Biomedical subjects

X E Guo

Publications and source records attributed to X E Guo.

15 recordsLinked to original sources

PubMed2006

Substrate modulation of osteoblast adhesion strength, focal adhesion kinase activation, and responsiveness to mechanical stimuli.

Osteoblast interactions with extracellular matrix (ECM) proteins are known to influence many cell functions, which may ultimately affect osseointegration of implants with the host bone tissue. Some adhesion-mediated events include activation of focal adhesion kinase, and subsequent changes in the cytoskeleton and cell morphology, which may lead to changes in adhesion strength and cell responsiveness to mechanical stimuli. In this study we examined focal adhesion kinase activation (FAK), F-actin cytoskeleton reorganization, adhesion strength, and osteoblast responsiveness to fluid shear when adhered to type I collagen (ColI), glass, poly-L-lysine (PLL), fibronectin (FN), vitronectin (VN), and serum (FBS). In general, surfaces that bind cells through integrins (FN, VN, FBS) elicited the highest adhesion strength, FAK activation, and F-actin stress fiber formation after both 15 and 60 minutes of adhesion. In contrast, cells attached through non-integrin mediated means (PLL, glass) showed the lowest FAK activation, adhesion strength, and little F-actin stress fiber formation. When subjected to steady fluid shear using a parallel plate flow chamber, osteoblasts plated on FN released significantly more PGE2 compared to those on glass. In contrast, PGE2 release of osteoblasts attached to FN or glass was not different in the absence of fluid shear, suggesting that differences in binding alone are insufficient to alter PGE2 secretion. The increased adhesion strength as well as PGE2 secretion of osteoblasts adhered via integrins may be due to increased F-actin fiber formation, which leads to increased cell stiffness.

Actins↗

PubMed2004

The influence of the fixed negative charges on mechanical and electrical behaviors of articular cartilage under unconfined compression.

Unconfined compression test has been frequently used to study the mechanical behaviors of articular cartilage, both theoretically and experimentally. It has also been used in explant and gel-cell-complex studies in tissue engineering. In biphasic and poroelastic theories, the effect of charges fixed on the proteoglycan macromolecules in articular cartilage is embodied in the apparent compressive Young's modulus and the apparent Poisson's ratio of the tissue, and the fluid pressure is considered to be the portion above the osmotic pressure. In order to understand how proteoglycan fixed charges might affect the mechanical behaviors of articular cartilage, and in order to predict the osmotic pressure and electric fields inside the tissue in this experimental configuration, it is necessary to use a model that explicitly takes into account the charged nature of the tissue and the flow of ions within its porous interstices. In this paper, we used a finite element model based on the triphasic theory to study how fixed charges in the porous-permeable soft tissue can modulate its mechanical and electrochemical responses under a step displacement in unconfined compression. The results from finite element calculations showed that: 1) A charged tissue always supports a larger load than an uncharged tissue of the same intrinsic elastic moduli. 2) The apparent Young's modulus (the ratio of the equilibrium axial stress to the axial strain) is always greater than the intrinsic Young's modulus of an uncharged tissue. 3) The apparent Poisson's ratio (the negative ratio of the lateral strain to the axial strain) is always larger than the intrinsic Poisson's ratio of an uncharged tissue. 4) Load support derives from three sources: intrinsic matrix stiffness, hydraulic pressure and osmotic pressure. Under the unconfined compression, the Donnan osmotic pressure can constitute between 13%-22% of the total load support at equilibrium. 5) During the stress-relaxation process following the initial instant of loading, the diffusion potential (due to the gradient of the fixed charge density and the associated gradient of ion concentrations) and the streaming potential (due to fluid convection) compete against each other. Within the physiological range of material parameters, the polarity of the electric potential depends on both the mechanical properties and the fixed charge density (FCD) of the tissue. For softer tissues, the diffusion effects dominate the electromechanical response, while for stiffer tissues, the streaming potential dominates this response. 6) Fixed charges do not affect the instantaneous strain field relative to the initial equilibrium state. However, there is a sudden increase in the fluid pressure above the initial equilibrium osmotic pressure. These new findings are relevant and necessary for the understanding of cartilage mechanics, cartilage biosynthesis, electromechanical signal transduction by chondrocytes, and tissue engineering.

Animals↗

PubMed2002

Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation.

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young's modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young's modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young's modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.

Biomechanical Phenomena↗

PubMed2002

Electrical signals for chondrocytes in cartilage.

An important step toward understanding signal transduction mechanisms modulating cellular activities is the accurate predictions of the mechanical and electro-chemical environment of the cells in well-defined experimental configurations. Although electro-kinetic phenomena in cartilage are well known, few studies have focused on the electric field inside the tissue. In this paper, we present some of our recent calculations of the electric field inside a layer of cartilage (with and without cells) in an open circuit one-dimensional (1D) stress relaxation experiment. The electric field inside the tissue derives from the streaming effects (streaming potential) and the diffusion effect (diffusion potential). Our results show that, for realistic cartilage material parameters, due to deformation-induced inhomogeneity of the fixed charge density, the two potentials compete against each other. For softer tissue, the diffusion potential may dominate over the streaming potential and vice versa for stiffer tissue. These results demonstrate that for proper interpretation of the mechano-electrochemical signal transduction mechanisms, one must not ignore the diffusion potential.

Animals↗

PubMed2001

Release of hydrogen chloride from combustibles in municipal solid waste.

Study of the inorganic chlorides in municipal solid waste (MSW) shows that the main source of inorganic chlorides in MSW is food. The main organic source of HCl emission from MSW is plastic. But wood, textiles, and food also produce a large amount of HCl when they are combusted. Each combustible shows a different HCl releasing temperature range. At 973 K, there are 30-70% of the total chlorine left in the char of each combustibles in MSW.

Air Pollutants↗

PubMed2000

Intracerebroventricular injection of senktide-induced Fos expression in vasopressin-containing hypothalamic neurons in the rat.

Intracerebroventricular injection of senktide, a selective agonist for neurokinin B receptor (NK3), induced Fos expression in many neurons of the rat hypothalamus. Fos-positive neurons were predominantly present in the supraoptic and paraventricular hypothalamic nuclei, and some of them were seen in the lateral preoptic area, lateral hypothalamic area, arcuate nucleus, perifornical region, posterior hypothalamic area, circular nucleus, and along relatively large blood vessels (lateral hypothalamic perivascular nucleus) in the anterior hypothalamus. A double labeling study was performed to examine if vasopressin-containing neurons in the hypothalamus could be activated by the treatment. Neurons with both Fos-like immunoreactivity (-LI) and vasopressin-LI were found in the paraventricular nucleus, supraoptic nucleus, circular nucleus and lateral hypothalamic perivascular nucleus. In the supraoptic nucleus, about 87% of vasopressin-containing neurons exhibited Fos-LI, which corresponded to about 64% of Fos-positive neurons in the nucleus. In the paraventricular nucleus, about 80% of vasopressin-like immunoreactive neurons exhibited Fos-LI, which constituted about 51% of the total population of Fos-positive neurons in the region. The results suggest that NK3 receptor may be involved in the modulation of release of vasopressin from the hypothalamus in the rat.

Animals↗

PubMed2000

Vertebral trabecular bone microscopic tissue elastic modulus and hardness do not change in ovariectomized rats.

Ovariectomized rats have been used extensively and have received substantial acceptance as animal models for postmenopausal osteoporosis. However, little is known about the microscopic tissue properties of rat vertebral bone, especially during osteoporosis caused by estrogen depletion. This study applied a new nanoindentation technique to quantify the microscopic mechanical properties of vertebral trabecular bone tissue in ovariectomized rats. Seventeen-week-old Sprague-Dawley rats underwent an ovariectomy. After death at 37 weeks, the fraction of the trabecular bone area of the lumbar vertebrae (L4) was measured with scanning electron microscopy and the elastic modulus and hardness were determined with the nanoindentation technique. The bone area fraction was reduced significantly after the ovariectomy. However, the elastic modulus and hardness did not change significantly at the microscopic level. The results indicate that estrogen-dependent osteoporosis in rats manifests in a loss of bone mass whereas the elastic and hardness properties of the surviving bone tissue remain relatively unchanged.

Animals↗

PubMed1999

Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur.

The mechanical properties of bone tissue are determined by composition as well as structural, microstructural and nanostructural organization. The aim of this study was to quantify the elastic properties of bone at the lamellar level and compare these properties among osteonal, interstitial and trabecular microstructures from the diaphysis and the neck of the human femur. A nanoindentation technique with a custom irrigation system was used for simultaneously measuring force and displacement of a diamond tip pressed 500 nm into the moist bone tissue. An isotropic elastic modulus was calculated from the unloading curve with an assumed Poisson ratio of 0.3, while hardness was defined as the maximal force divided by the corresponding contact area. The elastic moduli ranged from 6.9 +/- 4.3 GPa in trabecular tissue from the femoral neck of a 74 yr old female up to 25.0 +/- 4.3 GPa in interstitial tissue from the diaphyseal cortex of a 69 yr old female. The mean elastic modulus was found to be significantly influenced by the type of lamella (p < 10(-6)) and by donor (p < 10(-6)). The interaction between the type of lamella and the donor was also highly significant (p < 10(-6)). Hardness followed a similar distribution as elastic modulus among types of lamellae and donor, but with lower statistical contrast. It is concluded that the nanostructure of bone tissue must differ substantially among lamellar types, anatomical sites and individuals and suggests that tissue heterogeneity is of potential importance in bone fragility and adaptation.

Aged↗

PubMed1998

Micromechanics of osteonal cortical bone fracture.

Microcracks have been associated with age-related bone tissue fragility and fractures. The objective of this study was to develop a simple osteonal cortical bone model and apply linear elastic fracture mechanics theory to understand the micromechanics of the fracture process in osteonal cortical bone and its dependence on material properties. The linear fracture mechanics of our composite model of cortical bone, consisting of an osteon and interstitial bone tissue, was characterized in terms of a stress intensity factor (SIF) near the tip of a microcrack. The interaction between a microcrack and an osteon was studied for different types of osteons and various spacing between the crack and the osteon. The results of the analysis indicate that the fracture mechanics of osteonal cortical bone is dominated by the modulus ratio between the osteon and interstitial bone tissue: A soft osteon promotes microcrack propagation toward the osteon (and cement line) while a stiff one repels the microcrack from the osteon (and cement line). These findings suggest that newly formed, low-stiffness osteons may toughen cortical bone tissue by promoting crack propagation toward osteons. A relatively accurate empirical formula also was obtained to provide an easy estimation of the influence of osteons on the stress intensity factor.

Biomechanical Phenomena↗

PubMed1998

Creep contributes to the fatigue behavior of bovine trabecular bone.

Repetitive, low-intensity loading from normal daily activities can generate fatigue damage in trabecular bone, a potential cause of spontaneous fractures of the hip and spine. Finite element models of trabecular bone (Guo et al., 1994) suggest that both creep and slow crack growth contribute to fatigue failure. In an effort to characterize these damage mechanisms experimentally, we conducted fatigue and creep tests on 85 waisted specimens of trabecular bone obtained from 76 bovine proximal tibiae. All applied stresses were normalized by the previously measured specimen modulus. Fatigue tests were conducted at room temperature; creep tests were conducted at 4, 15, 25, 37, 45, and 53 degrees C in a custom-designed apparatus. The fatigue behavior was characterized by decreasing modulus and increasing hysteresis prior to failure. The hysteresis loops progressively displaced along the strain axis, indicating that creep was also involved in the fatigue process. The creep behavior was characterized by the three classical stages of decreasing, constant, and increasing creep rates. Strong and highly significant power-law relationships were found between cycles-to-failure, time-to-failure, steady-state creep rate, and the applied loads. Creep analyses of the fatigue hysteresis loops also generated strong and highly significant power law relationships for time-to-failure and steady-state creep rate. Lastly, the products of creep rate and time-to-failure were constant for both the fatigue and creep tests and were equal to the measured failure strains, suggesting that creep plays a fundamental role in the fatigue behavior of trabecular bone. Additional analysis of the fatigue strain data suggests that creep and slow crack growth are not separate processes that dominate at high and low loads, respectively, but are present throughout all stages of fatigue.

Animals↗

PubMed1998

Mechanical properties of human trabecular bone lamellae quantified by nanoindentation.

Improved preventive and therapeutic strategies for skeletal diseases such as osteoporosis rely on a better understanding of the mechanical properties of trabecular bone and their influence on cell mediated adaptation processes. The mechanical properties of trabecular bone are determined by composition as well as structural (trabecular architecture), microstructural (trabecular packets) and nanostructural (lamellae) organization. Density is the major predictor of the mechanical properties of trabecular structures and has been extended to the concept of fabric to include architectural anisotropy and improve even further the power of prediction. Recent advances in QCT and MRI technologies allow for precise assessment of 3D trabecular architecture and the mechanical consequences of structural changes can be increasingly well quantified by the means of computational methods. While single trabeculae have been tested using various techniques with contrasting results, little is known about the intrinsic mechanical properties of trabecular bone lamellae on which these computational methods rely. For instance, water and mineral content have a significant effect on the elastic, viscous, yield and postyield properties of bone tissue. In addition, collagen fiber orientation affects the mechanics of single remodeling units. Variations in composition and organization determined by age, accumulated damage or disease may therefore reduce the mechanical integrity of trabecular bone and deserve more attention. The aim of this work was to utilize a nanoindentation technique to quantify elastic modulus and hardness of human trabecular bone lamellae.

Aged↗

PubMed1997

Mechanical stimulation of tissue repair in the hydraulic bone chamber.

A hydraulically activated bone chamber model was utilized to investigate cellular and microstructural mechanisms of mechanical adaptation during bone repair. Woven trabecular bone and fibrotic granulation tissue filled the initially empty chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses. Without mechanical stimulation, active bone remodeling to lamellar trabecular bone and reconstitution of marrow elements were observed between 8 and 24 weeks. In subsequent loading studies, the hydraulic mechanism was activated on one randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800 cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of three-dimensional microcomputed tomography images revealed an increase in trabecular plate thickness and connectivity associated with the loaded repair tissue microstructure relative to unloaded contralateral controls. These microstructural alterations corresponded to an over 600% increase in the apparent modulus of the loaded bone tissue. A significant increase in the percentage of trabecular surfaces lined by osteoblasts immunopositive for type I procollagen after a few days of loading provided further evidence for mechanical stimulation of bone matrix synthesis. The local principal tissue strains associated with these adaptive changes were estimated to range from approximately -2000 to +3000 mustrain using digital image-based finite element methods. This study demonstrates the sensitivity of bone tissue and cells to a controlled in vivo mechanical stimulus and identifies microstructural mechanisms of mechanical adaptation during bone repair. The hydraulic bone chamber is introduced as an efficient experimental model to study the effects of mechanical and biological factors on bone repair and regeneration.

Animals↗

PubMed1994

Mechanical behavior of damaged trabecular bone.

The mechanical behavior of damaged trabecular bone may play a role in the etiology of age-related spine fractures since damaged bone exists in and may weaken the elderly vertebral body. To describe some characteristics of damaged trabecular bone, we measured the changes in modulus and strength that occur when bovine trabecular bone is loaded in compression to various strains beyond its elastic range. Twenty-three reduced-section specimens, taken from 17 different bones, were loaded from 0-X-0-9% strain, where X was one of four strains: 1.0% (n = 7), 2.5% (n = 6), 4.0% (n = 5), or 5.5% (n = 5). We found that modulus was reduced for all applied strains, whereas strength was reduced only for strain levels > or = 2.5%; the percentage changes in modulus and strength were independent of Young's modulus but were highly dependent on the magnitude of the applied strains; modulus was always reduced more than strength; and simple statistical models, using knowledge of only the applied strains, predicted well the percentage reductions in modulus (r2 = 0.97) and strength (r2 = 0.74). The modulus reductions reported here are in qualitative agreement with those for cortical bone in tensile loading, supporting the concept that the damage behaviors of cortical and trabecular bone are similar for low strains (< or = 4.0%). In addition, because modulus was always reduced more than strength, damaged trabecular bone may be stress protected in vivo by redistribution of stresses to undamaged bone.

Algorithms↗

PubMed1994

Trabecular bone exhibits fully linear elastic behavior and yields at low strains.

Using a protocol designed to reduce experimental artifacts associated with the conventional compression test for trabecular bone, we performed in vitro mechanical testing on bovine tibial trabecular bone to obtain accurate descriptions of the elastic and yield behaviors. Reduced-section cylindrical specimens were preconditioned for eight tension-compression (+/- 0.5% strain) cycles and then loaded to failure either in tension (n = 15) or compression (n = 14). We found that the pre-yield behavior for every specimen was fully linear, indicating that the initial nonlinear 'toe' is an experimental artifact. Analysis of variance on the moduli indicated that there was no significant difference between the tensile and compressive moduli before preconditioning. However, preconditioning decreased the tensile and compressive moduli on average by 8.8% (p < 0.01) and 5.3% (p < 0.01), respectively, with the decrease in tensile modulus being larger (p < 0.01). These small but significant decreases in modulus suggest that initial yielding involves microstructural damage (as opposed to plastic slip) of individual trabeculae and also indicate that the tensile and/or the compressive yield strain of (bovine tibial) trabecular bone is less than 0.5%. The mean tensile strength was approximately 70% of the mean compressive strength, although this difference in strengths may have been affected by the preconditioning-induced damage. Taken together, these results suggest that there are more similarities between the elastic and yield behaviors of trabecular and cortical bone than had been assumed previously.

Analysis of Variance↗

PubMed1994

Finite element modeling of damage accumulation in trabecular bone under cyclic loading.

A two-dimensional finite element model of an idealized trabecular bone specimen was developed to study trabecular bone damage accumulation during cyclic compressive loading. The specimen was modeled as a two-dimensional honeycomb-like structure made up of an array of hexagonal cells. Each trabecula was modeled as a linearly elastic beam element with the same material properties as cortical bone. Initial microcracks were assumed to exist within the oblique trabeculae and to grow according to the Paris law. Forces and moments were computed in each trabecula and the microcracks were allowed to propagate until fracture occurred. Between cycles, fractured trabeculae were removed from the finite element mesh, and force and moment distributions were calculated for the next cycle. This iterative process was continued until the simulated trabecular bone specimen showed a 10% reduction in modulus. Creep failure was also studied using a single cell analysis, in which a closed-form solution was obtained after prescribing the creep properties of the trabeculae. The results of the crack propagation analysis showed that fractures of only a small number of individual trabeculae can cause a substantial reduction in the modulus of the trabecular bone specimen model. Statistical tests were performed to compare the slopes and intercepts of the S-N curves of our model predictions to those of experimentally derived S-N curves for bovine trabecular bone. There was no significant difference (p > 0.2 for both slope and intercept) between our model predictions and the experimentally derived S-N curves for the low-stress, high-cycle range. For the high-stress, low-cycle range, the crack propagation model overestimated the fatigue life for a given stress level (for slope, p < 0.001), while the creep analysis agreed well with the experimental data (for slope, p > 0.2). These findings suggest that the primary failure mechanism for low-stress, high-cycle fatigue of trabecular bone is crack growth and propagation, while the primary failure mechanism for high-stress, low-cycle fatigue is creep deformation and fracture. Furthermore, our results suggest that the modulus of trabecular bone at the specimen level may be highly sensitive to fractures of individual trabeculae.

Algorithms↗