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ABSTRACT: Optical tweezers were used to scan individual Chronic Myelogenous Leukemia cells to determine if the cell death depends on the scanning conditions. Although increasing the scanning frequency or amplitude means greater force applied to the cells, their effects on cell death are not a simple increasing trend, as observed in the optical microscopy. Indeed, cell death sharply increased at particular screening frequencies and amplitudes, whereas other frequencies or amplitudes were less detrimental. These results suggest that cell damage was more sensitive to certain scanning conditions, rather than simply high applied forces. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
Journal of Cellular Physiology 04/2013; · 3.87 Impact Factor
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ABSTRACT: Controlling cell organization is important in tissue engineering. Guidance by aligned features on scaffolds or stimulation by physical signals can be used to induce cell alignment. We have previously demonstrated a preferred alignment of human MSCs (hMSCs) along the compression loading axis in 3D collagen construct. In this study, we aim to investigate the collagen concentration dependence of the compression-induced hMSC organization. Results demonstrated that the compression-induced alignment and elongation of hMSCs exhibited a biphasic dose-dependent relationship with collagen concentration, and associated well with both collagen ligand density and elastic modulus of the constructs. Moreover, collagen concentration and compression loading significantly affected the expression level of integrin beta 1 and antibody neutralization against this molecule aborted the compression-induced alignment and elongation responses. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Journal of Biomedical Materials Research Part A 11/2012; · 2.63 Impact Factor
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ABSTRACT: The elastic modulus of an oral cancer cell line UM1 is investigated by nanoindentation in an atomic force microscope with a flat-ended tip. The commonly used Hertzian method gives apparent elastic modulus which increases with the loading rate, indicating strong effects of viscoelasticity. On the contrary, a rate-jump method developed for viscoelastic materials gives elastic modulus values which are independent of the rate-jump magnitude. The results show that the rate-jump method can be used as a standard protocol for measuring elastic stiffness of living cells, since the measured values are intrinsic properties of the cells.
Journal of the mechanical behavior of biomedical materials. 04/2012; 8:134-42.
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ABSTRACT: The protein-protein interactions between hepatitis B surface antigen (HBsAg) and its antibodies (anti-HBs) were studied by measuring the binding force between microspheres coated with such proteins using optical tweezers. The interaction force between the protein-coated microspheres was found to be strongly influenced by the acidity of the surrounding liquid medium, as well as the experimental temperature, and it reaches a maximum value at around pH 7.5 and temperature around 37°C. By measuring the protein distribution on the surfaces of the microspheres and their contact areas using scanning electron microscopy, the specific binding force between an HBsAg and anti-HBs protein pair is estimated to be around 4.8 pN at the optimum pH value and temperature at an applied loading rate of around 1 pN/s.
IET Nanobiotechnology 03/2012; 6(1):9-15. · 1.83 Impact Factor
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ABSTRACT: Despite being an interface between two mechanically mismatched phases of the soft dentine and hard enamel, the dentine-enamel junction (DEJ) in a human tooth is in general capable of withstanding a long working life of repeated dynamic loading. The current poor understanding of the structure and properties of the DEJ has presented a major obstacle to designing better therapeutic protocols for complications concerning the DEJ. In this investigation, it was discovered that the DEJ is a thin, but gradual interface with characteristics transiting from those of dentine to those of enamel. The collagen fibres in dentine enter into the enamel side of the DEJ and terminate in a region in which the hydroxyapatite crystals begin to show enamel characteristics. Using focused ion beam machining, micro-beams were fabricated from regions within 50 μm of the DEJ and were subjected to bend tests. In spite of the similarity in the flexural strength of the DEJ and enamel, fractographs revealed cracks in the DEJ that propagated along structures with dentine characteristics. To the best of our knowledge, this is the first report on the testing of the mechanical properties of the DEJ.
Journal of the mechanical behavior of biomedical materials. 07/2011; 4(5):785-95.
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ABSTRACT: The elastic moduli of a range of polymers were characterized by nanoindentation on an atomic force microscope (AFM), using a recently proposed protocol involving a jump in the sample displacement rate. In this method any viscous behavior of the sample would not react to the rate jump, so that the response of the sample reflects only its elastic behavior. By assuming that the AFM tip is a flat-ended punch, this method involves calibration of only two cantilever tip-specific parameters. Experiments were conducted on PMMA at 353 K using load schedules comprising two such rate jumps in sequence and with different magnitudes. The results indicate that PMMA exhibits a constant elastic modulus at the test temperature, and that the AFM tip used is well described by the flat-ended punch approximation.
Philosophical Magazine 03/2011; 91(Nos. 7–9):1329-1338. · 1.51 Impact Factor
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ABSTRACT: Mesenchymal stem cell (MSC)-based engineering is promising for cartilage repair. However, the compositional mechanical relationship of the engineered structures has not been extensively studied, given the importance of such relationship in native cartilage tissues. In this study, a novel human MSC-collagen microsphere system was used to study the compositional mechanical relationship during in vitro chondrogenic differentiation using histological and biochemical methods and a microplate compression assay. The mechanical property was found positively correlating with newly deposited cartilage-relevant matrices, glycosaminoglycan, and type II collagen, and with the collagen crosslinker density, in agreement with the presence of thick collagen bundles upon structural characterization. On the other hand, the mechanical property negatively correlates with type I collagen and total collagen, suggesting that the initial collagen matrix scaffold of the microsphere system was being remodeled by the differentiating human MSCs. This study also demonstrated the application of a simple, sensitive, and nondestructive tool for monitoring the progression of chondrogenic differentiation of MSCs in tissue-engineered constructs and therefore contributes to future development of novel cartilage repair strategies.
Tissue Engineering Part A 10/2010; 17(5-6):777-88. · 4.64 Impact Factor
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ABSTRACT: Failure of the enamel adjacent to the defects in teeth with molar incisor hypomineralization (MIH) limits the success rate of the restorations placed in these teeth and this frequently leads to their ultimate extraction. To understand the cause, a state-of-the-art combination of focused ion beam (FIB) and nanoindentation techniques was used to evaluate the fracture properties and microstructure of enamel from specific regions of two MIH teeth.
Nanoindentation, bend tests on micro-cantilevers and transmission electron microscopy (TEM) were employed to compare the microstructure and mechanical properties of the unaffected, opaque and transitional region in two MIH teeth. Special attention was paid to the transitional region in all the experiments in an attempt to identify its role in affecting the overall integrity of the MIH teeth.
The enamel in the transitional region, despite its translucent appearance under the naked eye, was found, under TEM, to have prism sheaths that were significantly less mineralized than unaffected enamel and were proved to be weaker in holding the prisms together when measured using bend tests on micro-cantilever samples machined from the region.
The enamel in the transitional region adjacent to the demarcated defects in MIH has notable alterations in their prism sheaths which likely contribute to their lowered mechanical properties.
Journal of dentistry 11/2009; 38(3):237-44. · 2.00 Impact Factor
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ABSTRACT: In this paper, the usefulness of the specimen shaping ability of focused ion beam (FIB) milling in the micrometer scale and the high force resolution of the nanoindentation technique are demonstrated on human primary teeth. Micro-cantilevers, with a triangular cross-section <5 microm in width and 10 microm in length, were produced within 50 microm of the dentin-enamel junction (DEJ) using FIB milling, and were point-loaded at their free ends at 20 microN/s until failure using a nanoindenter. The elastic modulus and flexural strength of such micro-samples of human enamel, and their variation with respect to prism orientation, were studied and compared to data from bulk enamel measured using nanoindentation and three-point bend tests. The elastic modulus of the micro-cantilever samples was found to be comparable to that obtained by nanoindentation on bulk samples, but it demonstrated significant anisotropy commensurate with the microstructure of enamel which was not measurable using nanoindentation on bulk samples. The flexural strength of the enamel micro-cantilevers also exhibited strong anisotropy, and was about one order of magnitude higher than that of bulk specimens measured by three-point bending. Through a Weibull analysis, this size dependence of the strength was found to be similar to the normal behaviour in brittle materials. The flexural strength of the enamel samples was also found to be sensitive to changes in the degree of mineralization of the samples.
Journal of the mechanical behavior of biomedical materials. 09/2009; 2(4):375-83.
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ABSTRACT: Nonlinear viscoelastic problems are in general not analytically solvable. However, it is shown here that, for any viscoelastic materials describable by a constitutive law with linear elastic and (in general) nonlinear viscous elements arranged in any network fashion, such as the Maxwell or standard linear solid arrangements, it is always possible to eliminate the viscous terms by replacing the displacement, strain, and stress fields of the problem by the jumps in rates of these fields. After the viscous terms are eliminated, the problem is reduced to a linear elastic problem defined on the same spatial domain and with the same elastic constant as in the original viscoelastic problem. Such a reduced elastic problem is analytically solvable in many practical cases, and the solution yields a relation between jumps in the load rate and the displacement rate, pertinent to the boundary conditions in the original problem. Such a relation can often be used as the basis for an experimental scheme to measure the elastic constants of materials. The material can be time- or strain-dependent, and the value of the elastic constant measured corresponds to the time instant or the strain value when the jump in load or displacement rate is implemented.
Journal of Materials Research. 02/2009; 24(03):853 - 862.
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ABSTRACT: A method is proposed for quantitatively measuring the elastic modulus of materials using atomic force microscopy (AFM) nanoindentation. In this method, the cantilever deformation and the tip-sample interaction during the early loading portion are treated as two springs in series, and based on Sneddon's elastic contact solution, a new cantilever-tip property α is proposed which, together with the cantilever sensitivity A, can be measured from AFM tests on two reference materials with known elastic moduli. The measured α and A values specific to the tip and machine used can then be employed to accurately measure the elastic modulus of a third sample, assuming that the tip does not get significantly plastically deformed during the calibration procedure. AFM nanoindentation tests were performed on polypropylene (PP), fused quartz and acrylic samples to verify the validity of the proposed method. The cantilever-tip property and the cantilever sensitivity measured on PP and fused quartz were 0.514 GPa and 51.99 nm nA(-1), respectively. Using these measured quantities, the elastic modulus of acrylic was measured to be 3.24 GPa, which agrees well with the value measured using conventional depth-sensing indentation in a commercial nanoindenter.
Nanotechnology 12/2008; 19(49):495713. · 3.98 Impact Factor
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ABSTRACT: Hydrogel-based microspheres are commonly used for drug and cell delivery in regenerative medicine. Characterization of their physical and mechanical properties is important in monitoring their quality during fabrication and in predicting their performance upon injection. However, existing methods have limitations in measuring these micron-sized, soft and viscoelastic spherical structures. In this study, a protocol is developed to measure the elastic modulus of non-linear viscoelastic spheres by microplate compression, and is applied to collagen microspheres fabricated with or without cells. During the measurement, a microsphere is placed on a rigid surface and is compressed by a calibrated flexible microplate gripped to a rigid end. A step increase in the displacement rate of the rigid end of the flexible microplate is introduced and the reduced elastic modulus of the microsphere is calculated from the deformation response of the microsphere, using an equation derived in this study. The reduced elastic modulus of collagen microspheres with and without mesenchymal stem cells measured by this method was 9.1 kPa and 132 Pa, respectively.
Annals of biomedical engineering 08/2008; 36(7):1254-67. · 2.41 Impact Factor
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ABSTRACT: Hydrogel-based microspheres are commonly used for drug and cell delivery in regenerative medicine. Characterization of their
physical and mechanical properties is important in monitoring their quality during fabrication and in predicting their performance
upon injection. However, existing methods have limitations in measuring these micron-sized, soft and viscoelastic spherical
structures. In this study, a protocol is developed to measure the elastic modulus of non-linear viscoelastic spheres by microplate
compression, and is applied to collagen microspheres fabricated with or without cells. During the measurement, a microsphere
is placed on a rigid surface and is compressed by a calibrated flexible microplate gripped to a rigid end. A step increase
in the displacement rate of the rigid end of the flexible microplate is introduced and the reduced elastic modulus of the
microsphere is calculated from the deformation response of the microsphere, using an equation derived in this study. The reduced
elastic modulus of collagen microspheres with and without mesenchymal stem cells measured by this method was 9.1kPa and 132Pa,
respectively.
Annals of Biomedical Engineering 06/2008; 36(7):1254-1267. · 2.37 Impact Factor
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ABSTRACT: An in-plane transmission electron microscopy (TEM) investigation carried out on nano-scratches made in a Ni3Al foil revealed a high dislocation density within the scratch core, resulting in severe crystal rotations. The amount and sense of rotation were found to be asymmetrical about the longitudinal centre line of the scratch. Cross-sectional TEM analysis revealed that almost all the dislocations were confined within a semicircular zone having a radius similar to the calculated tip-sample contact size during scratching, in agreement with the in-plane TEM observations.
Philosophical Magazine. 03/2008; 88(9):1369-1388.
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ABSTRACT: The purpose of this study was to investigate and compare the chemical composition and nanomechanical properties at the bone-cement interface under non-weight-bearing and weight-bearing conditions, in order to understand the effect of weight-bearing on the bone-bonding behavior of strontium-containing hydroxyapatite (Sr-HA) cement. In one group, Sr-HA cement was injected into rabbit ilium (under non-weight-bearing conditions). Unilateral hip replacement was performed with Sr-HA cement (under weight-bearing conditions) in the other group. Six months later, scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) analysis and nanoindentation tests were conducted on the interfaces between cancellous bone and the Sr-HA cement. The nanoindentation results revealed two different transitional behaviors under different conditions. nder weight-bearing conditions, both the Young modulus and hardness at the interface were considerably higher than those at either the Sr-HA cement or cancellous bone. On the contrary, under non-weight-bearing conditions, both the Young modulus and hardness values at the interface were lower than those at the cancellous bone, but were higher than the Sr-HA cement. In addition, EDX results showed that the calcium and phosphorus contents at the interface under weight-bearing conditions were considerably higher than those under non-weight-bearing conditions. The differences in chemical composition and nanomechanical properties at the cement-bone interface under two different conditions indicate that weight-bearing produces significant effects on the bone-bonding behavior of the Sr-HA cement.
Journal of Biomedical Materials Research Part A 12/2007; 83(2):570-6. · 2.63 Impact Factor
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ABSTRACT: The purpose of this study was to investigate and compare the chemical composition and nanomechanical properties at the bone-cement interface under non-weight-bearing and weight-bearing conditions, in order to understand the effect of weight-bearing on the bone-bonding behavior of strontium-containing hydroxyapatite (Sr-HA) cement. In one group, Sr-HA cement was injected into rabbit ilium (under non-weight-bearing conditions). Unilateral hip replacement was performed with Sr-HA cement (under weight-bearing conditions) in the other group. Six months later, scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) analysis and nanoindentation tests were conducted on the interfaces between cancellous bone and the Sr-HA cement. The nanoindentation results revealed two different transitional behaviors under different conditions. nder weight-bearing conditions, both the Young modulus and hardness at the interface were considerably higher than those at either the Sr-HA cement or cancellous bone. On the contrary, under non-weight-bearing conditions, both the Young modulus and hardness values at the interface were lower than those at the cancellous bone, but were higher than the Sr-HA cement. In addition, EDX results showed that the calcium and phosphorus contents at the interface under weight-bearing conditions were considerably higher than those under non-weight-bearing conditions. The differences in chemical composition and nanomechanical properties at the cement-bone interface under two different conditions indicate that weight-bearing produces significant effects on the bone-bonding behavior of the Sr-HA cement. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Journal of Biomedical Materials Research Part A 10/2007; 83A(2):570 - 576. · 2.63 Impact Factor
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ABSTRACT: Nanoindentation is widely used to measure the mechanical properties of bio-tissues. However, viscoelastic effects during the nanoindentation are seldom considered rigorously, although they are in general very significant in bio-tissues. In this study, a recently developed method for correcting the viscoelastic effects during nanoindentation is applied to mice bone samples. This method is found to yield reliable elastic modulus and hardness results from forelimb and femur cortical bone samples of C57 BL/6N and ICR mice. The creep properties of the samples are also characterized by a novel procedure using nanoindentation. The measured mechanical properties correlate well with the calcium content of the bone samples.
Journal of Materials Science Materials in Medicine 10/2007; 18(9):1875-81. · 2.32 Impact Factor
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ABSTRACT: Many bioactive bone cements were developed for total hip replacement and found to bond with bone directly. However, the mechanical properties at the bone/bone cement interface under load bearing are not fully understood. In this study, a bioactive bone cement, which consists of strontium-containing hydroxyapatite (Sr-HA) powder and bisphenol-alpha-glycidyl dimethacrylate (Bis-GMA)-based resin, was evaluated in rabbit hip replacement for 6 months, and the mechanical properties of interfaces of cancellous bone/Sr-HA cement and cortical bone/Sr-HA cement were investigated by nanoindentation. The results showed that Young's modulus (17.6+/-4.2 GPa) and hardness (987.6+/-329.2 MPa) at interface between cancellous bone and Sr-HA cement were significantly higher than those at the cancellous bone (12.7+/-1.7 GPa; 632.7+/-108.4 MPa) and Sr-HA cement (5.2+/-0.5 GPa; 265.5+/-39.2 MPa); whereas Young's modulus (6.3+/-2.8 GPa) and hardness (417.4+/-164.5 MPa) at interface between cortical bone and Sr-HA cement were significantly lower than those at cortical bone (12.9+/-2.2 GPa; 887.9+/-162.0 MPa), but significantly higher than Sr-HA cement (3.6+/-0.3 GPa; 239.1+/-30.4 MPa). The results of the mechanical properties of the interfaces were supported by the histological observation and chemical composition. Osseointegration of Sr-HA cement with cancellous bone was observed. An apatite layer with high content of calcium and phosphorus was found between cancellous bone and Sr-HA cement. However, no such apatite layer was observed at the interface between cortical bone and Sr-HA cement. And the contents of calcium and phosphorus of the interface were lower than those of cortical bone. The mechanical properties indicated that these two interfaces were diffused interfaces, and cancellous bone or cortical bone was grown into Sr-HA cement 6 months after the implantation.
Biomaterials 04/2006; 27(9):1963-70. · 7.40 Impact Factor
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ABSTRACT: Continuum constitutive relations used in the design of macro-sized components assume that the elastic limit of a crystalline solid is time independent. Recent experiments using the nanoindentation technique, however, reveal that the elastic limit of submicron-sized metallic volumes decreases as time under load increases. A submicron metallic volume can sustain a static load in the elastic regime initially, but transition to plastic deformation may occur after some waiting time. In this paper, the characteristics of this type of delayed plasticity are reviewed. The available experimental data suggest that homogeneous nucleation of the plasticity events, which was frequently discussed in the recent literature, occurs only at sufficiently high loads within a narrow range. In a lower and broader load range, the nucleation of the plasticity events occurs at a history dependent rate, thus via a damage-accumulation mechanism not compatible with the homogeneous nucleation theory. A model based on the diffusion-controlled, subcritical growth of a Frank loop just underneath the indenter is proposed in this work to explain the history dependent nucleation of instability observed at lower loads. By fitting to the available nanoindentation data in Ni3Al, it is apparent that self-diffusion along the indenter-sample interface, rather than through the bulk, is likely to be the controlling factor for the growth of the Frank loop to a critical size to yield a dislocation avalanche.
Philosophical Magazine. 03/2006; 86(9):1287-1304.
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ABSTRACT: Molecular dynamics simulations are carried out to study the incipient dislocation plasticity in Ni3Al. Dislocation nucleation is found to occur preferentially at energetic atomic clusters with larger-than-average relative displacements. From the simulated distribution of the atomic relative displacements, a scaling model is proposed to predict the size dependence of the incipient plasticity condition in real-sized specimens.
Physical Review Letters 04/2005; 94(9):095501. · 7.37 Impact Factor
