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Abstract In many archaeological excavations, bone has been found in tow forms. In the form of tools and in the form of row material. Therefore, bone has been studied in several points and gives many beneficial information to researchers. In previous excavations less attention has been paid to the bones and other remains of human and animals, for example teeth and crown. These findings are now collecting and recording carefully. pale biologists, anthropologists, zoologists, and pale pathologists are surveying the information about economic, social and cultural condition in ancient society. In this research we will survey several applications of bone in the knowledge of antiquarian culture.

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Background: we aimed to evaluate the effect of body weight and Body Mass Index (BMI) on Bone Mineral Density (BMD) in healthy postmenopausal Iranian women. Material and Methods: Two hundred postmenopausal women (age between 51 and 69 years) who had presented to the nuclear medicine center at Shariati Hospital in Tehran, Iran between April 2012 and August 2013 were included in this cross sectional study. Of these 46 healthy women who met the study criteria constituted for evaluation. After recording weight and height of individuals, Body Mass Index (BMI) (kg/m2) was calculated as weight (kg) divided by height square (m²). Bone Mineral Density (BMD) in Femoral Neck (FN) and lumbar spine sites (L1-L4) were measured by dual-energy X-ray absorptiometry (DEXA). Results: We observed statistically significant negative correlation between BMD measurements at femoral neck and lumbar_1-4 spine with age and significant positive correlation with weight and BMI. Stepwise multiple linear regression analysis showed that only weight and age, after adjustments to BMI determined lumbar_1-4 spine BMD (R² = 23%) and femoral neck BMD (R² = 28.6%). Conclusions: These results suggest that the relationship between body weights and BMD is Stronger than the relationship between BMI and BMD. Therefore, in comparison with body mass index, body weight alone is a better predictor of bone mineral density.

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Background: In recent years we have successfully adopted an in vitro hepatogenic differentiation of mesenchymal stem cells (MSCs). In this protocol the biologically active hepatocyte-like cells were differentiated from the stem cells isolated from either bone marrow or umbilical cord blood (UCB) samples. The aim of the present study was to compare the efficiency of the hepatogenic differentiation of MSCs isolated from UCB and MSCs. Methods: Differentiation process of MSCs was carried out in a selective medium supporting hepatogenic differentiation for 3 weeks. Then using specific markers we have examined the hepatocyte formation following hepatogenic differentiation of the stem cells. Hepatogenic markers namely albumin, α-fetoprotein (AFP) and cytochrome P450 3A4 (CYP3A4) were monitored at different time intervals during differentiation. Results: Transdifferentiation of the UCB and bone marrow MSCs was also characterized by measuring albumin, AFP and CYP3A4 at mRNA levels using reverse transcription polymerase chain reaction (RT-PCR). AFP was expressed in the undifferentiated UCB-MSCs and increased on day 21 of differentiation. However, AFP was not detected in the undifferentiated bone marrow MSCs. But, AFP expression started during the first week of differentiation. Albumin expression was detected in hepatocytes from UCB as well as bone marrow. The expression of albumin and its secretion from hepatocyte prepared from bone marrow appeared earlier compared to the cells derived from UCB. Metabolic function of the hepatocytes evaluated by secretion of albumin in the culture media was also similar in the cells isolated from both the sources. Conclusions: The differentiation potential of MSCs derived from human UCB and bone marrow under in vitro condition is comparable. However, it appears that there is time-dependent difference in the onset of expression of liver specific markers particularly albumin synthesis in hepatocytes derived from different stem cells.

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Aims: In bone tissue engineering, the scaffold as a supportive structure, plays a vital role. Putting the scaffold in dynamic cell culture, such as perfusion bioreactor, makes the role of mechanical parameters such as shear stress and hydrodynamic pressure more important. On the other hand, these mechanical parameters are influenced by scaffold architecture. In this study, the effects of bone scaffold architecture on mechanical stimuli have been analyzed and their effects on the mesenchymal stem cell fate have been predicted.
Material & Methods: Using the tools of computer simulation, five bone scaffolds (Gyroid, high porous Gyroid, Diamond, IWP, and gradient architecture Gyroid) based on mathematical functions of minimal surfaces were designed and exposed in a simulated dynamic cell culture under the inlet velocities of 1, 10, 25, 50, and 100μm/s. Cell accumulation on the inner part of the scaffold was considered as an 8.5-micron layer. This layer was designed for Gyroid and IWP scaffolds.
Findings: Based on the results, Diamond scaffold showed the most efficient performance from the homogeneity of stresses point of view. In the presence of the cell layer, the von Mises stress was reported as 60 and 50 mPa on the Gyroid and IWP scaffolds, respectively which eases osteogenic differentiation.
Conclusion: In gradient architecture scaffolds under dynamic conditions, there is a gradient in shear stress that causes various signaling in different positions of theses scaffold and facilitates multi-differentiation of the cells on the same scaffold.

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Since one of the main problems in bone tissue repair is the bacterial infections, recently the development of drug-eluting nanocomposite scaffolds for bone regenerative medicine applications has attracted significant attention. In this study Polycaprolactone (PCL)-based composite scaffolds containing 10vol% of titanium dioxide nanoparticles (~21nm), and bioactive glass particles (~6µm), were prepared without drug and also loaded by Tetracycline hydrochloride (TCH) antibiotic (0.57, 1.15 mg/mL) through solvent casting method for bone tissue engineering applications. Structural characterizations based on Scanning Electron Microscopy (SEM), and FTIR analysis were utilized to study the chemical bonds of glass/ceramic particles, and antibiotic crystals on the surface. In addition, in vitro cytotoxicity, and antibacterial analysis were performed by MTT, and Agar well-diffusion assays, respectively. In this study polymeric and composite scaffolds were fabricated with TCH clusters decorated on the surface. It was shown that the bioactive glass/PCL scaffolds loaded by 0.57 mg/mL of TCH revealed significant antibacterial effect, despite the acceptable cell viability. These scaffolds seem to be of interest as a potential candidate in drug-eluting scaffolds for bone tissue engineering applications.

 

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Bone morphogenetic proteins (BMPs) are a subfamily of multifunctional superfamily transforming growth factor-beta (TGF-β), thus they have a lot of similarity in biosynthesis, structure, signaling and biological function with other members of the superfamily. They are involved in growth and differentiation of embryo to maintenance of adult cells. Among this family member, BMP-2 is a valuable protein that acts in different processes such as spinal fusions, articular cartilage damage therapy, tumor inhibition, gingivitis and dental treatment. The high importance of this protein and its low production rate in body caused several researches in the field of producing recombinant BMP-2 in different hosts. Recombinant production of the protein in bacterial host caused the decrease in production costs and therefore led to the common use of BMP-2 in treatment of various diseases. To date, positive effects of intact BMP-2 and its derivative peptides, in order to osteoinduction in fracture treatment and jaw bone regeneration for dental implantation, were considerable. Considering high clinical significance of BMP-2, there is a necessity for more investigations in relation to this protein.

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Objective: Osteon has been introduced as a bone substitute material. It is biphasic calcium phosphate (BCP) that use in dentistry. The aim of the present study was to evaluate the effect of osteon on the proliferation, cell viability and differentiation of saos-2 cells in vitro. Also it was compared with cerasorb bone graft. Materials and Methods: Two different bone grafts materials, osteon and cerasorb, were used to evaluate the effect on proliferation and differentiation rate of saos-2 cells. On day 15 the cell proliferation and cell viability was measured by MTT assay. For determination of differentiation, alkaline phosphatase and alizarin red test was used. Results: Osteon and cerasorb groups showed significantly higher alkaline phosphatase activity and cell differentiation. Cell viability of both bone grafts was significantly lower than control group and cell proliferation was higher in osteon group. Osteon has more suitable biological property compare to cerasorb. Conclusions: The results of the present study showed that osteon and cersorb bone grafts allow proliferation and differentiation of saos-2 cells in vitro.

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Internal immobilization of fractured parts of bone depends on the drilling of fracture site and screw fixation of implanted devices to the bone. During drilling, the temperature may rise allowable temperature of 47°C and causes irreversible thermal necrosis. This study is concerned with methods of drilling to determine the best processing condition to minimize the osteonecrosis. Drilling tests were performed with two drilling techniques: conventional, and high speed drilling on the bovine femur and increase of temperature in drilling site, duration of temperature raise and thrust force were measured. The result for conventional drilling shows that in all processing conditions, the generated heat is over the allowable limit, which makes thermal necrosis inevitable. On other hand, it was found that increase of cutting speed of drill bit to 7000 rpm, leads to considerable decrease of thrust force and increase of heat dissipation with chips, simultaneously and leads to decrease of local temperature raise in drilling site. But with more increase of rotational speed of drill bit, because of not sensible change in drilling force and considerable increase of friction between chips, drill bit body and drilled hole, amount of temperature elevation is increased.

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In this paper, the cyclic behavior and available ductility of batten columns subjected to constant axial and cyclic lateral load (seismic condition) and their failure mode are evaluated numerically using nonlinear finite element analysis. The column specimens were steel I-shape sections and were analyzed as an equivalent cantilever column. Batten columns are compression members composed of two or more similar longitudinal components (chords) that are connected at points along their length with batten plates as transverse connectors. These connectors ensure that the column behaves as one integral unit to achieve maximum axial capacity. In the past decades, many research activities were conducted on the buckling problem of batten columns. When a batten column is subjected to lateral load or bending moment about its hollow axis (axis perpendicular to battens) in addition to axial compression, the additional internal actions will be imposed to its members (chords and battens). In this case, it is expected that the batten column will have different behavior and failure modes. If the lateral load or displacement is due to seismic actions, more complexities will exist in the column behavior due to nonlinearities and its post-failure response. Few researches were reported about the behavior of batten columns in seismic conditions and their ductility. In this research, the backbone curves for batten columns have been also developed based on their cyclic response. The component backbone curve represents the nonlinear behavior of component in plastic hinge locations and was used in the nonlinear pushover analysis. The backbone curve for some structural components has been found in many standard and guidelines of seismic evaluation like as FEMA356. Using the backbone curve, the available ductility of column considering its post failure response under cyclic lateral loads, could be evaluated. The backbone curve for batten columns does not exist in any guideline or research reports. Because of differences between behavior and failure modes of batten and solid web columns under seismic action, it was expected that their backbone curves had been substantially different. In this research, cyclic response of batten columns with different geometries have been investigated subjected to cyclic lateral and 3 level of constant axial load. Using cyclic curves, the backbone curves of considered batten columns have been developed. The results show that the available ductility of batten columns is considerably low compared with solid web columns. The failure mode of batten columns is local buckling of bottom chords (in flanges and web) in combination with overall buckling of these chords symmetrically. It is also shown that the backbone curves of batten columns are different from solid web columns. The backbone curves of batten columns are semi-ductile (Type 2) based on FEMA356 classification and don’t have any residual strength. Finally, a conservative backbone curve has been proposed for engineering applications.

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The problem of bone fracture in medicine due to an accident, aging or diseases, has existed from times when humans started to work and activity. The process of bone drilling is an essential part of internal immobilization in orthopaedic and trauma surgery. The force required to chip formation in drilling process, resulting in heat generation in drill site that leads to the occurrence of thermal necrosis. This research experimentally investigates the effect of ultrasonic vibration on thrust force in drilling of bovine femur bone. This method induces high-frequency and law-amplitude vibration in the feed direction during cutting, and has the potential to spread tiny cracks in bone and decrease friction leading to reduce of cutting forces and also increase the speed of chip disposal leading to reduction of machining forces, totally. Experimental results demonstrate that ultrasonic assisted drilling of bone produces fewer thrust force than conventional drilling and rotational speed of 1000 rpm is the optimal speed to achieve at minimum thrust force for all feed rates. Moreover, this method is due to the force independence of the feed rate in the rotational speed of 1000 rpm, is applicable in orthopedic surgery.

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Orthopedic plates are currently used in bone healing process. However they cause density loss because of the change in natural stress patterns.The aim of this study was to evaluate a newly developed bone plate using functional graded material in term of stress pattern. In the present study, 3D finite element models of tibial bone plate with variable stiffness of a graded material and traditional bone plates made of stainless steel and Ti alloy have been developed by using the ABAQUS software. Effects on the predicted stresses at the fracture site in the presence of a distance between the plate and fractured bone were also studied. For this purpose, a 3D model of tibia was created with the exact geometry of the real bone geometry by using CT scan images of a human left leg. Results showed that the bone plate with graded material offers less stress-shielding to the bone, providing a higher compressive stress at bone to induce accelerated healing in comparison with Ti alloy and stainless-steel bone plate. Results also showed that the use of non-contact plates provide a favorable mechanical environment for the following fracture healing.

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This paper focuses on a class of continuum robot manipulators that uses cables for actuation. In order to realize more natural and various motions like human musculoskeletal, tendon-driven manipulators is studied. It is challenging to design the manipulator structure which consists of bones and redundant muscles. A comprehensive study is presented including the theoretical analysis of the mechanical design, kinematics, dynamics and tracking control of a planar continuum backbone robot. Lagrange's equation is applied to the dynamic problem and the system is controlled by a computed torque/time delay approach. This paper explores the fundamental limitations of dynamic problem for different loading conditions and the behavior is formulated based on the motion constraints. For example, the cable forces are computed considering the yield stress. Moreover the effects of cable configuration are examined by comparing the model performance. Meanwhile, the geometrical parameters have an important effect on manipulation. The analysis is applied on two main robot structures considering geometrically constrained deformable continuum body. The simulation results illustrate the efficiency of the proposed design and controller. Nevertheless, the field of continuum and hyper-redundant manipulation holds great promise also in the experimental domains.

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Objective: Demyelination of CNS axons occurs under pathological conditions such as multiple sclerosis and spinal cord injuries, but can be repaired by cell therapy. Within the CNS remyelination can be achieved by transplantation of neural stem cells (NSCs). NSCs are self-renewing cells that maintain the capacity to differentiate into CNS-specific cell types and can differentiate into the three main neural phenotypes: astroglia, oligodendroglia and neurons. They may also replace or repair diseased CNS tissue. Methods: Bone marrow stromal cells (BMSCs) were aseptically isolated from the tibia and femurs of young adult Sprague Dawley rats. BMSCs were evaluated by fibronectin and CD31 markers. BMSC-derived NSCs were evaluated by nestin and NF-68. An ethidium bromide-induced demyelinated dorsal column lesion was produced in young adult rats. Transplanting NSCs derived-BMSCs into demyelinated lesions after 3 days in adult rat spinal cords was done. Three weeks after transplantation of NSCs, the spinal cords were processed to evaluate remyelination by Luxol fast blue staining. Results: After passage 3, BMSCs were evaluated and the result, showed the percentage of immunoreactive cells to fibronectin (94.7±2.65), however BMSC-derived NSCs expressed nestin (86.15±0.64) and NF-68 (84.55±0.94) which correlated with fibronectin down regulation. Histologically, the lesions showed slightly irregular elongated areas and had an average length of 1336.36±39.43 µm. Transplanted NSCs were capable of eliciting remyelination. Conclusion: These data support the conclusion that transplantation of NSCs results in functional remyelination of a dorsal column lesion and have valuable applications in the treatment of neurodegenerative diseases such as spinal cord injuries.

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In this study, it has been tried to provide a new model for the structure of a backbone arm, to repel the shortcoming in the generation and transmission of the motion for the continuum robots. Backbone arms such as natural structures include continuum backbones with superior properties such as the ability to adapt to the environment. The actuation power is distributed over the robot’s length and makes the shape continuously deformable. In this paper, it has been suggested to add a linkage between the backbones and the branched tendons for power transfer between the drive and backbones. The ratio of the drive torque to backbone torque is introduced as the transfer ratio. The new design is capable to create a variety of transfer ration during a cycle of motion. The state space equations are extracted by Lagrange equations. Dealing the interference of bone-bone and bone-links as geometric constraints are applied to the design and it determines the allowable range of the continuum robot's geometric parameters. This design is examined with planar simulations. To show the effectiveness of the proposed design, several simulation results are illustrated. Optimum geometrical parameters for the constant torque ratio are calculated.In contrast to previous cases with the widely used; the goal is achieved with this novel backbone continuum robot.

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Objective: Bone morphogenetic protein-7 (BMP-7) is a multifunctional growth factor predominantly recognized for its osteoinductive properties. Due to the high cost of this protein, the availability of BMP-7 for treatment is limited. The heterologous production of recombinant hBMP-7 has been performed in a number of expression systems. In this study a novel form of BMP-7 was expressed in eukaryotic and prokaryotic hosts. Methods: For expression in the prokaryotic system, the novel protein was secreted to the periplasmic space of Escherichia coli using a pelB signal sequence followed by single-step purification by Ni²⁺-charged column chromatography. In the mammalian cell expression system, we transferred a full-length cDNA encoding precursor of the novel protein to CHO cells then selected stable clones by using the appropriate antibiotic concentration. Expressions in both systems were confirmed by Western blot analysis. Results: The novel recombinant protein was produced as a 36-38 kDa dimer in the CHO cell line and a 16 kDa monomer in the Escherichia coli system. Quantitative analysis according to ELISA showed that the expression levels of the mutant protein in the eukaryotic and prokaryotic expression systems were 40 ng/ml and 135 ng/ml of the culture media, respectively. Conclusion: In this study, the expression level in Escherichia coli was at least three times more than observed in the CHO cells. However, further optimization is required to obtain a dimer protein in Escherichia coli. The results show that periplasmic expression may be suitable for the production of complex proteins such as BMPs.

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Objective: Biodegradable polycaprolactone/starch composites can be used for bone tissue engineering applications. The effect of the ratio of components on composite properties is of tremendous importance. Methods: Polycaprolactone/starch composite of 80/20 and 70/30 ratios were fabricated by dissolving them in chloroform followed by evaporation of the solvent. Results: The composites were characterized by fourier transform infrared spectroscopy. Their bioactivity was evaluated by studying the apatite formation ability after immersing the specimens in simulated body fluid. The results of compressive test on samples showed that the composite’s modulus and strength approximated that of human trabecular bone. Mass loss in distilled water and starch degradation rate in PBS was evaluated, which showed that the starch ratio was effective in composite degradation. MTT analysis and alkaline phosphatase levels showed that this composite had no toxicity and could increase G-299 cell line osteoblastic activities. Conclusion: The increase in cellular osteoblastic activities and the ability for apatite formation on the composite surface, in addition to the polycaprolactone/starch samples' mechanical properties shows their capability to be used as substitutes for bone. Because this composite degradation rate is controlled by changing the starch ratio, it has the potential for use in bone tissue engineering applications. Samples that have a 70/30 ratio are considered optimal due to their enhanced cellular response and better mechanical properties.

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Human bones experience different modes of loading including tension, compression, bending, and torsion. The modes of loading depend on the activities done by the body. Regarding the crack shape and loading modes, by the time only the first mode of fracture has been studied in order to analyze the fracture toughness. However, it is necessary to analyze different modes of fracture in order to find more reliable results. In this research, finite element analysis and calculations for geometric coefficients were done to obtain the toughness of bone. Hence, first, second, and combined modes of fracture in cortical samples having cracks were studied numerically and experimentally. To this end, bovine tibia was used to make standard tensile samples for implementation in Arkan’s device. Some optimizations were made on the Arcan’s device. These were included of bone fixation in the device and ability of performing tests in different angels. Stress intensity factor (Kc) was obtained for different fracture modes. Results showed a decrease in KIc respect to change in loading angle while KIIc acted vice versa. Performing some extra optimizations, the device can be used for tortional fracture mode in a torsional test device.

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Quantitative computed tomography (QCT) -based finite element analysis is a commonly accepted approach for prediction of mechanical behavior of bones. The objective of this research is to suggest linear criterion in order to accelerate and increase the precision of predicting of failure load in femoral bone. Accordingly, ten fresh frozen femora were QCT scanned and performed to use in this study. The specimens were loaded under eight different orientations. Finite element model for these samples were generated from QCT images, and related mechanical properties were calculated for each single voxel based on the value of density. In addition, the models were analyzed by linear finite element method. Risk factor that defines as the strain energy density divided to yield strain energy for each element was used for calculations of failure load. These values were sorted for particular loads in finite element model, and the correlations between experimental and numerical results were compared. Finally, eight linear criterions for eight different load conditions were presented which shows magnificent correlation between empirical results (average slope: 0.8903 and average R2: 0.8668). These correlations make it possible to accelerate the prediction of femoral fracture load in various orientations. This research shows a robust and fast method for prediction of failure in bones that can be used for multiple loads and orientations.

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Connected dominating set (CDS) problem is the most widely used method for backbone formation ‎in wireless sensor networks. To date, numerous algorithms have been proposed for backbone ‎construction on minimum CDS (MCDS) problem in unit disk graphs (UDG); however, only a few ‎algorithms have been proposed on MCDS problem in disk graphs with bidirectional links (DGB) ‎and on degree-constrained minimum-weight CDS (DC-MWCDS) problem in UDG. To the best of ‎our knowledge, no work has been done on DC-MWCDS problem in DGB. In this paper, we present ‎OEDC-MWCDS problem (optimal energy and degree constrained minimum-weight connected ‎dominating set) for constructing energy efficient backbone in wireless sensor networks. Then, we ‎model a wireless sensor network as a disk graph with bidirectional links and propose a backbone ‎construction algorithm called EBC-PSO (Energy efficient Backbone Construction utilizing Particle ‎Swarm Optimization algorithm) to obtain a CDS with the minimum weight subject to the optimal ‎energy and degree constraint. The main objective of the proposed algorithm is to find the optimal ‎values of energy and degree of constraint to maximize network lifetime. In the proposed algorithm, ‎optimal coefficients of minimum remaining energy and maximum degree of nodes are determined ‎utilizing PSO algorithm. Then, in the selection of DS nodes, these coefficients are used. Simulation ‎results verify the performance of the proposed algorithm in terms of network lifetime and ‎backbone size.‎