[Show abstract][Hide abstract] ABSTRACT: The avascular intervertebral disc (IVD) receives nutrition via transport from surrounding vasculature; poor nutrition is believed to be a main cause of disc degeneration. In this study, we investigated the effects of mechanical deformation and anisotropy on the transport of two important nutrients-oxygen and glucose-in human annulus fibrosus (AF). The diffusivities of oxygen and glucose were measured under three levels of uniaxial confined compression-0, 10, and 20%-and in three directions-axial, circumferential, and radial. The glucose partition coefficient was also measured at three compression levels. Results for glucose and oxygen diffusivity in AF ranged from 4.46 × 10(-7) to 9.77 × 10(-6) cm(2)/s and were comparable to previous studies; the glucose partition coefficient ranged from 0.71 to 0.82 and was also similar to previous results. Transport properties were found to decrease with increasing deformation, likely caused by fluid exudation during tissue compression and reduction in pore size. Furthermore, diffusivity in the radial direction was lower than in the axial or circumferential directions, indicating that nutrient transport in human AF is anisotropic. This behavior is likely a consequence of the layered structure and unique collagen architecture of AF tissue. These findings are important for better understanding nutritional supply in IVD and related disc degeneration.
Annals of Biomedical Engineering 06/2012; 40(12). · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of tissue engineering is to use substitutes to repair and restore organ function. Bioreactors are an indispensable tool for monitoring and controlling the unique environment for engineered constructs to grow. However, in order to determine the biochemical properties of engineered constructs, samples need to be destroyed. In this study, we developed a novel technique to nondestructively online-characterize the water content and fixed charge density of cartilaginous tissues. A new technique was developed to determine the tissue mechano-electrochemical properties nondestructively. Bovine knee articular cartilage and lumbar annulus fibrosus were used in this study to demonstrate that this technique could be used on different types of tissue. The results show that our newly developed method is capable of precisely predicting the water volume fraction (less than 3% disparity) and fixed charge density (less than 16.7% disparity) within cartilaginous tissues. This novel technique will help to design a new generation of bioreactors which are able to actively determine the essential properties of the engineered constructs, as well as regulate the local environment to achieve the optimal conditions for cultivating constructs.
Journal of Biomechanical Engineering 09/2011; 133(9):094504. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intervertebral disc (IVD) is the largest avascular structure in the human body. As such, important nutrients, such as glucose and oxygen, that are necessary for cellular survival and functioning, must be transported into the disc via diffusion. As a result, steep concentration gradients develop across the tissue, dependent upon both cellular demand (i.e., metabolism) and transport. Both mechanical loading and tissue degeneration may alter nutrient distributions in the IVD. This may, in turn, affect IVD cell activity and viability.
[Show abstract][Hide abstract] ABSTRACT: The intervertebral disc (IVD) is avascular, receiving nutrition from surrounding vasculature. Theoretical modelling can supplement experimental results to understand nutrition to IVD more clearly. A new, 3D finite element model of the IVD was developed to investigate effects of endplate calcification and mechanical deformation on glucose distributions in IVD. The model included anatomical disc geometry, non-linear coupling of cellular metabolism with pH and oxygen concentration and strain-dependent properties of the extracellular matrix. Calcification was simulated by reducing endplate permeability (∼79%). Mechanical loading was applied based on in vivo disc deformation during the transition from supine to standing positions. Three static strain conditions were considered: supine, standing and weight-bearing standing. Minimum glucose concentrations decreased 45% with endplate calcification, whereas disc deformation led to a 4.8-63% decrease, depending on the endplate condition (i.e. normal vs. calcified). Furthermore, calcification more strongly affected glucose concentrations in the nucleus compared to the annulus fibrous region. This study provides important insight into nutrient distributions in IVD under mechanical deformation.
Computer Methods in Biomechanics and Biomedical Engineering 02/2011; 14(2):195-204. · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intervertebral disc is an avascular cartilaginous structure that plays an important role in supporting loads through the spine and providing flexibility to the spinal column. The triphasic theory [1,2] has been used successfully to describe many of the mechanical, chemical and electrical behaviors of cartilaginous tissues. As an example of applying the triphasic theory, Yao and Gu  conducted a finite element simulation of human intervertebral disc during compressive stress relaxation using commercial software (FEMLAB). Due to the limitation of the commercial software, in the simulation reported in , the computational grid (mesh) is fixed throughout the simulation and the mesh size was not optimized for the specific geometry of the disc.
[Show abstract][Hide abstract] ABSTRACT: Degeneration of the intervertebral disc (IVD) has been associated with low back pain, which is one of the major socio-economic problems in the United States. Since IVD is the largest avascular cartilaginous structure in the human body, poor nutrient supply has been suggested as a potential mechanism for IVD degeneration. Biosynthesis of extracellular matrix is an energy demanding process which is required to maintain tissue integrity . Cells consume glucose and oxygen to produce adenosine triphosphate (ATP), the main energy form in cells. Glycolysis, the primary metabolic pathway for production of ATP in IVD cells, is strongly regulated by local oxygen concentration and pH (which is governed by lactate concentration) . Therefore, energy metabolism may play an important role in the malnutrition pathway leading to IVD degeneration. The objective of this study was to investigate the effect of mechanical loading on cellular energy metabolism in whole disc and in agarose gels.
[Show abstract][Hide abstract] ABSTRACT: Although the exact cause is not clear, low back pain has been attributed to degeneration of the intervertebral disc (IVD) of the spine, which has been linked to poor nutritional supply to the disc. Because the IVD is the largest avascular structure in the human body, disc cells must rely on diffusional transport for delivery of important nutrients, such as oxygen and glucose, from the surrounding vasculature. Thus, understanding factors affecting nutritional supply to the cells is important in elucidating the etiology of disc degeneration and related back pain. While knowledge of how mechanical strain affects nutritional transport is important in understanding these phenomena, little can be found in the literature regarding strain-dependent diffusion of nutrients in human IVD.
[Show abstract][Hide abstract] ABSTRACT: Degeneration of the intervertebral disc (IVD) of the spine is a common condition which has been implicated as a factor leading to low back pain. Poor nutritional supply is believed to be a primary contributor to IVD degeneration. Because the disc is the largest avascular structure in the body, cells must rely on transport of important nutrients, such as glucose and oxygen, from the surrounding vasculature in order to maintain cell viability in the disc tissue. Due to difficulty in obtaining data in vivo, theoretical modeling is a useful tool to supplement experimental results and predict in vivo conditions.
[Show abstract][Hide abstract] ABSTRACT: A new method for measuring the fixed charge density (FCD) in intervertebral disc (IVD) tissues employing a two-point electrical conductivity approach was developed. In this technique, the tissue is first confined and equilibrated in a potassium chloride (KCl) solution, and the tissue conductivity is then measured. This is then repeated with a second concentration of KCl solution. The FCD can be determined from the conductivity measurements. Using this method, the FCD values of bovine annulus fibrosus (AF) and nucleus pulposus (NP) tissues were determined to be 0.060 +/- 0.027 mEq/g wet tissue and 0.19 +/- 0.039 mEq/g wet tissue, respectively. The FCD of AF was significantly lower than that of NP tissue, similar to results in the literature for human IVD tissues. In order to verify the accuracy of the new method, the glycosaminoglycan (GAG) contents of the tissues were measured and used to estimate the tissue FCD. A strong correlation (R (2) = 0.84-0.87) was found to exist between FCD values measured and those estimated from GAG contents, indicating that the conductivity approach is a reliable technique for measuring the FCD of IVD tissues.
Annals of Biomedical Engineering 09/2009; 37(12):2566-73. · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Poor nutritional supply has been a major concern for the health of intervertebral disc (IVD) since the IVD is the largest avascular tissue in the human body. The transport of vital nutrients to cells relies on diffusion and convection through the extracellular matrix (ECM) in the IVD. Transport and metabolism of nutrients (e.g., oxygen and glucose) within the IVD depend on many factors, including the material properties of ECM (e.g., permeability, elastic modulus, and solute diffusivity), cellular metabolic rates, nutritional supply at the edge of the IVD, and mechanical loading [1–6]. Tissue degeneration alters the material properties of the IVD, such as an increase in elastic modulus and a decrease in water content, fixed charge density, permeability and solute diffusivity . However, the effect of tissue degeneration on transport and metabolism of nutrients in the IVD under mechanical loading has not been elucidated. The objective of this study was to numerically investigate the distribution of glucose, oxygen and lactate in the degenerated IVD under static unconfined compression using the mechano-electrochemical mixture theory .
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to develop and demonstrate the utility of a novel method of evaluating intracellular levels of extracellular matrix (ECM) components in intervertebral disc (IVD) cells using flow cytometry. By using this method, this study discriminated between cell populations in porcine IVD and examined the response of IVD cells to monolayer cultures, a traditional method of cell expansion, by measuring phenotypic attributes of ECM component production. It was found that monolayer cultures affected collagen production of IVD cells while there were differences in collagen type II production between the cells isolated from the annulus fibrosus (AF) and nucleus pulposus (NP) regions of IVD. Size distributions of fresh and cultured cells were also presented while the relationships between cell size and intracellular collagen level revealed heterogeneous cell populations in AF and NP regions. Furthermore, this study showed that the intracellular collagen signals of IVD cells were significantly enhanced by the treatments of Brefeldin-A and ascorbic acid. This suggests that Brefeldin-A and ascorbic acid could be used to increase the sensitivity of flow cytometric analysis on intracellular collagen levels by maximizing collagen accumulation inside cells. Since a unique feature of the flow cytometric screening tool is the ability to discriminate between various cell populations in a single sample, the flow cytometric method developed in this study may have the potential to identify specific collagen-producing cell populations from tissues or cell cultures.
Cellular and Molecular Bioengineering 06/2009; 2(2):264-273. · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Temperature effects on the viscoelastic properties of the human supraspinatus tendon were investigated using static stress-relaxation experiments and the quasi-linear viscoelastic (QLV) theory. Twelve supraspinatus tendons were randomly assigned to one of two test groups for tensile testing using the following sequence of temperatures: (1) 37, 27, and 17 degrees C (Group I, n=6), or (2) 42, 32, and 22 degrees C (Group II, n=6). QLV parameter C was found to increase at elevated temperatures, suggesting greater viscous mechanical behavior at higher temperatures. Elastic parameters A and B showed no significant difference among the six temperatures studied, implying that the viscoelastic stress response of the supraspinatus tendon is not sensitive to temperature over shorter testing durations. Using regression analysis, an exponential relationship between parameter C and test temperature was implemented into QLV theory to model temperature-dependent viscoelastic behavior. This modified approach facilitates the theoretical determination of the viscoelastic behavior of tendons at arbitrary temperatures.
Journal of biomechanics 02/2009; 42(4):546-9. · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nutrition supply is a concern for the health of avascular cartilaginous tissues such as intervertebral disc (IVD). Maintaining tissue integrity relies on cellular biosynthesis of extracellular matrix, which is an energy demanding process . In the IVD, energy is mainly generated through glycolysis (i.e., glucose consumption). Metabolism of nutrients (e.g., oxygen and glucose) within the IVD depends on local concentrations of nutrients, and coupling effects between nutrient level and metabolic rate [2,3]. Our previous theoretical study had developed a new theoretical formulation by incorporating the metabolic rates of solutes into the mechano-electrochemical mixture theory [4,5]. By using this new theoretical model, the distribution of oxygen and lactate can be predicted within the IVD under static and dynamics compressions . However, the effect of compression on glucose consumption in the IVD has not been studied. The objective of this study was to examine the effects of compression on glucose consumption in the IVD under static and dynamic unconfined compression numerically.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to examine the effects of mechanical compression on metabolism and distributions of oxygen and lactate in the intervertebral disc (IVD) using a new formulation of the triphasic theory. In this study, the cellular metabolic rates of oxygen and lactate were incorporated into the newly developed formulation of the mechano-electrochemical mixture model [Huang, C.-Y., Gu, W.Y., 2007. Effect of tension-compression nonlinearity on solute transport in charged hydrated fibrosus tissues under dynamic unconfined compression. Journal of Biomechanical Engineering 129, 423-429]. The model was used to numerically analyze metabolism and transport of oxygen and lactate in the IVD under static or dynamic compression. The theoretical analyses demonstrated that compressive loading could affect transport and metabolism of nutrients. Dynamic compression increased oxygen concentration, reduced lactate accumulation, and promoted oxygen consumption and lactate production (i.e., energy conversion) within the IVD. Such effects of dynamic loading were dependent on strain level and loading frequency, and more pronounced in the IVD with less permeable endplate. In contrast, static compression exhibited inverse effects on transport and metabolism of oxygen and lactate. The theoretical predictions in this study are in good agreement with those in the literature. This study established a new theoretical model for analyzing cellular metabolism of nutrients in hydrated, fibrous soft tissues under mechanical compression.
Journal of Biomechanics 02/2008; 41(6):1184-96. · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cartilage is a charged hydrated fibrous tissue exhibiting a high degree of tension-compression nonlinearity (i.e., tissue anisotropy). The effect of tension-compression nonlinearity on solute transport has not been investigated in cartilaginous tissue under dynamic loading conditions. In this study, a new model was developed based on the mechano-electrochemical mixture model [Yao and Gu, 2007, J. Biomech. Model Mechanobiol., 6, pp. 63-72, Lai et al., 1991, J. Biomech. Eng., 113, pp. 245-258], and conewise linear elasticity model [Soltz and Ateshian, 2000, J. Biomech. Eng., 122, pp. 576-586; Curnier et al., 1995, J. Elasticity, 37, pp. 1-38]. The solute desorption in cartilage under unconfined dynamic compression was investigated numerically using this new model. Analyses and results demonstrated that a high degree of tissue tension-compression nonlinearity could enhance the transport of large solutes considerably in the cartilage sample under dynamic unconfined compression, whereas it had little effect on the transport of small solutes (at 5% dynamic strain level). The loading-induced convection is an important mechanism for enhancing the transport of large solutes in the cartilage sample with tension-compression nonlinearity. The dynamic compression also promoted diffusion of large solutes in both tissues with and without tension-compression nonlinearity. These findings provide a new insight into the mechanisms of solute transport in hydrated, fibrous soft tissues.
Journal of Biomechanical Engineering 07/2007; 129(3):423-9. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since the intervertebral disc (IVD) is the largest avascular cartilaginous structure in the human body, poor nutrient supply has been suggested as a potential mechanism for disc degeneration. The previous theoretical studies have shown that the distributions of nutrients and metabolites (e.g., oxygen, glucose, and lactate) within the IVD depended on tissue diffusivities, nutrient supply, cellular metabolic rates, and coupling effects between nutrient and metabolite [1,2]. Our recent theoretical study suggested that dynamic compression can promote transport of neutral solute in the anisotropic cartilaginous tissue by enhancing both diffusive and convective solute fluxes . However, the effect of compression on distributions of nutrients and metabolites in the IVD has not been studied. The objective of this study was to examine the effects of compression on distributions of oxygen and lactate in the IVD under static and dynamic unconfined compression using a new formulation of the triphasic theory.
[Show abstract][Hide abstract] ABSTRACT: Disorders of the rotator cuff, particularly tears of the rotator cuff tendons, cause significant shoulder disability. Among numerous factors thought to be responsible for the initiation and progression of supraspinatus tears are those related to the tendon's biomechanical properties. We hypothesized that in supraspinatus tendons subjected to tensile loading a strain gradient (difference) exists between the articular and bursal tendon surfaces, that regional strain differences exist on each of these two tendon surfaces, and that tendon surface strains vary with glenohumeral abduction. To test these hypotheses, the intrinsic inhomogeneous deformational characteristics of the articular and bursal surfaces of eight intact human cadaveric supraspinatus tendons were studied at three glenohumeral abduction angles using a novel multiple strain measuring system which simultaneously recorded surface marker displacements on two opposing soft tissue surfaces. Under applied tensile loads, the articular surface exhibited greater strain at 22 degrees (7.4+/-2.6% vs. 1.3+/-0.7%, p=0.0002) and 63 degrees (6.4+/-1.6% vs. 2.7+/-1.2%, p=0.0001) whereas the bursal surface exhibited greater strain at 90 degrees (7.6+/-2.8% vs. 4.9+/-0.4%, p=0.013). At all abduction angles, insertion strains were higher than those of the mid-tendon and tendon-muscle junction regions. The existence of inhomogeneous surface strains in the intact supraspinatus tendon demonstrates that intratendinous shear occurs within the tendon. The higher strain on the articular side of the tendon, especially at the insertion region, suggests a propensity for tears to initiate in the articular tendinous zone.
Journal of Orthopaedic Research 08/2005; 23(4):924-30. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The tensile and compressive properties of human glenohumeral cartilage were determined by testing 120 rectangular strips in uniaxial tension and 70 cylindrical plugs in confined compression, obtained from five human glenohumeral joints. Specimens were harvested from five regions across the articular surface of the humeral head and two regions on the glenoid. Tensile strips were obtained along two orientations, parallel and perpendicular to the split-line directions. Two serial slices through the thickness, corresponding to the superficial and middle zones of the cartilage layers, were prepared from each tensile strip and each compressive plug. The equilibrium tensile modulus and compressive aggregate modulus of cartilage were determined from the uniaxial tensile and confined compression tests, respectively. Significant differences in the tensile moduli were found with depth and orientation relative to the local split-line direction. Articular cartilage of the humeral head was significantly stiffer in tension than that of the glenoid. There were significant differences in the aggregate compressive moduli of articular cartilage between superficial and middle zones in the humeral head. Furthermore, tensile and compressive stress-strain responses exhibited nonlinearity under finite strain, while the tensile modulus differed by up to two orders of magnitude from the compressive aggregate modulus at 0% strain, demonstrating a high degree of tension-compression nonlinearity. The complexity of the mechanical properties of human glenohumeral cartilage was exposed in this study, showing anisotropy, inhomogeneity, and tension-compression nonlinearity within the same joint. The observed differences in the tensile properties of human glenohumeral cartilage suggest that the glenoid may be more susceptible to cartilage degeneration than the humeral head.
Journal of Biomechanics 05/2005; 38(4):799-809. · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A biphasic-CLE-QLV model proposed in our recent study [2001, J. Biomech. Eng., 123, pp. 410-417] extended the biphasic theory of Mow et al. [1980, J. Biomech. Eng., 102, pp. 73-84] to include both tension-compression nonlinearity and intrinsic viscoelasticity of the cartilage solid matrix by incorporating it with the conewise linear elasticity (CLE) model [1995, J. Elasticity, 37, pp. 1-38] and the quasi-linear viscoelasticity (QLV) model [Biomechanics: Its foundations and objectives, Prentice Hall, Englewood Cliffs, 1972]. This model demonstrates that a simultaneous prediction of compression and tension experiments of articular cartilage, under stress-relaxation and dynamic loading, can be achieved when properly taking into account both flow-dependent and flow-independent viscoelastic effects, as well as tension-compression nonlinearity. The objective of this study is to directly test this biphasic-CLE-QLV model against experimental data from unconfined compression stress-relaxation tests at slow and fast strain rates as well as dynamic loading. Twelve full-thickness cartilage cylindrical plugs were harvested from six bovine glenohumeral joints and multiple confined and unconfined compression stress-relaxation tests were performed on each specimen. The material properties of specimens were determined by curve-fitting the experimental results from the confined and unconfined compression stress relaxation tests. The findings of this study demonstrate that the biphasic-CLE-QLV model is able to describe the strain-rate-dependent mechanical behaviors of articular cartilage in unconfined compression as attested by good agreements between experimental and theoretical curvefits (r2 = 0.966 +/- 0.032 for testing at slow strain rate; r2 = 0.998 +/- 0.002 for testing at fast strain rate) and predictions of the dynamic response (r2 = 0.91 +/- 0.06). This experimental study also provides supporting evidence for the hypothesis that both tension-compression nonlinearity and intrinsic viscoelasticity of the solid matrix of cartilage are necessary for modeling the transient and equilibrium responses of this tissue in tension and compression. Furthermore, the biphasic-CLE-QLV model can produce better predictions of the dynamic modulus of cartilage in unconfined dynamic compression than the biphasic-CLE and biphasic poroviscoelastic models, indicating that intrinsic viscoelasticity and tension-compression nonlinearity of articular cartilage may play important roles in the load-support mechanism of cartilage under physiologic loading.
Journal of Biomechanical Engineering 03/2003; 125(1):84-93. · 1.75 Impact Factor