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Biomedical subjects

W Y Gu

Publications and source records attributed to W Y Gu.

11 recordsLinked to original sources

Convection and diffusion in charged hydrated soft tissues: a mixture theory approach.

The extracellular matrix of cartilage is a charged porous fibrous material. Transport phenomena in such a medium are very complex. In this study, solute diffusive flux and convective flux in porous fibrous media were investigated using a continuum mixture theory approach. The intrinsic diffusion coefficient of solute in the mixture was defined and its relation to drag coefficients was presented. The effect of mechanical loading on solute diffusion in cartilage under unconfined compression with a frictionless boundary condition was analyzed numerically using the model developed. Both strain-dependent hydraulic permeability and diffusivity were considered. Analyses and results show that (1) In porous media, the convective velocity for each solute phase is different. (2) The solute convection in tissue is governed by the relative convective velocity (i.e., relative to solid velocity). (3) Under the assumption that all the frictional interactions among solutes are negligible, the relative convective velocity for alpha-solute phase is equal to the relative solvent velocity multiplied by its convective coefficient (H (alpha)) which is also known as the hindrance factor in the literature. The relationship between the convective coefficient and the relative diffusivity of solute is presented. (4) Solute concentration profile within the cartilage sample depends on the phase of dynamic compression.

Compressive Strength↗

Analysis of the dynamic permeation experiment with implication to cartilaginous tissue engineering.

In the present study, a I-D dynamic permeation of a monovalent electrolyte solution through a negatively charged-hydrated cartilaginous tissue is analyzed using the mechano-electrochemical theory developed by Lai et al. (1991) as the constitutive model for the tissue. The spatial distributions of stress, strain, fluid pressure, ion concentrations, electrical potential, ion and fluid fluxes within and across the tissue have been calculated. The dependencies of these mechanical, electrical and physicochemical responses on the tissue fixed charge density, with specified modulus, permeability, diffusion coefficients, and frequency and magnitude of pressure differential are determined. The results demonstrate that these mechanical, electrical and physicochemical fields within the tissue are intrinsically and nonlinearly coupled, and they all vary with time and depth within the tissue.

Animals↗

New insight into deformation-dependent hydraulic permeability of gels and cartilage, and dynamic behavior of agarose gels in confined compression.

Equilibrium, creep, and dynamic behaviors of agarose gels (2.0-14.8%) in confined compression were investigated in this study. The hydraulic permeabilities of gels were determined by curve-fitting creep data to the biphasic model (J. Biomech. Eng. 102 (1980) 73) and found to be similar in value to those published in the literature (AIChE J. 42 (1996) 1220). A new relationship between intrinsic permeability and volume fraction of water was found for agarose gel, capable of predicting deformation-dependent permeabilities of bovine articular cartilage and 2% agarose gel published in literature. This relationship is accurate for gels and cartilage over a wide range of permeabilities (four orders of magnitude variation). The dynamic stiffness of the gels increases with gel concentration and loading frequency (0.01-1.0Hz). The increase in dynamic stiffness with loading frequency is less pronounced for gels with higher concentrations. The results of this study provide a new insight into deformation-dependent permeability behavior of agarose gel and cartilage, and are important for understanding biological responses of cells to interstitial fluid flow in gel or in cartilage under dynamic mechanical loading.

Cartilage, Articular↗

Apparatus for measuring the swelling dependent electrical conductivity of charged hydrated soft tissues.

This paper describes a new apparatus and method for measuring swelling dependent electrical conductivity of charged hydrated soft tissues. The apparatus was calibrated using a conductivity standard. Swelling dependent specific conductivity of porcine annulus fibrosis (AF) samples was determined. The conductivity values for porcine AF were similar to those for human and bovine articular cartilage found in the literature. Results revealed a significant linear correlation between specific conductivity and water content for porcine AF tissues tested in phosphate buffered saline (PBS).

Animals↗

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗

The anisotropic hydraulic permeability of human lumbar anulus fibrosus. Influence of age, degeneration, direction, and water content.

STUDY DESIGN: Experimental investigation to determine the effect of intervertebral disc degeneration on the kinetic behavior of fluid in human anulus fibrosus. OBJECTIVES: To measure the hydraulic permeability coefficient of anulus fibrosus specimens in the axial, circumferential, and radial directions to determine the anisotropic permeability behavior of nondegenerate and degenerate human intervertebral discs over a range of ages. SUMMARY OF BACKGROUND DATA: Fluid, a major component of normal intervertebral discs, plays a significant role in their load-supporting mechanisms. Transport of fluid through the intervertebral disc is important for cell nutrition and disc viscoelastic and swelling behaviors. The hydraulic permeability coefficient is the most important material property governing the rate of fluid transport. However, little is known about the anisotropic behavior of this kinetic property and how it is influenced by disc degeneration. METHODS: Using a permeation testing apparatus developed recently, testing was performed on 306 axial, circumferential, and radial anulus fibrosus specimens from the posterolateral region of 30 human lumbar (L2-L3) discs. A new method, flow-controlled testing protocol, was developed to measure the hydraulic permeability coefficient. RESULTS: The hydraulic permeability coefficient of anulus fibrosus depended significantly on the disc degenerative grade (P = 0.0001) and flow direction (P = 0.0001). For the nondegenerate group (Grade I), the hydraulic permeability was significantly anisotropic (P < 0.05), with the greatest value in the radial direction (1.924 x 10(-15) m4/Ns) and the lowest value in the circumferential direction (1.147 x 10(-15) m4/Ns). This anisotropic kinetic (flow) behavior of anulus fibrosus varied with disc degeneration. For the Grade III specimen group, there was no significant difference in hydraulic permeability coefficient among the three major directions (P = 0.37). With disc degeneration, the hydraulic permeability coefficient was decreased in the radial direction and increased in the axial and circumferential directions. The variations of hydraulic permeability coefficient from nondegenerate discs (Grade I) to mildly degenerate discs (Grade II) in each direction were significant (P < 0.05). However, the changes in permeability from Grade II to Grade III groups were not significant (P > 0.05) except in the circumferential direction (3.8% increase; P < 0.05). CONCLUSIONS: The hydraulic permeability of human nondegenerate anulus fibrosus is direction-dependent (i.e., anisotropic), with the greatest permeability in the radial direction. With disc degeneration, the radial permeability of anulus fibrosus decreases, mainly because of decreased water content, and the axial and circumferential permeability coefficients increase, mainly because of structural change, leading to more isotropic permeability behavior for Grade III discs.

Age Factors↗

Streaming potential of human lumbar anulus fibrosus is anisotropic and affected by disc degeneration.

The streaming potential responses of non-degenerate and degenerate human anulus fibrosus were measured in a one-dimensional permeation configuration under static and dynamic loading conditions. The goal of this study was to investigate the influence of the changes in tissue structure and composition on the electrokinetic behavior of intervertebral disc tissues. It was found that the static streaming potential of the anulus fibrosus depended on the degenerative grade of the discs (p = 0.0001) and on the specimen orientation in which the fluid flows (p = 0.0001). For a statically applied pressure of 0.07 MPa, the ratio of streaming potential to applied pressure ranged from 5.3 to 6.9 mV/MPa and was largest for Grade I tissue with axial orientation and lowest for Grade III tissue with circumferential orientation. The dynamic streaming potential responses of anulus fibrosus were sensitive to the degeneration of the disc: the total harmonic distortion factor increased by 108%, from 3.92 +/- 0.66% (mean +/- SD) for Grade I specimens to 8.15 +/- 3.05% for Grades II and III specimens. The alteration of streaming potential reflects the changes in tissue composition and structure with degeneration. To our knowledge, this is the first reported data for the streaming potential of human intervertebral disc tissues. Knowledge of the streaming potential response of the intervertebral disc provides an understanding of potentially important signal transduction mechanisms in the disc and of the etiology of intervertebral disc degeneration.

Adolescent↗

On the conditional equivalence of chemical loading and mechanical loading on articular cartilage.

Osmotic pressure loading of articular cartilage has been customarily invoked to be equivalent to mechanical loading. In the literature, this equivalence is defined by the amount of water squeezed from the tissue, i.e. if the amount of water content lost by these two modes of loading are the same, it has been generally regarded that the two loadings are equivalent. This assumption has never been proven. Using the water content lost concept, in this paper, we derived the exact conditions under which an osmotic pressure loading of cartilage can be considered to be equivalent to a mechanical loading. However, the mechanical loading condition satisfying this equivalency criterion, i.e. an isotropic loading delivered via a porous permeable rigid platen uniformly applied all around the specimen, is not practically achievable. Moreover, even if this were achieved experimentally, the interstitial fluid pressure caused by the two loading conditions are not the same. This result has important ramifications for interpretation of experimental data from mechanical stimulations of cartilage explant studies.

Algorithms↗

A mixture theory for charged-hydrated soft tissues containing multi-electrolytes: passive transport and swelling behaviors.

A new mixture theory was developed to model the mechano-electrochemical behaviors of charged-hydrated soft tissues containing multi-electrolytes. The mixture is composed of n + 2 constituents (1 charged solid phase, 1 noncharged solvent phase, and n ion species). Results from this theory show that three types of force are involved in the transport of ions and solvent through such materials: (1) a mechanochemical force (including hydraulic and osmotic pressures); (2) an electrochemical force; and (3) an electrical force. Our results also show that three types of material coefficients are required to characterize the transport rates of these ions and solvent: (1) a hydraulic permeability; (2) mechano-electrochemical coupling coefficients; and (3) an ionic conductance matrix. Specifically, we derived the fundamental governing relationships between these forces and material coefficients to describe such mechano-electrochemical transduction effects as streaming potential, streaming current, diffusion (membrane) potential, electro-osmosis, and anomalous (negative) osmosis. As an example, we showed that the well-known formula for the resting cell membrane potential (Hodgkin and Huxley, 1952a, b) could be derived using our new n + 2 mixture model (a generalized triphasic theory). In general, the n + 2 mixture theory is consistent with and subsumes all previous theories pertaining to specific aspects of charged-hydrated tissues. In addition, our results provided the stress, strain, and fluid velocity fields within a tissue of finite thickness during a one-dimensional steady diffusion process. Numerical results were provided for the exchange of Na+ and Ca++ through the tissue. These numerical results support our hypothesis that tissue fixed charge density (CF) plays a significant role in modulating kinetics of ions and solvent transport through charged-hydrated soft tissues.

Biological Transport↗

A triphasic analysis of negative osmotic flows through charged hydrated soft tissues.

Osmotic flow and ion transport in a one-dimensional steady diffusion process through charged hydrated soft tissues such as articular cartilage were analysed using the triphasic theory (Lai et al., 1991, J. biomech. Engng 113, 245-258). It was found that solvent would flow from the high NaCl concentration side to the low concentration side (i.e. negative osmosis) when the fixed charge density within the tissue (or membrane) separating the two electrolyte (NaCl) solutions was lower than a critical value. The condition for negative osmosis was derived based on a linear version of the triphasic theory. Distributions of ion concentration and strain field within the tissue were calculated numerically. Quantitative results of osmotic flow rates (ordinary and negative osmosis), ion flux and electric potential across the tissue during this diffusion process suggest that the negative osmosis phenomenon is due to the friction between ions and water since they could flow through the tissues at different rates and different directions.

Biomechanical Phenomena↗

Transport of fluid and ions through a porous-permeable charged-hydrated tissue, and streaming potential data on normal bovine articular cartilage.

Using the triphasic mechano-electrochemical theory [Lai et al., J. biomech. Engng 113, 245-258 (1991)], we analyzed the transport of water and ions through a finite-thickness layer of charged, hydrated soft tissue (e.g. articular cartilage) in a one-dimensional steady permeation experiment. For this problem, we obtained numerically the concentrations of the ions, the strain field and the fluid and ion velocities inside when the specimen is subject to an applied mechanical pressure and/or osmotic pressure across the layer. The relationships giving the dependence of streaming potential and permeability on the negative fixed charge density (FCD) of the tissue were derived analytically for the linear case, and calculated for the nonlinear case. Among the results obtained were: (1) at a fluid pressure difference of 0.1 MPa across the specimen layer, there is a 10% flow-induced compaction at the downstream boundary; (2) the flow-induced compaction causes the FCD to increase and the neutral salt concentration to decrease in the downstream direction; (3) while both ions move downstream, relative to the solvent (water), the anions (Cl-) move with the flow whereas cations (Na+) move against the flow. The difference in ion velocities depends on the FCD, and this difference attained a maximum at a physiological FCD of around 0.2 meq ml-1; (4) the apparent permeability decreases nonlinearly with FCD, and the apparent stiffness of the tissue increases with FCD; and (5) the streaming potential is not a monotonic function of the FCD but rather it has a maximum value within the physiological range of FCD for articular cartilage. Finally, experimental data on streaming potential were obtained from bovine femoral cartilage. These data support the triphasic theoretical prediction of non-monotonicity of streaming potential as a function of the FCD.

Animals↗