranieri 65, I60131 Ancona (Italy); Institute for Physical Chemistry of Ceramics, Russian Academy of Science, Ozernaya 48, 119361 Moscow (Russian Federation); Giannoni, P [Biorigen Srl, Via Peschiera 16, 16122 Genova (Italy); Favia, A [Dipartimento di Anatomia Umana e Istologia, Universita degli Studi di Bari, P.le Giulio Cesare Policlinico, 70122 Bari (Italy); Cancedda, R [Dipartimento di Oncologia, Biologia e Genetica, Universita' di Genova, Istituto Nazionale per la Ricerca sul Cancro-Genova, Largo R. Benzi 10, 16132 Genova (Italy); Rustichelli, F [INFM, Department of Sciences Applied to Complex Systems, Polytechnic University of Marche, Via Ranieri 65, I60131 Ancona (Italy); Lagomarsino, S [Istituto di Fotonica e Nanotecnologie-CNR, V Cineto Romano 42, 00156 Rome (Italy); Medical Physics Specialisation School, University of Milan (Italy)

    2006-03-21

    The mechanism of mineralized matrix deposition was studied in a tissue engineering approach in which bone tissue is formed when porous ceramic constructs are loaded with bone marrow stromal cells and implanted in vivo. We investigated the local interaction between the mineral crystals of the engineered bone and the biomaterial by means of microdiffraction, using a set-up based on an x-ray waveguide. We demonstrated that the newly formed bone is well organized inside the scaffold pore, following the growth model of natural bone. Combining wide angle (WAXS) and small angle (SAXS) x-ray scattering with high spatial resolution, we were able to determine the orientation of the crystallographic c-axis inside the bone crystals, and the orientation of the mineral crystals and collagen micro-fibrils with respect to the scaffold. In this work we analysed six samples and for each of them two pores were studied in detail. Similar results were obtained in all cases but we report here only the most significant sample. (note)

  9. Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

    Science.gov (United States)

    Li, Feng; Wang, Xujun; Niyibizi, Christopher

    2010-01-01

    Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

  10. Consideration of multiple load cases is critical in modelling orthotropic bone adaptation in the femur.

    Science.gov (United States)

    Geraldes, Diogo M; Modenese, Luca; Phillips, Andrew T M

    2016-10-01

    Functional adaptation of the femur has been investigated in several studies by embedding bone remodelling algorithms in finite element (FE) models, with simplifications often made to the representation of bone's material symmetry and mechanical environment. An orthotropic strain-driven adaptation algorithm is proposed in order to predict the femur's volumetric material property distribution and directionality of its internal structures within a continuum. The algorithm was applied to a FE model of the femur, with muscles, ligaments and joints included explicitly. Multiple load cases representing distinct frames of two activities of daily living (walking and stair climbing) were considered. It is hypothesised that low shear moduli occur in areas of bone that are simply loaded and high shear moduli in areas subjected to complex loading conditions. In addition, it is investigated whether material properties of different femoral regions are stimulated by different activities. The loading and boundary conditions were considered to provide a physiological mechanical environment. The resulting volumetric material property distribution and directionalities agreed with ex vivo imaging data for the whole femur. Regions where non-orthogonal trabecular crossing has been documented coincided with higher values of predicted shear moduli. The topological influence of the different activities modelled was analysed. The influence of stair climbing on the properties of the femoral neck region is highlighted. It is recommended that multiple load cases should be considered when modelling bone adaptation. The orthotropic model of the complete femur is released with this study.

  11. Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

    Science.gov (United States)

    Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

    2016-01-01

    This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations.

  12. Comparison of structural, architectural and mechanical aspects of cellular and acellular bone in two teleost fish.

    Science.gov (United States)

    Cohen, Liat; Dean, Mason; Shipov, Anna; Atkins, Ayelet; Monsonego-Ornan, Efrat; Shahar, Ron

    2012-06-01

    The histological diversity of the skeletal tissues of fishes is impressive compared with that of other vertebrate groups, yet our understanding of the functional consequences of this diversity is limited. In particular, although it has been known since the mid-1800s that a large number of fish species possess acellular bones, the mechanical advantages and consequences of this structural characteristic - and therefore the nature of the evolution of this feature - remain unclear. Although several studies have examined the material properties of fish bone, these have used a variety of techniques and there have been no direct contrasts of acellular and cellular bone. We report on a comparison of the structural and mechanical properties of the ribs and opercula between two freshwater fish - the common carp Cyprinus carpio (a fish with cellular bone) and the tilapia Oreochromis aureus (a fish with acellular bone). We used light microscopy to show that the bones in both fish species exhibit poor blood supply and possess discrete tissue zones, with visible layering suggesting differences in the underlying collagen architecture. We performed identical micromechanical testing protocols on samples of the two bone types to determine the mechanical properties of the bone material of opercula and ribs. Our data support the consensus of literature values, indicating that Young's moduli of cellular and acellular bones are in the same range, and lower than Young's moduli of the bones of mammals and birds. Despite these similarities in mechanical properties between the bone tissues of the fish species tested here, cellular bone had significantly lower mineral content than acellular bone; furthermore, the percentage ash content and bone mineral density values (derived from micro-CT scans) show that the bone of these fishes is less mineralized than amniote bone. Although we cannot generalize from our data to the numerous remaining teleost species, the results presented here suggest

  13. A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice.

    Science.gov (United States)

    Cao, Jay J; Gregoire, Brian R

    2016-04-01

    Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty-five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P diet increased body weight (P weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. Published by Elsevier Inc.

  14. From histology to micro-CT:Measuring and modeling resorption cavities and their relation to bone competence

    Institute of Scientific and Technical Information of China (English)

    Jef; Vanderoost; G; Harry; van; Lenthe

    2014-01-01

    The process of bone remodelling plays an essential role in the emergence and maintenance of bone geometry and its internal structure.Osteoclasts are one of the three main bone cell types that play a crucial role in the bone remodelling cycle.At the microstructural level,osteoclasts create bone deficits by eroding resorption cavities.Understanding how these cavities impair the mechanical quality of the bone is not only relevant in quantifying the impact of resorption cavities in healthy bone and normal aging,but maybe even more so in quantifying their role in metabolic bone diseases.Meta-bolic bone diseases and their treatment are both known to affect the bone remodelling cycle;hence,the bone mechanical competence can and will be affected.How-ever,the current knowledge of the precise dimensions of these cavities and their effect on bone competence is rather limited.This is not surprising considering the difficulties in deriving three-dimensional(3D)properties from two-dimensional(2D)histological sections.The measurement difficulties are reflected in the evalua-tion of how resorption cavities affect bone competence.Although detailed 3D models are generally being used to quantify the mechanical impact of the cavities,the representation of the cavities themselves has basicallybeen limited to simplified shapes and averaged cavityproperties.Qualitatively,these models indicate that cav-ity size and location are important,and that the effectof cavities is larger than can be expected from simplebone loss.In summary,the dimensions of osteoclastresorption cavities were until recently estimated from2D measures;hence,a careful interpretation of resorp-tion cavity dimensions is necessary.More effort needsto go into correctly quantifying resorption cavities usingmodern 3D imaging techniques like micro-computedtomography(micro-CT)and synchrotron radiation CT.Osteoclast resorption cavities affect bone competence.The structure-function relationships have been ana-lysed using

  15. Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis.

    Science.gov (United States)

    Angeloni, Valentina; Contessi, Nicola; De Marco, Cinzia; Bertoldi, Serena; Tanzi, Maria Cristina; Daidone, Maria Grazia; Farè, Silvia

    2017-09-18

    Breast cancer (BC) represents the most incident cancer case in women (29%), with high mortality rate. Bone metastasis occurs in 20-50% cases and, despite advances in BC research, the interactions between tumor cells and the metastatic microenvironment are still poorly understood. In vitro 3D models gained great interest in cancer research, thanks to the reproducibility, the 3D spatial cues and associated low costs, compared to in vivo and 2D in vitro models. In this study, we investigated the suitability of a poly-ether-urethane (PU) foam as 3D in vitro model to study the interactions between BC tumor-initiating cells and the bone microenvironment. PU foam open porosity (>70%) appeared suitable to mimic trabecular bone structure. The PU foam showed good mechanical properties under cyclic compression (E=69-109kPa), even if lower than human trabecular bone. The scaffold supported osteoblast SAOS-2 cell line proliferation, with no cytotoxic effects. Human adipose derived stem cells (ADSC) were cultured and differentiated into osteoblast lineage on the PU foam, as shown by alizarin red staining and RT-PCR, thus offering a bone biomimetic microenvironment to the further co-culture with BC derived tumor-initiating cells (MCFS). Tumor aggregates were observed after three weeks of co-culture by e-cadherin staining and SEM; modification in CaP distribution was identified by SEM-EDX and associated to the presence of tumor cells. In conclusion, we demonstrated the suitability of the PU foam to reproduce a bone biomimetic microenvironment, useful for the co-culture of human osteoblasts/BC tumor-initiating cells and to investigate their interaction. 3D in vitro models represent an outstanding alternative in the study of tumor metastases development, compared to traditional 2D in vitro cultures, which oversimplify the 3D tissue microenvironment, and in vivo studies, affected by low reproducibility and ethical issues. Several scaffold-based 3D in vitro models have been proposed

  16. Longitudinal assessment of in vivo bone dynamics in a mouse tail model of postmenopausal osteoporosis.

    Science.gov (United States)

    Lambers, Floor M; Kuhn, Gisela; Schulte, Friederike A; Koch, Kathleen; Müller, Ralph

    2012-02-01

    Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse micro-computed tomography (μCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo μCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (-35%) compared to SHM (+16%) in trabecular bone (P bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P bone stiffness for OVX (-16%) compared to SHM (+11%, P tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P bone formation rate (P bone biology is a promising method for future research.

  17. Analogy of strain energy density based bone-remodeling algorithm and structural topology optimization.

    Science.gov (United States)

    Jang, In Gwun; Kim, Il Yong; Kwak, Byung Ban

    2009-01-01

    In bone-remodeling studies, it is believed that the morphology of bone is affected by its internal mechanical loads. From the 1970s, high computing power enabled quantitative studies in the simulation of bone remodeling or bone adaptation. Among them, Huiskes et al. (1987, "Adaptive Bone Remodeling Theory Applied to Prosthetic Design Analysis," J. Biomech. Eng., 20, pp. 1135-1150) proposed a strain energy density based approach to bone remodeling and used the apparent density for the characterization of internal bone morphology. The fundamental idea was that bone density would increase when strain (or strain energy density) is higher than a certain value and bone resorption would occur when the strain (or strain energy density) quantities are lower than the threshold. Several advanced algorithms were developed based on these studies in an attempt to more accurately simulate physiological bone-remodeling processes. As another approach, topology optimization originally devised in structural optimization has been also used in the computational simulation of the bone-remodeling process. The topology optimization method systematically and iteratively distributes material in a design domain, determining an optimal structure that minimizes an objective function. In this paper, we compared two seemingly different approaches in different fields-the strain energy density based bone-remodeling algorithm (biomechanical approach) and the compliance based structural topology optimization method (mechanical approach)-in terms of mathematical formulations, numerical difficulties, and behavior of their numerical solutions. Two numerical case studies were conducted to demonstrate their similarity and difference, and then the solution convergences were discussed quantitatively.

  18. Independent scattering model and velocity dispersion in trabecular bone: comparison with a multiple scattering model.

    Science.gov (United States)

    Haïat, G; Naili, S

    2011-02-01

    Speed of sound measurements are used clinically to assess bone strength. Trabecular bone is an attenuating composite material in which negative values of velocity dispersion have been measured; this behavior remaining poorly explained physically. The aim of this work is to describe the ultrasonic propagation in trabecular bone modeled by infinite cylinders immersed in a saturating matrix and to derive the physical determinants of velocity dispersion. An original homogenization model accounting for the coupling of independent scattering and absorption phenomena allows the computation of phase velocity and of dispersion while varying bone properties. The first step of the model consists in the computation of the attenuation coefficient at all frequencies. The second step of the model corresponds to the application of the general Kramers-Krönig relationship to derive the frequency dependence of phase velocity. The model predicts negative values of velocity dispersion in agreement with experimental results obtained in phantoms mimicking trabecular bone. In trabecular bone, only negative values of velocity dispersion are predicted by the model, which span within the range of values measured experimentally. However, the comparison of the present results with results obtained in Haiat et al. (J Acoust Soc Am 124:4047-4058, 2008) assuming multiple scattering indicates that accounting for multiple scattering phenomena leads to a better prediction of velocity dispersion in trabecular bone.

  19. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    , as an add-on therapy. We investigated the changes in bone structure and density using µCT in 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24-wks of treatment. Trabecular tunnelling was evident in 11 (48%) biopsies from the PTH-group, whereas no tunnelling was detected in the placebo...

  20. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    2011-01-01

    , as an add-on therapy. We investigated the changes in bone structure and density using µCT in 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24-wks of treatment. Trabecular tunnelling was evident in 11 (48%) biopsies from the PTH-group, whereas no tunnelling was detected in the placebo...

  1. Engineering a human bone marrow model: a case study on ex vivo erythropoiesis.

    Science.gov (United States)

    Mantalaris, A; Keng, P; Bourne, P; Chang, A Y; Wu, J H

    1998-01-01

    Bone marrow, with its intricate, three-dimensional tissue structure facilitating cell-cell interactions, provides a microenvironment supporting the production of hundreds of billions of multilineal blood cells everyday. We have developed a three-dimensional bone marrow culture system in which marrow cells are cultured in a reactor packed with porous microspheres. The culture supports a three-dimensional growth configuration and multilineal hemopoiesis mimicking the bone marrow in vivo. We studied ex vivo human erythropoiesis using the three-dimensional culture system. The system sustained extensive erythropoiesis at low erythropoietin concentrations (0.2 U/mL), plus stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and insulin-like growth factor-I. Erythroid cell production lasted for more than 5 weeks, and the percentage of erythroid cells in the nonadherent cell population was approximately 60%. Flow cytometric analysis using cell surface markers specific for erythroid cells (CD71 and glycophorin-A) indicated that the culture produced early, intermediate, and late erythroid cells. As the culture progressed, the erythroid cell population shifted gradually toward mature cell types. When compared to the three-dimensional culture, the traditional flask cultures failed to support extensive erythropoiesis under the same conditions. This indicates that the three-dimensional bone marrow culture system provides a microenvironment conducive to erythropoiesis under more physiological conditions and is a better bone marrow model.

  2. Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy.

    Science.gov (United States)

    Wille, Marie-Luise; Langton, Christian M

    2016-02-01

    The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R(2)=99.9% and R(2)=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment.

  3. Postcranial pneumaticity and bone structure in two clades of neognath birds.

    Science.gov (United States)

    Gutzwiller, Sarah C; Su, Anne; O'Connor, Patrick M

    2013-06-01

    Most living birds exhibit some degree of postcranial skeletal pneumaticity, aeration of the postcranial skeleton by pulmonary air sacs and/or directly from the lungs. The extent of pneumaticity varies greatly, ranging from taxa that are completely apneumatic to those with air filling most of the postcranial skeleton. This study examined the influence of skeletal pneumatization on bone structural parameters in a sample of two size- and foraging-style diverse (e.g., subsurface diving vs. soaring specialists) clades of neognath birds (charadriiforms and pelecaniforms). Cortical bone thickness and trabecular bone volume fraction were assessed in one cervical and one thoracic vertebra in each of three pelecaniform and four charadriiform species. Results for pelecaniforms indicate that specialized subsurface dive foragers (e.g., the apneumatic anhinga) have thicker cortical bone and a higher trabecular bone volume fraction than their non-diving clademates. Conversely, the large-bodied, extremely pneumatic brown pelican (Pelecanus occidentalis) exhibits thinner cortical bone and a lower trabecular bone volume fraction. Such patterns in bone structural parameters are here interpreted to pertain to decreased buoyancy in birds specialized in subsurface dive foraging and decreased skeletal density (at the whole bone level) in birds of larger body size. The potential to differentially pneumatize the postcranial skeleton and alter bone structure may have played a role in relaxing constraints on body size evolution and/or habitat exploitation during the course of avian evolution. Notably, similar patterns were not observed within the equally diverse charadriiforms, suggesting that the relationship between pneumaticity and bone structure is variable among different clades of neognath birds.

  4. Model of Break-Bone Fever via Beta-Derivatives

    Directory of Open Access Journals (Sweden)

    Abdon Atangana

    2014-01-01

    Full Text Available Using the new derivative called beta-derivative, we modelled the well-known infectious disease called break-bone fever or the dengue fever. We presented the endemic equilibrium points under certain conditions of the physical parameters included in the model. We made use of an iteration method to solve the extended model. To show the efficiency of the method used, we have presented in detail the stability and the convergence of the method for solving the system (2. We presented the uniqueness of the special solution of system (2 and finally the numerical simulations were presented for various values of beta.

  5. Model of Break-Bone Fever via Beta-Derivatives

    Science.gov (United States)

    Atangana, Abdon; Oukouomi Noutchie, Suares Clovis

    2014-01-01

    Using the new derivative called beta-derivative, we modelled the well-known infectious disease called break-bone fever or the dengue fever. We presented the endemic equilibrium points under certain conditions of the physical parameters included in the model. We made use of an iteration method to solve the extended model. To show the efficiency of the method used, we have presented in detail the stability and the convergence of the method for solving the system (2). We presented the uniqueness of the special solution of system (2) and finally the numerical simulations were presented for various values of beta. PMID:25295263

  6. Comparison of the influences of structural characteristics on bulk mechanical behaviour: experimental study using a bone surrogate.

    Science.gov (United States)

    Levasseur, A; Ploeg, H-L; Petit, Y

    2012-01-01

    An experimental study was conducted to classify the influence of trabecular architecture and cortical shell thickness on the mechanical properties using a bone surrogate. Thirty-six rectangular prisms and 18 vertebral-shaped specimens were fabricated with fused deposition modelling (FDM) as a bone surrogate with controlled structural characteristics (cortical wall thickness, strut spacing, strut angle and strut orientation). The apparent density of the FDM specimens was evaluated using quantitative computed tomography (QCT) imaging and related to the apparent elastic modulus measured with compression testing. The effects of the structural parameters on the apparent elastic modulus were analysed using analysis of variance (ANOVA). The results obtained corroborate that the structural parameters have a significant effect on the apparent mechanical properties of the bulk material. The cortical shell thickness was found to have more influence than trabecular architecture. Therefore, accurate modelling of the cortical shell thickness should be considered more important than trabecular architecture in development of bone finite element models and bone surrogates.

  7. Three-dimensional quantification of structures in trabecular bone using measures of complexity

    DEFF Research Database (Denmark)

    Marwan, Norbert; Kurths, Jürgen; Thomsen, Jesper Skovhus

    2009-01-01

    The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three-dimensiona......The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three......-dimensional (3D) imaging of bone challenges the development of data analysis techniques able to assess changes of the 3D microarchitecture of trabecular bone. We introduce an approach based on spatial geometrical properties and define structural measures of complexity for 3D image analysis. These measures...

  8. Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT

    DEFF Research Database (Denmark)

    Frederiksen, Katrine Diemer; Hanson, Stine; Hansen, Stinus;

    2016-01-01

    Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral densit...... increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.......Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density...

  9. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    Science.gov (United States)

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  10. Comparison of the trabeculae structure of the spongy bone of the bilateral pastern bones in racehorses based on the imaging analysis of radiograms.

    Science.gov (United States)

    Dzierzecka, M; Czerwinski, E

    2010-01-01

    On the basis of a digital analysis of radiograms it was checked if, and to what extent, the extended loading of one of the sides of the body of racehorses leads to differences in the microstructure of the spongy bone of the bilateral pastern bones of the thoracic limbs. The research material consisted of radiograms of the pastern bones of the right and left thoracic limbs of racehorses. On the basis of computer image radiological analysis with the use of the "Trabecula,, programme, a quantative evaluation of the structure of the spongy bone of the pastern bones was conducted. It was noted that the differences between the right and the left pastern bones, despite extensive loading of the left thoracic limb, were not statistically significant as far as all studied parameters of the trabecula structure of the spongy bone were concerned.

  11. Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

    Science.gov (United States)

    Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

    2014-03-01

    Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A

  12. Three-dimensional quantification of structures in trabecular bone using measures of complexity.

    Science.gov (United States)

    Marwan, Norbert; Kurths, Jürgen; Thomsen, Jesper Skovhus; Felsenberg, Dieter; Saparin, Peter

    2009-02-01

    The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three-dimensional (3D) imaging of bone challenges the development of data analysis techniques able to assess changes of the 3D microarchitecture of trabecular bone. We introduce an approach based on spatial geometrical properties and define structural measures of complexity for 3D image analysis. These measures evaluate different aspects of organization and complexity of 3D structures, such as complexity of its surface or shape variability. We apply these measures to 3D data acquired by high-resolution microcomputed tomography (microCT) from human proximal tibiae and lumbar vertebrae at different stages of osteoporotic bone loss. The outcome is compared to the results of conventional static histomorphometry and exhibits clear relationships between the analyzed geometrical features of trabecular bone and loss of bone density, but also indicate that the measures reveal additional information about the structural composition of bone, which were not revealed by the static histomorphometry. Finally, we have studied the dependency of the developed measures of complexity on the spatial resolution of the microCT data sets.

  13. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    Science.gov (United States)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  14. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone.

    Science.gov (United States)

    Meakin, Lee B; Price, Joanna S; Lanyon, Lance E

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones' strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone's mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them.

  15. Fine mapping of bone structure and strength QTLs in heterogeneous stock rat.

    Science.gov (United States)

    Alam, Imranul; Koller, Daniel L; Cañete, Toni; Blázquez, Gloria; Mont-Cardona, Carme; López-Aumatell, Regina; Martínez-Membrives, Esther; Díaz-Morán, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Stridh, Pernilla; Diez, Margarita; Olsson, Tomas; Johannesson, Martina; Baud, Amelie; Econs, Michael J; Foroud, Tatiana

    2015-12-01

    We previously demonstrated that skeletal structure and strength phenotypes vary considerably in heterogeneous stock (HS) rats. These phenotypes were found to be strongly heritable, suggesting that the HS rat model represents a unique genetic resource for dissecting the complex genetic etiology underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone structure and strength phenotypes using 1524 adult male and female HS rats between 17 to 20 weeks of age. Structure measures included femur length, neck width, head width; femur and lumbar spine (L3-5) areas obtained by DXA; and cross-sectional areas (CSA) at the midshaft, distal femur and femoral neck, and the 5th lumbar vertebra measured by CT. In addition, measures of strength of the whole femur and femoral neck were obtained. Approximately 70,000 polymorphic SNPs distributed throughout the rat genome were selected for genotyping, with a mean linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes were estimated across the entire genome for each rat using a multipoint haplotype reconstruction method, which calculates the probability of descent at each locus from each of the 8 HS founder strains. The haplotypes were then tested for association with each structure and strength phenotype via a mixed model with covariate adjustment. We identified quantitative trait loci (QTLs) for structure phenotypes on chromosomes 3, 8, 10, 12, 17 and 20, and QTLs for strength phenotypes on chromosomes 5, 10 and 11 that met a conservative genome-wide empiric significance threshold (FDR=5%; P<3×10(-6)). Importantly, most QTLs were localized to very narrow genomic regions (as small as 0.3 Mb and up to 3 Mb), each harboring a small set of candidate genes, both novel and previously shown to have roles in skeletal development and homeostasis.

  16. Modeling selective elimination of quiescent cancer cells from bone marrow.

    Science.gov (United States)

    Cavnar, Stephen P; Rickelmann, Andrew D; Meguiar, Kaille F; Xiao, Annie; Dosch, Joseph; Leung, Brendan M; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E; Takayama, Shuichi; Luker, Gary D

    2015-08-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    OpenAIRE

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque...

  18. Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain.

    Science.gov (United States)

    Nencini, Sara; Ringuet, Mitchell; Kim, Dong-Hyun; Chen, Yu-Jen; Greenhill, Claire; Ivanusic, Jason J

    2017-01-01

    Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.

  19. The effect of patulin on femoral bone structure in male rabbits

    Directory of Open Access Journals (Sweden)

    Veronika Kováčová

    2015-05-01

    Full Text Available A lot of kinds of crops are susceptible to fungal attack, leading to considerable financial losses and damage the health of humans and animals. Patulin, a toxic fungal metabolite, can be found mainly in apple and apple products, with much less frequent contamination in other food products. Because of its high incidence and harmful health effects, patulin belongs to a class of mycotoxins, which are strictly monitored. However, its effect on bone structure is still unknown. This study was designed to investigate the impact of patulin on femoral bone structure in adult male rabbits. Four month-old male rabbits were randomly divided into two groups of three animals each. Rabbits from the experimental group (group A, n=3 were intramuscularly administered with patulin at dose 10 μg.kg-1 body weight (b.w. twice a week for 4 weeks. The second group without patulin administration served as a control (group B, n=3. At the end of the experiment, body weight, femoral weight and length, cortical bone thickness and histological structure of femoral bones from all rabbits were determined. The results did not show any significant differences in body weight, femoral weight and length between experimental and control groups of rabbits. On the other hand, intramuscular application of patulin induced a significant increase in cortical bone thickness (p <0.05 and considerable changes in qualitative histological characteristics of compact bone in adult male rabbits. In patulin-intoxicated males, the primary vascular longitudinal bone tissue was absent near endosteal border. On the other hand, this tissue occurred near periosteum and also in the middle part of the femoral bone in these rabbits. The values for the primary osteons' vascular canals were significantly lower (p <0.05 in males exposed to patulin as compared to the control group. Based on these findings we can conclude that intramuscular patulin administration demonstrably influences cortical bone thickness

  20. Effects of altered crystalline structure and increased initial compressive strength of calcium sulfate bone graft substitute pellets on new bone formation.

    Science.gov (United States)

    Urban, Robert M; Turner, Thomas M; Hall, Deborah J; Infanger, Susan I; Cheema, Naveed; Lim, Tae-Hong; Moseley, Jon; Carroll, Michael; Roark, Michael

    2004-01-01

    A new, modified calcium sulfate has been developed with a different crystalline structure and a compressive strength similar to many calcium phosphate materials, but with a resorption profile only slightly slower than conventional surgical-grade calcium sulfate. A canine bilateral defect model was used to compare restoration of defects treated with the modified calcium sulfate compared to treatment using conventional calcium sulfate pellets after 6, 13, and 26 weeks. The modified calcium sulfate pellets were as effective as conventional calcium sulfate pellets with regard to the area fraction and compressive strength of newly formed bone in the treated bone defects. Mechanical testing demonstrated that the initial compressive strength of the modified material was increased nearly three-fold compared to that of conventional surgical-grade calcium sulfate. This increase potentially allows for its use in a broader range of clinical applications, such as vertebral and subchondral defects.

  1. New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

    Institute of Scientific and Technical Information of China (English)

    Sakae Tanaka; Taiji Adachi; Tatsuhiko Kuroda; Toshitaka Nakamura; Masataka Shiraki; Toshitsugu Sugimoto; Yasuhiro Takeuchi; Mitsuru Saito; John P Bilezikian

    2014-01-01

    Daily 20-mg and once-weekly 56.5-mg teriparatide (parathyroid hormone 1–34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

  2. Variability of Structural and Biomechanical Parameters of Pelophylax Esculentus (Amphibia, Anura Limb Bones

    Directory of Open Access Journals (Sweden)

    Broshko Ye. O.

    2014-07-01

    Full Text Available Variability of Structural and Biomechanical Prameters of Pelophylax esculentus (Amphibia, Anura Limb Bones. Broshko Ye. O. — Structural and biomechanical parameters of Edible Frog, Pelophylax esculentus (Linnaeus, 1758, limb bones, namely, mass, linear dimensions, parameters of the shaft’s cross-sectional shape (cross-sectional area, moments of inertia, radiuses of inertia were investigated. Some coefficients were also estimated: diameters ratio (df/ds, cross-sectional index (ik, principal moments of inertia ratio (Imax/Imin.. Coefficients of variation of linear dimensions (11.9-20.0 % anrelative bone mass (22-35 % were established. Moments of inertia of various bones are more variable (CV = 41.67-56.35 % in relation to radii of inertia (CV = 9.68-14.67 %. Shaft’s cross-sectional shape is invariable in all cases. However, there is high individual variability of structural and biomechanical parameters of P. esculentus limb bones. Variability of parameters was limited by the certain range. We suggest the presence of stable norm in bone structure. Stylopodium bones have the primary biomechanical function among the elements of limb skeleton, because their parameters most clearly responsive to changes in body mass.

  3. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model

    Science.gov (United States)

    Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2011-01-01

    Abstract Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29+, CD44+ and CD166+ after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. PMID

  4. Building a Structural Model: Parameterization and Structurality

    Directory of Open Access Journals (Sweden)

    Michel Mouchart

    2016-04-01

    Full Text Available A specific concept of structural model is used as a background for discussing the structurality of its parameterization. Conditions for a structural model to be also causal are examined. Difficulties and pitfalls arising from the parameterization are analyzed. In particular, pitfalls when considering alternative parameterizations of a same model are shown to have lead to ungrounded conclusions in the literature. Discussions of observationally equivalent models related to different economic mechanisms are used to make clear the connection between an economically meaningful parameterization and an economically meaningful decomposition of a complex model. The design of economic policy is used for drawing some practical implications of the proposed analysis.

  5. Evaluation of osteoporotic bone structure through synchrotron radiation X-ray microfluorescence images

    Energy Technology Data Exchange (ETDEWEB)

    Lima, I. [Nuclear Engineering Program/COPPE/UFRJ, P.O. Box 68509, Av. Horacio Macedo 2030, Sala I-133, Cidade Universitaria, 21941-914 Rio de Janeiro, RJ (Brazil)], E-mail: inaya@lin.ufrj.br; Anjos, M.J. [Nuclear Engineering Program/COPPE/UFRJ, P.O. Box 68509, Av. Horacio Macedo 2030, Sala I-133, Cidade Universitaria, 21941-914 Rio de Janeiro, RJ (Brazil); Physics Institute, UERJ (Brazil); Farias, M.L.F. [University Hospital, UFRJ (Brazil); Pantaleao, T.U.; Correa da Costa, V.M. [Biophysics Institute, UFRJ (Brazil); Lopes, R.T. [Nuclear Engineering Program/COPPE/UFRJ, P.O. Box 68509, Av. Horacio Macedo 2030, Sala I-133, Cidade Universitaria, 21941-914 Rio de Janeiro, RJ (Brazil)

    2008-12-15

    The abnormal accumulation or deficiency of trace elements may theoretically impair the formation of bone and contribute to osteoporosis. In this context, the knowledge of major and trace elements is very important in order to clarify many issues regarding diseases of the bone, such as osteoporosis, that remain unresolved. Several kinds of imaging techniques can be useful to access morphology and the minerals present in osteoporotic bones. In this work, synchrotron radiation X-ray microfluorescence was used as an X-ray imaging technique to investigate bone structures. Therefore, this research aims to improve the knowledge about some aspects of bone quality. The measurements were carried out at the Brazilian Synchrotron Laboratory Light Laboratory, in Brazil. A white beam with an energy range of 4-23 keV, a 45 deg./45 deg. geometry and a capillary optics were used. It was demonstrated that bone quality can and must be evaluated not only by considering the architecture of bones but also by taking into account the concentration and the distribution of minerals. Our results showed that the elemental distributions in bone zones on a micron scale were very helpful to understand functions in those structures.

  6. Implementation and Integration of a Finite Element Model into the Bone Remodeling Model to Characterize Skeletal Loading

    Science.gov (United States)

    Werner, C. R.; Lewandowski, B.; Boppana, A.; Pennline, J. A.

    2017-01-01

    NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

  7. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    Science.gov (United States)

    2013-01-01

    is currently limited by high costs and associated complications, including life-threatening cervical swelling4 and ectopic bone formation.5...fibrous ver- sus collagen zones. Biomechanical evaluation Immediately after euthanasia, eight excised radii and ul- nae per group (seven for the wrap group...serve as controls for the biomechanical evaluation. The specimens were tested to flexural failure in a 4-point bending configuration with 10- mm spacing

  8. A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health

    Science.gov (United States)

    Ward, Wendy E.; Kaludjerovic, Jovana; Dinsdale, Elsa C.

    2016-01-01

    Over the past decade, our research group has characterized and used a mouse model to demonstrate that “nutritional programming” of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-β-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health. PMID:27187422

  9. A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health.

    Science.gov (United States)

    Ward, Wendy E; Kaludjerovic, Jovana; Dinsdale, Elsa C

    2016-05-11

    Over the past decade, our research group has characterized and used a mouse model to demonstrate that "nutritional programming" of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-β-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health.

  10. Biomechanical properties of bone in a mouse model of Rett syndrome.

    Science.gov (United States)

    Kamal, Bushra; Russell, David; Payne, Anthony; Constante, Diogo; Tanner, K Elizabeth; Isaksson, Hanna; Mathavan, Neashan; Cobb, Stuart R

    2015-02-01

    Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2(stop/y) male mice in which Mecp2 is silenced in all cells and female Mecp2(stop/+) mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.

  11. Computation of bone remodelling after Duracon knee arthroplasty using a thermodynamic-based model.

    Science.gov (United States)

    Bougherara, H; Nazgooei, S; Sayyidmousavi, A; Marsik, F; Marík, I A

    2011-07-01

    The present study utilizes a recently developed literature model for the bone remodelling process to predict the evolution of bone density following Duracon total knee arthroplasty (TKA). In this model, which is based on chemical kinetics and irreversible thermodynamics, bone is treated as a self-organizing system capable of exchanging matter, energy, and entropy with its surroundings. Unlike previous models in which mechanical loading is regarded as the only stimulus for bone remodelling, the present model establishes a unique coupling between mechanical loading and the chemical reactions involved in the process of bone remodelling. This model was incorporated into the finite element software ANSYS by means of a macro to compute density distribution in distal femoral bone both before and after TKA. Consistent with dual-energy X-ray absorptiometry (DEXA) scans reported in the literature, the results showed that the most severe bone loss occurs in the anterior region of the distal femur and that there is more bone resorption in the lateral than the medial condyle following TKA. Furthermore, the bone density distribution predicted using the present model showed a gradual and uniform pattern and thus a more realistic bone evolution contrary to the strain energy density model, where there is no gradual bone density evolution.

  12. [Phytoestrogens role in bone functional structure protection in the ovariectomized rat].

    Science.gov (United States)

    Mihalache, Gr; Mihalache, Gr D; Indrei, L L; Indrei, Anca; Hegsted, Maren

    2002-01-01

    Effects of soy protein diet on bone formation and density were evaluated in ovariectomized rats as a model for postmenopausal women. Twenty-seven 9-month-old rats were assigned to 3 treatment groups for the 9-week study: sham-surgery (Sh, n = 9); ovariectomy (Ovx, n = 9); ovariectomy + soy diet (OvxS, n = 9). Rats had free access to an AIN-93 M diet or AIN-93 M diet with 7% soy protein concentration and water. At sacrifice, rear legs were removed, and the right femur and tibia were cleaned manually. Serum alkaline phosphatase, a marker of bone formation, was measured colorimetrically. Bone density was measured using Archimedes' Principle. Alkaline phosphatase activity was greater in OvxS (114 +/- 19 U/L) and Ovx (128 +/- 26 U/L) compared to Sh (110 +/- 22 U/L). Femur bone density was greater for OvxS (1.520 +/- 0.02 g/cc) compared to Ovx (1.510 +/- 0.017 g/cc), but not to Sh (1532 +/- 0.025 g/cc). Tibia bone density was greater for OvxS (1.560 +/- 0.019 g/cc) compared to Ovx (1.553 +/- 0.015 g/cc), but not to Sh (1566 +/- 0.03 g/cc). In conclusion soy protein diet increased the rate of bone formation and bone density in some bones, suggesting that may help prevent bone loss in postmenopausal women.

  13. Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

    Directory of Open Access Journals (Sweden)

    Pilar Sepulveda

    2002-09-01

    Full Text Available For thirty years it has been known that certain compositions of Na2O-CaO-P2O5-SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.

  14. Bone tissue incorporates in vitro gallium with a local structure similar to gallium-doped brushite.

    Science.gov (United States)

    Korbas, M; Rokita, E; Meyer-Klaucke, W; Ryczek, J

    2004-01-01

    During mineral growth in rat bone-marrow stromal cell cultures, gallium follows calcium pathways. The dominant phase of the cell culture mineral constitutes the poorly crystalline hydroxyapatite (HAP). This model system mimics bone mineralization in vivo. The structural characterization of the Ga environment was performed by X-ray absorption spectroscopy at the Ga K-edge. These data were compared with Ga-doped synthetic compounds (poorly crystalline hydroxyapatite, amorphous calcium phosphate and brushite) and with strontium-treated bone tissue, obtained from the same culture model. It was found that Sr(2+) substitutes for Ca(2+) in the HAP crystal lattice. In contrast, the replacement by Ga(3+) yielded a much more disordered local environment of the probe atom in all investigated cell culture samples. The coordination of Ga ions in the cell culture minerals was similar to that of Ga(3+), substituted for Ca(2+), in the Ga-doped synthetic brushite (Ga-DCPD). The Ga atoms in the Ga-DCPD were coordinated by four oxygen atoms (1.90 A) of the four phosphate groups and two oxygen atoms at 2.02 A. Interestingly, the local environment of Ga in the cell culture minerals was not dependent on the onset of Ga treatment, the Ga concentration in the medium or the age of the mineral. Thus, it was concluded that Ga ions were incorporated into the precursor phase to the HAP mineral. Substitution for Ca(2+ )with Ga(3+) distorted locally this brushite-like environment, which prevented the transformation of the initially deposited phase into the poorly crystalline HAP.

  15. Three-dimensional visualization and characterization of bone structure using reconstructed in-vitro μCT images: A pilot study for bone microarchitecture analysis

    Energy Technology Data Exchange (ETDEWEB)

    Latief, Fourier Dzar Eljabbar, E-mail: fourier@fi.itb.ac.id [Physics of Earth and Complex Systems, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Dewi, Dyah Ekashanti Octorina [2Biomedical Engineering Research Division, School of Electrical Engineering and Informatics, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Shari, Mohd Aliff Bin Mohd [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40000 Shah Alam, Selangor (Malaysia)

    2014-03-24

    Micro Computed Tomography (μCT) has been largely used to perform micrometer scale imaging of specimens, bone biopsies and small animals for the study of porous or cavity-containing objects. One of its favored applications is for assessing structural properties of bone. In this research, we perform a pilot study to visualize and characterize bone structure of a chicken bone thigh, as well as to delineate its cortical and trabecular bone regions. We utilize an In-Vitro μCT scanner Skyscan 1173 to acquire a three dimensional image data of a chicken bone thigh. The thigh was scanned using X-ray voltage of 45 kV and current of 150 μA. The reconstructed images have spatial resolution of 142.50 μm/pixel. Using image processing and analysis e.i segmentation by thresholding the gray values (which represent the pseudo density) and binarizing the images, we were able to visualize each part of the bone, i.e., the cortical and trabecular regions. Total volume of the bone is 4663.63 mm{sup 3}, and the surface area of the bone is 7913.42 mm{sup 2}. The volume of the cortical is approximately 1988.62 mm{sup 3} which is nearly 42.64% of the total bone volume. This pilot study has confirmed that the μCT is capable of quantifying 3D bone structural properties and defining its regions separately. For further development, these results can be improved for understanding the pathophysiology of bone abnormality, testing the efficacy of pharmaceutical intervention, or estimating bone biomechanical properties.

  16. Bone structural changes after gastric bypass surgery evaluated by HR-pQCT

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram Vinod; Støving, René Klinkby; Frederiksen, Katrine Diemer

    2017-01-01

    maximal at month 12 and stabilized from month 12 to 24. CONCLUSIONS: Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk......Objective, design and methods: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured areal bone mineral density at the hip and spine by dual-energy x...... measured at the same time points. RESULTS: After a 24.1% mean weight loss from baseline to month 12 (pweight plateaued from month 12 to 24 (-0.9%, p=0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5% and 7% reduction...

  17. Structural variation in the nasal bone region of European moose (Alces alces L.).

    Science.gov (United States)

    Nygrén, K; Paatsama, S; de Gritz, B

    1990-01-01

    The ontogeny of typical (normal) nasal bone region of the European moose (Alces alces L.) and the 3 variants of the pattern, was studied. The variants, named as "extra bone type", "punctured type" and "open type" referring the morphology of the internasal suture, were originally observed in Finnish male and female moose skulls in 1971. All of the variants were later found in hunting trophy exhibitions presenting male moose trophies from Sweden, Norway, Baltic Republics of USSR and Poland. The frequencies of the variants showed regional differences. By using histological, radiological and OTC bone labelling methods, all of the nasal bone types were observed in this study in embryonal (N = 36), newborn (N = 21), juvenile (N = 38) and adult (N = 12) moose. Two twin embryos showed different nasal bone structure. The variation is considered to be of congenital origin.

  18. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.

    Science.gov (United States)

    Chen, Guobao; Yang, Li; Lv, Yonggang

    2016-04-01

    To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing.

  19. The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models.

    Science.gov (United States)

    Kobayashi, Megumi; Matsumoto, Chiho; Hirata, Michiko; Tominari, Tsukasa; Inada, Masaki; Miyaura, Chisato

    2012-01-01

    We have invented a mouse model of periodontitis associated with alveolar bone loss induced by lipopolysaccharide. Ovariectomized (OVX) animals are widely used as a model for osteoporosis due to estrogen deficiency. To define the relationship between periodontitis and osteoporosis, we examined the influence of estrogen deficiency on the mouse alveolar bone mass. In OVX mice, bone loss was detected not only in the femur, but also in the alveolar bone, indicating that estrogen deficiency could induce resorption in alveolar bone. In experiments using a combination of osteoporosis and periodontitis models, OVX significantly enhanced the alveolar bone loss in the model of periodontitis. Therefore, postmenopausal osteoporosis may enhance the risk of periodontitis associated with inflammatory alveolar bone resorption.

  20. Structural system identification: Structural dynamics model validation

    Energy Technology Data Exchange (ETDEWEB)

    Red-Horse, J.R.

    1997-04-01

    Structural system identification is concerned with the development of systematic procedures and tools for developing predictive analytical models based on a physical structure`s dynamic response characteristics. It is a multidisciplinary process that involves the ability (1) to define high fidelity physics-based analysis models, (2) to acquire accurate test-derived information for physical specimens using diagnostic experiments, (3) to validate the numerical simulation model by reconciling differences that inevitably exist between the analysis model and the experimental data, and (4) to quantify uncertainties in the final system models and subsequent numerical simulations. The goal of this project was to develop structural system identification techniques and software suitable for both research and production applications in code and model validation.

  1. CT assisted biomimetic artificial bone des

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-gang; ZHANG Chao-zong; GUO Zhi-ping; TIAN Jie-mo

    2001-01-01

    @@ In the recent years, bioceramic materials have been widely used in the clinics. They are mainly fabricated as the substitution of human hard tissue, such as artificial bone and false tooth. As a medical implant, those that have similar structure to human bone have better biocompatibility and osteoinductional property. So it is necessary to design bone model close to human bone.

  2. Structural dynamic modifications via models

    Indian Academy of Sciences (India)

    T K Kundra

    2000-06-01

    Structural dynamic modification techniques attempt to reduce dynamic design time and can be implemented beginning with spatial models of structures, dynamic test data or updated models. The models assumed in this discussion are mathematical models, namely mass, stiffness, and damping matrices of the equations of motion of a structure. These models are identified/extracted from dynamic test data viz. frequency response functions (FRFs). Alternatively these models could have been obtained by adjusting or updating the finite element model of the structure in the light of the test data. The methods of structural modification for getting desired dynamic characteristics by using modifiers namely mass, beams and tuned absorbers are discussed.

  3. Bilateral vascularized femoral bone transplant: a new model of vascularized bone marrow transplantation in rats, part I.

    Science.gov (United States)

    Agaoglu, Galip; Carnevale, Kevin A; Zins, James E; Siemionow, Maria

    2006-06-01

    We present a new model of vascularized bone marrow transplantation-bilateral vascularized femoral bone (BVFB) isograft transplant based on abdominal aorta and inferior vena cava. A total of 7 BVFB isograft transplants were performed between Lewis (RT1) rats. In the donor, both femoral bones were harvested based on the abdominal aorta and inferior vena cava. In the recipient, the harvested isograft transplants were transferred into the inguinal region (in 3 animals) and into the abdominal cavity (in 4 animals). The mean operation time was 3 hours and 35 minutes. The mean warm ischemic time was 35 minutes. The vascular pedicles of the transplants that were transferred into the inguinal region were thrombosed at day 7 posttransplantation. The vascular pedicles of transplants into the abdominal cavity were patent and the bones were viable during the follow-up period of 63 days posttransplant. We have confirmed the feasibility of BVFB transplantation based on abdominal aorta and inferior vena cava.

  4. Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Aspenberg Per

    2002-08-01

    Full Text Available Abstract Background Avascular necrosis of bone (osteonecrosis can cause structural failure and subsequent deformation, leading to joint dysfunction and pain. Structural failure is the result of resorption of necrotic bone during revascularization, before new bone has formed or consolidated enough for loadbearing. Bone resorption can be reduced by bisphosphonates. If resorption of the necrotic bone could be reduced during the revascularization phase until sufficient new bone has formed, it would appear that structural failure could be avoided. Methods To test whether resorption of necrotic bone can be prevented, structural grafts were subjected to new bone ingrowth during systemic bisphosphonate treatment in a rat model. Results In rats treated with alendronate the necrotic bone was not resorbed, whereas it was almost entirely resorbed in the controls. Conclusion Systemic alendronate treatment prevents resorption of necrotic bone during revascularization. In patients with osteonecrosis, bisphosphonates may therefore prevent collapse of the necrotic bone.

  5. Experimental validation of a nonlinear μFE model based on cohesive-frictional plasticity for trabecular bone.

    Science.gov (United States)

    Schwiedrzik, J; Gross, T; Bina, M; Pretterklieber, M; Zysset, P; Pahr, D

    2016-04-01

    Trabecular bone is a porous mineralized tissue playing a major load bearing role in the human body. Prediction of age-related and disease-related fractures and the behavior of bone implant systems needs a thorough understanding of its structure-mechanical property relationships, which can be obtained using microcomputed tomography-based finite element modeling. In this study, a nonlinear model for trabecular bone as a cohesive-frictional material was implemented in a large-scale computational framework and validated by comparison of μFE simulations with experimental tests in uniaxial tension and compression. A good correspondence of stiffness and yield points between simulations and experiments was found for a wide range of bone volume fraction and degree of anisotropy in both tension and compression using a non-calibrated, average set of material parameters. These results demonstrate the ability of the model to capture the effects leading to failure of bone for three anatomical sites and several donors, which may be used to determine the apparent behavior of trabecular bone and its evolution with age, disease, and treatment in the future.

  6. Integrated materials–structural models

    DEFF Research Database (Denmark)

    Stang, Henrik; Geiker, Mette Rica

    2008-01-01

    Reliable service life models for load carrying structures are significant elements in the evaluation of the performance and sustainability of existing and new structures. Furthermore, reliable service life models are prerequisites for the evaluation of the sustainability of maintenance strategies......, repair works and strengthening methods for structures. A very significant part of the infrastructure consists of reinforced concrete structures. Even though reinforced concrete structures typically are very competitive, certain concrete structures suffer from various types of degradation. A framework...

  7. In Vivo Models for the Evaluation of the Osteogenic Potency of Bone Substitutes Seeded with Mesenchymal Stem Cells of Human Origin: A Concise Review.

    Science.gov (United States)

    Westhauser, Fabian; Senger, Anne-Sophie; Reible, Bruno; Moghaddam, Arash

    2017-09-01

    Research concerning bone substitutes is one of the most challenging fields in orthopedic research and has a high clinical relevance, especially since the currently available bone substitutes are limited in their osteostimulative capabilities. In vitro models for the evaluation of the properties of bone substitutes allow the use of human mesenchymal stem cells (hMSCs) seeded onto scaffolds, but suffer from the lack of a physiological environment for those cells. Most in vivo models include the use of non-hMSC and are therefore lacking in clinical relevance. To overcome these issues, in vivo models were created that allow the evaluation of hMSC-seeded bone substitutes, combining the advantages of the use of human cells with the physiological conditions of an organism in vivo. In brief, models usually aim for bone formation in immunocompromised rodents. The subcutaneous implantation of scaffolds is most widely performed, showing low complication rates along with good results, but suffering from inferior vascularization of the implants and the absence of the realistic structural and mechanical conditions of bone. Orthotopic implantation, for example in calvarian or long bone defects, provides the most appropriate surrounding for hMSC-seeded scaffolds. However, parallel host-induced bone formation is a major limitation. This review summarizes in vivo models for the evaluation of the osteogenic potency of bone substitutes seeded with mesenchymal stem cells of human origin.

  8. Non-invasive bone competence analysis by high-resolution pQCT: an in vitro reproducibility study on structural and mechanical properties at the human radius.

    Science.gov (United States)

    Mueller, Thomas L; Stauber, Martin; Kohler, Thomas; Eckstein, Felix; Müller, Ralph; van Lenthe, G Harry

    2009-02-01

    Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength. Bone strength depends, among others, on bone density, bone geometry and its internal architecture. With the recent introduction of a new generation high-resolution 3D peripheral quantitative computed tomography (HR-pQCT) system, direct quantification of structural bone parameters has become feasible. Furthermore, it has recently been demonstrated that bone mechanical competence can be derived from HR-pQCT based micro-finite element modeling (microFE). However, reproducibility data for HR-pQCT-derived mechanical indices is not well-known. Therefore, the aim of this study was to quantify reproducibility of HR-pQCT-derived indices. We measured 14 distal formalin-fixed cadaveric forearms three times and analyzed three different regions for each measurement. For each region cortical and trabecular parameters were determined. Reproducibility was assessed with respect to precision error (PE) and intraclass correlation coefficient (ICC). Reproducibility values were found to be best in all three regions for the full bone compartment with an average PE of 0.79%, followed by the cortical compartment (PE=1.19%) and the trabecular compartment with an average PE of 2.31%. The mechanical parameters showed similar reproducibility (PE=0.48%-2.93% for bone strength and stiffness, respectively). ICC showed a very high reproducibility of subject-specific measurements, ranging from 0.982 to 1.000, allowing secure identification of individual donors ranging from healthy to severely osteoporotic subjects. From these in vitro results we conclude that HR-pQCT derived morphometric and mechanical parameters are highly reproducible such that differences in bone structure and strength can be detected with a reproducibility error smaller than 3%; hence, the technique has a high potential to become a tool for detecting bone quality and bone competence of individual subjects.

  9. Structural Influence on the Mechanical Response of Adolescent Gottingen Porcine Cranial Bone

    Science.gov (United States)

    2016-10-01

    and implications for mechanisms of pediatric brain injury. Journal of Biomechanical Engineering. 2000;122(4):364–371. 9. Coats B, Margulies SS...34. Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. The Journal of Bone & Joint Surgery . 1977;59(7):954–962...American Journal of Anatomy. 1967;120(1):7–31. 5. McElhaney JH, Fogle JL, Melvin JW, Haynes RR, Roberts VL, Alem NM. Mechanical properties of

  10. Bone Morphogenetic Protein-2 Nonviral Gene Therapy in a Goat Iliac Crest Model for Bone Formation

    NARCIS (Netherlands)

    Loozen, Loek D.; van der Helm, Yvonne J. M.; Oner, F. Cumhur; Dhert, W.J.A.; Kruyt, Moyo C.; Alblas, Jacqueline

    2015-01-01

    Treatment and reconstruction of large bone defects, delayed unions, and nonunions is challenging and has resulted in an ongoing search for novel tissue-engineered therapies. Bone morphogenetic protein-2 (BMP-2) gene therapy is a promising strategy to provide sustained production of BMP-2 locally. Al

  11. Development of a Three-Dimensional (3D Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

    Directory of Open Access Journals (Sweden)

    Ying-Chao Chou

    2016-04-01

    Full Text Available This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

  12. Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

    Science.gov (United States)

    Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

    2016-04-20

    This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

  13. Bone tissue stiffness in the mandibular condyle is dependent on the direction and density of the cancellous structure.

    NARCIS (Netherlands)

    Eijden, T.M. van; Ruijven, L.J. van; Giesen, E.B.W.

    2004-01-01

    Variation in the apparent stiffness of cancellous bone is generally ascribed to variation in cancellous structure and density, while the bone tissue stiffness is assumed to be constant. The purpose of the present study was to examine whether the bone tissue stiffness is dependent on the direction an

  14. Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

    Directory of Open Access Journals (Sweden)

    Hongbin Lu

    Full Text Available This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point. The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate

  15. Bone marrow lambda-type light chain crystalline structures associated with multiple myeloma.

    Science.gov (United States)

    Schvartz, H; Bonhomme, P; Caulet, S; Beorchia, A; Patey, M; Caulet, T

    1985-01-01

    A 58-year-old man showed bone marrow crystalline structures associated with a lambda light chain producing multiple myeloma. Analysis and processing of electron images clearly displayed the periodic structure of the crystals. Immunochemistry suggested that they contained the whole or a fragmented constant portion of immunoglobulin.

  16. Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures

    NARCIS (Netherlands)

    Biemond, J.E.; Eufrasio, T.S.; Hannink, G.J.; Verdonschot, N.J.J.; Buma, P.

    2011-01-01

    The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a per

  17. Trabecular bone structure correlates with hand posture and use in hominoids.

    Science.gov (United States)

    Tsegai, Zewdi J; Kivell, Tracy L; Gross, Thomas; Nguyen, N Huynh; Pahr, Dieter H; Smaers, Jeroen B; Skinner, Matthew M

    2013-01-01

    Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan), suspensory (Pongo, Hylobates and Symphalangus) and manipulative (Homo) taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus) correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link between inferred

  18. Trabecular bone structure correlates with hand posture and use in hominoids.

    Directory of Open Access Journals (Sweden)

    Zewdi J Tsegai

    Full Text Available Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan, suspensory (Pongo, Hylobates and Symphalangus and manipulative (Homo taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link

  19. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  20. Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

    Science.gov (United States)

    Sibonga, J. D.; Feiveson, A. H.

    2014-01-01

    This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an

  1. Oncologic doses of zoledronic acid induce site specific suppression of bone modelling in rice rats.

    Science.gov (United States)

    Exposto, C R; Oz, U; Callard, J S; Allen, M J; Khurana, H; Atri, A D'; Mo, X; Fernandez, S A; Tatakis, D N; Edmonds, K; Westgate, P M; Huja, S S

    2017-06-01

    To examine the effect of zoledronic acid (ZOL) on cortical bone modelling and healing of extraction sockets in the jaw bones of a rodent model. We hypothesized ZOL suppresses both the bone formation in the modelling mode in the jaw bones and alters the extraction site healing. Rice rats were administered saline solution and two dose regimens of ZOL: 0.1 mg/kg, twice a week, for 4 weeks (n=17, saline=8 & ZOL=9) and a higher dose of 0.4 mg/kg, weekly, for 9 weeks (n=30, saline=15 & ZOL=15). Two pairs of fluorochrome bone labels were administered. Extraction of maxillary teeth was performed in maxilla. Mineral apposition rate, mineralizing surface and bone formation rate (BFR) were quantified on periodontal (PDL), alveolar and basal bone surfaces, and in the trabecular bone of proximal tibia. Bone volume (BV) was evaluated at extraction sockets. Multivariate Gaussian models were used to account for repeated measurements, and analyzes were conducted in SAS V9.3. ZOL suppressed bone modelling (BFR/BS) at the PDL surfaces in the mandible (Pmodelling mode in the jaws demonstrates the site specific effects of ZOL in rice rats. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. PERCEPTION OF MEDICAL STUDENTS TOWARDS ARTIFICIAL BONES AND POP MODELS OF VISCERA

    Directory of Open Access Journals (Sweden)

    Sumit Tulshidas Patil

    2015-03-01

    Full Text Available Background: In learning of anatomy, bones and viscera are very important. Now days, artificial bones are replacing the original bones for study purpose due to unavailability. Original viscera are available for students only at dissection hours. So we have tried to find out perception of medical students towards artificial bones and POP models of viscera. Materials and Methods: We had prepared a questionnaire consisting of 20 questions, 10 related to bones and 10 related to the POP models of viscera and asked 150 students of 1st year MBBS to answer it. Results: All the 150 students agreed that bones are necessary for study but only 36 students have bone set (14 original & 22 artificial. Maximum students get the bones only when made available from department. While 107 (71% students said they would prefer original specimen of viscera, over POP models, for studying; but still 126 (84% wanted to keep the POP models of viscera while studying its relations from text book. Conclusions: Good quality artificial bones should be promoted for students, if original bones are not available. It will be better than having nothing. POP models of viscera cannot replace original viscera but due to its handy quality will be helpful for understanding.

  3. Mathematical modeling of appendicular bone growth in glaucous-winged gulls.

    Science.gov (United States)

    Hayward, James L; Henson, Shandelle M; Banks, John C; Lyn, Sheena L

    2009-01-01

    Development of locomotor activity is crucial in tetrapods. In birds, this development leads to different functions for hindlimbs and forelimbs. The emergence of walking and flying as very different complex behavior patterns only weeks after hatching provides an interesting case study in animal development. We measured the diaphyseal lengths and midshaft diameters of three wing bones (humerus, ulna, and carpometacarpus) and three leg bones (femur, tibiotarsus, and tarsometatarsus) of 79 juvenile (ages 0-42 days) and 13 adult glaucous-winged gulls (Larus glaucescens), a semiprecocial species. From a suite of nine alternative mathematical models, we used information-theoretic criteria to determine the best model(s) for length and diameter of each bone as a function of age; that is, we determined the model(s) that obtained the best tradeoff between the minimized sum of squared residuals and the number of parameters used to fit the model. The Janoschek and Holling III models best described bone growth, with at least one of these models yielding an R(2) > or = 0.94 for every dimension except tarsometatarsus diameter (R(2) = 0.87). We used the best growth models to construct accurate allometric comparisons of the bones. Early maximal absolute growth rates characterize the humerus, femur, and tarsometatarsus, bones that assume adult-type support functions relatively early during juvenile development. Leg bone lengths exhibit more rapid but less sustained relative growth than wing bone lengths. Wing bone diameters are initially smaller than leg bone diameters, although this relationship is reversed by fledging. Wing bones and the femur approach adult length by fledging but continue to increase in diameter past fledging; the tibiotarsus and tarsometatarsus approach both adult length and diameter by fledging. In short, the pattern of bone growth in this semiprecocial species reflects the changing behavioral needs of the developing organism. 2008 Wiley-Liss, Inc.

  4. Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

    Science.gov (United States)

    Zhang, Jingwei; Sun, Lanying; Luo, Xiaoman; Barbieri, Davide; de Bruijn, Joost D; van Blitterswijk, Clemens A; Moroni, Lorenzo; Yuan, Huipin

    2017-02-08

    Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone

  5. Elemental and structural studies at the bone-cartilage interface

    Energy Technology Data Exchange (ETDEWEB)

    Kaabar, W., E-mail: w.kaabar@surrey.ac.uk [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Daar, E. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Bunk, O. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen (Switzerland); Farquharson, M.J. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada); Laklouk, A. [Al-Fateh University, Tripoli (Libya); Bailey, M.; Jeynes, C. [Surrey Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom); Gundogdu, O. [Umuttepe Campus, University of Kocaeli, 41380 Kocaeli (Turkey); Bradley, D.A. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2011-10-01

    Micro-Proton Induced X-ray Emission ({mu}-PIXE) and Proton Induced Gamma-ray Emission (PIGE) techniques were employed in the investigation of trace and essential elements distribution in normal and diseased human femoral head sections affected by osteoarthritis (OA). PIGE was exploited in the determination of elements of low atomic number z<15 such as Na and F whereas elements with z>15 viz Ca, Z, P and S were determined by PIXE. Accumulations of key elements in the bone and cartilage sections were observed, significant S and Na concentrations being found in the cartilage region particularly in normal tissues. Zn showed enhanced concentrations at the bone-cartilage interface. At a synchrotron facility, small angle X-ray scattering (SAXS) was utilized on a decalcified human femoral head section affected by OA, direct measurements being made of spatial alterations of collagen fibres. The SAXS results showed a slight decrease in the axial periodicity between normal collagen type I and that in diseased tissue in various sites, in contrast with the findings of others.

  6. Infill Optimization for Additive Manufacturing -- Approaching Bone-like Porous Structures.

    Science.gov (United States)

    Wu, Jun; Aage, Niels; Westermann, Ruediger; Sigmund, Ole

    2017-01-23

    Porous structures such as trabecular bone are widely seen in nature. These structures are lightweight and exhibit strong mechanical properties. In this paper, we present a method to generate bone-like porous structures as lightweight infill for additive manufacturing. Our method builds upon and extends voxel-wise topology optimization. In particular, for the purpose of generating sparse yet stable structures distributed in the interior of a given shape, we propose upper bounds on the localized material volume in the proximity of each voxel in the design domain. We then aggregate the local per-voxel constraints by their p-norm into an equivalent global constraint, in order to facilitate an efficient optimization process. Implemented on a high-resolution topology optimization framework, our results demonstrate mechanically optimized, detailed porous structures which mimic those found in nature. We further show variants of the optimized structures subject to different design specifications, and we analyze the optimality and robustness of the obtained structures.

  7. In vivo XCT bone characterization of lattice structured implants fabricated by additive manufacturing

    Directory of Open Access Journals (Sweden)

    A-F. Obaton

    2017-08-01

    Full Text Available Several cylindrical specimens and dental implants, presenting diagonal lattice structures with different cell sizes (600, 900 and 1200 μm were additively manufactured by selective laser melting process. Then they were implanted for two months in a sheep. After removal, they were studied by Archimedes’ method as well as X-ray computed tomography in order to assess the penetration of bone into the lattice. We observed that the additive manufactured parts were geometrically conformed to the theoretical specifications. However, several particles were left adhering to the surface of the lattice, thereby partly or entirely obstructing the cells. Nevertheless, bone penetration was clearly visible. We conclude that the 900 μm lattice cell size is more favourable to bone penetration than the 1200 μm lattice cell size, as the bone penetration is 84% for 900 μm against 54% for 1200 μm cell structures. The lower bone penetration value for the 1200 μm lattice cell could possibly be attributed to the short residence time in the sheep. Our results lead to the conclusion that lattice implants additively manufactured by selective laser melting enable better bone integration.

  8. Bone disease in diabetes

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V.; Hansen, Stinus; Frost, Morten

    2017-01-01

    Type 1 and type 2 diabetes are generally accepted to be associated with increased bone fracture risk. However, the pathophysiological mechanisms of diabetic bone disease are poorly understood, and whether the associated increased skeletal fragility is a comorbidity or a complication of diabetes...... remains under debate. Although there is some indication of a direct deleterious effect of microangiopathy on bone, the evidence is open to question, and whether diabetic osteopathy can be classified as a chronic, microvascular complication of diabetes remains uncertain. Here, we review the current...... knowledge of potential contributory factors to diabetic bone disease, particularly the association between diabetic microangiopathy and bone mineral density, bone structure, and bone turnover. Additionally, we discuss and propose a pathophysiological model of the effects of diabetic microvascular disease...

  9. PRODUCT STRUCTURE DIGITAL MODEL

    Directory of Open Access Journals (Sweden)

    V.M. Sineglazov

    2005-02-01

    Full Text Available  Research results of representation of product structure made by means of CADDS5 computer-aided design (CAD system, Product Data Management Optegra (PDM system and Product Life Cycle Management Wind-chill system (PLM, are examined in this work. Analysis of structure component development and its storage in various systems is carried out. Algorithms of structure transformation required for correct representation of the structure are considered. Management analysis of electronic mockup presentation of the product structure is carried out for Windchill system.

  10. Elemental and structural studies at the bone-cartilage interface

    Science.gov (United States)

    Bradley, D. A.; Kaabar, W.; Gundogdu, O.

    2012-02-01

    The techniques μProton-Induced X-and γ-ray Emission, μ-PIXE and μ-PIGE, were used to investigate trace and essential element distributions in sections of normal and osteoarthritic (OA) human femoral head. μ-PIGE yielded 2-D mappings of Na and F while Ca, Z, P and S were mapped by μ-PIXE. The concentration of chondroitin sulphate supporting functionality in healthy cartilage is significantly reduced in OA samples. Localised Zn points to osteoblastic/osteoclastic activity at the bone-cartilage interface. Small-angle X-ray scattering applied to decalcified OA-affected tissue showed spatial alterations of collagen fibres of decreased axial periodicity compared to normal collagen type I.

  11. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  12. Drilling in cortical bone: a finite element model and experimental investigations.

    Science.gov (United States)

    Lughmani, Waqas A; Bouazza-Marouf, Kaddour; Ashcroft, Ian

    2015-02-01

    Bone drilling is an essential part of many orthopaedic surgery procedures, including those for internal fixation and for attaching prosthetics. Estimation and control of bone drilling forces are critical to prevent drill-bit breakthrough, excessive heat generation, and mechanical damage to the bone. An experimental and computational study of drilling in cortical bone has been conducted. A 3D finite element (FE) model for prediction of thrust forces experienced during bone drilling has been developed. The model incorporates the dynamic characteristics involved in the process along with geometrical considerations. An elastic-plastic material model is used to predict the behaviour of cortical bone during drilling. The average critical thrust forces and torques obtained using FE analysis are found to be in good agreement with the experimental results.

  13. Bone regeneration by octacalcium phosphate collagen composites in a dog alveolar cleft model.

    Science.gov (United States)

    Matsui, K; Matsui, A; Handa, T; Kawai, T; Suzuki, O; Kamakura, S; Echigo, S

    2010-12-01

    Octacalcium phosphate (OCP) and porcine atelocollagen sponge composites (OCP/Col) markedly enhanced bone regeneration in a rat cranial defect model. To assess clinical application, the authors examined whether OCP/Col would enhance bone regeneration in an alveolar cleft model in an adult dog, which was assumed to reflect patients with alveolar cleft. Disks of OCP/Col or collagen were implanted into the defect and bone regeneration by OCP/Col or collagen was investigated 4 months after implantation. Macroscopically, the OCP/Col-treated alveolus was obviously augmented and occupied by radio-opacity, and the border between the original bone and the defect was indistinguishable. Histological analysis revealed it was filled and bridged with newly formed bone; a small quantity of the remaining implanted OCP was observed. X-ray diffraction patterns of the area of implanted OCP/Col indicated no difference from those of dog bone. In the collagen-treated alveolus, the hollowed alveolus was mainly filled with fibrous connective tissue, and a small amount of new bone was observed at the defect margin. These results suggest that bone was obviously repaired when OCP/Col was implanted into the alveolar cleft model in a dog, and OCP/Col would be a significant bone regenerative material to substitute for autogeneous bone.

  14. Trabecular bone structure analysis in the limited spatial resolution regime of in vivo MRI.

    Science.gov (United States)

    Magland, Jeremy F; Wehrli, Felix W

    2008-12-01

    To develop a method for processing and visualization of trabecular bone networks on the basis of magnetic resonance (MR) images acquired in the limited spatial resolution regime of in vivo imaging at which trabecular thickness is comparable to voxel size. A sequence of processing steps for analyzing the topologic structure of trabecular bone networks is presented and evaluated using three types of datasets: images of synthetic structures with various levels of superimposed Gaussian noise, micro-computed tomographic images of human trabecular bone downsampled to in vivo resolution, and in vivo micro-MR images from a prior longitudinal study investigating the structural implications of testosterone treatment of hypogonadal men. The simulated images were analyzed at a voxel size of 150 microm(3), the clinical MR image data had been acquired with 137 x 137 x 410 microm(3) voxel size. The technique is a modification to the virtual bone biopsy processing chain that involves a sinc convolution step immediately preceding binarization, and employs the Manzanera-Bernard thinning algorithm for obtaining the three-dimensional skeleton before topologic classification. The detectability of plate and rod bone elements was also analyzed theoretically. As compared with previously published techniques, the approach produced a more accurate bone skeleton in the micro-computed tomographic and simulation experiments, with clear improvement in preservation of rod and plate elements. Simulations suggest that rods are detectable down to a diameter of approximately 50% of the MR image voxel length, whereas plates can be detected at thicknesses of 20% or more of voxel length. For in vivo studies, it was shown that the method could recover the treatment response in terms of the ensuing topologic changes in patients undergoing antiresorptive treatment. The algorithm for processing of in vivo micro-MR images of trabecular bone is superior to prior approaches in preserving the topology of the

  15. Phylogenetic, functional, and structural components of variation in bone growth rate of amniotes.

    Science.gov (United States)

    Cubo, Jorge; Legendre, Pierre; de Ricqlès, Armand; Montes, Laëtitia; de Margerie, Emmanuel; Castanet, Jacques; Desdevises, Yves

    2008-01-01

    The biological features observed in every living organism are the outcome of three sets of factors: historical (inherited by homology), functional (biological adaptation), and structural (properties inherent to the materials with which organs are constructed, and the morphogenetic rules by which they grow). Integrating them should bring satisfactory causal explanations of empirical data. However, little progress has been accomplished in practice toward this goal, because a methodologically efficient tool was lacking. Here we use a new statistical method of variation partitioning to analyze bone growth in amniotes. (1) Historical component. The variation of bone growth rates contains a significant phylogenetic signal, suggesting that the observed patterns are partly the outcome of shared ancestry. (2) Functional causation. High growth rates, although energy costly, may be adaptive (i.e., they may increase survival rates) in taxa showing short growth periods (e.g., birds). In ectothermic amniotes, low resting metabolic rates may limit the maximum possible growth rates. (3) Structural constraint. Whereas soft tissues grow through a multiplicative process, growth of mineralized tissues is accretionary (additive, i.e., mineralization fronts occur only at free surfaces). Bone growth of many amniotes partially circumvents this constraint: it is achieved not only at the external surface of the bone shaft, but also within cavities included in the bone cortex as it grows centrifugally. Our approach contributes to the unification of historicism, functionalism, and structuralism toward a more integrated evolutionary biology.

  16. Preclinical mouse models for assessing axial compression of long bones during exercise.

    Science.gov (United States)

    Stadelmann, Vincent A; Brun, Julia; Bonnet, Nicolas

    2015-01-01

    The aim of this laboratory method is to describe two approaches for the investigation of bone responses to mechanical loading in mice in vivo. The first is running exercise, because it is easily translatable clinically, and the second is axial compression of the tibia, because it is precisely controllable. The effects of running exercise, and in general physical activity, on bone tissue have been shown to be both direct through mechanical loading (ground impact and muscle tension) and indirect through metabolic changes. Therefore, running exercise has been considered the most convenient preclinical model for demonstrating the general idea that exercise is good for bone health, either early in age for increasing peak bone mass or later in age by slowing down bone loss. However, numerous combinations of protocols have been reported, which makes it difficult to formulate a simple take-home message. This laboratory method also provides a detailed description of in vivo direct mechanical axial compression of the mouse tibia. The effects of mechanical loading depend on the force (strain), frequency, waveform and duration of application, and they range from bone anabolism with low bone remodeling, inducing lamellar bone accumulation, to bone catabolism with high bone remodeling, leading to microdamage, woven bone formation and bone loss. Direct in vivo loading models are extensively used to study mechanotransduction pathways, and contribute by this way to the development of new bone anabolism treatments. Although it is particularly difficult to assemble an internationally adopted protocol description, which would give reproducible bone responses, here we have attempted to provide a comprehensive guide for best practice in performing running exercise and direct in vivo mechanical loading in the laboratory.

  17. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues.

    Science.gov (United States)

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  18. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    Directory of Open Access Journals (Sweden)

    Gong Zhang

    2016-01-01

    Full Text Available Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  19. Repair of segmental long bone defect in a rabbit radius nonunion model: comparison of cylindrical porous titanium and hydroxyapatite scaffolds.

    Science.gov (United States)

    Zhang, Ming; Wang, Guang-lin; Zhang, Hong-fang; Hu, Xu-dong; Shi, Xiao-yuan; Li, Sen; Lin, Wei

    2014-06-01

    A segmental long bone defect in a rabbit radius nonunion model was repaired using cylindrical porous titanium (Ti) and hydroxyapatite (HA) scaffolds. Each scaffold was produced using the same method, namely, a slurry foaming method. Repairing ability was characterized using x-radiographic score 12 and 24 weeks postprocedure; failure load of the radius-ulna construct, under three-point bending, 12 weeks postprocedure; and the percentage of newly formed bone within the implant, 12 and 24 weeks after postprocedure. For each of these parameters, the difference in the results when porous Ti scaffold was used compared with when HA scaffolds were used was not significant; both porous scaffolds showed excellent repairing ability. Because the trabecular bone is a porous tissue, the interconnected porous scaffolds have the advantages of natural bone, and vasculature can grow into the porous structure to accelerate the osteoconduction and osteointegration between the implant and bone. The porous Ti scaffold not only enhanced the bone repair process, similar to porous HA scaffolds, but also has superior biomechanical properties. The present results suggest that porous Ti scaffolds may have promise for use in the clinical setting.

  20. Histological and mechanical evaluation of self-setting calcium phosphate cements in a sheep vertebral bone void model.

    Science.gov (United States)

    Kobayashi, Naomi; Ong, Kevin; Villarraga, Marta; Schwardt, Jeffrey; Wenz, Robert; Togawa, Daisuke; Fujishiro, Takaaki; Turner, A Simon; Seim, Howard B; Bauer, Thomas W

    2007-06-15

    We investigated the histological and compressive properties of three different calcium phosphate cements (CPCs) using a sheep vertebral bone void model. One of the CPCs contained barium sulfate to enhance its radiopacity. Bone voids were surgically created in the lumbar region of 23 ovine spines - L3, L4, and L5 (n = 69 total vertebral bodies) - and the voids were filled with one of the three CPCs. A fourth group consisted of whole intact vertebrae. Histologic evaluation was performed for 30 of the 69 vertebrae 2 or 4 months after surgery along with radiographic evaluation. Compressive testing was performed on 39 vertebrae 4 months after surgery along with micro-CT analysis. All three CPCs were biocompatible and extremely osteoconductive. Osteoclasts associated with adjacent bone formation suggest that each cement can undergo slow resorption and replacement by bone and bone marrow. Compressive testing did not reveal a significant difference in the ultimate strength, ultimate strain, and structural modulus, among the three CPCs and intact whole vertebrae. Micro-CT analysis revealed good osseointegration between all three CPCs and adjacent bone. The barium sulfate did not affect the CPCs biocompatibility or mechanical properties. These results suggest that CPC might be a good alternative to polymethylmethacrylate for selected indications.

  1. Comparative Protein Structure Modeling Using MODELLER.

    Science.gov (United States)

    Webb, Benjamin; Sali, Andrej

    2016-06-20

    Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley & Sons, Inc.

  2. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure.

    Science.gov (United States)

    Fliedner, T M; Graessle, D; Paulsen, C; Reimers, K

    2002-08-01

    It is the purpose of this presentation to review the unique structure and function of bone marrow anchored hematopoiesis in their significance for its response mechanisms to an exposure to ionizing radiation. The ultimate objective of bone marrow hematopoiesis is to maintain in the peripheral blood a constant level of the different blood cell types (erythrocytes, granulocytes, platelets, lymphocytes, etc.). All of them have their particular turnover kinetics (such as granulocytes 120 x 10(9)/d, erythrocytes 200 x 10(9)/d or thrombocytes 150 x 10(9)/d), are semi-autonomous in their steady state regulatory mechanisms and dependent on a life-long supply of mature cells from a stem cell pool with unlimited replicative and pluripotent differentiative potential. The present knowledge of hematopoietic cellular renewal is the result of years of basic experimental and clinical studies using radionuclides in various metabolic forms including (59)Fe, (32)P (DF (32)P), (51)Cr, (131)I, (60)Co, (3)H ((3)HTdR) and (14)C ((14)CTdR). To understand the physiology but in particular the radiation-pathophysiology, it is essential to recognize in detail the infrastructure of the bone marrow as a distinct unit. Indispensable for a life-long cell production is the capsule of the marrow - the bone cortex -, the arterial supply of blood connected to the sinusoidal microvascular architecture with its sinusoids contorti and recti as well as the central (cell collecting) sinusoids. It is further of importance to recognize the significance of nerval regulation of blood flow, characterized by myelinated and unmyelinated nerve fibers. The type of unique lining cells of the sinusoids is the prerequisite for the cell traffic between the hemopoietic parenchyma and the blood. This in turn cannot be achieved without an alternative opening and closing of the sinusoidal segments which - in turn - requires a rigid long capsule to assure an - in toto - constant volume of each bone marrow unit. If a bone

  3. Autoimmunity as a trigger for structural bone damage in rheumatoid arthritis.

    Science.gov (United States)

    Schett, Georg

    2017-03-01

    Bone loss is a central feature of rheumatoid arthritis (RA). It is considered to represent a sign of irreversible structural damage triggered by chronic inflammation. Recent evidence, however, suggests that autoantibodies are an important and earlier driver for bone damage in RA. This article summarizes current evidence for the role of RA-related autoantibodies in mediating bone loss. Rheumatoid factor and antibodies recognizing modified (citrullinated) proteins are the central features of autoimmunity in RA patients. Despite being used as diagnostic markers for many years, ascertaining the differentiation of RA from other forms of inflammatory arthritides, the role of these antibodies as pathogenic players has long been unrecognized. Recently, several pieces of evidence suggested that bone-resorbing osteoclasts are highly responsive to RA-related autoantibodies, providing a novel link between autoimmunity and bone. These developments have allowed unraveling the underlying mechanisms, which are responsible for the well-known clinical observation that RA-related autoantibodies are associated with a more severe disease course. At present, rheumatoid factor and antibodies recognizing citrullinated proteins are considered as potent osteoclast inducers and triggers for bone loss in arthritis.

  4. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

  5. Characterization of Microgravity Effects on Bone Structure and Strength Using Fractal Analysis

    Science.gov (United States)

    Acharya, Raj S.; Shackelford, Linda

    1996-01-01

    Protecting humans against extreme environmental conditions requires a thorough understanding of the pathophysiological changes resulting from the exposure to those extreme conditions. Knowledge of the degree of medical risk associated with the exposure is of paramount importance in the design of effective prophylactic and therapeutic measures for space exploration. Major health hazards due o musculoskeletal systems include the signs and symptoms of hypercalciuria, lengthy recovery of lost bone tissue after flight, the possibility of irreversible trabecular bone loss, the possible effect of calcification in the soft tissues, and the possible increase in fracture potential. In this research, we characterize the trabecular structure with the aid of fractal analysis. Our research to relate local trabecular structural information to microgravity conditions is an important initial step in understanding the effect of microgravity and countermeasures on bone condition and strength. The proposed research is also closely linked with Osteoporosis and will benefit the general population.

  6. Ultrastructural studies on the origin and structure of matrix vesicles in bone of young rats.

    Science.gov (United States)

    Ornoy, A; Atkin, I; Levy, J

    1980-01-01

    Tibiae of young rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to study the origin and structure of matrix vesicles in periosteal bone. SEM studies have shown that periosteal osteoblasts have elongated processes with globular structures of 0.1 micron in diameter attached to the cell surface and processes. Similar structures were found to cover the inner surface of osteoblastic lacunae. The SEM studies have further shown that in the periosteal surface (forming bone) the above-described globules once mineralized, aggregated to form larger, nonhomogeneous mineralized spherules in which, by proper treatment with NaOCl, hydroxyapatite crystals could be exposed. Endosteal osteoblasts had fewer processes, devoid of the globular structures. Similarly, osteocytic and osteoclastic processes, although elongated and numberous, were not covered by the globular structures. In the matrix, collagen fibers of forming bone were randomly orientated, while in the deeper areas of bone they formed bundles with a longitudinal orientation. TEM studies have shown that the structures found on the osteoblastic surface and in the matrix are membrane-bound matrix vesicles which seem to be formed by budding from cell processes. Preformed membrane-bound vesicles were also observed by TEM inside sections of osteoblastic processes. These vesicles resembled the extracellular matrix vesicles in size and shape, thus giving the impression that at least some of the matrix vesicles are preformed cellular structures. While comparing SEM with TEM, it can be conducted that in bone, as in cartilage, matrix vesicles which probably serve as the initial locus of calcification, are formed directly by osteoblasts.

  7. [Animal models for bone and joint disease. CIA, CAIA model].

    Science.gov (United States)

    Hirose, Jun; Tanaka, Sakae

    2011-02-01

    The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.

  8. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  9. Oscillating water column structural model

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Guild [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bull, Diana L [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jepsen, Richard Alan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gordon, Margaret Ellen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-09-01

    An oscillating water column (OWC) wave energy converter is a structure with an opening to the ocean below the free surface, i.e. a structure with a moonpool. Two structural models for a non-axisymmetric terminator design OWC, the Backward Bent Duct Buoy (BBDB) are discussed in this report. The results of this structural model design study are intended to inform experiments and modeling underway in support of the U.S. Department of Energy (DOE) initiated Reference Model Project (RMP). A detailed design developed by Re Vision Consulting used stiffeners and girders to stabilize the structure against the hydrostatic loads experienced by a BBDB device. Additional support plates were added to this structure to account for loads arising from the mooring line attachment points. A simplified structure was designed in a modular fashion. This simplified design allows easy alterations to the buoyancy chambers and uncomplicated analysis of resulting changes in buoyancy.

  10. Infill Optimization for Additive Manufacturing - Approaching Bone-like Porous Structures

    DEFF Research Database (Denmark)

    Wu, Jun; Aage, Niels; Westermann, Ruediger

    2017-01-01

    Porous structures such as trabecular bone are widely seen in nature. These structures exhibit superior mechanical properties whilst being lightweight. In this paper, we present a method to generate bone-like porous structures asl ightweight infill for additive manufacturing. Our method builds upon...... and extends voxel-wise topology optimization. In particular, for the purpose of generating sparse yet stable structures distributed in the interior of a given shape, we propose upper bounds on the localized material volume in the proximity of each voxel in the design domain. We then aggregate the local per......-voxel constraints by their p-norm into an equivalent global constraint, in order to facilitate an efficient optimization process. Implemented on a high-resolution topology optimization framework, our results demonstrate mechanically optimized, detailed porous structures which mimic those found innature. We further...

  11. Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

    OpenAIRE

    Fathilah, Siti Noor; Mohamed, Norazlina; Muhammad, Norliza; Mohamed, Isa Naina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

    2013-01-01

    Background Labisia Pumila var. alata (LPva) has shown potential as an alternative to estrogen replacement therapy (ERT) in prevention of estrogen-deficient osteoporosis. In earlier studies using postmenopausal model, LPva was able to reverse the ovariectomy-induced changes in biochemical markers, bone calcium, bone histomorphometric parameters and biomechanical strength. The mechanism behind these protective effects is unclear but LPva may have regulated factors that regulate bone remodeling....

  12. The rational use of animal models in the evaluation of novel bone regenerative therapies

    OpenAIRE

    Perić, Mihaela; DUMIĆ-ČULE, Ivo; Grčević, Danka; Matijašić, Mario; Verbanac, Donatella; Paul, Ruth; Grgurević, Lovorka; Trkulja, Vladimir; Bagi, Čedo M.; Vukičević, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poo...

  13. Establishment of Animal Model for Bone Metastasis of Walker 256 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    PANG; Fang-fang; SHEN; Hong-tao; HE; Ming; DONG; Ke-jun; WU; Shao-yong; DOU; Liang; SHI; Yan-jun; ZHANG; Shuang; WANG; Xiao-ming; ZHAO; Qin-zhang; YANG; Xu-ran; XU; Yong-ning; LAN; Xiao-xi; CAI; Li; JIANG; Shan

    2013-01-01

    Bone metastasis is a common complication of cancer.It often occurs in lung,breast and prostate cancer,and may cause osteolytic lesions,or cause few osteoblastic lesions.It has already advanced cancer When cancer metastasis to bone,which usually cannot be cured.It is one of the important factors leading to the death of cancer patients.Studying animal model of bone

  14. Mimicking Bone Healing Process to Self Repair Concrete Structure Novel Approach Using Porous Network Concrete

    NARCIS (Netherlands)

    Sangadji, S.; Schlangen, H.E.J.G.

    2013-01-01

    To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete

  15. Mimicking Bone Healing Process to Self Repair Concrete Structure Novel Approach Using Porous Network Concrete

    NARCIS (Netherlands)

    Sangadji, S.; Schlangen, H.E.J.G.

    2013-01-01

    To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete st

  16. The regulation of bone turnover in ameloblastoma using an organotypic in vitro co-culture model

    Science.gov (United States)

    Eriksson, Tuula M; Day, Richard M; Fedele, Stefano; Salih, Vehid M

    2016-01-01

    Ameloblastoma is a rare, odontogenic neoplasm with benign histopathology, but extensive, local infiltrative capacity through the bone tissue it originates in. While the mechanisms of ameloblastoma invasion through the bone and bone absorption are largely unknown, recent investigations have indicated a role of the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand regulatory mechanisms. Here, we present results obtained using a novel in vitro organotypic tumour model, which we have developed using tissue engineering techniques. Using this model, we analysed the expression of genes involved in bone turnover and detected a 700-fold increase in receptor activator of nuclear factor kappa-B ligand levels in the co-culture models with ameloblastoma cells cultured with bone cells. The model described here can be used for gene expression studies, as a basis for drug testing or for a more tailored platform for testing of the behaviour of different ameloblastoma tumours in vitro.

  17. Acupuncture Increases Bone Strength by Improving Mass and Structure in Established Osteoporosis after Ovariectomy in Rats

    Institute of Scientific and Technical Information of China (English)

    WenPing Zhang; Masayuki Kanehara; YanJun Zhang; ZhiFeng Yu; GuoXia Zhang; YouXin Yang; Saori Tachi; Torao Ishida

    2006-01-01

    The effects of acupuncture on bone biomechanical properties and histomorphometry in ovariectomized (OVX) rats were studied. Twenty-four 8-week-old female Sprague-Dawley rats were randomly assigned to three groups: sham, model and acupuncture. Rats in the model and acupuncture groups were ovariectomized,while those in the sham group underwent a sham operation. All rats were anesthetized and fastened for 15minutes, and for the acupuncture group, needling on Pishu (BL20) and Shenshu (BL23) was performed.Blood and urine were collected to measure serum osteocalcin (OC) and urinary calcium, phosphorus or deoxypyridinoline (Dpd). After 16 weeks of treatment, all the rats were killed and their tibiae and femora were removed. The tibiae were used for analyses of bone histomorphometry and the femora for a three-point bending test. Acupuncture gave significant protection against ovariectomy-caused decline on femoral strength in the mechanical test, increased the trabecular bone volume and thickness, lowered the trabecular separation of tibiae and restricted the excretion of phosphorus and Dpd, while promoting the concentrations of serum osteocalcin as compared with model rats. These results seemed to indicate that acupuncture on the points of Pishu (BL20) and Shenshu (BL23) not only promoted the bone formation but also suppressed the bone resorption induced by OVX in osteoporotic rats, which suggests that it would be a potentially useful and convenient method in preventing osteoporosis.

  18. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

    Science.gov (United States)

    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates.

  19. Probabilistic Modeling of Timber Structures

    DEFF Research Database (Denmark)

    Köhler, J.D.; Sørensen, John Dalsgaard; Faber, Michael Havbro

    2005-01-01

    The present paper contains a proposal for the probabilistic modeling of timber material properties. It is produced in the context of the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS) and of the COST action E24 'Reliability of Timber Structures'. The present pro...... probabilistic model for these basic properties is presented and possible refinements are given related to updating of the probabilistic model given new information, modeling of the spatial variation of strength properties and the duration of load effects.......The present paper contains a proposal for the probabilistic modeling of timber material properties. It is produced in the context of the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS) and of the COST action E24 'Reliability of Timber Structures'. The present...

  20. Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation

    Directory of Open Access Journals (Sweden)

    Paixão Fabio B

    2008-01-01

    Full Text Available Abstract Background Animal models of fracture consolidation are fundamental for the understanding of the biological process of bone repair in humans, but histological studies are rare and provide only qualitative results. The objective of this article is to present the histomorphometric study of the bone healing process using an experimental model of osteotomy in rabbit fibula without interference of synthesis material. Methods Fifteen rabbits were submitted to fibular osteotomy without any fixation device. Groups of five animals were submitted to pharmacological euthanasia during a period of one (group A, two (group B and four weeks (group C after osteotomy. Histomorphometric evaluation was performed in the histological sections. Results During week one there was intense cellularity (67/field, a large amount of woven bone (75.7% and a small amount of lamellar bone (7.65%. At two weeks there was a decrease in woven bone (41.59% and an increase in lamellar bone (15.16%. At four weeks there was a decrease of cellularity (19.17/field and lamellar bone (55.56% exceeded the quantity of woven bone (31.68%. Conclusion Histomorphometric (quantitative evaluation of the present study was shown to be compatible with bone healing achieved in qualitative experimental models that have been commended in the literature.

  1. Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

    Science.gov (United States)

    Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

    2017-03-07

    Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

  2. Thermostability of bone tissue after immobilization induced osteopenia in a rat model.

    Directory of Open Access Journals (Sweden)

    Krzysztof Wójtowicz

    2008-12-01

    Full Text Available Immobilization of load-bearing bones results in imbalance of bone turnover followed by bone loss and impairment of its mechanical function. The question is whether immobilization induced bone loss is accompanied by deterioration of properties of the bone tissue components. Thermally induced transformations of collagen reflect the overall condition of the structure and cross-links in collagen network. The aim of the present study was to investigate whether immobilization induced osteopenia effects stability of collagen in bone tissue. Bone loss was developed by unilateral hindlimb immobilization in adult rats. Effects of unloading on cortical tissue from tibiae were studied after three weeks of unloading (I3R0 and four weeks after remobilization and free convalescence (I3R4 in both tibiae. Thermodynamic parameters of collagen degradation in bone were determined from differential scanning calorimetry (DSC analysis of partially dehydrated cortical bone samples from tibiae in the range of temperatures from 60 degrees C up to 300 degrees C. All bone samples were thermally very stable showing first clear endothermal process with a peak temperature within a range from 150 degrees C to 169 degrees C, for different samples. The next endotherm, wider and flatter, was observed between 245-298 degrees C with a peak at 255 degrees C - 260 degrees C. There were significant side-to-side (right to left differences for both endothermal processes in tibiae samples from experimental groups: I3R0 and I3R4. Immobilization of load-bearing bones influences stability of collagen in bone tissue. Free remobilization was not sufficient for recovery of thermal parameters of bone.

  3. Effect of vibration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    Science.gov (United States)

    Suzuki, N.; Kitamura, K.; Nemoto, T.; Shimizu, N.; Wada, S.; Kondo, T.; Tabata, M. J.; Sodeyama, F.; Ijiri, K.; Hattori, A.

    In osteoclastic activity during space flight as well as hind limb unloading by tail suspension, inconsistent results have been reported in an in vivo study. The bone matrix plays an important role in the response to physical stress. However, there is no suitable in vitro co-culture system of osteoblasts and osteoclasts including bone matrix. On the other hand, fish scale is a calcified tissue that contains osteoblasts, osteoclasts, and bone matrix, all of which are similar to those found in human bones. Recently, we developed a new in vitro model system using goldfish scale. This system can detect the activities of osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers and precisely analyze the co-relationship between osteoblasts and osteoclasts. Using this system, we analyzed the bone metabolism under various degrees of acceleration (0.5-, 1-, 2-, 4-, and 6-G) by vibration with a G-load apparatus. After loading for 5 and 10 min, the scales were incubated for 6 and 24 h. The osteoblastic and osteoclastic activities were then measured. The osteoblastic activities gradually increased corresponding to 1-G to 6-G acceleration. In addition, ER mRNA expression was the highest under 6-G acceleration. On the other hand, the osteoclastic activity decreased at 24 h of incubation under low acceleration (0.5- and 1-G). This change coincided with TRAP mRNA expression. Under 2-G acceleration, the strength of suppression in osteoclastic activity was the highest. The strength of the inhibitory action under 4- and 6-G acceleration was lower than that under 2-G acceleration. In our co-culture system, osteoblasts and osteoclasts in the scale sensitively responded to several degrees of acceleration. Therefore, we strongly believe that our in vitro co-culture system is useful for the analysis of bone metabolism under loading or unloading.

  4. Architectural and Biochemical Adaptations in Skeletal Muscle and Bone Following Rotator Cuff Injury in a Rat Model

    Science.gov (United States)

    Sato, Eugene J.; Killian, Megan L.; Choi, Anthony J.; Lin, Evie; Choo, Alexander D.; Rodriguez-Soto, Ana E.; Lim, Chanteak T.; Thomopoulos, Stavros; Galatz, Leesa M.; Ward, Samuel R.

    2015-01-01

    Background: Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Methods: Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Results: Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. Conclusions: These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Clinical Relevance: Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise. PMID:25834081

  5. Ti-6Al-4V triply periodic minimal surface structures for bone implants fabricated via selective laser melting.

    Science.gov (United States)

    Yan, Chunze; Hao, Liang; Hussein, Ahmed; Young, Philippe

    2015-11-01

    Triply periodic minimal surface (TPMS) structures have already been shown to be a versatile source of biomorphic scaffold designs. Therefore, in this work, Ti-6Al-4V Gyroid and Diamond TPMS lattices having an interconnected high porosity of 80-95% and pore sizes in the range of 560-1600 μm and 480-1450 μm respectively were manufactured by selective laser melting (SLM) for bone implants. The manufacturability, microstructure and mechanical properties of the Ti-6Al-4V TPMS lattices were evaluated. Comparison between 3D micro-CT reconstructed models and original CAD models of the Ti-6Al-4V TPMS lattices shows excellent reproduction of the designs. The as-built Ti-6Al-4V struts exhibit the microstructure of columnar grains filled with very fine and orthogonally oriented α' martensitic laths with the width of 100-300 nm and have the microhardness of 4.01 ± 0.34 GPa. After heat treatment at 680°C for 4h, the α' martensite was converted to a mixture of α and β, in which the α phase being the dominant fraction is present as fine laths with the width of 500-800 nm and separated by a small amount of narrow, interphase regions of dark β phase. Also, the microhardness is decreased to 3.71 ± 0.35 GPa due to the coarsening of the microstructure. The 80-95% porosity TPMS lattices exhibit a comparable porosity with trabecular bone, and the modulus is in the range of 0.12-1.25 GPa and thus can be adjusted to the modulus of trabecular bone. At the same range of porosity of 5-10%, the moduli of cortical bone and of the Ti-6Al-4V TPMS lattices are in a similar range. Therefore, the modulus and porosity of Ti-6Al-4V TPMS lattices can be tailored to the levels of human bones and thus reduce or avoid "stress shielding" and increase longevity of implants. Due to the biomorphic designs, and high interconnected porosity and stiffness comparable to human bones, SLM-made Ti-6Al-4V TPMS lattices can be a promising material for load bearing bone implants.

  6. Mechanical Stimulus Inhibits the Growth of a Bone Tissue Model Cultured In Vitro

    Institute of Scientific and Technical Information of China (English)

    Zong-ming Wan; Lu Liu; Jian-yu Li; Rui-xin Li; Yong Guo; Hao Li; Jian-ming Zhang; Xi-zheng Zhang

    2013-01-01

    Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vitro. Methods Cancellous bone were extracted from rabbit femoral head and cut into 1-mm-thick and 8-mm-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000μεrespectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection. Results After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000μεwere significantly lower than those in the unstressed bone tissues (all P Conclusions The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteoblasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000με.

  7. SPAR Model Structural Efficiencies

    Energy Technology Data Exchange (ETDEWEB)

    John Schroeder; Dan Henry

    2013-04-01

    The Nuclear Regulatory Commission (NRC) and the Electric Power Research Institute (EPRI) are supporting initiatives aimed at improving the quality of probabilistic risk assessments (PRAs). Included in these initiatives are the resolution of key technical issues that are have been judged to have the most significant influence on the baseline core damage frequency of the NRC’s Standardized Plant Analysis Risk (SPAR) models and licensee PRA models. Previous work addressed issues associated with support system initiating event analysis and loss of off-site power/station blackout analysis. The key technical issues were: • Development of a standard methodology and implementation of support system initiating events • Treatment of loss of offsite power • Development of standard approach for emergency core cooling following containment failure Some of the related issues were not fully resolved. This project continues the effort to resolve outstanding issues. The work scope was intended to include substantial collaboration with EPRI; however, EPRI has had other higher priority initiatives to support. Therefore this project has addressed SPAR modeling issues. The issues addressed are • SPAR model transparency • Common cause failure modeling deficiencies and approaches • Ac and dc modeling deficiencies and approaches • Instrumentation and control system modeling deficiencies and approaches

  8. Polarization in Raman spectroscopy helps explain bone brittleness in genetic mouse models

    Science.gov (United States)

    Makowski, Alexander J.; Pence, Isaac J.; Uppuganti, Sasidhar; Zein-Sabatto, Ahbid; Huszagh, Meredith C.; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

    2014-01-01

    Abstract. Raman spectroscopy (RS) has been extensively used to characterize bone composition. However, the link between bone biomechanics and RS measures is not well established. Here, we leveraged the sensitivity of RS polarization to organization, thereby assessing whether RS can explain differences in bone toughness in genetic mouse models for which traditional RS peak ratios are not informative. In the selected mutant mice—activating transcription factor 4 (ATF4) or matrix metalloproteinase 9 (MMP9) knock-outs—toughness is reduced but differences in bone strength do not exist between knock-out and corresponding wild-type controls. To incorporate differences in the RS of bone occurring at peak shoulders, a multivariate approach was used. Full spectrum principal components analysis of two paired, orthogonal bone orientations (relative to laser polarization) improved genotype classification and correlation to bone toughness when compared to traditional peak ratios. When applied to femurs from wild-type mice at 8 and 20 weeks of age, the principal components of orthogonal bone orientations improved age classification but not the explanation of the maturation-related increase in strength. Overall, increasing polarization information by collecting spectra from two bone orientations improves the ability of multivariate RS to explain variance in bone toughness, likely due to polarization sensitivity to organizational changes in both mineral and collagen. PMID:25402627

  9. Polarization in Raman spectroscopy helps explain bone brittleness in genetic mouse models

    Science.gov (United States)

    Makowski, Alexander J.; Pence, Isaac J.; Uppuganti, Sasidhar; Zein-Sabatto, Ahbid; Huszagh, Meredith C.; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

    2014-11-01

    Raman spectroscopy (RS) has been extensively used to characterize bone composition. However, the link between bone biomechanics and RS measures is not well established. Here, we leveraged the sensitivity of RS polarization to organization, thereby assessing whether RS can explain differences in bone toughness in genetic mouse models for which traditional RS peak ratios are not informative. In the selected mutant mice-activating transcription factor 4 (ATF4) or matrix metalloproteinase 9 (MMP9) knock-outs-toughness is reduced but differences in bone strength do not exist between knock-out and corresponding wild-type controls. To incorporate differences in the RS of bone occurring at peak shoulders, a multivariate approach was used. Full spectrum principal components analysis of two paired, orthogonal bone orientations (relative to laser polarization) improved genotype classification and correlation to bone toughness when compared to traditional peak ratios. When applied to femurs from wild-type mice at 8 and 20 weeks of age, the principal components of orthogonal bone orientations improved age classification but not the explanation of the maturation-related increase in strength. Overall, increasing polarization information by collecting spectra from two bone orientations improves the ability of multivariate RS to explain variance in bone toughness, likely due to polarization sensitivity to organizational changes in both mineral and collagen.

  10. Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

    Directory of Open Access Journals (Sweden)

    Lidia Ibáñez

    2014-01-01

    Full Text Available Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2, an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−. Bone microarchitecture was analyzed by μCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. Results. Sham-operated or ovariectomized Nrf2−/− mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/− mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

  11. TH-C-18A-02: Machine Learning and STAPLE Based Simultaneous Longitudinal Segmentation of Bone and Marrow Structures From Dual Energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Fehr, D; Schmidtlein, C; Hwang, S; Deasy, J; Veeraraghavan, H [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: To develop a fully-automatic longitudinal bone and marrow segmentation method in the pelvic region from dual energy computed tomography (DECT). Methods: We developed a two-step automatic bone and marrow segmentation method for simultaneous longitudinal evaluation of patients with metastatic bone disease using dual energy CT (DECT). Our approach transforms the DECT images into a multi-material decomposition (MMD) model that represents the voxels as a mixture of multiple materials. A support vector machine (SVM) was trained using a single scan. In the first step of the longitudinal segmentation the trained SVM model detects bone and marrow structures on all available longitudinal scans. Segmentation is further refined through active contour segmentation. In the second step, the segmentations from the individual scans are merged by employing the simultaneous truth and performance level estimation (STAPLE) algorithm. The scans are registered using affine and deformable registration. We found that our approach improves the segmentation in all the scans under reliable registration performance between the same scans. Improving registration was not under the scope of this work. Results: We applied our approach to segment bone and marrow in DECT scans in the pelvic regions for multiple patients. Each patient had three to five follow up scans. All the patients in the analysis had artificial metal prostheses which introduced challenges for the registration. Our algorithm achieved reasonable accurate segmentation despite the presence of metal artifacts and high-density oral contrast in neighboring structures. Our approach obtained an overall segmentation accuracy of 80% using DICE metric. Conclusion: We developed a two-step automatic longitudinal segmentation technique for bone and marrow region structures in the pelvic areas from dual energy CT. Our approach achieves robust segmentation despite the presence of confounding structures with similar intensities as the

  12. Effect of vitamin D deficiency during pregnancy on offspring bone structure, composition and quality in later life.

    Science.gov (United States)

    Lanham, S A; Roberts, C; Habgood, A K; Alexander, S; Burne, T H J; Eyles, D W; Trueman, C N; Cooper, M; McGrath, J J; Oreffo, R O C

    2013-02-01

    During foetal development, calcium requirements are met as a consequence of maternal adaptations independent of vitamin D status. In contrast, after birth, dependency on vitamin D appears necessary for calcium metabolism and skeletal health. We used a rodent model (Sprague-Dawley rats), to determine if maternal vitamin D deficiency during pregnancy had a deleterious effect on bone structure at birth. Vitamin D deplete females were maintained under deplete conditions until birth of the pups, whereupon all dams were fed a vitamin D replete diet. Offspring were harvested at birth, and 140 days of age. Bones were analyzed using micro-computed tomography and strength tested to study differences in bone structure, density and strength and subjected to elemental analysis using plasma mass spectrometry to determine strontium, barium and calcium contents. Offspring from deplete mothers displayed altered trabecular parameters in the femur at birth and 140 days of age. In addition, at 140 days of age there was evidence of premature mineralization of the secondary ossification centre of the femoral head. Elemental analysis showed increased strontium uptake in the femur of the developmentally vitamin D-deficient offspring. Vitamin D depletion during development in the offspring may have a long-lasting effect, despite repletion of vitamin D from birth. This may have consequences for human health given the low vitamin D levels seen during pregnancy and current lifestyle of sun avoidance due to the risk of skin cancer.

  13. Dairy food intake, peripheral bone structure, and muscle mass in elderly ambulatory women.

    Science.gov (United States)

    Radavelli-Bagatini, Simone; Zhu, Kun; Lewis, Joshua R; Prince, Richard L

    2014-07-01

    Previous studies suggest that dairy intake may be associated with reduced bone and muscle loss with aging, but there are limited data in the very old. We evaluated the association between intake of dairy foods and peripheral bone structure and muscle mass in 564 elderly women aged 80 to 92 (mean 84.7) years, who were participants of the Calcium Intake Fracture Outcome Study/CAIFOS Aged Extension Study (CAIFOS/CARES) cohort and attended the 10-year follow-up. Assessments included dairy consumption (milk, yogurt, and cheese) by a validated food frequency questionnaire, 15% tibia bone mass, area and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), and appendicular bone and skeletal muscle mass by dual-energy X-ray absorptiometry (DXA). Women were categorized according to tertiles of dairy intake: first tertile (≤ 1.5 servings/d), second tertile (1.5 to 2.2 servings/d) and third tertile (≥ 2.2 servings/d). Controlling for confounding factors, pQCT assessment at the 15% tibia showed that compared with those in the first tertile of dairy intake, women in the third tertile had 5.7% greater total bone mass (p = 0.005), principally because of an increase in cortical and subcortical bone mass (5.9%, p = 0.050), resulting in a 6.2% increase in total vBMD (p = 0.013). Trabecular but not cortical and subcortical vBMD was also higher (7.8%, p = 0.044). DXA assessment showed that women in the third tertile of dairy intake had greater appendicular bone mass (7.1%, p = 0.007) and skeletal muscle mass (3.3%, p = 0.014) compared with tertile 1. The associations with bone measures were dependent on dairy protein and calcium intakes, whereas the association with appendicular muscle mass was not totally dependent on dairy protein intake. Our results suggest a positive association of dairy intake with appendicular bone mineralization and muscle mass in elderly women. Because many fractures in this age group are of the appendicular skeleton

  14. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Qin; Ya-Nan Wang

    2012-01-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper.The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model.Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model),but also predict the realtime development pattern of BMC and BFE,as well as the dynamics of osteoblasts (OBA),osteoclasts (OCA),nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme,which can hardly be monitored through experiment.In conclusion,the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass.More importantly,this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated.The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies.Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  15. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    Directory of Open Access Journals (Sweden)

    Cen Fu

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD, micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD, cortical volumetric BMD (vBMD and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV, trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC, bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  16. Alterations in archaeological bones thermally treated: structure and morphology; Alteraciones en huesos arqueologicos termicamente tratados: estructura y morfologia

    Energy Technology Data Exchange (ETDEWEB)

    Pijoan, C.M.; Mansilla, J.; Leboreiro, I. [Direccion de Antropologia Fisica, INAH, Gandhi s/n, Polanco, 11560 Mexico D. F. (Mexico); Lara, V.H. [Universidad Autonoma Metropolitana-lztapalapa, Michoacan esquina La Purisima, Apdo.Postal 55-534, Mexico D. F. (Mexico); Bosch, P. [Instituto de Investigaciones en Materiales, UNAM, Circuito Exterior, Ciudad Universitaria, 04510 Mexico D. F. (Mexico)

    2004-07-01

    Archaeological bones found close to Mexico city (Tlatelcomila) have been characterized by X-ray Diffraction, Small Angle X-ray Spectroscopy and Scanning Electron Microscopy. These techniques, which are not conventionally used in archaeological research, provided useful information. The boiled bones were clearly distinguished from grilled bones. The degree of deterioration of the bone structure was quantified through parameters such as gyration radius or fractal dimension. The morphology followed the structural modifications and changes resulting from thermic exposure. (Author) 23 refs., 1 tab., 2 figs.

  17. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    Science.gov (United States)

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  18. Parallel plate model for trabecular bone exhibits volume fraction-dependent bias

    NARCIS (Netherlands)

    J.S. Day (Judd); M. Ding; A. Odgaard; D.R. Sumner (Dale); I. Hvid (Ivan); H.H. Weinans (Harrie)

    2000-01-01

    textabstractUnbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal t

  19. Life-history traits of the Miocene Hipparion concudense (Spain inferred from bone histological structure.

    Directory of Open Access Journals (Sweden)

    Cayetana Martinez-Maza

    Full Text Available Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain. The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens' age within groups enabled us to characterize the age structure of both samples, which is

  20. Life-history traits of the Miocene Hipparion concudense (Spain) inferred from bone histological structure.

    Science.gov (United States)

    Martinez-Maza, Cayetana; Alberdi, Maria Teresa; Nieto-Diaz, Manuel; Prado, José Luis

    2014-01-01

    Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain) has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain). The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens' age within groups enabled us to characterize the age structure of both samples, which is typical of

  1. Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

    Directory of Open Access Journals (Sweden)

    Mira Moussa

    2015-04-01

    Full Text Available Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8. Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3% and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%. These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

  2. Dehydrothermally Cross-Linked Collagen Membrane with a Bone Graft Improves Bone Regeneration in a Rat Calvarial Defect Model.

    Science.gov (United States)

    An, Yin-Zhe; Heo, Young-Ku; Lee, Jung-Seok; Jung, Ui-Won; Choi, Seong-Ho

    2017-08-10

    In this study, the bone regeneration efficacy of dehydrothermally (DHT) cross-linked collagen membrane with or without a bone graft (BG) material was evaluated in a critical-sized rat model. An 8-mm-diameter defect was created in the calvaria of 40 rats, which were randomized into four groups: (1) control; (2) DHT; (3) BG; and, (4) DHT + BG. Evaluations were made at 2 and 8 weeks after surgery using micro-computed tomographic (micro-CT), histological, and histomorphometric analyses. Micro-CT analysis showed an increase in the new bone volume (NBV) of the BG and DHT + BG groups at 2 weeks after surgery, representing a significant difference (p DHT + BG groups, and a significant difference was no longer observed between the two groups. Histologic analysis demonstrated that the graft materials sustained the center of the defect in the BG and DHT + BG groups, which was shown in histomorphometric analysis as well. These results suggest that DHT membrane is a safe biomaterial with adequate tissue integration, and has a positive effect on new bone formation. Moreover, the best effects were achieved when DHT was used in conjunction with BG materials.

  3. Models as coherent sign structures

    NARCIS (Netherlands)

    Gazendam, H.W.M.; Jorna, R.J.J.M.; Gazendam, H.W.M.; Cijsouw, R.S.

    2003-01-01

    This chapter explains how models function as the glue that keeps organizations together. In an analysis of models from a semiotic and cognitive point of view, assumptions about evolutionary dynamics and bounded rationality are used. It is concluded that a model is a coherent sign structure,

  4. TEMPORAL MODELING OF DNA DEGRADATION IN BONE REMAINS

    Directory of Open Access Journals (Sweden)

    Andrei Stefan

    2012-06-01

    Full Text Available The aim of this study is to follow the changes that occur, in time, at DNA level and to establish an efficient and reliable protocol for ancestral DNA extraction from bones found in archaeological sites. To test whether the protocol is efficient and capable of yielding good quality DNA, extraction was first performed on fresh bones. The material consists of fresh pig (Sus scrofa and cow (Bos taurus bones that were grounded by using a drill operating at low speed. The bone powder was then incubated in lysis buffer in the presence of proteinase K. DNA isolation and purification were done by using the phenol:chloroform protocol and DNA was precipitated with absolute ethanol stored at -20oC. The extractions were carried out once every month for a total of four extractions

  5. Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.

    Science.gov (United States)

    Valta, Maija P; Zhao, Hongjuan; Ingels, Alexandre; Thong, Alan E; Nolley, Rosalie; Saar, Matthias; Peehl, Donna M

    2014-06-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

  6. Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2014-09-01

    Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

  7. Genetic regulation of bone strength: a review of animal model studies.

    Science.gov (United States)

    Adams, Douglas J; Ackert-Bicknell, Cheryl L

    2015-01-01

    Population- and family-based studies have established that fragility fracture risk is heritable; yet, the genome-wide association studies published to date have only accounted for a small fraction of the known variation for fracture risk of either the femur or the lumbar spine. Much work has been carried out using animal models toward finding genetic loci that are associated with bone strength. Studies using animal models overcome some of the issues associated with using patient data, but caution is needed when interpreting the results. In this review, we examine the types of tests that have been used for forward genetics mapping in animal models to identify loci and/or genes that regulate bone strength and discuss the limitations of these test methods. In addition, we present a summary of the quantitative trait loci that have been mapped for bone strength in mice, rats and chickens. The majority of these loci co-map with loci for bone size and/or geometry and thus likely dictate strength via modulating bone size. Differences in bone matrix composition have been demonstrated when comparing inbred strains of mice, and these matrix differences may be associated with differences in bone strength. However, additional work is needed to identify loci that act on bone strength at the materials level.

  8. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  9. Computer modelling of bone's adaptation: the role of normal strain, shear strain and fluid flow.

    Science.gov (United States)

    Tiwari, Abhishek Kumar; Prasad, Jitendra

    2017-04-01

    Bone loss is a serious health problem. In vivo studies have found that mechanical stimulation may inhibit bone loss as elevated strain in bone induces osteogenesis, i.e. new bone formation. However, the exact relationship between mechanical environment and osteogenesis is less clear. Normal strain is considered as a prime stimulus of osteogenic activity; however, there are some instances in the literature where osteogenesis is observed in the vicinity of minimal normal strain, specifically near the neutral axis of bending in long bones. It suggests that osteogenesis may also be induced by other or secondary components of mechanical environment such as shear strain or canalicular fluid flow. As it is evident from the literature, shear strain and fluid flow can be potent stimuli of osteogenesis. This study presents a computational model to investigate the roles of these stimuli in bone adaptation. The model assumes that bone formation rate is roughly proportional to the normal, shear and fluid shear strain energy density above their osteogenic thresholds. In vivo osteogenesis due to cyclic cantilever bending of a murine tibia has been simulated. The model predicts results close to experimental findings when normal strain, and shear strain or fluid shear were combined. This study also gives a new perspective on the relation between osteogenic potential of micro-level fluid shear and that of macro-level bending shear. Attempts to establish such relations among the components of mechanical environment and corresponding osteogenesis may ultimately aid in the development of effective approaches to mitigating bone loss.

  10. Attributes of Bio-Oss(®) and Moa-Bone(®) graft materials in a pilot study using the sheep maxillary sinus model.

    Science.gov (United States)

    Smith, M M; Duncan, W J; Coates, D E

    2017-09-04

    The aim of this pilot study was to characterize surface morphology and to evaluate resorption and osseous healing of two deproteinated bovine bone graft materials after sinus grafting in a large animal model. Surfaces of a novel particulate bovine bone graft, Moa-Bone(®) were compared with Bio-Oss(®) using scanning electron microscopy. Six sheep then had maxillary sinus grafting bilaterally, covered with BioGide(®) . Grafted maxillae were harvested after 4, 6 and 12 weeks. Healing was described for half of each site using resin-embedded ground sections. For the other half, paraffin-embedded sections were examined using tartrate resistant acid phosphatase staining for osteoclast activity, runt-related transcription factor2 immunohistochemistry for pre-osteoblasts and osteoblasts and proliferating cell nuclear antigen for proliferative cells. Moa-Bone(®) had a smoother, more porous fibrous structure with minimal globular particles compared with Bio-Oss(®) . After 4 weeks, woven bone formed on both grafts and the Moa-Bone(®) particles also showed signs of resorption. After 12 weeks, Moa-Bone(®) continued to be resorbed, however Bio-Oss(®) did not; both grafts were surrounded by maturing lamellar bone. Moa-Bone(®) was associated with earlier evidence of runt-related transcription factor 2-positive cells. Moa-Bone(®) but not Bio-Oss(®) was associated with strong tartrate resistant acid phosphatase-positive osteoclasts on the graft surface within resorption lacunae at both 4 and 6 weeks post-grafting. Both materials supported osseous healing and maturation without inflammation. Moa-Bone(®) showed marked osteoclast activity after 4 and 6 weeks and demonstrated positive attributes for grafting, if complete remodeling of the graft within the site is desired. Further optimization of Moa-Bone(®) for maxillofacial applications is warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

    2015-03-05

    Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear.

  12. Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on vertebral in the rabbit model of osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Jie Zhang; Yu-Ming Chen; Chen Sheng-Guo; Kaken Habaerxi; Shawuti Alimujiang; Yu Chen; Ming-Zhen Peng; Rong Yue; Yu-Lian Wu; De-Quan Wang

    2014-01-01

    Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of48NewZealand white rabbits were randomly divided into groupⅠ(blank control group), group Ⅱ(CSC injection group), group Ⅲ(CSC/bBMP injection group) and control group.White rabbit osteoporosis model was established rapidly by using castration method+methylprednisolone candidate.After modeling, groups Ⅱ, Ⅲ were given corresponding vertebral body injection material, and4 animals were sacrificed respectively at24 h,6 weeks,12 weeks after vertebral plasty.Tissue pathological status, vertebral mineral density and vertebral body bone mechanical strength were observed.Results:Vertebral body structure form was normal in the groups Ⅱand Ⅲ.Trabecular bone coarsens, connection and repair were observed in micro fracture and bone defects, bone trabecular connectivity was superior to group Ⅰ significantly; vertebral body compression strength in the groupⅠ was on the decline, vertebral compression strength in the groups Ⅱand Ⅲ was on the rise, the largest vertebra.PostoperativeBMC andBMD in groups Ⅱand Ⅲ were incresed, andsignificantly higher than group Ⅰ after6 weeks(P<0.05),BMC and BMD in group Ⅲ after12 weeks were higher than the other three groups.Conclusion:Compound bBMPCSC has good bone induction.It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula, and can significantly improve the vertebral strength, as a vertebral packing material with good application prospect.

  13. Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery.

    Science.gov (United States)

    Vallet-Regí, María; Izquierdo-Barba, Isabel; Colilla, Montserrat

    2012-03-28

    This review article describes the importance of structure and functionalization in the performance of mesoporous silica bioceramics for bone tissue regeneration and local drug delivery purposes. Herein, we summarize the pivotal features of mesoporous bioactive glasses, also known as 'templated glasses' (TGs), which present chemical compositions similar to those of conventional bioactive sol-gel glasses and the added value of an ordered mesopore arrangement. An in-depth study concerning the possibility of tailoring the structural and textural characteristics of TGs at the nanometric scale and their influence on bioactive behaviour is discussed. The highly ordered mesoporous arrangement of cavities allows these materials to confine drugs to be subsequently released, acting as drug delivery devices. The functionalization of mesoporous silica walls has been revealed as the cornerstone in the performance of these materials as controlled release systems. The synergy between the improved bioactive behaviour and local sustained drug release capability of mesostructured materials makes them suitable to manufacture three-dimensional macroporous scaffolds for bone tissue engineering. Finally, this review tackles the possibility of covalently grafting different osteoinductive agents to the scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process.

  14. Use of organometallic chelates in broiler diet: effect on the performance and bone structure. Preliminary results

    Directory of Open Access Journals (Sweden)

    Biagina Chiofalo

    2010-01-01

    Full Text Available On 26,000 Ross 508 broiler chickens (two groups of 13,000 per pen the effect of dietary substitution with in organic trace minerals or organometallic chelates on performances and bones tructure c trace minerals or organometallic chelates on performances and bone structure was studied. Treatments consisted of a commercial diet integrated with 0.5% of a vitamin-mineral premix containing inorganic trace minerals (CTR or organometallic chelates (MHA using Methionine Hydroxy Analog. Production performance was measured during the 52 d trial period and bone structure was evalu- ated at the slaughter (52 d. Significant (P=0.038 higher values were observed in the finishing period (41 to 52 d for the body weight of the treated group (3560 g vs. 3358 g. The same trend was observed for the ADG (MHA 87.6 g/d vs. CTR 71 g/d; P<0.05. Concerning ash percentage significant higher values were observed in the CTR group for femur (49.01% vs. 51.45%; P<0.01 and tibia (53.87% vs. 49.79%; P<0.001; femur showed also higher values for bone radiopacity (MHA 0.21 px vs. CTR 0.26 px; P=0.035. MHA group showed significant higher value for morphometric measures of the femur and tibia. Results suggest that organometallic chelates can be included in the diet without compromising broiler performance.

  15. The micro-architecture of human cancellous bone from fracture neck of femur patients in relation to the structural integrity and fracture toughness of the tissue

    Directory of Open Access Journals (Sweden)

    C. Greenwood

    2015-12-01

    Full Text Available Osteoporosis is clinically assessed from bone mineral density measurements using dual energy X-ray absorption (DXA. However, these measurements do not always provide an accurate fracture prediction, arguably because DXA does not grapple with ‘bone quality’, which is a combined result of microarchitecture, texture, bone tissue properties, past loading history, material chemistry and bone physiology in reaction to disease. Studies addressing bone quality are comparatively few if one considers the potential importance of this factor. They suffer due to low number of human osteoporotic specimens, use of animal proxies and/or the lack of differentiation between confounding parameters such as gender and state of diseased bone. The present study considers bone samples donated from patients (n = 37 who suffered a femoral neck fracture and in this very well defined cohort we have produced in previous work fracture toughness measurements (FT which quantify its ability to resist crack growth which reflects directly the structural integrity of the cancellous bone tissue. We investigated correlations between BV/TV and other microarchitectural parameters; we examined effects that may suggest differences in bone remodelling between males and females and compared the relationships with the FT properties. The data crucially has shown that TbTh, TbSp, SMI and TbN may provide a proxy or surrogate for BV/TV. Correlations between FT critical stress intensity values and microarchitecture parameters (BV/TV, BS/TV, TbN, BS/BV and SMI for osteoporotic cancellous tissue were observed and are for the first time reported in this study. Overall, this study has not only highlighted that the fracture model based upon BMD could potentially be improved with inclusion of other microarchitecture parameters, but has also given us clear clues as to which of them are more influential in this role.

  16. Histomorphometric and ultrastructural analysis of the tendon-bone interface after rotator cuff repair in a rat model.

    Science.gov (United States)

    Kanazawa, Tomonoshin; Gotoh, Masafumi; Ohta, Keisuke; Honda, Hirokazu; Ohzono, Hiroki; Shimokobe, Hisao; Shiba, Naoto; Nakamura, Kei-Ichiro

    2016-09-20

    Successful rotator cuff repair requires biological anchoring of the repaired tendon to the bone. However, the histological structure of the repaired tendon-bone interface differs from that of a normal tendon insertion. We analysed differences between the normal tendon insertion and the repaired tendon-bone interface after surgery in the mechanical properties, histomorphometric analysis, and 3-dimensional ultrastructure of the cells using a rat rotator cuff repair model. Twenty-four adult Sprague-Dawley (SD) rats underwent complete cuff tear and subsequent repair of the supraspinatus tendon. The repaired tendon-bone interface was evaluated at 4, 8, and 12 weeks after surgery. At each time point, shoulders underwent micro-computed tomography scanning and biomechanical testing (N = 6), conventional histology and histomorphometric analysis (N = 6), and ultrastructural analysis with focused ion beam/scanning electron microscope (FIB/SEM) tomography (N = 4). We demonstrated that the cellular distribution between the repaired tendon and bone at 12 weeks after surgery bore similarities to the normal tendon insertion. However, the ultrastructure of the cells at any time point had a different morphology than those of the normal tendon insertion. These morphological differences affect the healing process, partly contributing to re-tearing at the repair site. These results may facilitate future studies of the regeneration of a normal tendon insertion.

  17. Prevention of alveolar bone loss in an osteoporotic animal model via interference of semaphorin 4d.

    Science.gov (United States)

    Zhang, Y; Wei, L; Miron, R J; Zhang, Q; Bian, Z

    2014-11-01

    Semaphorin 4d (Sema4d) has been proposed as a novel target gene for the treatment of osteoporosis. Recently, we fabricated a site-specific bone-targeting system from polymeric nanoparticles that demonstrates an ability to prevent bone loss in an osteoporotic model by interfering with Sema4d gene expression using small interference RNA (siRNA) molecules. The aim of the present investigation was to determine the effects of this targeting system on the periodontium, an area of high bone turnover. We demonstrated, by single photon emission computed tomography, that intravenous injection of this molecule in ovariectomized Balb/C mice is able to target alveolar bone peaking 4 hr post-injection. We then compared, by histological analysis, the bone volume/total volume (BV/TV), alveolar bone height loss, immunohistochemical expression of Sema4d, and total number of osteoclasts in mandibular alveolar bone. Four treatment modalities were compared as follows: (1) sham-operated, (2) OVX-operated, (3) OVX+estrogen replacement therapy, and (4) OVX+siRNA-Sema4d animals. The results from the present study demonstrate that an osteoporotic condition significantly increases alveolar bone height loss, and that the therapeutic effects via bone-targeting systems featuring interference of Sema4d are able to partly counteract alveolar bone loss caused by osteoporosis. While the future therapeutic demand for the large number of patients suffering from osteoporosis faces many challenges, we demonstrate within the present study an effective drug-delivery moiety with anabolic effects on the bone remodeling cycle able to locate and target alveolar bone regeneration.

  18. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats.

    Science.gov (United States)

    Shenoy, Priyank A; Kuo, Andy; Vetter, Irina; Smith, Maree T

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  19. Bone Structure and Estimated Bone Strength in Obese Patients Evaluated by High-Resolution Peripheral Quantitative Computed Tomography

    DEFF Research Database (Denmark)

    Andersen, Stine; Frederiksen, Katrine Diemer; Hansen, Stinus;

    2014-01-01

    Obesity is associated with high bone mineral density (BMD), but whether obesity-related higher bone mass increases bone strength and thereby protect against fractures is uncertain. We estimated effects of obesity on bone microarchitecture and estimated strength in 36 patients (12 males and 24...... females, age 25-56 years and BMI 33.2-57.6 kg/m(2)) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m(2)) in regard to gender, menopausal status, age (±6 years) and height (±6 cm) using high resolution peripheral quantitative computed tomography and dual energy X-ray absorptiometry...

  20. Bone marrow-derived progenitor cells augment venous remodeling in a mouse dorsal skinfold chamber model.

    Directory of Open Access Journals (Sweden)

    Megan E Doyle

    Full Text Available The delivery of bone marrow-derived cells (BMDCs has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM and Lin(-/Sca-1(+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1(+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1(+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif ligand 2 (CXCL2 and interferon gamma (IFNγ that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, and platelet derived growth factor-BB (PDGF-BB compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45(+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1(+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment.

  1. Characterization of a rat model of metastatic prostate cancer bone pain

    Directory of Open Access Journals (Sweden)

    Paolo Donato De Ciantis

    2010-11-01

    Full Text Available Paolo Donato De Ciantis1, Kiran Yashpal2, James Henry3, Gurmit Singh11Department of Pathology and Molecular Pathology, 2Pain Research Laboratories, 3Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, CanadaPurpose: The objectives of this study were to establish and characterize a novel animal model of metastatic prostate cancer-induced bone pain.Methods: Copenhagen rats were injected with 106 MATLyLu (MLL prostate cancer cells or phosphate-buffered saline by per cutaneous intra femoral injections into the right hind leg distal epiphysis. Over 13 days, rats progressively developed a tumor within the distal femoral epiphysis. On days 3, 7, 10, and 13 post injection, rats were subjected to the incapacitance and Randall–Selitto behavioral tests as they are believed to be indirect reflections of tumor induced pain. Ipsilateral hind limbs were subjected to X-ray and computed tomography (CT scans and histological sections were stained with hematoxylin and eosin (H&E.Results: Intra femoral injections of MLL cells resulted in the progressive development of a tumor leading to bone destruction and nociceptive behaviors. Tumor development resulted in the redistribution of weight to the contralateral hind leg and significantly reduced the paw withdrawal threshold of the ipsilateral hind paw as observed via the incapacitance and Randall–Selitto tests, respectively. X-ray and computed tomography scans along with H&E stains indicated tumor-associated structural damage to the distal femur. This model was challenged with administration of meloxicam. Compared with vehicle-injected controls, the meloxicam-treated rats displayed smaller nociceptive responses as observed with the incapacitance and Randall–Selitto tests, suggesting that meloxicam was effective in reducing the pain-related symptoms displayed by model animals and that the model behaved in a predictable way to cyclooxygenase-2 treatment.Conclusions: This

  2. Temporal structures in shell models

    DEFF Research Database (Denmark)

    Okkels, F.

    2001-01-01

    The intermittent dynamics of the turbulent Gledzer, Ohkitani, and Yamada shell-model is completely characterized by a single type of burstlike structure, which moves through the shells like a front. This temporal structure is described by the dynamics of the instantaneous configuration of the shell...

  3. Structuring very large domain models

    DEFF Research Database (Denmark)

    Störrle, Harald

    2010-01-01

    View/Viewpoint approaches like IEEE 1471-2000, or Kruchten's 4+1-view model are used to structure software architectures at a high level of granularity. While research has focused on architectural languages and with consistency between multiple views, practical questions such as the structuring a...

  4. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  5. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering. PMID:26604759

  6. Cellulose and collagen derived micro-nano structured scaffolds for bone tissue engineering.

    Science.gov (United States)

    Aravamudhan, Aja; Ramos, Daisy M; Nip, Jonathan; Harmon, Matthew D; James, Roshan; Deng, Meng; Laurencin, Cato T; Yu, Xiaojun; Kumbar, Sangamesh G

    2013-04-01

    Scaffold based bone tissue engineering (BTE) has made great progress in regenerating lost bone tissue. Materials of natural and synthetic origin have been used for scaffold fabrication. Scaffolds derived from natural polymers offer greater bioactivity and biocompatibility with mammalian tissues to favor tissue healing, due to their similarity to native extracellular matrix (ECM) components. Often it is a challenge to fabricate natural polymer based scaffolds for BTE applications without compromising their bioactivity, while maintaining adequate mechanical properties. In this work, we report the fabrication and characterization of cellulose and collagen based micro-nano structured scaffolds using human osteoblasts (HOB) for BTE applications. These porous micro-nano structured scaffolds (average pore diameter 190 +/- 10 microm) exhibited mechanical properties in the mid range of human trabecular bone (compressive modulus 266.75 +/- 33.22 MPa and strength 12.15 3 +/- 2.23 MPa). These scaffolds supported the greater adhesion and phenotype maintenance of cultured HOB as reflected by higher levels of osteogenic enzyme alkaline phosphatase and mineral deposition compared to control polyester micro-nano structured scaffolds of identical pore properties. These natural polymer based micro-nano structured scaffolds may serve as alternatives to polyester based scaffolds for BTE applications.

  7. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  8. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  9. The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

    Science.gov (United States)

    Sardone, Laura Donata

    Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

  10. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.

    Science.gov (United States)

    Wang, Lei; Zhou, Shuxia; Liu, Baolin; Lei, Delin; Zhao, Yinghua; Lu, Chao; Tan, Aixing

    2006-12-01

    Distraction osteogenesis is widely used in treating deformities, defects, and fractures of both long bones and craniofacial bones. Demands for acceleration of bone consolidation are increased in distraction osteogenesis. Nerve growth factor (NGF) can enhance innervation and bone regeneration in a fracture model and stimulate differentiation of osteoblastic cells. In this study, we tested the ability of locally applied NGF to enhance bone regeneration in a rabbit model of mandibular distraction osteogenesis. Twenty rabbits underwent bilateral distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human NGFbeta (hNGFbeta) in buffer was injected into the callus after distraction. The contralateral side received placebo injections. Rabbits were euthanized at consolidation times of 14 and 28 days. Specimens were subjected to radiography, callus dimensions measurement, mechanical testing, and bone histological and histomorphometric analysis. The maximum load, bone volume/total volume, mineral apposition rate of the 1st to 11th day, and mineralized bone percentage were significantly higher in the hNGFbeta side at 14 and 28 days (p<0.05). The data indicate that locally applied hNGFbeta can accelerate callus maturation and may be an option to shorten the consolidation period in distraction osteogenesis.

  11. Modelling the temperature evolution of bone under high intensity focused ultrasound.

    Science.gov (United States)

    ten Eikelder, H M M; Bošnački, D; Elevelt, A; Donato, K; Di Tullio, A; Breuer, B J T; van Wijk, J H; van Dijk, E V M; Modena, D; Yeo, S Y; Grüll, H

    2016-02-21

    Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR

  12. Modelling the temperature evolution of bone under high intensity focused ultrasound

    Science.gov (United States)

    ten Eikelder, H. M. M.; Bošnački, D.; Elevelt, A.; Donato, K.; Di Tullio, A.; Breuer, B. J. T.; van Wijk, J. H.; van Dijk, E. V. M.; Modena, D.; Yeo, S. Y.; Grüll, H.

    2016-02-01

    Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR

  13. Probabilistic modeling of timber structures

    DEFF Research Database (Denmark)

    Köhler, Jochen; Sørensen, John Dalsgaard; Faber, Michael Havbro

    2007-01-01

    The present paper contains a proposal for the probabilistic modeling of timber material properties. It is produced in the context of the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS) [Joint Committee of Structural Safety. Probabilistic Model Code, Internet Publ...... is presented and possible refinements are given related to updating of the probabilistic model given new information, modeling of the spatial variation of strength properties and the duration of load effects.......The present paper contains a proposal for the probabilistic modeling of timber material properties. It is produced in the context of the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS) [Joint Committee of Structural Safety. Probabilistic Model Code, Internet...... and comments from participants of the COST E24 action and the members of the JCSS. The paper contains a description of the basic reference properties for timber strength parameters and ultimate limit state equations for timber components. The recommended probabilistic model for these basic properties...

  14. Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover.

    Science.gov (United States)

    Metzger, Corinne E; Narayanan, Anand; Zawieja, David C; Bloomfield, Susan A

    2017-04-01

    Bone loss is a common comorbidity of inflammatory bowel disease (IBD), leading to elevated fracture risk in these patients. Inflammatory factors associated with IBD cause increased bone resorption and decreased bone formation with multiple factors implicated as instigators of these alterations. In this project, we examined the influence of IBD on osteocyte proteins in male rats (2 months old) divided into two groups: induced gut inflammation via 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, and vehicle control. We examined the prevalence of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an anti-inflammatory cytokine, interleukin-10 (IL-10), the anabolic factor insulin-like growth factor-I (IGF-I), osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin in osteocytes in three bone compartments 4 weeks after initiation of gut inflammation. Histomorphometry of the proximal tibia and fourth lumbar vertebra revealed lower bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S) with TNBS. Tibial mid-shaft periosteal BFR was also lower with TNBS. Immunohistochemical staining of the distal femur demonstrated that %TNF-α(+) , %IL-6(+) , %RANKL(+) , and %OPG(+) osteocytes were elevated in cancellous bone in TNBS animals compared to vehicle. These changes were coincident with increased bone resorption. With regression analysis, %RANKL(+) osteocytes statistically predicted the increase in cancellous Oc.S (R(2)  = 0.565). Increased %sclerostin(+) osteocytes observed in the TNBS treatment predicted declines in cancellous OS (R(2)  = 0.581) as well as BFR in cancellous and cortical bone (R(2)  = 0.674, R(2)  = 0.908, respectively). Contrary to our hypothesis, %IGF-I(+) osteocytes increased in TNBS animals. In conclusion, the IBD model produced a systemic inflammation that altered the regulatory protein profile in osteocytes that

  15. Influence of Orthotropy on Biomechanics of Peri-Implant Bone in Complete Mandible Model with Full Dentition

    Directory of Open Access Journals (Sweden)

    Xi Ding

    2014-01-01

    Full Text Available Objective. The study was to investigate the impact of orthotropic material on the biomechanics of dental implant, based on a detailed mandible with high geometric and mechanical similarity. Materials and Methods. Multiple data sources were used to elaborate detailed biological structures and implant CAD models. In addition, an extended orthotropic material assignment methodology based on harmonic fields was used to handle the alveolar ridge region to generate compatible orthotropic fields. The influence of orthotropic material was compared with the commonly used isotropic model and simplified orthotropic model. Results. The simulation results showed that the values of stress and strain on the implant-bone interface almost increased in the orthotropic model compared to the isotropic case, especially for the cancellous bone. However, the local stress concentration was more obvious in the isotropic case compared to that in orthotropic case. The simple orthotropic model revealed irregular stress and strain distribution, compared to the isotropic model and the real orthotropic model. The influence of orthotropy was little on the implant, periodontal ligament, tooth enamel, and dentin. Conclusion. The orthotropic material has significant effect on stress and strain of implant-bone interface in the mandible, compared with the isotropic simulation. Real orthotropic mechanical properties of mandible should be emphasized in biomechanical studies of dental implants.

  16. Nonlinear hierarchical multiscale modeling of cortical bone considering its nanoscale microstructure.

    Science.gov (United States)

    Ghanbari, J; Naghdabadi, R

    2009-07-22

    We have used a hierarchical multiscale modeling scheme for the analysis of cortical bone considering it as a nanocomposite. This scheme consists of definition of two boundary value problems, one for macroscale, and another for microscale. The coupling between these scales is done by using the homogenization technique. At every material point in which the constitutive model is needed, a microscale boundary value problem is defined using a macroscopic kinematical quantity and solved. Using the described scheme, we have studied elastic properties of cortical bone considering its nanoscale microstructural constituents with various mineral volume fractions. Since the microstructure of bone consists of mineral platelet with nanometer size embedded in a protein matrix, it is similar to the microstructure of soft matrix nanocomposites reinforced with hard nanostructures. Considering a representative volume element (RVE) of the microstructure of bone as the microscale problem in our hierarchical multiscale modeling scheme, the global behavior of bone is obtained under various macroscopic loading conditions. This scheme may be suitable for modeling arbitrary bone geometries subjected to a variety of loading conditions. Using the presented method, mechanical properties of cortical bone including elastic moduli and Poisson's ratios in two major directions and shear modulus is obtained for different mineral volume fractions.

  17. Determining the critical size of a rabbit rib segmental bone defect model.

    Science.gov (United States)

    Liu, Fengzhen; Chen, Kun; Hou, Lei; Li, Keyi; Wang, Dawei; Zhang, Bin; Wang, Xiumei

    2016-10-01

    In order to establish and standardize the rabbit rib segmental bone defect model, it is of vital importance to determine rabbit rib critical size defect (CSD). According to the general time needed for spontaneous long-bone regeneration, three-month observation period was set to determine the CSD. The rabbit rib segmental bone defects with different sizes from 1 to 5 cm with or without periosteum were performed in the eighth rib of 4-month-old male New Zealand rabbits and underwent X-ray examinations at the 4th, 8th and 12th weeks postoperatively. The gross and histological examinations at postoperative week 12 were evaluated, which showed that the critical sizes in the rabbit rib models with and without periosteum were 5 and 2 cm, respectively. This study provides prerequisite data for establishing rabbit rib CSD model and evaluating bone materials using this model.

  18. Open forward and inverse problems in theoretical modeling of bone tissue adaptation.

    Science.gov (United States)

    Zadpoor, Amir Abbas

    2013-11-01

    Theoretical modeling of bone tissue adaptation started several decades ago. Many important problems have been addressed in this area of research during the last decades. However, many important questions remain unanswered. In this paper, an overview of open problems in theoretical modeling of bone tissue adaptation is presented. First, the principal elements of bone tissue adaptation models are defined and briefly reviewed. Based on these principal elements, four categories of open problems are identified. Two of these categories primarily include forward problems, while two others include inverse problems. In every one of the identified categories, important open problems are highlighted and their importance is discussed. It is shown that most of previous studies on the theoretical modeling of bone tissue adaptation have been focused on the problems of the first category and not much is done in three other categories. The paper tries to highlight these potentially important problems that have been so far largely overlooked and to inspire new avenues of research.

  19. Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse.

    Science.gov (United States)

    Barbe, Mary F; Jain, Nisha X; Massicotte, Vicky S; Popoff, Steven N; Barr-Gillespie, Ann E

    2015-01-01

    We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: (1) HRHF, (2) low repetition low force (LRLF); or (3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions.

  20. [Structural and functional characteristics of bone tissue and blood cytokines in health and disease of the joints].

    Science.gov (United States)

    Kariakina, E V; Norkin, I A; Gladkova, E V; Persova, E A; Matveeva, O V; Puchin'ian, D M

    2014-02-01

    Change of structural and functional state of bone in patients with primary osteoarthrosis of the hip joint compared to healthy individuals is characterized by decreased bone formation with a relative predominance of resorption. Osteopenic syndrome develops in the background of evident imbalance of a blood cytokine profile with increasing the level of proinflammatory and the variability of the level of anti-inflammatory cytokines.

  1. Advanced computational workflow for the multi-scale modeling of the bone metabolic processes.

    Science.gov (United States)

    Dao, Tien Tuan

    2017-06-01

    Multi-scale modeling of the musculoskeletal system plays an essential role in the deep understanding of complex mechanisms underlying the biological phenomena and processes such as bone metabolic processes. Current multi-scale models suffer from the isolation of sub-models at each anatomical scale. The objective of this present work was to develop a new fully integrated computational workflow for simulating bone metabolic processes at multi-scale levels. Organ-level model employs multi-body dynamics to estimate body boundary and loading conditions from body kinematics. Tissue-level model uses finite element method to estimate the tissue deformation and mechanical loading under body loading conditions. Finally, cell-level model includes bone remodeling mechanism through an agent-based simulation under tissue loading. A case study on the bone remodeling process located on the human jaw was performed and presented. The developed multi-scale model of the human jaw was validated using the literature-based data at each anatomical level. Simulation outcomes fall within the literature-based ranges of values for estimated muscle force, tissue loading and cell dynamics during bone remodeling process. This study opens perspectives for accurately simulating bone metabolic processes using a fully integrated computational workflow leading to a better understanding of the musculoskeletal system function from multiple length scales as well as to provide new informative data for clinical decision support and industrial applications.

  2. Analysis of dengue fever risk using geostatistics model in bone regency

    Science.gov (United States)

    Amran, Stang, Mallongi, Anwar

    2017-03-01

    This research aim is to analysis of dengue fever risk based on Geostatistics model in Bone Regency. Risk levels of dengue fever are denoted by parameter of Binomial distribution. Effect of temperature, rainfalls, elevation, and larvae abundance are investigated through Geostatistics model. Bayesian hierarchical method is used in estimation process. Using dengue fever data in eleven locations this research shows that temperature and rainfall have significant effect of dengue fever risk in Bone regency.

  3. Osteogenic Effects of Dedifferentiated Fat Cell Transplantation in Rabbit Models of Bone Defect and Ovariectomy-Induced Osteoporosis

    OpenAIRE

    Kikuta, Shinsuke; Tanaka, Nobuaki; Kazama, Tomohiko; Kazama, Minako; Kano, Koichiro; Ryu, Junnosuke; Tokuhashi, Yasuaki; Matsumoto, Taro

    2013-01-01

    We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was obser...

  4. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  5. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone.

    Directory of Open Access Journals (Sweden)

    Mary Higby Schweitzer

    Full Text Available Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures.

  6. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone.

    Science.gov (United States)

    Schweitzer, Mary Higby; Moyer, Alison E; Zheng, Wenxia

    2016-01-01

    Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures.

  7. Handbook of structural equation modeling

    CERN Document Server

    Hoyle, Rick H

    2012-01-01

    The first comprehensive structural equation modeling (SEM) handbook, this accessible volume presents both the mechanics of SEM and specific SEM strategies and applications. The editor, contributors, and editorial advisory board are leading methodologists who have organized the book to move from simpler material to more statistically complex modeling approaches. Sections cover the foundations of SEM; statistical underpinnings, from assumptions to model modifications; steps in implementation, from data preparation through writing the SEM report; and basic and advanced applications, inclu

  8. Bioinspired structure of bioceramics for bone regeneration in load-bearing sites.

    Science.gov (United States)

    Zhang, Faming; Chang, Jiang; Lu, Jianxi; Lin, Kaili; Ning, Congqin

    2007-11-01

    The major problem with the use of porous bioceramics as bone regeneration grafts is their weak mechanical strength, which has not been overcome to date. Here we described a novel way to solve this problem. Beta-tricalcium phosphate (beta-TCP) bioceramics with a bioinspired structure were designed and prepared with a porous cancellous core (porosity: 70-90%) inside and a dense compact shell (porosity: 5-10%) outside that mimics the characteristics of natural bone. They showed excellent mechanical properties, with a compressive strength of 10-80MPa and an elastic modulus of 180MPa-1.0GPa, which could be tailored by the dense/porous cross-sectional area ratio obeying the rule of exponential growth. The in vitro degradation of the bioinspired bioceramics was faster than that of dense bioceramics but slower than that of porous counterparts. The changes in mechanical properties of the bioinspired ceramics during in vitro degradation were also investigated. A concept of the bioinspired macrostructure design of natural bone was proposed which provided a simple but effective way to increase the mechanical properties of porous bioceramics for load-bearing bone regeneration applications. It should be readily applicable to other porous materials.

  9. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

    Science.gov (United States)

    Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

    2016-08-01

    Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

  10. An alternative model of vascularized bone marrow transplant: partial femur transplantation.

    Science.gov (United States)

    Chen, Jian-Wu; Chen, Chen; Su, Ying-Jun; Yan, Lun; Wang, Shi-Ping; Guo, Shu-Zhong

    2014-12-01

    The vascularized whole femur transplantation model is one of the commonly used vascularized bone marrow transplant models. It involves technical complexity and morbidities. To optimize this model, we took 2/3 femur as the carrier of bone marrow cells, and developed a vascularized partial femur model. Four experimental groups were carried out, namely, the syngeneic partial femur transplantation, allogeneic partial femur transplantation with or without cyclosporine A, and allogeneic whole femur transplantation with cyclosporine A. The results showed that the partial femur model was technically simpler and shortened the operative and ischemia time compared to the whole femur model. Gross and histologic appearance confirmed the viability of femur, and its bone marrow inside the bone could also maintain normal morphologically at 60-day posttransplant. Besides, donor multilineage chimerism could be continuously detected in immunosuppressed allogeneic partial femur recipients at 1-, 2-, 3-, 4-, and 8-week posttransplant, and it showed no significant differences when compared with whole femur transplantation. Meanwhile, long-term engraftment of donor-origin cells was also confirmed in recipients' bone marrow, lymph nodes, and spleen, but not in thymus. Therefore, the vascularized partial femur can serve as a continuous resource of bone morrow cells and may provide a useful tool for the study of immune tolerance in vascularized composite allotransplantation.

  11. A mathematical model for bone tissue regeneration inside a specific type of scaffold.

    Science.gov (United States)

    Sanz-Herrera, J A; Garcia-Aznar, J M; Doblare, M

    2008-10-01

    Bone tissue regeneration using scaffolds is receiving an increasing interest in orthopedic surgery and tissue engineering applications. In this study, we present the geometrical characterization of a specific family of scaffolds based on a face cubic centered (FCC) arrangement of empty pores leading to analytical formulae of porosity and specific surface. The effective behavior of those scaffolds, in terms of mechanical properties and permeability, is evaluated through the asymptotic homogenization theory applied to a representative volume element identified with the unit cell FCC. Bone growth into the scaffold is estimated by means of a phenomenological model that considers a macroscopic effective stress as the mechanical stimulus that regulates bone formation. Cell migration within the scaffold is modeled as a diffusion process based on Fick's law which allows us to estimate the cell invasion into the scaffold microstructure. The proposed model considers that bone growth velocity is proportional to the concentration of cells and regulated by the mechanical stimulus. This model allows us to explore what happens within the scaffold, the surrounding bone and their interaction. The mathematical model has been numerically implemented and qualitatively compared with previous experimental results found in the literature for a scaffold implanted in the femoral condyle of a rabbit. Specifically, the model predicts around 19 and 23% of bone regeneration for non-grafted and grafted scaffolds, respectively, both with an initial porosity of 76%.

  12. Effects of architecture, density and connectivity on the properties of trabecular bone: a two-dimensional, Voronoi cell based model study

    Science.gov (United States)

    Ruiz, Osvaldo; Schouwenaars, Rafael; Ramírez, Edgar I.; Jacobo, Víctor H.; Ortiz, Armando

    2011-10-01

    Trabecular bone, rather than being considered as a homogeneous material, must be analysed as a structure of interconnected beam and plate-like elements. The arrangement and morphology of these elements depend on the specific tissue studied as well as on the physiology of the individual. It is therefore impossible to define the mechanical properties trabecular bone in general. To estimate the properties of an individual structure, flexible numerical models must be developed, which allow the calculation of elastic constants and resistance of tissue previously characterised by non-destructive observation. Voxel-based modelling of structures observed by X-ray microtomography is computation intensive. Here, synthetic 2D-microstructures are analysed, constructed as a collection of Voronoi-cells obtained from the observation of plane sections of cancellous bone. The effect of architecture (vertebra and femur), bone density and loss of trabecular connectivity was researched. The study confirms findings of earlier experimental and numerical studies relating to the effect of these parameters; the technique is efficient in terms of experimental effort and numerical analysis. Consequently, the use of synthetic microstructures based on a Voronoi-cell approximation of the real bone architecture may be a promising approach for the prediction of the mechanical properties of trabecular bone.

  13. Characterization of an ovine bilateral critical sized bone defect iliac wing model to examine treatment modalities based on bone tissue engineering.

    Science.gov (United States)

    Lansdowne, Jennifer L; Devine, Declan; Eberli, Ursula; Emans, Pieter; Welting, Tim J M; Odekerken, Jim C E; Schiuma, Damiano; Thalhauser, Martin; Bouré, Ludovic; Zeiter, Stephan

    2014-01-01

    Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  14. Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Jennifer L. Lansdowne

    2014-01-01

    Full Text Available Critical sized bone defect (CSBD animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control or filled with autologous corticocancellous bone graft (clinical gold standard, positive control was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  15. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI.

  16. Coralline hydroxyapatite is a suitable bone graft substitute in an intra-articular goat defect model.

    Science.gov (United States)

    Koëter, S; Tigchelaar, S J; Farla, P; Driessen, L; van Kampen, A; Buma, P

    2009-07-01

    Intra-articular defects can be filled with an autologous bone graft taken from the iliac crest. This can be indicated after trauma or following correcting osteotomy. Patients may encounter donor site morbidity after this procedure. In this in vivo study, we studied if coralline hydroxyapatite (CHA) is a suitable material to replace autologous bone graft to fill a defect in the femoral trochlea of goats. CHA did not evoke any negative reaction in the synovium, and the articular cartilage was comparable to controls. In the bone graft group, we found scattered areas of (enchondral formed) bone. Most bone graft had been resorbed or remodeled, and the scarce remnants were incorporated into new bone. Resorption of CHA was limited or absent and most CHA was surrounded by new bone. In areas with fragmented CHA, close to the joint surface, numerous giant cells were found. The study shows that in this animal model, CHA inserted in a defect that directly communicates with the joint space incorporates into bone. This study did not show any negative effects of CHA in a joint environment.

  17. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    Science.gov (United States)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  18. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Directory of Open Access Journals (Sweden)

    Chiara Arrigoni

    2016-08-01

    Full Text Available Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps.

  19. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Science.gov (United States)

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps. PMID:27571063

  20. Effect of ovariectomy on BMD, micro-architecture and biomechanics of cortical and cancellous bones in a sheep model.

    Science.gov (United States)

    Wu, Zi-xiang; Lei, Wei; Hu, Yun-yu; Wang, Hai-qiang; Wan, Shi-yong; Ma, Zhen-sheng; Sang, Hong-xun; Fu, Suo-chao; Han, Yi-sheng

    2008-11-01

    Osteoporotic/osteopenia fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) and dual energy X-ray absorptionmeter (DEXA) to investigate the changes in micro-architecture and bone mineral density (BMD) in a sheep model resulted from ovariectomy (OVX). Biomechanical tests were performed to evaluate the strength of the trabecular bone. Twenty adult sheeps were randomly divided into three groups: sham group (n=8), group 1 (n=4) and group 2 (n=8). In groups 1 and 2, all sheep were ovariectomized (OVX); in the sham group, the ovaries were located and the oviducts were ligated. In all animals, BMD for lumbar spine was obtained during the surgical procedure. BMD at the spine, femoral neck and femoral condyle was determined 6 months (group 1) and 12 months (group 2) post-OVX. Lumbar spines and femora were obtained and underwent BMD scan, micro-CT analysis. Compressive mechanical properties were determined from biopsies of vertebral bodies and femoral condyles. BMD, micro-architectural parameters and mechanical properties of cancellous bone did not decrease significantly at 6 months post-OVX. Twelve months after OVX, BMD, micro-architectural parameters and mechanical properties decreased significantly. The results of linear regression analyses showed that trabecular thickness (Tb.Th) (r=0.945, R2=0.886) and bone volume fraction (BV/TV) (r=0.783, R2=0.586) had strong (R2>0.5) correlation to compression stress. In OVX sheep, changes in the structural parameters of trabecular bone are comparable to the human situation during osteoporosis was induced. The sheep model presented seems to meet the criteria for an osteopenia model for fracture treatment with respect to morphometric and mechanical properties. But the duration of OVX must be longer than 12 months to ensure the animal model can be established successfully.

  1. Geometric and mechanical properties evaluation of scaffolds for bone tissue applications designing by a reaction-diffusion models and manufactured with a material jetting system

    Directory of Open Access Journals (Sweden)

    Marco A. Velasco

    2016-10-01

    Full Text Available Scaffolds are essential in bone tissue engineering, as they provide support to cells and growth factors necessary to regenerate tissue. In addition, they meet the mechanical function of the bone while it regenerates. Currently, the multiple methods for designing and manufacturing scaffolds are based on regular structures from a unit cell that repeats in a given domain. However, these methods do not resemble the actual structure of the trabecular bone which may work against osseous tissue regeneration. To explore the design of porous structures with similar mechanical properties to native bone, a geometric generation scheme from a reaction-diffusion model and its manufacturing via a material jetting system is proposed. This article presents the methodology used, the geometric characteristics and the modulus of elasticity of the scaffolds designed and manufactured. The method proposed shows its potential to generate structures that allow to control the basic scaffold properties for bone tissue engineering such as the width of the channels and porosity. The mechanical properties of our scaffolds are similar to trabecular tissue present in vertebrae and tibia bones. Tests on the manufactured scaffolds show that it is necessary to consider the orientation of the object relative to the printing system because the channel geometry, mechanical properties and roughness are heavily influenced by the position of the surface analyzed with respect to the printing axis. A possible line for future work may be the establishment of a set of guidelines to consider the effects of manufacturing processes in designing stages.

  2. Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a rat tibia defect model

    Directory of Open Access Journals (Sweden)

    Xu W

    2011-08-01

    Full Text Available Weiguo Xu1, Cornelia Ganz2, Ulf Weber2, Martin Adam2, Gerd Holzhüter2, Daniel Wolter3, Bernhard Frerich3, Brigitte Vollmar1, Thomas Gerber21Institute for Experimental Surgery, 2Institute of Physics, 3Department of Oral, Maxillofacial and Plastic Surgery, University of Rostock, Rostock, GermanyAbstract: In clinical practice, vertebral compression fractures occur after trauma and osteoporosis. Kyphoplasty is a minimally invasive procedure using bone filler material for the treatment of such fractures. A full synthetic injectable bone substitute (SIBS was manufactured by means of spray drying. The aim of this study was to characterize the SIBS and to analyze the remodelling process during degradation of the biomaterial and new bone formation after implantation. SIBS is an aqueous suspension of donut-like microparticles. These microparticles consist of nanocrystallites of synthetic hydroxyapatite embedded in amorphous silica gel. After implantation of SIBS in a proximal tibial diaphyseal defect in 52 rats, grafts were harvested for subsequent analysis on different days. Newly formed bone originating from endosteum was observed on day 6. Hematomas in the medullary space and cortical wounds disappeared on day 12. The wound region was completely replaced by a composite of newly formed cancellous bone, extracellular matrix, and SIBS. At day 63 the cortical defect was fully healed by bone, while newly formed bone in the medullary space almost disappeared and was replaced with bone marrow. In conclusion, SIBS demonstrated a unique structure with osteoinductive and bioresorbable properties, which induced fast bone regeneration. Therefore, a clinical application of SIBS for kyphoplasty is promising.Keywords: bone remodelling, electron microscopy, histomorphometry, nanotechnology, tissue engineering

  3. Chronic lead poisoning magnifies bone detrimental effects in an ovariectomized rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Lee, Ching Ming; Terrizzi, Antonela Romina; Bozzini, Clarisa; Piñeiro, Adriana Emilce; Conti, María Inés; Martínez, María Pilar

    2016-01-01

    Lead (Pb) is a persistent environmental contaminant that is mainly stored in bones being an important source of endogenous lead exposure during periods of increased bone resorption as occurs in menopause. As no evidence exists of which bone biomechanical properties are impaired in those elderly women who had been exposed to Pb during their lifetime, the aim of the present study is to discern whether chronic lead poisoning magnifies the deterioration of bone biology that occurs in later stages of life. We investigated the effect of Pb in the femora of ovariectomized (OVX) female Wistar rats who had been intoxicated with 1000 ppm of Pb acetate in drinking water for 8 months. Structural properties were determined using a three-point bending mechanical test, and geometrical and material properties were evaluated after obtaining the load/deformation curve. Areal Bone Mineral Density (BMD) was estimated using a bone densitometer. Femoral histomorphometry was carried out on slices dyed with H&E (Hematoxylin and Eosin). Pb and OVX decreased all structural properties with a higher effect when both treatments were applied together. Medullar and cortical area of femurs under OVX increased, allowing the bone to accommodate its architecture, which was not observed under Pb intoxication. Pb and OVX significantly decreased BMD, showing lead treated ovariectomized rats (PbOVX) animals the lowest BMD levels. Trabecular bone volume per total volume (BV/TV%) was decreased in OVX and PbOVX animals in 54% compared to the control animals (pbone biomechanics of OVX rats with a consequent enhancement of the risk of fracture. These results enable the discussion of the detrimental effects of lead intoxication in bone biology in elderly women. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. Long bone defect models for tissue engineering applications: criteria for choice.

    Science.gov (United States)

    Horner, Elizabeth A; Kirkham, Jennifer; Wood, David; Curran, Stephen; Smith, Mark; Thomson, Brian; Yang, Xuebin B

    2010-04-01

    The replacement and repair of bone lost due to trauma, cancer, or congenital defects is a major clinical challenge. Skeletal tissue engineering is a potentially powerful strategy in modern regenerative medicine, and research in this field has increased greatly in recent years. Tissue engineering strategies seek to translate research findings in the fields of materials science, stem cell biology, and biomineralization into clinical applications, demanding the use of appropriate in vivo models to investigate bone regeneration of the long bone. However, identification of the optimal in vivo segmental bone defect model from the literature is difficult due to the use of different animal species (large and small mammals), different bones (weight-bearing and nonweight bearing), and multiple protocols, including the use of various scaffolds, cells, and bioactives. The aim of this review is to summarize the available animal models for evaluating long bone regeneration in vivo. We highlight the differences not only in species and sites but also in defect size, means of defect creation, duration of study, and fixation method. A critical evaluation of the most clinically relevant models is addressed to guide the researcher in his/her choice of the most appropriate model to use in future hypothesis-driven investigations.

  5. Octacalcium phosphate (OCP) collagen composites enhance bone healing in a dog tooth extraction socket model.

    Science.gov (United States)

    Iibuchi, S; Matsui, K; Kawai, T; Sasaki, K; Suzuki, O; Kamakura, S; Echigo, S

    2010-02-01

    The authors have reported that a scaffold constructed of synthetic octacalcium phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) enhanced bone regeneration more than sintered beta-tricalcium phosphate collagen composite or sintered hydroxyapatite collagen composite with a rat calvarial defect model. To aim for clinical application, the present study investigated whether OCP/Col would enhance bone healing in a dog tooth extraction socket model. Six adult, male, beagle dogs were used. The tooth extraction socket model was made by extracting bilateral third maxillary incisors and the subsequent removal of buccal bone. Disks of OCP/Col were implanted into one side of the model and the other side was untreated. The specimens were fixed 1 or 3 months after implantation. In radiographic analysis, the OCP/Col-treated group showed a wider range of radiopacity than the untreated control. Histologically, the OCP/Col-treated group showed more abundant newly formed bone than untreated control, and the implanted OCP was gradually resorbed. In morphometrical analysis, enlargement of the buccal alveolus in the OCP/Col group was significantly greater than in the untreated control. This study showed that implanted OCP/Col would be replaced by newly formed bone and OCP/Col implantation would enhance bone healing in a tooth socket model.

  6. Assessing cement injection behaviour in cancellous bone: an in vitro study using flow models.

    Science.gov (United States)

    Bou-Francis, Antony; López, Alejandro; Persson, Cecilia; Hall, Richard M; Kapur, Nikil

    2014-10-01

    Understanding the cement injection behaviour during vertebroplasty and accurately predicting the cement placement within the vertebral body is extremely challenging. As there is no standardized methodology, we propose a novel method using reproducible and pathologically representative flow models to study the influence of cement properties on injection behaviour. The models, confined between an upper glass window and a lower aluminium plate, were filled with bone marrow substitute and then injected (4, 6 and 8 min after cement mixing) with commercially available bone cements (SimplexP, Opacity+, OsteopalV and Parallax) at a constant flow rate (3 mL/min). A load cell was used to measure the force applied on the syringe plunger and calculate the peak pressure. A camera was used to monitor the cement flow during injection and calculate the following parameters when the cement had reached the boundary of the models: the time to reach the boundary, the filled area and the roundness. The peak pressure was comparable to that reported during clinical vertebroplasty and showed a similar increase with injection time. The study highlighted the influence of cement formulations and model structure on the injection behaviour and showed that cements with similar composition/particle size had similar flow behaviour, while the introduction of defects reduced the time to reach the boundary, the filled area and the roundness. The proposed method provides a novel tool for quick, robust differentiation between various cement formulations through the visualization and quantitative analysis of the cement spreading at various time intervals. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. Mathematical model for osteobstruction in bone regeneration mechanisms: a headway in skeletal tissue engineering.

    Science.gov (United States)

    Ogunsalu, C; Arunaye, F I; Ezeokoli, C; Gardner, M; Rohrer, M; Prasad, H

    2012-11-01

    In this paper, we formulate a mathematical model for the evaluation of parameters responsible for the retardation and eventual acceleration of bone regeneration on the contralateral side of the mandible of experimental animals, following the discovery of a new mechanism of bone regeneration called the osteobstruction mechanism (a negative mechanism of bone regeneration as opposed to the well established and extensively documented positive mechanisms such as osteogenesis, osteoinduction and osteoconduction). This osteobstructive mechanism was demonstrated by episodes of overtaking and reovertaking on single photon emission computed tomography (SPECT) following evaluation of osteoblastic activities in a sequential animal experiment to validate both the Ogunsalu sandwich technique (a double guided tissue technique; D-GTR) and the interceed membrane technique (a single guided tissue regeneration technique; S-GTR) utilizing SPECT, histological and histomorphometric evaluation. This work is now given special attention in terms of mathematical analysis because of limited experimental observations since experiments cannot be observed infinitely. Mathematical modelling is as such essential to generalize the results of this osteobstructive mechanism in bone regeneration. We utilize the Fisher's equation to describe bone cell mobilization during bone regeneration by two different techniques: the Ogunsalu sandwich bone regeneration technique (D-GTR) and the S-GTR.

  8. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

    Directory of Open Access Journals (Sweden)

    GVA Stadelmann

    2008-07-01

    Full Text Available It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400µm from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.

  9. Decellularized bone matrix grafts for calvaria regeneration

    Science.gov (United States)

    Lee, Dong Joon; Diachina, Shannon; Lee, Yan Ting; Zhao, Lixing; Zou, Rui; Tang, Na; Han, Han; Chen, Xin; Ko, Ching-Chang

    2016-01-01

    Decellularization is a promising new method to prepare natural matrices for tissue regeneration. Successful decellularization has been reported using various tissues including skin, tendon, and cartilage, though studies using hard tissue such as bone are lacking. In this study, we aimed to define the optimal experimental parameters to decellularize natural bone matrix using 0.5% sodium dodecyl sulfate and 0.1% NH4OH. Then, the effects of decellularized bone matrix on rat mesenchymal stem cell proliferation, osteogenic gene expression, and osteogenic differentiations in a two-dimensional culture system were investigated. Decellularized bone was also evaluated with regard to cytotoxicity, biochemical, and mechanical characteristics in vitro. Evidence of complete decellularization was shown through hematoxylin and eosin staining and DNA measurements. Decellularized bone matrix displayed a cytocompatible property, conserved structure, mechanical strength, and mineral content comparable to natural bone. To study new bone formation, implantation of decellularized bone matrix particles seeded with rat mesenchymal stem cells was conducted using an orthotopic in vivo model. After 3 months post-implantation into a critical-sized defect in rat calvaria, new bone was formed around decellularized bone matrix particles and also merged with new bone between decellularized bone matrix particles. New bone formation was analyzed with micro computed tomography, mineral apposition rate, and histomorphometry. Decellularized bone matrix stimulated mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo, achieving effective bone regeneration and thereby serving as a promising biological bone graft. PMID:28228929

  10. Decellularized bone matrix grafts for calvaria regeneration

    Directory of Open Access Journals (Sweden)

    Dong Joon Lee

    2016-12-01

    Full Text Available Decellularization is a promising new method to prepare natural matrices for tissue regeneration. Successful decellularization has been reported using various tissues including skin, tendon, and cartilage, though studies using hard tissue such as bone are lacking. In this study, we aimed to define the optimal experimental parameters to decellularize natural bone matrix using 0.5% sodium dodecyl sulfate and 0.1% NH4OH. Then, the effects of decellularized bone matrix on rat mesenchymal stem cell proliferation, osteogenic gene expression, and osteogenic differentiations in a two-dimensional culture system were investigated. Decellularized bone was also evaluated with regard to cytotoxicity, biochemical, and mechanical characteristics in vitro. Evidence of complete decellularization was shown through hematoxylin and eosin staining and DNA measurements. Decellularized bone matrix displayed a cytocompatible property, conserved structure, mechanical strength, and mineral content comparable to natural bone. To study new bone formation, implantation of decellularized bone matrix particles seeded with rat mesenchymal stem cells was conducted using an orthotopic in vivo model. After 3 months post-implantation into a critical-sized defect in rat calvaria, new bone was formed around decellularized bone matrix particles and also merged with new bone between decellularized bone matrix particles. New bone formation was analyzed with micro computed tomography, mineral apposition rate, and histomorphometry. Decellularized bone matrix stimulated mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo, achieving effective bone regeneration and thereby serving as a promising biological bone graft.

  11. 4D Shape-Preserving Modelling of Bone Growth

    DEFF Research Database (Denmark)

    Andresen, Per Rønsholt; Nielsen, Mads; Kreiborg, Sven

    1998-01-01

    From a set of temporally separated scannings of the same anatomical structure we wish to identify and analyze the growth in terms of a metamorphosis. That is, we study the tempral change of shape which may prowide an understanding of the biological processes which govern the growth process. We...... subdivide the growth analysis into growth simulation, growth modelling, and finally the growth analysis. In this paper, we present results of growth simulation of the mandible from 3 scannings of the same patient in the age of 9 months, 21 months, and 7 years. We also present the first growth models...... and growth analyzes. The ultimative goal is to predict/simulate human growth which would be extremely useful in many surgical procedures....

  12. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    OpenAIRE

    Priyank Ashok Shenoy; Andy Kuo; Irina Vetter; Maree Therese Smith

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century,...

  13. Modelling structured data with Probabilistic Graphical Models

    Science.gov (United States)

    Forbes, F.

    2016-05-01

    Most clustering and classification methods are based on the assumption that the objects to be clustered are independent. However, in more and more modern applications, data are structured in a way that makes this assumption not realistic and potentially misleading. A typical example that can be viewed as a clustering task is image segmentation where the objects are the pixels on a regular grid and depend on neighbouring pixels on this grid. Also, when data are geographically located, it is of interest to cluster data with an underlying dependence structure accounting for some spatial localisation. These spatial interactions can be naturally encoded via a graph not necessarily regular as a grid. Data sets can then be modelled via Markov random fields and mixture models (e.g. the so-called MRF and Hidden MRF). More generally, probabilistic graphical models are tools that can be used to represent and manipulate data in a structured way while modeling uncertainty. This chapter introduces the basic concepts. The two main classes of probabilistic graphical models are considered: Bayesian networks and Markov networks. The key concept of conditional independence and its link to Markov properties is presented. The main problems that can be solved with such tools are described. Some illustrations are given associated with some practical work.

  14. Transgenic medaka fish as models to analyze bone homeostasis under micro-gravity conditions in vivo

    Science.gov (United States)

    Winkler, C.; Wagner, T.; Renn, J.; Goerlich, R.; Schartl, M.

    Long-term space flight and microgravity results in bone loss that can be explained by reduced activity of bone-forming osteoblast cells and/or an increase in activity of bone resorbing osteoclast cells. Osteoprotegerin (OPG), a secreted protein of 401 amino acids, has been shown to regulate the balance between osteoblast and osteoclast formation and thereby warrants constant bone mass under normal gravitational conditions. Consistent with this, earlier reports using transgenic mice have shown that increased activation of OPG leads to exc essive bone formation (osteopetrosis), while inactivation of OPG leads to bone loss (osteoporosis). Importantly, it has recently been reported that expression of murine OPG is regulated by vector averaged gravity (Kanematsu et al., 2002, Bone 30, p553). The small bony fish medaka (Oryzias latipes ) has attracted increasing attention as genetic model system to study developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two related genes, opr-1 and opr -2, from medaka. Our phylogenetic analysis revealed that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian OPG gene. Both opr genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast cells. We have characterized their promoter regions and identified consensus binding sites for transcription factors of the bone-morphogenetic-protein (BMP) p thway and for core-binding-factor-1Aa (cbfa1). Cbfa1 has been shown to be the key regulator of OPG expression during several steps of osteoblast differentiation in mammals. This opens the possibility that the mechanisms controlling bone formation in teleost fish and higher vertebrates are regulated by related mechanisms. We are currently generating transgenic medakafish expressing a GFP reporter gene under control of the

  15. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice.

    Science.gov (United States)

    Mori-Okamoto, Junko; Otawara-Hamamoto, Yoko; Yamato, Hideyuki; Yoshimura, Hiroyuki

    2004-05-01

    Pomegranate is known to contain estrogens (estradiol, estrone, and estriol) and show estrogenic activities in mice. In this study, we investigated whether pomegranate extract is effective on experimental menopausal syndrome in ovariectomized mice. Prolongation of the immobility time in forced swimming test, an index of depression, was measured 14 days after ovariectomy. The bone mineral density (BMD) of the tibia was measured by X-ray absorptiometry and the structure and metabolism of bone were also analyzed by bone histomorphometry. Administration of pomegranate extract (juice and seed extract) for 2 weeks to ovariectomized mice prevented the loss of uterus weight and shortened the immobility time compared with 5% glucose-dosed mice (control). In addition, ovariectomy-induced decrease of BMD was normalized by administration of the pomegranate extract. The bone volume and the trabecular number were significantly increased and the trabecular separation was decreased in the pomegranate-dosed group compared with the control group. Some histological bone formation/resorption parameters were significantly increased by ovariectomy but were normalized by administration of the pomegranate extract. These changes suggest that the pomegranate extract inhibits ovariectomy-stimulated bone turnover. It is thus conceivable that pomegranate is clinically effective on a depressive state and bone loss in menopausal syndrome in women.

  16. Effects of Maternal Hypoxia during Pregnancy on Bone Development in Offspring: A Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-01-01

    Full Text Available Low birth weight is associated with reduced bone mass and density in adult life. However, effects of maternal hypoxia (MH on offspring bone development are not known. Objective. The current study investigated the effects of fetal growth restriction induced by MH during the last half of gestation on bone structure and volume in the offspring of the fetus near term and the pup in adolescence. Methods. During 35–62-day gestation (term, 69d, guinea pigs were housed in room air (21% O2; control or 12% O2 (MH. Offspring femur and tibia were collected at 62d gestation and 120d after birth. Results. MH decreased fetal birth weight but did not affect osteogenic potential pools in the fetal bone marrow. Histological analysis showed no effects of MH on tibial growth plate thickness in either fetal or postnatal offspring, although there was increased VEGF mRNA expression in the growth plate of postnatal offspring. MH did not change primary spongiosa height but lowered collagen-1 mRNA expression in postnatal offspring. There was increased mRNA expression of adipogenesis-related gene (FABP4 in bone from the MH postnatal offspring. Conclusion. MH during late gestation did not change the pool of osteogenic cells before birth or growth plate heights before and after birth. However, MH reduced expression of bone formation marker (collagen-1 and increased expression of fat formation marker (FABP4 in postnatal offspring bone.

  17. Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.

    Science.gov (United States)

    Grosjean, Frédéric; Nasi, Sonia; Schneider, Pascal; Chobaz, Véronique; Liu, Alexandra; Mordasini, Vanessa; Moullec, Kristell; Vezzoni, Paolo; Lavanchy, Christine; Busso, Nathalie; Acha-Orbea, Hans; Ehirchiou, Driss

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal accumulation of dendritic Langerhans cells, which is often accompanied by osteolytic lesions. It has been reported that osteoclast-like cells play a major role in the pathogenic bone destruction seen in patients with LCH and these cells are postulated to originate from the fusion of DCs. However, due to the lack of reliable animal models the pathogenesis of LCH is still poorly understood. In this study, we have established a mouse model of histiocytosis- recapitulating human disease for osteolytic lesions seen in LCH patients. At 12 weeks after birth, severe bone lesions were observed in our multisystem histiocytosis (Mushi) model, when CD8α conventional dendritic cells (DCs) are transformed (MuTuDC) and accumulate. Most importantly, our study demonstrates that bone loss in LCH can be accounted for the transdifferentiation of MuTuDCs into functional osteoclasts both in vivo and in vitro. Moreover, we have shown that injected MuTuDCs reverse the osteopetrotic phenotype of oc/oc mice in vivo. In conclusion, our results support a crucial role of DCs in bone lesions in histiocytosis patients. Furthermore, our new model of LCH based on adoptive transfer of MuTuDC lines, leading to bone lesions within 1-2 weeks, will be an important tool for investigating the pathophysiology of this disease and ultimately for evaluating the potential of anti-resorptive drugs for the treatment of bone lesions.

  18. Electron Microscopy and Analytical X-ray Characterization of Compositional and Nanoscale Structural Changes in Fossil Bone

    Science.gov (United States)

    Boatman, Elizabeth Marie

    The nanoscale structure of compact bone contains several features that are direct indicators of bulk tissue mechanical properties. Fossil bone tissues represent unique opportunities to understand the compact bone structure/property relationships from a deep time perspective, offering a possible array of new insights into bone diseases, biomimicry of composite materials, and basic knowledge of bioapatite composition and nanoscale bone structure. To date, most work with fossil bone has employed microscale techniques and has counter-indicated the survival of bioapatite and other nanoscale structural features. The obvious disconnect between the use of microscale techniques and the discernment of nanoscale structure has prompted this work. The goal of this study was to characterize the nanoscale constituents of fossil compact bone by applying a suite of diffraction, microscopy, and spectrometry techniques, representing the highest levels of spatial and energy resolution available today, and capable of complementary structural and compositional characterization from the micro- to the nanoscale. Fossil dinosaur and crocodile long bone specimens, as well as modern ratite and crocodile femurs, were acquired from the UC Museum of Paleontology. Preserved physiological features of significance were documented with scanning electron microscopy back-scattered imaging. Electron microprobe wavelength-dispersive X-ray spectroscopy (WDS) revealed fossil bone compositions enriched in fluorine with a complementary loss of oxygen. X-ray diffraction analyses demonstrated that all specimens were composed of apatite. Transmission electron microscopy (TEM) imaging revealed preserved nanocrystallinity in the fossil bones and electron diffraction studies further identified these nanocrystallites as apatite. Tomographic analyses of nanoscale elements imaged by TEM and small angle X-ray scattering were performed, with the results of each analysis further indicating that nanoscale structure is

  19. Analysing bone regeneration using topological optimisation

    Directory of Open Access Journals (Sweden)

    Diego Alexander Garzón Alvarado

    2010-04-01

    Full Text Available The present article's object is to present the mathematical foundations of topological optimisation aimed at carrying out a study of bone regeneration. Bone structure can be economically adopted to different mechanical demands responding to topological optimisation models (having "minimum" mass and "high" resistance. Such analysis is essential for formulating physical therapy in patients needing partial or total strengthening of a particular bone's tissue structure. A mathematical model is formulated, as are the methods for resolving it.

  20. The combination of structural parameters and areal bone mineral density improves relation to proximal femur strength

    DEFF Research Database (Denmark)

    Hansen, Stinus; Jensen, Jens-Erik Beck; Ahrberg, Fabian

    2011-01-01

    The aim of this study was to assess structural indices from high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the human proximal femur along with areal bone mineral density (aBMD) and compare the relationship of these parameters to bone strength in vitro. Thirty......-one human proximal femur specimens (8 men and 23 women, median age 74 years, range 50-89) were examined with HR-pQCT at four regions of interest (femoral head, neck, major and minor trochanter) with 82 μm and in a subgroup (n = 17) with 41 μm resolution. Separate analyses of cortical and trabecular geometry...

  1. Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones.

    Science.gov (United States)

    Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

    2014-08-01

    Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography.

  2. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells

    Science.gov (United States)

    2016-01-01

    Background Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. Materials and Methods In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Results Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Conclusion Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft. PMID:27606597

  3. Validation of scaffold design optimization in bone tissue engineering: finite element modeling versus designed experiments.

    Science.gov (United States)

    Uth, Nicholas; Mueller, Jens; Smucker, Byran; Yousefi, Azizeh-Mitra

    2017-02-21

    This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for

  4. Wavelet based characterization of ex vivo vertebral trabecular bone structure with 3T MRI compared to microCT

    Energy Technology Data Exchange (ETDEWEB)

    Krug, R; Carballido-Gamio, J; Burghardt, A; Haase, S; Sedat, J W; Moss, W C; Majumdar, S

    2005-04-11

    Trabecular bone structure and bone density contribute to the strength of bone and are important in the study of osteoporosis. Wavelets are a powerful tool to characterize and quantify texture in an image. In this study the thickness of trabecular bone was analyzed in 8 cylindrical cores of the vertebral spine. Images were obtained from 3 Tesla (T) magnetic resonance imaging (MRI) and micro-computed tomography ({micro}CT). Results from the wavelet based analysis of trabecular bone were compared with standard two-dimensional structural parameters (analogous to bone histomorphometry) obtained using mean intercept length (MR images) and direct 3D distance transformation methods ({micro}CT images). Additionally, the bone volume fraction was determined from MR images. We conclude that the wavelet based analyses delivers comparable results to the established MR histomorphometric measurements. The average deviation in trabecular thickness was less than one pixel size between the wavelet and the standard approach for both MR and {micro}CT analysis. Since the wavelet based method is less sensitive to image noise, we see an advantage of wavelet analysis of trabecular bone for MR imaging when going to higher resolution.

  5. Autoradiographic studies of the intensity of morphogenetic processes in the bone skeleton under modeling microgravity

    Science.gov (United States)

    Rodionova, N. V.; Zolotova-Haidamaka, N. V.; Nithevich, T. P.

    In ontogenesis the development of long skeleton bones and reconstruction of bone structures during adaptive remodeling are performed due to a combination of the bone apposition and bone resorption processes. With the use of radioactive markers of specific biosyntheses -3H-thymidine and 3H-glycine we studied the dynamics and peculiarities of these processes under hypokinesia by unloading the hind limbs of young white rats (tail suspension method) during 28 days. The radionuclides were administered in a single dose at the end of the experiment and the biomaterial was taken 1, 24, 48, 120 and 192 h. after injection. In histoautographs the counts were made of a nuclei labeling index (3H-thymidine), of the number of silver grains over the cells and in the forming bone matrix in growth and remodeling zones of the femoral bone (3H-glycine). The tendency for a reduction of a labeling index in the 3H-thymidine-labeled osteogenic cells in the periost and endost has been established. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. 3H-glycine is assimilated by osteogenic cells 30 min after the radionuclide injection and following 24 h. it is already incorporated into the forming bone matrix. As a result an appositional bone addition by 192 h. the silver grains are registered in the bone matrix as "labeling lines". A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is indicative of a decrease of the osteoplastic process under hypokinesia, particulary in the periost. At the same time the resorption and remodeling bone zones reveal regions of an intensive 3H-glycine uptake after 1 and 24 h. We associate this latter fact with an activation of collagen proteins in the differentiating fibroblasts (instead of osteoblasts) in these locations. This is confirmed by our previous

  6. Evaluation of Clinical Results and Complications of Structural Allograft Reconstruction after Bone Tumor Surgery

    Directory of Open Access Journals (Sweden)

    Mohammad Gharedaghi

    2016-07-01

    cases of infection occurred in the adjuvant chemotherapy plus radiation therapy group. Allograft fracture occurred in six patients and prevalence was the same in all groups. Only in six cases of radio-chemotherapy nonunion occurred, so we used autogenous bone graft for union. Local recurrence was observed in six patients: three belonged to the adjuvant chemotherapy group and the other three were in the chemo-radiotherapy group; no significant difference was observed between these two groups. However, there was a significant difference between these two and the group that received no adjuvant therapy. Also, there were 11 cases of metastases and Restriction of knee joint motion occurred in 48 cases of osteo-cartilaginous grafts of the distal femur and proximal tibia. Conclusion: Although structural allograft is an appropriate choice in limb reconstruction after massive resection of involved tissues in malignant and invasive bone tumors, the risk of complications such as nonunion and infection in massive allograft increases in cases of adjuvant (chemotherapy and radiotherapy modalities of treatment. Whereas the rate of tumor recurrence, metastasis, and restrictions in range of motion during a short term follow up after implantation showed no significant difference among the evaluated groups. Consequently, further attention and constant periodic visits of the patients and checking for local recurrence and distant metastasis should be done after surgery.

  7. NMR relaxation times of trabecular bone-reproducibility, relationships to tissue structure and effects of sample freezing

    Energy Technology Data Exchange (ETDEWEB)

    Prantner, Viktoria; Isaksson, Hanna; Nissi, Mikko J; Jurvelin, Jukka S [Department of Physics and Mathematics, University of Eastern Finland, PO Box 1627, 70211 Kuopio (Finland); Naervaeinen, Johanna; Groehn, Olli H J [Department of Neurobiology, A I Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, 70211 Kuopio (Finland); Lammentausta, Eveliina [Department of Diagnostic Radiology, Oulu University Hospital, PO Box 50, 90029 OYS, Oulu (Finland); Avela, Janne, E-mail: hanna.isaksson@uef.f [Department of Biology of Physical Activity, University of Jyvaeskylae, PO Box 35, 40014 Jyvaeskylae (Finland)

    2010-12-07

    Nuclear magnetic resonance (NMR) spectroscopy provides a potential tool for non-invasive evaluation of the trabecular bone structure. The objective of this study was to determine the reproducibility of the NMR relaxation parameters (T{sub 2}, Carr-Purcel-T{sub 2}, T{sub 1}{rho}) for fat and water and relate those to the structural parameters obtained by micro-computed tomography ({mu}CT). Especially, we aimed to evaluate the effect of freezing on the relaxation parameters. For storing bone samples, freezing is the standard procedure during which the biochemical and cellular organization of the bone marrow may be affected. Bovine trabecular bone samples were stored at -20 {sup 0}C for 7 days and measured by NMR spectroscopy before and after freezing. The reproducibility of NMR relaxation parameters, as expressed by the coefficient of variation, ranged from 3.1% to 27.9%. In fresh samples, some correlations between NMR and structural parameters (Tb.N, Tb.Sp) were significant (e.g. the relaxation rate for T{sub 2} of fat versus Tb.Sp: r = -0.716, p < 0.01). Freezing did not significantly change the NMR relaxation times but the correlations between relaxation parameters and the {mu}CT structural parameters were not statistically significant after freezing, suggesting some nonsystematic alterations of the marrow structure. Therefore, the use of frozen bone samples for NMR relaxation studies may provide inferior information about the trabecular bone structure.

  8. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    OpenAIRE

    Boos Alois; Auer Joerg A; Nuss Katja; Rechenberg Brigitte von

    2006-01-01

    Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Result...

  9. Bone marrow combined with dental bud cells promotes tooth regeneration in miniature pig model.

    Science.gov (United States)

    Kuo, Tzong-Fu; Lin, Hsin-Chi; Yang, Kai-Chiang; Lin, Feng-Huei; Chen, Min-Huey; Wu, Chang-Chin; Chang, Hao-Hueng

    2011-02-01

    Growth factors and morphogens secreted by bone marrow mesenchymal stem cells (BMSCs) of bone marrow fluid may promote tooth regeneration. Accordingly, a tissue engineering approach was utilized to develop an economical strategy for obtaining the growth factors and morphogens from BMSCs. Unerupted second molar tooth buds harvested from miniature pigs were cultured in vitro to obtain dental bud cells (DBCs). Bone marrow fluid, which contains BMSCs, was collected from the porcine mandible before operation. DBCs suspended in bone marrow fluid were seeded into a gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer scaffold (GCHT scaffold). The DBCs/bone marrow fluid/GCHT scaffold was autografted into the original alveolar sockets of the pigs. Radiographic and histological examinations were applied to identify the structure of regenerated tooth at 40 weeks postimplantation. The present results showed that one pig developed a complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum, blood vessel, and periodontal ligament in indiscriminate shape. Three animals had an unerupted tooth that expressed dentin matrix protein-1, vascular endothelial growth factor, and osteopontin; and two other pigs also had dental-like structure with dentin tubules. This study reveals that DBCs adding bone marrow fluid and a suitable scaffold can promote the tooth regeneration in autogenic cell transplantation.

  10. Biomechanical Models and Experi ments in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Christian; ODDOU; Julien; PIERRE; Karim; OUDINA; Hervé; PETITE

    2005-01-01

    1 IntroductionThe understanding of the interactions between convective and diffusive phenomena of fluid dynamics origin, on the one side, associate reactive effects of biochemical nature, on the other, is a fundamental challenge and key problem in the context of bone tissue engineering. From the mastering of the complex biological phenomena related to the substrate degradation and remodelling of the extra cellular matrix that take place during the in vitro tissue culturing processes using cell seeded implan...

  11. The rational use of animal models in the evaluation of novel bone regenerative therapies.

    Science.gov (United States)

    Peric, Mihaela; Dumic-Cule, Ivo; Grcevic, Danka; Matijasic, Mario; Verbanac, Donatella; Paul, Ruth; Grgurevic, Lovorka; Trkulja, Vladimir; Bagi, Cedo M; Vukicevic, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poorly designed animal studies with inappropriate endpoints and inaccurate conclusions are being conducted. In this review, we discuss animal models, procedures, methods and technologies used in bone repair studies with the aim to assist investigators in planning and performing scientifically sound experiments that respect the wellbeing of animals. In the process of designing an animal study for bone repair investigators should consider: skeletal characteristics of the selected animal species; a suitable animal model that mimics the intended clinical indication; an appropriate assessment plan with validated methods, markers, timing, endpoints and scoring systems; relevant dosing and statistically pre-justified sample sizes and evaluation methods; synchronization of the study with regulatory requirements and additional evaluations specific to cell-based approaches. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease.

    Science.gov (United States)

    Kim, Jin-Woo; Tatad, Jacquiline Czar I; Landayan, Maria Erika A; Kim, Sun-Jong; Kim, Myung-Rae

    2015-12-01

    Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n=48) and sham-operated group (n=48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n=36 each) and control group (n=12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; Pbone architectures with higher necrotic bone fraction and lower number of osteoclasts (Pbone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain.

    Directory of Open Access Journals (Sweden)

    Louis Doré-Savard

    Full Text Available Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT. Bone metastases were visualized as early as day 8 by MRI (T(1-Gd-DTPA before pain detection. PET (Na(18F co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining. Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal and ATF3 (DRG neuronal activation, sustained by astrocyte (GFAP and microglia (Iba1 reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future.

  14. Effects of Hydroxyapatite on Bone Graft Resorption in an Experimental Model of Maxillary Alveolar Arch Defects

    Directory of Open Access Journals (Sweden)

    Ozgur Pilanci

    2013-06-01

    Full Text Available Most commonly used treatments use autologous bone grafts to address bony defects in patients with cleft palate. Major disadvantages of autogenous bone grafts include donor site morbidity and resorption. Suggestions to overcome such problems include biomaterials that can be used alone or in combination with bone. We examined the effect of hydroxyapatite cement on bone graft resorption in a rabbit maxillary alveolar defect model. We divided 16 young adult albino New Zealand rabbits into two groups. A defect 1 cm wide was created in each rabbit's maxillary arch. In Group 1, the removed bone was disrupted, and the pieces were replaced in the defect. In the other group, the pieces were replaced after mixing (1:1 with hydroxyapatite cement. Quantitative computed tomographic evaluation of these grafts was performed in axial and coronal planes for each rabbit at 2 and 12 weeks. In axial images at 12 weeks, the group without cement showed mean bone resorption of 15%. In the cement group, a mean volumetric increase of 68% was seen. No resorption occurred when bone grafts were mixed with hydroxyapatite cement. [Arch Clin Exp Surg 2013; 2(3.000: 170-175

  15. Two Different Isomers of Vitamin E Prevent Bone Loss in Postmenopausal Osteoporosis Rat Model

    Directory of Open Access Journals (Sweden)

    Norliza Muhammad

    2012-01-01

    Full Text Available Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV and trabecular number (Tb.N and an increase in trabecular separation (Tb.S. The increase in osteoclast surface (Oc.S and osteoblast surface (Ob.S in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.

  16. Modeling and determination of directionality of the kerf in epifluorescence sharp bone trauma analysis.

    Science.gov (United States)

    Capuani, Caroline; Telmon, Norbert; Moscovici, Jacques; Molinier, François; Aymeric, Andre; Delisle, Marie-Bernadette; Rougé, Daniel; Guilbeau-Frugier, Céline

    2014-11-01

    Characteristics of sharp bone trauma can be extremely useful to determine the origin of cut marks and to provide information regarding the context of death. Using human ribs and clavicle bones, this study analyzes the characteristics of bone kerfs made by different bladed implements, thanks to epifluorescence macroscopy. This technique, which is a nondestructive tool that uses autofluorescence of bones, documents bone damage precisely with high resolution. Both qualitative and quantitative criteria are analyzed. Our results identify unique class characteristics on bone lesions, allowing modeling kerf depending on the weapon, regardless of the type of bone that is wounded. Moreover, we demonstrate for the first time microscopic criteria of directionality, using fluorescence excitation. Orientation of cracks, flakes, and lateral pushing back especially helps in determining the tip and the end of the lesion, leading to the position of the aggressor. Kerf wall characteristics and striation location are also very useful. Epifluorescence macroscopy could be a new tool of choice in anthropology through cut mark analysis in establishing how the blade was used and providing details about the blow.

  17. Compressive behaviour of gyroid lattice structures for human cancellous bone implant applications.

    Science.gov (United States)

    Yánez, A; Herrera, A; Martel, O; Monopoli, D; Afonso, H

    2016-11-01

    Electron beam melting (EBM) was used to fabricate porous titanium alloy structures. The elastic modulus of these porous structures was similar to the elastic modulus of the cancellous human bone. Two types of cellular lattice structures were manufactured and tested: gyroids and diamonds. The design of the gyroid structures was determined by the main angle of the struts with respect to the axial direction. Thus, structures with angles of between 19 and 68.5° were manufactured. The aim of the design was to reduce the amount of material needed to fabricate a structure with the desired angles to increase the range of stiffness of the scaffolds. Compression tests were conducted to obtain the elastic modulus and the strength. Both parameters increased as the angle decreased. Finally, the specific strength of the gyroid structures was compared with that of the diamond structures and other types of structures. It is shown that, for angles lower than 35°, the gyroid structures had a high strength to weight ratios.

  18. Effects of different dosages of parathyroid hormone-related protein 1-34 on the bone metabolism of the ovariectomized rat model of osteoporosis.

    Science.gov (United States)

    Xu, Jin; Rong, Haiqin; Ji, Hong; Wang, Dong; Wang, Jie; Zhang, Wenwen; Zhang, Yanling

    2013-09-01

    Intermittent and low-dose parathyroid hormone (PTH) injection to stimulate bone formation has been used in the treatment of osteoporosis. The N-terminal fragment 1-34 of PTH is quite similar in structure and function to N-terminal PTH-related protein (PTHrP). PTH(1-34) and PTHrP also share a coreceptor, the PTH/PTHrP receptor. Therefore, some studies have suggested that PTHrP could effectively stimulate bone formation, similar to PTH. We used an ovariectomized (OVX) rat model of osteoporosis to study the effects of PTHrP(1-34) on bone metabolism by measuring bone mineral density (BMD), bone histomorphometrics, and biomechanical parameters. We found that subcutaneous injection of PTHrP(1-34) (40 or 80 μg/kg body weight every day) in OVX rats increased lumbar and femoral BMD, improved bone biomechanical properties, enhanced bone strength, and promoted bone formation. We selected 40 μg/kg as the preferred therapeutic dose of PTHrP(1-34) and investigated the effects of frequency of treatment (per 1, 2, 3, or 7 days) on bone metabolism in OVX rats. We found that injection of PTHrP(1-34) once per day or every other day significantly improved the BMD and strength of OVX rats. Serum calcium and phosphate levels in all treated rats did not vary significantly from control rats. Based on our results, intermittent low-dose PTHrP(1-34) injection promoted bone formation in OVX rats, suggesting a high potential for therapeutic use in osteoporosis patients.

  19. A Digital Model to Simulate Effects of Bone Architecture Variations on Texture at Spatial Resolutions of CT, HR-pQCT, and μCT Scanners

    Directory of Open Access Journals (Sweden)

    T. Lowitz

    2014-01-01

    Full Text Available The quantification of changes in the trabecular bone structure induced by musculoskeletal diseases like osteoarthritis, osteoporosis, rheumatoid arthritis, and others by means of a texture analysis is a valuable tool which is expected to improve the diagnosis and monitoring of a disease. The reaction of texture parameters on different alterations in the architecture of the fine trabecular network and inherent imaging factors such as spatial resolution or image noise has to be understood in detail to ensure an accurate and reliable determination of the current bone state. Therefore, a digital model for the quantitative analysis of cancellous bone structures was developed. Five parameters were used for texture analysis: entropy, global and local inhomogeneity, local anisotropy, and variogram slope. Various generic structural changes of cancellous bone were simulated for different spatial resolutions. Additionally, the dependence of the texture parameters on tissue mineralization and noise was investigated. The present work explains changes in texture parameter outcomes based on structural changes originating from structure modifications and reveals that a texture analysis could provide useful information for a trabecular bone analysis even at resolutions below the dimensions of single trabeculae.

  20. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    Directory of Open Access Journals (Sweden)

    Howell David S

    2003-02-01

    Full Text Available Abstract Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. Methods To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8 with 0.6% dl-homocysteine (hCySH for the first 8 weeks of life in comparison to controls (n = 10, and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. Results hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO43- and lower Ca2+/CO32- molar ratios than in controls. Mineral crystallization was unchanged. Conclusion In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic

  1. Three-Dimensional Bone Adaptation of the Proximal Femur

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The bone remodeling of a three-dimensional model of the proximal femur is considered. The bone adaptation is numerically described as an evolution in time formulated such that the structural change goes in an optimal direction within each time step for the optimal boundary conditions. In the bone...... remodeling scheme is included the memory of past loadings to account for the delay in the bone response to the load changes. In order to get a realistic bone adaptation process, the bone structure at the onset of the remodeling needs to be realistic too. A start design is obtained by structural optimization...

  2. Structures in Molecular Clouds: Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kane, J O; Mizuta, A; Pound, M W; Remington, B A; Ryutov, D D

    2006-04-20

    We attempt to predict the observed morphology, column density and velocity gradient of Pillar II of the Eagle Nebula, using Rayleigh Taylor (RT) models in which growth is seeded by an initial perturbation in density or in shape of the illuminated surface, and cometary models in which structure is arises from a initially spherical cloud with a dense core. Attempting to mitigate suppression of RT growth by recombination, we use a large cylindrical model volume containing the illuminating source and the self-consistently evolving ablated outflow and the photon flux field, and use initial clouds with finite lateral extent. An RT model shows no growth, while a cometary model appears to be more successful at reproducing observations.

  3. [State of the microscopic and crystalline structures, the microhardness and mineral saturation of human bone tissue after prolonged space flight].

    Science.gov (United States)

    Gazenko, O G; Prokhonchukov, A A; Panikarovskiĭ, V V; Tigranian, R A; Kolesnik, A G

    1977-01-01

    The bone tissue removed by autopsy from the crewmembers of the orbital station Salyut-1 after their 23-day space flight was investigated histologically, crystallographically, biophysically and biochemically. The comprehensive studies showed good correlation of the parameters studied. The microscopic and crystalline structures of bone tissue of every skeletal bone tested (ox calcis, frmoral epiphysis and diaphysis, vertebrae, ribs, sternum) did not differ from the normal. The data were in agreement with the parameters of bone microhardness and mineralization which also remained within the normal limits. No pathological changes in the above parameters were noted. Greater packing of the crystal lattice, increased microhardness and mineralization of bone tissue can be attributed to the effect of exercises.

  4. Muscle-bone interactions: From experimental models to the clinic? A critical update.

    Science.gov (United States)

    Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; Verschueren, Sabine M P; Vanderschueren, Dirk; Gielen, Evelien; Jardí, Ferran

    2016-09-01

    Bone is a biomechanical tissue shaped by forces from muscles and gravitation. Simultaneous bone and muscle decay and dysfunction (osteosarcopenia or sarco-osteoporosis) is seen in ageing, numerous clinical situations including after stroke or paralysis, in neuromuscular dystrophies, glucocorticoid excess, or in association with vitamin D, growth hormone/insulin like growth factor or sex steroid deficiency, as well as in spaceflight. Physical exercise may be beneficial in these situations, but further work is still needed to translate acceptable and effective biomechanical interventions like vibration therapy from animal models to humans. Novel antiresorptive and anabolic therapies are emerging for osteoporosis as well as drugs for sarcopenia, cancer cachexia or muscle wasting disorders, including antibodies against myostatin or activin receptor type IIA and IIB (e.g. bimagrumab). Ideally, increasing muscle mass would increase muscle strength and restore bone loss from disuse. However, the classical view that muscle is unidirectionally dominant over bone via mechanical loading is overly simplistic. Indeed, recent studies indicate a role for neuronal regulation of not only muscle but also bone metabolism, bone signaling pathways like receptor activator of nuclear factor kappa-B ligand (RANKL) implicated in muscle biology, myokines affecting bone and possible bone-to-muscle communication. Moreover, pharmacological strategies inducing isolated myocyte hypertrophy may not translate into increased muscle power because tendons, connective tissue, neurons and energy metabolism need to adapt as well. We aim here to critically review key musculoskeletal molecular pathways involved in mechanoregulation and their effect on the bone-muscle unit as a whole, as well as preclinical and emerging clinical evidence regarding the effects of sarcopenia therapies on osteoporosis and vice versa.

  5. Osteoblast function and bone histomorphometry in a murine model of Rett syndrome.

    Science.gov (United States)

    Blue, Mary E; Boskey, Adele L; Doty, Stephen B; Fedarko, Neal S; Hossain, Mir Ahamed; Shapiro, Jay R

    2015-07-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2. Approximately 50% of affected females have decreased bone mass. We studied osteoblast function using a murine model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared to wild type (WT) mice. Micro-CT of tibia from 5 week-old Mecp2-null mice showed significant alterations in trabecular bone including reductions in bone volume fraction (-29%), number (-19%), thickness (-9%) and connectivity density (-32%), and increases in trabecular separation (+28%) compared to WT. We also found significant reductions in cortical bone thickness (-18%) and in polar moment of inertia (-45%). In contrast, cortical and trabecular bone from 8 week-old WT and HET female mice were not significantly different. However, mineral apposition rate, mineralizing surface and bone formation rate/bone surface were each decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric analysis of femurs showed decreased numbers of osteoblasts but similar numbers of osteoclasts compared to WT, altered osteoblast morphology and decreased tissue synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts cultured from Mecp2-null mice, which unlike WT osteoblasts did not express MeCP2, had increased growth rates, but reductions in mRNA expression of type I collagen, Runx2 and Osterix compared to WT osteoblasts. These results indicate that MeCP2 deficiency leads to altered bone growth. Osteoblast dysfunction was more marked in Mecp2-null male than in HET female mice, suggesting that expression of MeCP2 plays a critical role in bone development.

  6. BMP-2 induced early bone formation in spine fusion using rat ovariectomy osteoporosis model.

    Science.gov (United States)

    Park, Sung Bae; Park, Seong Hoon; Kim, Na-Hyung; Chung, Chun Kee

    2013-10-01

    Bone morphogenetic proteins (BMPs) enhance bone formation. Numerous animal studies have established that BMPs can augment spinal fusion. However, there is a lack of data on the effect of BMP-2 on spinal fusion in the osteoporotic spine. To investigate whether recombinant human BMP-2 (rhBMP-2) enhances spine fusion in an ovariectomized rat model. In vivo animal study. Female Sprague-Dawley rats (n=60) were ovariectomized or sham operated and randomized into three groups: Sham (sham operated+fusion), ovariectomy (OVX) (OVX+fusion), and BMP (OVX+fusion+BMP-2). Six weeks after ovariectomy, unilateral lumbar spine fusion was performed using autologous iliac bone with/without rhBMP-2 delivered on a collagen matrix. For each group, gene expression and histology were evaluated at 3 and 6 weeks after fusion, and bone parameters were measured by microcomputed tomography at 3, 6, 9, and 12 weeks. Real-time reverse-transcription polymerase chain reaction at 3 weeks showed markedly increased expression of osteoblast-related markers (namely alkaline phosphatase, osteocalcin, Runx2, Smad1, and Smad5) in the BMP group compared with the other groups (p=.0005, .0005, .003, .009 and .012, respectively). Although the Sham and OVX groups showed both sparse and compacted bones between transverse processes at 6 weeks, the BMP group had a significantly larger bone mass within the fusion bed at 3 weeks and later. All rats in the BMP group had bridging bone at 3 weeks; at 12 weeks, bridging bones in the Sham and OVX groups were about 50% and 25%, respectively, of that in the BMP group. Recombinant human BMP-2 enhances spinal fusion in OVX rats and acts during early bone formation. Therapeutic BMP-2 may therefore improve the outcome of spinal fusion in the osteoporotic patient. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Characterizing trabecular bone structure for assessing vertebral fracture risk on volumetric quantitative computed tomography

    Science.gov (United States)

    Nagarajan, Mahesh B.; Checefsky, Walter A.; Abidin, Anas Z.; Tsai, Halley; Wang, Xixi; Hobbs, Susan K.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

    2015-03-01

    While the proximal femur is preferred for measuring bone mineral density (BMD) in fracture risk estimation, the introduction of volumetric quantitative computed tomography has revealed stronger associations between BMD and spinal fracture status. In this study, we propose to capture properties of trabecular bone structure in spinal vertebrae with advanced second-order statistical features for purposes of fracture risk assessment. For this purpose, axial multi-detector CT (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. A semi-automated method was used to annotate the trabecular compartment in the central vertebral slice with a circular region of interest (ROI) to exclude cortical bone; pixels within were converted to values indicative of BMD. Six second-order statistical features derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the ROI were then extracted and used in conjunction with a generalized radial basis functions (GRBF) neural network to predict the failure load of the specimens; true failure load was measured through biomechanical testing. Prediction performance was evaluated with a root-mean-square error (RMSE) metric. The best prediction performance was observed with GLCM feature `correlation' (RMSE = 1.02 ± 0.18), which significantly outperformed all other GLCM features (p GLCM feature correlation also significantly outperformed MDCTmeasured mean BMD (RMSE = 1.11 ± 0.17) (pGLCM-derived texture features.

  8. Evaluation of injectable constructs for bone repair with a subperiosteal cranial model in the rat.

    Directory of Open Access Journals (Sweden)

    Marta Kisiel

    Full Text Available While testing regenerative medicine strategies, the use of animal models that match the research questions and that are related to clinical translation is crucial. During the initial stage of evaluating new strategies for bone repair, the main goal is to state whether the strategies efficiently induce the formation of new bone tissue at an orthotopic site. Here, we present a subperiosteal model in rat calvaria that allow the evaluation of a broad range of approaches including bone augmentation, replacement and regeneration. The model is a fast to perform, minimally invasive, and has clearly defined control groups. The procedure enables to evaluate the outcomes quantitatively using micro-computed tomography and qualitatively by histology and immunohistochemistry. We established this new model, using bone morphogenetic protein-2 as an osteoinductive factor and hyaluronic acid hydrogel as injectable biomaterial. We showed that this subperiosteal cranial model offers a minimally invasive and promising solution for a rapid initial evaluation of injectables for bone repair. We believe that this approach could be a powerful platform for orthopedic research and regenerative medicine.

  9. Automated morphological analysis of bone marrow cells in microscopic images for diagnosis of leukemia: nucleus-plasma separation and cell classification using a hierarchical tree model of hematopoesis

    Science.gov (United States)

    Krappe, Sebastian; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

    2016-03-01

    The morphological differentiation of bone marrow is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually under the use of bright field microscopy. This is a time-consuming, subjective, tedious and error-prone process. Furthermore, repeated examinations of a slide may yield intra- and inter-observer variances. For that reason a computer assisted diagnosis system for bone marrow differentiation is pursued. In this work we focus (a) on a new method for the separation of nucleus and plasma parts and (b) on a knowledge-based hierarchical tree classifier for the differentiation of bone marrow cells in 16 different classes. Classification trees are easily interpretable and understandable and provide a classification together with an explanation. Using classification trees, expert knowledge (i.e. knowledge about similar classes and cell lines in the tree model of hematopoiesis) is integrated in the structure of the tree. The proposed segmentation method is evaluated with more than 10,000 manually segmented cells. For the evaluation of the proposed hierarchical classifier more than 140,000 automatically segmented bone marrow cells are used. Future automated solutions for the morphological analysis of bone marrow smears could potentially apply such an approach for the pre-classification of bone marrow cells and thereby shortening the examination time.

  10. Characterization of the inflammatory response to four commercial bone graft substitutes using a murine biocompatibility model

    Directory of Open Access Journals (Sweden)

    Markel DC

    2012-01-01

    Full Text Available David C Markel1, S Trent Guthrie2, Bin Wu3, Zheng Song4, Paul H Wooley41Department of Orthopaedics, Providence Hospital and Medical Centers, Southfield, MI, 2Henry Ford Hospital, Detroit, MI, 3Department of Biomedical Engineering, Wayne State University, Detroit, MI, 4Orthopaedic Research Institute, Wichita, KS, USAAbstract: Bone grafting is utilized in nearly all orthopedic subspecialties and in most anatomic regions. Bone graft substitutes have the potential to offer similar efficacy as autogenous grafts without the morbidity of harvest. Several studies have noted the efficacy of new-generation bone substitute products, but few studies have evaluated their safety. This study characterizes and quantifies the inflammatory reaction to four different commercially available bone graft substitutes, which were examined using the in vivo murine air pouch biocompatibility model. One coralline hydroxyapatite product was chosen as an example of a purely osteoconductive material. Three demineralized bone matrix products were chosen to represent products that are both osteoconductive and osteoinductive. Samples were implanted in a murine air pouch and harvested after 14 days in situ. Pouch fluid was extracted, mRNA isolated, and reverse transcription polymerase chain reactions carried out to detect interleukin-1 gene expression as a marker for inflammation. In addition, multiple histological characteristics were examined to quantify cellular responses to the implanted materials. All bone graft substitutes induced a significant inflammatory response compared with negative controls. Histology and polymerase chain reaction data indicated that the level of inflammatory reaction was elevated in materials with a higher demineralized bone matrix to carrier proportion. The hydroxyapatite product generated a low inflammatory reaction. In conclusion, this study used an in vivo model of biocompatibility to demonstrate that a significant inflammatory reaction occurs

  11. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... insulin-like growth factor-binding protein 3 were the only significant findings on blood analysis. Deoxypyridinoline crosslinks in urine were higher in rats with an enterocystoplasty than in controls.CONCLUSIONS: Enterocystoplasty in rats neither impairs skeletal growth nor bone quantity, but leads......, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone...

  12. Track structure in biological models.

    Science.gov (United States)

    Curtis, S B

    1986-01-01

    High-energy heavy ions in the galactic cosmic radiation (HZE particles) may pose a special risk during long term manned space flights outside the sheltering confines of the earth's geomagnetic field. These particles are highly ionizing, and they and their nuclear secondaries can penetrate many centimeters of body tissue. The three dimensional patterns of ionizations they create as they lose energy are referred to as their track structure. Several models of biological action on mammalian cells attempt to treat track structure or related quantities in their formulation. The methods by which they do this are reviewed. The proximity function is introduced in connection with the theory of Dual Radiation Action (DRA). The ion-gamma kill (IGK) model introduces the radial energy-density distribution, which is a smooth function characterizing both the magnitude and extension of a charged particle track. The lethal, potentially lethal (LPL) model introduces lambda, the mean distance between relevant ion clusters or biochemical species along the track. Since very localized energy depositions (within approximately 10 nm) are emphasized, the proximity function as defined in the DRA model is not of utility in characterizing track structure in the LPL formulation.

  13. A review of mouse critical size defect models in weight bearing bones.

    Science.gov (United States)

    Harris, Jonathan S; Bemenderfer, Thomas B; Wessel, Alexander R; Kacena, Melissa A

    2013-07-01

    Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection - and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research--develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.

  14. Protective effects of Tualang honey on bone structure in experimental postmenopausal rats

    Directory of Open Access Journals (Sweden)

    Siti Sarah Mohamad Zaid

    2012-07-01

    Full Text Available OBJECTIVE: The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats. METHODS: Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8: four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum. The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey. Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water, and the baseline control group was sacrificed without treatment. RESULTS: All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV, trabecular thickness (Tb.Th and trabecular number (Tb.N and a significant decrease in inter-trabecular space (Tb.Sp compared with the ovariectomized control group. The trabecular thickness (Tb.Th in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group. CONCLUSION: In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.

  15. Finite element micro-modelling of a human ankle bone reveals the importance of the trabecular network to mechanical performance: new methods for the generation and comparison of 3D models.

    Science.gov (United States)

    Parr, W C H; Chamoli, U; Jones, A; Walsh, W R; Wroe, S

    2013-01-04

    Most modelling of whole bones does not incorporate trabecular geometry and treats bone as a solid non-porous structure. Some studies have modelled trabecular networks in isolation. One study has modelled the performance of whole human bones incorporating trabeculae, although this required considerable computer resources and purpose-written code. The difference between mechanical behaviour in models that incorporate trabecular geometry and non-porous models has not been explored. The ability to easily model trabecular networks may shed light on the mechanical consequences of bone loss in osteoporosis and remodelling after implant insertion. Here we present a Finite Element Analysis (FEA) of a human ankle bone that includes trabecular network geometry. We compare results from this model with results from non-porous models and introduce protocols achievable on desktop computers using widely available softwares. Our findings show that models including trabecular geometry are considerably stiffer than non-porous whole bone models wherein the non-cortical component has the same mass as the trabecular network, suggesting inclusion of trabecular geometry is desirable. We further present new methods for the construction and analysis of 3D models permitting: (1) construction of multi-property, non-porous models wherein cortical layer thickness can be manipulated; (2) maintenance of the same triangle network for the outer cortical bone surface in both 3D reconstruction and non-porous models allowing exact replication of load and restraint cases; and (3) creation of an internal landmark point grid allowing direct comparison between 3D FE Models (FEMs).

  16. Structure and modeling of turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Novikov, E.A. [Univ. of California, San Diego, La Jolla, CA (United States)

    1995-12-31

    The {open_quotes}vortex strings{close_quotes} scale l{sub s} {approximately} LRe{sup -3/10} (L-external scale, Re - Reynolds number) is suggested as a grid scale for the large-eddy simulation. Various aspects of the structure of turbulence and subgrid modeling are described in terms of conditional averaging, Markov processes with dependent increments and infinitely divisible distributions. The major request from the energy, naval, aerospace and environmental engineering communities to the theory of turbulence is to reduce the enormous number of degrees of freedom in turbulent flows to a level manageable by computer simulations. The vast majority of these degrees of freedom is in the small-scale motion. The study of the structure of turbulence provides a basis for subgrid-scale (SGS) models, which are necessary for the large-eddy simulations (LES).

  17. Effect of sex in the MRMT-1 model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Al-Dihaissy, Tamara; Mezzanotte, Laura;

    2015-01-01

    An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo...

  18. A model for the ultrastructure of bone based on electron microscopy of ion-milled sections.

    Directory of Open Access Journals (Sweden)

    Elizabeth A McNally

    Full Text Available The relationship between the mineral component of bone and associated collagen has been a matter of continued dispute. We use transmission electron microscopy (TEM of cryogenically ion milled sections of fully-mineralized cortical bone to study the spatial and topological relationship between mineral and collagen. We observe that hydroxyapatite (HA occurs largely as elongated plate-like structures which are external to and oriented parallel to the collagen fibrils. Dark field images suggest that the structures ("mineral structures" are polycrystalline. They are approximately 5 nm thick, 70 nm wide and several hundred nm long. Using energy-dispersive X-ray analysis we show that approximately 70% of the HA occurs as mineral structures external to the fibrils. The remainder is found constrained to the gap zones. Comparative studies of other species suggest that this structural motif is ubiquitous in all vertebrates.

  19. Anorexia nervosa and bone

    National Research Council Canada - National Science Library

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk...

  20. Instructive function of surface structure of calcium phosphate ceramics in bone regeneration

    NARCIS (Netherlands)

    Zhang, Jingwei

    2016-01-01

    The incidence of patients which require spinal fusion or bone regeneration in large bone defects caused by trauma, tumors, tumor resection, infections or abnormal skeletal development, is on the rise. Traditionally, in both spinal fusion surgery and other bone regeneration approaches, bone grafts

  1. Instructive function of surface structure of calcium phosphate ceramics in bone regeneration

    NARCIS (Netherlands)

    Zhang, Jingwei

    2016-01-01

    The incidence of patients which require spinal fusion or bone regeneration in large bone defects caused by trauma, tumors, tumor resection, infections or abnormal skeletal development, is on the rise. Traditionally, in both spinal fusion surgery and other bone regeneration approaches, bone grafts ar

  2. Methodologies for Development of Patient Specific Bone Models from Human Body CT Scans

    Science.gov (United States)

    Chougule, Vikas Narayan; Mulay, Arati Vinayak; Ahuja, Bharatkumar Bhagatraj

    2016-06-01

    This work deals with development of algorithm for physical replication of patient specific human bone and construction of corresponding implants/inserts RP models by using Reverse Engineering approach from non-invasive medical images for surgical purpose. In medical field, the volumetric data i.e. voxel and triangular facet based models are primarily used for bio-modelling and visualization, which requires huge memory space. On the other side, recent advances in Computer Aided Design (CAD) technology provides additional facilities/functions for design, prototyping and manufacturing of any object having freeform surfaces based on boundary representation techniques. This work presents a process to physical replication of 3D rapid prototyping (RP) physical models of human bone from various CAD modeling techniques developed by using 3D point cloud data which is obtained from non-invasive CT/MRI scans in DICOM 3.0 format. This point cloud data is used for construction of 3D CAD model by fitting B-spline curves through these points and then fitting surface between these curve networks by using swept blend techniques. This process also can be achieved by generating the triangular mesh directly from 3D point cloud data without developing any surface model using any commercial CAD software. The generated STL file from 3D point cloud data is used as a basic input for RP process. The Delaunay tetrahedralization approach is used to process the 3D point cloud data to obtain STL file. CT scan data of Metacarpus (human bone) is used as the case study for the generation of the 3D RP model. A 3D physical model of the human bone is generated on rapid prototyping machine and its virtual reality model is presented for visualization. The generated CAD model by different techniques is compared for the accuracy and reliability. The results of this research work are assessed for clinical reliability in replication of human bone in medical field.

  3. Structuring as a Basis for Product Modelling

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik; Hansen, Claus Thorp

    1999-01-01

    Structure means the way which things are built up. A composite product does not exhibit one structure, but hides in its structure of parts several different structuring principles, which fit the production, service, transport etc. Structuring of product models is complex where many factors...... are influencing. This paper identifies four factors that are influencing the structure of a product model: genetics, functionality/property, product life and product assortment. Three principles, which support determination of product model structures, are proposed....

  4. The reconstruction principle of bone structure%骨结构的重建理念

    Institute of Scientific and Technical Information of China (English)

    张文贤; 李盛华

    2011-01-01

    背景:在骨折治疗原则上,主要体现在从生物学和机械力学两方面进行骨结构重建,把生物固定与机械固定,髓内固定与髓外固定相结合.目的:介绍骨折治疗、骨结构重建理念的发展历程和研究进展.方法:应用计算机检索中国期刊全文数据库(CNKI:2006-01/2011-05)、Pubmed数据库和Medline database(2006-01/2011-05)数据库有关骨结构的重建理念的文章,检索词分别为"骨结构,重建,理念"和"bone structure,rebuild,principle",语言分别设定为中文和英文.结果与结论:共收集30篇有关骨结构的重建理念的文章,排除重复或类似的同一研究,14篇符合综述要求.骨折的治疗理念已经由机械力学固定体系逐渐转向生物学固定体系.骨折治疗必须着重于寻求骨折稳固和软组织完整之间的一种平衡,植入物和器械设计明显改善.近年来,又出现了数字化虚拟人体技术、生物力学有限元理论、创伤控制论、骨质疏松的药理学研究、用组织工程学理论和技术修复创伤缺损等.总的来说,骨结构重建的理念就是患者为中心,在宏观与微观的层次上选择骨折治疗最合理的方法,引导和促进骨的愈合、功能恢复.%BACKGROUND: In principle, fracture treatment mainly focuses on bone remodeling from the biological and mechanical aspectsto combine mechanical fixation with biological fixation as well as combine intramedullary fixation with extramedullary fixation.OBJECTIVE: To introduce the principle development of fracture treatment and bone remodeling.METHODS: A computer-based search of CNKI (2006-01/2011-05) and PubMed (2006-01/2011-05) for bone remodelingarticles using the keywords of “bone structure, rebuild, principle” in Chinese and English, respectively.RESULTS AND CONCLUSION: In 30 collected articles, 14 were included in result analysis. The treatment concept of fractureshas been gradually changed from mechanical fixation system to

  5. A new thermal model for bone drilling with applications to orthopaedic surgery.

    Science.gov (United States)

    Lee, JuEun; Rabin, Yoed; Ozdoganlar, O Burak

    2011-12-01

    This paper presents a new thermal model for bone drilling with applications to orthopaedic surgery. The new model combines a unique heat-balance equation for the system of the drill bit and the chip stream, an ordinary heat diffusion equation for the bone, and heat generation at the drill tip, arising from the cutting process and friction. Modeling of the drill bit-chip stream system assumes an axial temperature distribution and a lumped heat capacity effect in the transverse cross-section. The new model is solved numerically using a tailor-made finite-difference scheme for the drill bit-chip stream system, coupled with a classic finite-difference method for the bone. The theoretical investigation addresses the significance of heat transfer between the drill bit and the bone, heat convection from the drill bit to the surroundings, and the effect of the initial temperature of the drill bit on the developing thermal field. Using the new model, a parametric study on the effects of machining conditions and drill-bit geometries on the resulting temperature field in the bone and the drill bit is presented. Results of this study indicate that: (1) the maximum temperature in the bone decreases with increased chip flow; (2) the transient temperature distribution is strongly influenced by the initial temperature; (3) the continued cooling (irrigation) of the drill bit reduces the maximum temperature even when the tip is distant from the cooled portion of the drill bit; and (4) the maximum temperature increases with increasing spindle speed, increasing feed rate, decreasing drill-bit diameter, increasing point angle, and decreasing helix angle. The model is expected to be useful in determination of optimum drilling conditions and drill-bit geometries.

  6. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

    Science.gov (United States)

    Iwaniec, U T; Philbrick, K A; Wong, C P; Gordon, J L; Kahler-Quesada, A M; Olson, D A; Branscum, A J; Sargent, J L; DeMambro, V E; Rosen, C J; Turner, R T

    2016-10-01

    Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies

  7. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis.

    Science.gov (United States)

    Huang, Jialiang; Wu, Chuanlong; Tian, Bo; Zhou, Xiao; Ma, Nian; Qian, Yufen

    2016-03-22

    Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg(-1)∙day(-1), respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  8. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis

    Directory of Open Access Journals (Sweden)

    Jialiang Huang

    2016-03-01

    Full Text Available Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS control (sham OVX + ligature + PBS (vehicle, and OVX + ligature + low or high (2 or 5 mg∙kg−1∙day−1, respectively doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p. every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT, hematoxylin and eosin (H&E staining, and tartrate-resistant acid phosphatase (TRAP staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  9. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wei [Department of Out-Patient, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wang, Wei; Huang, Jing [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Ren, Ning [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wu, Sheng-Xi, E-mail: shengxi@fmmu.edu.cn [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Li, Yong-Qi, E-mail: devneuro@fmmu.edu.cn [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2010-05-14

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1{beta} was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  10. Dating of cremated bones

    NARCIS (Netherlands)

    Lanting, JN; Aerts-Bijma, AT; van der Plicht, J; Boaretto, E.; Carmi, I.

    2001-01-01

    When dating unburnt bone, bone collagen, the organic fraction of the bone, is used. Collagen does not survive the heat of the cremation pyre, so dating of cremated bone has been considered impossible. Structural carbonate in the mineral fraction of the bone, however, survives the cremation process.

  11. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    Energy Technology Data Exchange (ETDEWEB)

    Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bretschi, Maren; Bäuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Hillengass, Jens [Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Bendl, Rolf [Medical Informatics, Heilbronn University, Max-Planck-Strasse 39, 74081 Heilbronn, Germany and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2013-12-15

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  12. Bone Micro-CT Assessments in an Orchidectomised Rat Model Supplemented with Eurycoma longifolia

    Directory of Open Access Journals (Sweden)

    Rosmaliza Ramli

    2012-01-01

    Full Text Available Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model. Forty-eight-aged (10–12 months old Sprague Dawley rats were divided into six groups of sham-operated (SHAM, orchidectomised control (ORX, orchidectomised + 7 mg/rat testosterone enanthate (TEN and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30, orchidectomised + Eurycoma longifolia 60 mg/kg (EL60, orchidectomised + Eurycoma longifolia 90 mg/kg (EL90. Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.

  13. Monte Carlo modeling of photon transport in buried bone tissue layer for quantitative Raman spectroscopy

    Science.gov (United States)

    Wilson, Robert H.; Dooley, Kathryn A.; Morris, Michael D.; Mycek, Mary-Ann

    2009-02-01

    Light-scattering spectroscopy has the potential to provide information about bone composition via a fiber-optic probe placed on the skin. In order to design efficient probes, one must understand the effect of all tissue layers on photon transport. To quantitatively understand the effect of overlying tissue layers on the detected bone Raman signal, a layered Monte Carlo model was modified for Raman scattering. The model incorporated the absorption and scattering properties of three overlying tissue layers (dermis, subdermis, muscle), as well as the underlying bone tissue. The attenuation of the collected bone Raman signal, predominantly due to elastic light scattering in the overlying tissue layers, affected the carbonate/phosphate (C/P) ratio by increasing the standard deviation of the computational result. Furthermore, the mean C/P ratio varied when the relative thicknesses of the layers were varied and the elastic scattering coefficient at the Raman scattering wavelength of carbonate was modeled to be different from that at the Raman scattering wavelength of phosphate. These results represent the first portion of a computational study designed to predict optimal probe geometry and help to analyze detected signal for Raman scattering experiments involving bone.

  14. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    Directory of Open Access Journals (Sweden)

    Boos Alois

    2006-08-01

    Full Text Available Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

  15. Model-based 3D segmentation of the bones of joints in medical images

    Science.gov (United States)

    Liu, Jiamin; Udupa, Jayaram K.; Saha, Punam K.; Odhner, Dewey; Hirsch, Bruce E.; Siegler, Sorin; Simon, Scott; Winkelstein, Beth A.

    2005-04-01

    There are several medical application areas that require the segmentation and separation of the component bones of joints in a sequence of acquired images of the joint under various loading conditions, our own target area being joint motion analysis. This is a challenging problem due to the proximity of bones at the joint, partial volume effects, and other imaging modality-specific factors that confound boundary contrast. A model-based strategy is proposed in this paper wherein a rigid model of the bone is generated from a segmentation of the bone in the image corresponding to one position of the joint by using the live wire method. In other images of the joint, this model is used to search for the same bone by minimizing an energy functional that utilizes both boundary- and region-based information. An evaluation of the method by utilizing a total of 60 data sets on MR and CT images of the ankle complex and cervical spine indicates that the segmentations agree very closely with the live wire segmentations yielding true positive and false positive volume fractions in the range 89-97% and 0.2-0.7%. The method requires 1-2 minutes of operator time and 6-7 minutes of computer time, which makes it significantly more efficient than live wire - the only method currently available for the task.

  16. Parallel plate model for trabecular bone exhibits volume fraction-dependant bias

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; Odgaard, A;

    2000-01-01

    Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia......, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods...

  17. Differential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Function

    Science.gov (United States)

    Fusaro, Maria; Dalle Carbonare, Luca; Dusso, Adriana; Arcidiacono, Maria Vittoria; Valenti, Maria Teresa; Aghi, Andrea; Pasho, Sabina; Gallieni, Maurizio

    2015-01-01

    Background Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin) and Matrix Gla Protein (MGP). Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification. Methods Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically. Results Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries. Conclusions These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients. PMID:26241483

  18. Differential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Function.

    Directory of Open Access Journals (Sweden)

    Maria Fusaro

    Full Text Available Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin and Matrix Gla Protein (MGP. Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification.Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically.Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries.These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients.

  19. Structural and Qualitative Bone Remodeling Around Repetitive Loaded Implants in Rabbits.

    Science.gov (United States)

    Kuroshima, Shinichiro; Yasutake, Munenori; Tsuiki, Kotaro; Nakano, Takayoshi; Sawase, Takashi

    2015-10-01

    Bone mechanical function is regulated by bone quality and bone mineral density (BMD) that reflect bone strength. The preferential alignment of biological apatite (BAp) c-axis/collagen fibers and osteocytes is a determinant factor of bone quality. However, the effect of mechanical loading on bone quality around dental implants is unclear. The aim of this study was to clarify the effects of mechanical loading on osseointegration, bone volume BMD, and bone quality around dental implants. Twenty anodized Ti-6Al-4V alloy implants (KYOCERA Co., Kyoto, Japan) were placed in the proximal tibial metaphysis of 10 rabbits. Twelve weeks after surgery, mechanical loading was applied along the long axis of the implant (50 N, 3 Hz, 1,800 cycles, 2 days/week) for 8 weeks. Osseointegration, bone volume, BMD, and bone quality were evaluated using light microscopy, microcomputed tomography, polarized light microscopy, and microbeam X-ray diffractometer. Mechanical loading increased osseointegration, bone volume, and BMD. Bone quality around dental implant was altered with increased osteocyte numbers and the preferential alignment direction and degree of BAp c-axis/collagen fibers. These findings suggest that mechanical loading effectively induces bone anabolic responses around dental implants. Altered bone quality may upregulate bone strength, contributing to long-term implant stability. © 2015 Wiley Periodicals, Inc.

  20. Virtual Temporal Bone Anatomy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Background The Visible Human Project(VHP) initiated by the U.S. National Library of Medicine has drawn much attention and interests from around the world. The Visible Chinese Human (VCH) project has started in China. The current study aims at acquiring a feasible virtual methodology for reconstructing the temporal bone of the Chinese population, which may provide an accurate 3-D model of important temporal bone structures that can be used in teaching and patient care for medical scientists and clinicians. Methods A series of sectional images of the temporal bone were generated from section slices of a female cadaver head. On each sectional image, SOIs (structures of interest) were segmented by carefully defining their contours and filling their areas with certain gray scale values. The processed volume data were then inducted into the 3D Slicer software(developed by the Surgical Planning Lab at Brigham and Women's Hospital and the MIT AI Lab) for resegmentation and generation of a set of tagged images of the SOIs. 3D surface models