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James C Iatridis

Publications and source records attributed to James C Iatridis.

18 recordsLinked to original sources
PubMed2006

A numerical study to determine pericellular matrix modulus and evaluate its effects on the micromechanical environment of chondrocytes.

Chondrocyte biosynthesis is highly sensitive to mechanical strain. A thin pericellular matrix (PCM) surrounds the cell and plays an important role in mechanotransduction. PCM material properties are difficult to measure directly because of its size and connectivity to both cell and extracellular matrix (ECM). The purpose of this study was to develop a method of calculating linear elastic properties of the PCM using an inverse finite element approach with experimental properties of cell and chondron taken from the literature. Finite element models were constructed of both the equivalent chondron case and the chondrocyte-PCM structure, and a Fibonacci search obtained PCM moduli that matched the ECM strain field between the two cases. The most important result was that ECM strain adjacent to a chondron inclusion was sensitive to the chondron properties and may be used to calculate PCM mechanical properties, consistent with our strain field hypotheses. PCM moduli obtained through this method range from 43 to 240 kPa, were significantly higher than previously published but resulted in only a 0.5-21% decrease in relative effective cell strain. Similarities between effective strain ratios led to the conclusion that matching experimental techniques used to measure cell and PCM properties was more important than absolute values of the properties.

Animals↗
PubMed2006

Correlating material properties with tissue composition in enzymatically digested bovine annulus fibrosus and nucleus pulposus tissue.

Aging and degeneration of the intervertebral disk are accompanied by decreases in water and proteoglycan contents, and structural alterations. The aim of this study was to determine the impact of compositional changes on the material properties of intervertebral disk tissues. Confined compression stress-relaxation experiments were applied to bovine caudal annulus fibrosus and nucleus pulposus tissue specimens that were separated into three experimental groups: in situ, free-swelling control (PBS), and digestion (chondroitinase-ABC). Measurements of glycosaminoglycan (GAG) and water content, as well as nonlinear finite deformation biphasic theory and multiple linear regression analyses were performed. The compressive modulus HA0 and permeability k0 of in situ specimens were 0.37+/-0.06 MPa and 0.49+/-0.08x10(-15) m4 N-1 s-1 for nucleus, and 0.74+/-0.13 MPa and 0.42+/-0.05x10(-15) m4 N-1 s-1 for annulus, respectively. There was a larger effect of swelling and digestion on the material properties and biochemical composition of nucleus pulposus than for annulus fibrosus. Alterations in proteoglycan and water content affected the compressive modulus and permeability, although the permeability was somewhat more strongly affected by water content than by proteoglycan content. Correlation coefficients r<or=0.75 for the multiple regression indicated water and GAG content can moderately predict material properties, however other compositional and structural factors must be considered.

Animals↗
PubMed2006

In vitro organ culture of the bovine intervertebral disc: effects of vertebral endplate and potential for mechanobiology studies.

STUDY DESIGN: Whole bovine coccygeal discs were cultured under static load, with or without vertebral endplates (VEPs), and assessed for cell viability, biochemical stability, biosynthetic activity, and biosynthetic responsiveness to changes in mechanical load. OBJECTIVES: To assess the effects of VEPs on biochemical and cellular stability of disc cells during in vitro culture of large disc explants. To determine whether cultured discs could respond to mechanical perturbation. SUMMARY OF BACKGROUND DATA: Previous methods for culturing the intervertebral disc have focused on rabbit and rat discs, but the small size of these discs limits the relevance of these culture systems to the human condition. Bovine coccygeal discs have similar dimensions to the human lumbar disc (i.e., similar size and nominal stresses), but long-term culture of these discs has not been reported. METHODS: Bovine coccygeal discs were harvested with or without VEPs, cultured under static load (5 kg, approximately 0.25 MPa, in situ swelling pressure) for up to 1 week, and evaluated for changes in hydration, glycosaminoglycan content, cell viability, and biosynthetic activity. Additionally, the biochemical and biosynthetic response of discs cultured without VEP to increasing the load to a 20-kg (approximately 1 MPa, the estimated stress in human lumbar disc during heavy lifting) static load for 6 hours was assessed. RESULTS: During the first 24 hours, culturing discs with endplates was moderately better with regards to maintaining in situ anulus hydration and nucleus glycosaminoglycan levels. The endplates, however, obstructed media flow to the disc, resulting in a marked decrease in cell viability after 1 week of culture. Nucleus pulposus cell viability was maintained in discs cultured without endplates, but there was a significant drop in biosynthetic activity within 2 days of culture. Despite this drop, the disc cells in the discs without VEP remained biosynthetically responsive to changes in mechanical loading. CONCLUSIONS: It is possible to maintain cell viability and the biosynthetic responsiveness of large discs for up to 1 week in vitro when the discs are cultured under static load and without VEP.

Animals↗
PubMed2006

Role of endplates in contributing to compression behaviors of motion segments and intervertebral discs.

The purpose of this study was to gain an improved understanding of the mechanical behavior of the intervertebral disc in the presence and absence of the vertebral endplates. Mechanical behaviors of rat caudal motion segments, vertebrae and isolated disc explants under two different permeability conditions were investigated and viscoelastic behaviors were evaluated using a stretched-exponential function to describe creep and recovery behaviors. The results demonstrated that both vertebrae and discs underwent significant deformations in the motion segment even under relatively low-loading conditions. Secondly, disruption of the collagenous network had minimal impact on equilibrium deformations of disc explants as compared to disc deformations occurring in the motion segments provided that vertebral deformations were accounted for; however, differences in endplate permeability conditions had a significant effect on viscoelastic behaviors. Creep occurred more quickly than recovery for motion segment and explant specimens. In addition, disc explants and motion segments both exhibited non-recoverable deformations under axial compression under low- and high-loading conditions. Results have important implications for interpreting the role of vertebral endplates in contributing to disc mechanical behaviors and direct application to mechanobiology studies involving external loading to rodent tail intervertebral discs.

Animals↗
PubMed2006

Effects of mechanical loading on intervertebral disc metabolism in vivo.

The overall goal of this work is to define more clearly which mechanical loading conditions are associated with accelerated disc degeneration. This article briefly reviews recent studies describing the effects of mechanical loading on the metabolism of intervertebral disc cells and defines hypothetical models that provide a framework for quantitative relationships between mechanical loading and disc-cell metabolism. Disc cells respond to mechanical loading in a manner that depends on loading magnitude, frequency, and duration. On the basis of the current data, four models have been proposed to describe the effects of continuous loading on cellular metabolism: (1) on/off response, in which messenger ribonucleic acid (mRNA) transcription remains altered for the duration of loading; (2) maintenance, characterized by an initial change in mRNA levels with return to baseline levels; (3) adaptation, in which mRNA transcription is altered and remains at a new steady state; and (4) no response. In addition, five hypothetical mechanisms that describe the long-term consequences of these metabolic changes on disc-remodeling are presented. The transient nature of gene expression along with enzyme activation/inhibition is associated with changes at the protein level. The hypothetical models presented provide a framework for obtaining quantitative relationships between mechanical loading, gene expression, and changes at the compositional level; however, additional factors, such as regulatory mechanisms, must also be considered when describing disc-remodeling. A more quantitative relationship between mechanical loading effects and the metabolic response of the disc will contribute to injury prevention, facilitate more effective rehabilitation treatments, and help realize the potential of biologic and tissue engineering approaches toward disc repair.

Animals↗
PubMed2005

The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc.

The goal of this study was to determine the time-dependent response of the intervertebral disc cells to in vivo dynamic compression. Forty-seven skeletally mature Wistar rats (>12 months old) were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Using a load magnitude (1 MPa) and frequency (1.0 Hz) that were previously shown to significantly alter mRNA levels in the disc, the effects of 0.5 and 4 h of loading were investigated and compared to a sham group and our previous 2 h results. Annulus and nucleus tissue of loaded (c8-9) and internal control discs (c6-7 and c10-11) were separately analyzed by real-time RT-PCR for levels of mRNA coding for various anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) proteins. In the annulus, mRNA levels increased for Collagen types I & II, and MMP 3 & 13 with increasing load duration. In contrast, the nucleus had the largest increases in aggrecan, ADAMTs-4, MMP-3 and MMP-13 after 2 h of loading, with aggrecan and MMP-13 mRNA levels returning to control values after 4 h of loading. Taken in context with our previous studies, we conclude that intervertebral disc cells from the nucleus and annulus have distinct responses to dynamic mechanical compression in vivo with sensitivity to compression magnitude, frequency and duration.

ADAM Proteins↗
PubMed2005

Mechanical damage to the intervertebral disc annulus fibrosus subjected to tensile loading.

Damage of the annulus fibrosus is implicated in common spinal pathologies. The objective of this study was to obtain a quantitative relationship between both the number of cycles and the magnitude of tensile strain resulting in damage to the annulus fibrosus. Four rectangular tensile specimens oriented in the circumferential direction were harvested from the outer annulus of 8 bovine caudal discs (n = 32) and subjected to one of four tensile testing protocols: (i) ultimate tensile strain (UTS) test; (ii) baseline cyclic test with 4 series of 400 cycles of baseline cyclic loading (peak strain = 20% UTS); (iii & iv) acute and fatigue damage cyclic tests consisting of 4 x 400 cycles of baseline cyclic loading with intermittent loading to 1 and 100 cycles, respectively, with peak tensile strain of 40%, 60%, and 80% UTS. Normalized peak stress for all mechanically loaded specimens was reduced from 0.89 to 0.11 of the baseline control levels, and depended on the magnitude of damaging strain and number of cycles at that damaging strain. Baseline, acute, and fatigue protocols resulted in permanent deformation of 3.5%, 6.7% and 9.6% elongation, respectively. Damage to the laminate structure of the annulus in the absence of biochemical activity in this study was assessed using histology, transmission electron microscopy, and biochemical measurements and was most likely a result of separation of annulus layers (i.e., delamination). Permanent elongation and stress reduction in the annulus may manifest in the motion segment as sub-catastrophic damage including increased neutral zone, disc bulging, and loss of nucleus pulposus pressure. The preparation of rectangular tensile strip specimens required cutting of collagen fibers and may influence absolute values of results, however, it is not expected to affect the comparisons between loading groups or dose-response reported.

Animals↗
PubMed2004

Confined compression experiments on bovine nucleus pulposus and annulus fibrosus: sensitivity of the experiment in the determination of compressive modulus and hydraulic permeability.

The biphasic material properties for nucleus pulposus tissue in confined compression have not been reported previously, and are required for a better understanding of intervertebral disc function and to provide material properties for use in finite-element models. The aims of this study were to determine linear and non-linear material properties for nucleus pulposus and annulus fibrosus tissues in confined compression, to define the influence of swelling conditions on these properties, and to determine the changes in the compressive modulus and hydraulic permeability induced by the repetition of the stress-relaxation experiment after a return to swelling pressure equilibrium. Specimens from caudal bovine nucleus and annulus were tested in confined compression stress-relaxation experiments and analyzed to quantify the compressive modulus and hydraulic permeability using linear and non-linear biphasic models. Our results suggested the use of confined swelling pre-test condition and non-linear biphasic model, which provided the material parameters with lowest relative variance and water content most representative of physiological conditions. Smaller compressive modulus and higher hydraulic permeability were obtained for the nucleus (H(A0)=0.31+/-0.04 MPa, k(0)=0.67+/-0.09 x 10(-15)m(4)/Ns) than for the annulus (H(A0)=0.74+/-0.13 MPa, k(0)=0.23+/-0.19 x 10(-15)m(4)/Ns), with relatively weak non-linearities. Strains up to 20% resulted in material properties that were significantly altered upon retesting. These altered material properties are an effort to quantify non-recoverable damage that occurs in disc tissue and suggest that in vivo exposure of disc tissues to low strain-rate and high-deformation loading conditions which outpace biological repair may result in altered mechanical behaviors.

Animals↗
PubMed2004

Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization.

STUDY DESIGN: A review of the literature on macromechanical factors that accelerate disc degeneration with particular focus on distinguishing the roles of immobilization and overloading. OBJECTIVE: This review examines evidence from the literature in the areas of biomechanics, epidemiology, animal models, and intervertebral disc physiology. The purpose is to examine: 1) what are the degeneration-related alterations in structural, material, and failure properties in the disc; and 2) evidence in the literature for causal relationships between mechanical loading and alterations in those structural and material properties that constitute disc degeneration. SUMMARY OF BACKGROUND DATA: It is widely assumed that the mechanical environment of the intervertebral disc at least in part determines its rate of degeneration. However, there are two plausible and contrasting theories as to the mechanical conditions that promote degeneration: 1) mechanical overload; and 2) reduced motion and loading. RESULTS: There are a greater number of studies addressing the "wear and tear" theory than the immobilization theory. Evidence is accumulating to support the notion that there is a "safe window" of tissue mechanical conditions in which the discs remain healthy. CONCLUSIONS: It is concluded that probably any abnormal loading conditions (including overload and immobilization) can produce tissue trauma and/or adaptive changes that may result in disc degeneration. Adverse mechanical conditions can be due to external forces, or may result from impaired neuromuscular control of the paraspinal and abdominal muscles. Future studies will need to evaluate additional unquantified interactions between biomechanics and factors such as genetics and behavioral responses to pain and disability.

Animals↗
PubMed2004

Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo.

Cytoskeleton-dependent changes in cell shape are well-established factors regulating a wide range of cellular functions including signal transduction, gene expression, and matrix adhesion. Although the importance of mechanical forces on cell shape and function is well established in cultured cells, very little is known about these effects in whole tissues or in vivo. In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology. Tissue stretch ex vivo (average 25% tissue elongation from 10 min to 2 h) caused a significant time-dependent increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P < 0.01). At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. Fibroblasts in stretched tissue had larger, "sheetlike" cell bodies with shorter processes. In contrast, fibroblasts in unstretched tissue had a "dendritic" morphology with smaller, more globular cell bodies and longer processes. Tissue stretch in vivo for 30 min had effects that paralleled those ex vivo. Stretch-induced cell body expansion ex vivo was inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent responses of fibroblasts to changes in tissue length demonstrated in this study have important implications for our understanding of normal movement and posture, as well as therapies using mechanical stimulation of connective tissue including physical therapy, massage, and acupuncture.

Actins↗
PubMed2004

Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression.

The goal of this study was to characterize the anabolic and catabolic mRNA response of the disc to dynamic loading to determine if variations in the magnitude and/or frequency of loading could elicit different cellular responses. Sixty-eight Wistar rats were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Seventy-two hours after surgery, animals were anesthetized and loaded at either 1 or 0.2 MPa at a frequency of 1, 0.2 or 0.01 Hz for 2 h (6 groups). The surgical control (Sham) animals underwent anesthesia with no loading. Loaded (c8-9) and internal-control discs (c6-7 and c10-11) were dissected and annulus and nucleus tissue were separately analyzed by real-time RT-PCR for levels of anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) mRNA. In the nucleus, a frequency-dependent response was seen at 1 MPa with anabolic genes stimulated at 0.01 Hz and catabolic genes at 1 Hz. In the annulus all frequencies resulted in significant up-regulation of catabolic mRNA at 1 MPa loading. In general loading at 0.2 MPa or 0.2 Hz had little effect on gene expression. The results suggest that gene expression of the annulus appears to be more dependent on the magnitude of applied stress, while the nucleus is both magnitude- and frequency-dependent.

ADAM Proteins↗
PubMed2003

Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo.

STUDY DESIGN: An in vivo analysis of the intervertebral disc's cellular response to dynamic compression and immobilization was performed using a rat-tail model. OBJECTIVE: To assess the effects of immobilization and short-term dynamic compression on intervertebral disc cell expression of anabolic and catabolic genes. SUMMARY OF BACKGROUND DATA: Static compressive loads applied in vivo alter the composition of the disc matrix and cell viability in a dose-dependent manner. The effects of in vivo dynamic compression, which is a more physiologic load, and reported risk factor for low back pain have not been investigated. METHODS: An Ilizarov-type device was implanted on the rat tail and used to determine the effects from 72 hours of immobilization (n = 6), 2 hours of dynamic compression (1 MPa/0.2 Hz) (n = 8), and the coupled effect of immobilization followed by compression (n = 8). Real-time reverse transcription-polymerase chain reaction was used to measure changes in anabolic and catabolic gene levels relative to both internal control subjects and a sham-operated group (n = 7). RESULTS: Immobilization and dynamic compression affect anabolic and catabolic genes, with an overall downregulation of types 1 and 2 collagen and upregulation of aggrecanase, collagenase, and stromelysin in the anulus. The effects of immobilization and compression appear to be additive for collagen types 1 and 2 in the anulus, but not in the nucleus, and not for catabolic genes. CONCLUSIONS: Short-duration dynamic compression and immobilization alter gene expression in the rat disc. In studying the response of the disc to loading, it is necessary to look at both anabolic and catabolic pathways, and to consider strain history.

Aggrecans↗
PubMed2003

Influence of fixed charge density magnitude and distribution on the intervertebral disc: applications of a poroelastic and chemical electric (PEACE) model.

A 3-dimensional formulation for a poroelastic and chemical electric (PEACE) model is presented and applied to an intervertebral disc slice in a 1-dimensional validation problem and a 2-dimensional plane stress problem. The model was used to investigate the influence of fixed charge density magnitude and distribution on this slice of disc material. Results indicated that the mechanical, chemical, and electrical behaviors were all strongly influenced by the amount as well as the distribution of fixed charges in the matrix. Without any other changes in material properties, alterations in the fixed charge density (proteoglycan content) from a healthy to a degenerated distribution will cause an increase in solid matrix stresses and can affect whether the tissue imbibes or exudes fluid under different loading conditions. Disc tissue with a degenerated fixed charge density distribution exhibited greater solid matrix stresses and decreased streaming potential, all of which have implications for disc nutrition, disc biomechanics, and tissue remodeling. It was also seen that application of an electrical potential across the disc can induce fluid transport.

Adult↗
PubMed2003

Subcutaneous tissue mechanical behavior is linear and viscoelastic under uniaxial tension.

Subcutaneous tissue is part of a bodywide network of "loose" connective tissue including interstitial connective tissues separating muscles and surrounding all nerves and blood vessels. Despite its ubiquitous presence in the body and its potential importance in a variety of therapies utilizing mechanical stretch, as well as normal movement and exercise, very little is known about loose connective tissue's biomechanical behavior. This study aimed to determine elastic and viscoelastic mechanical properties of ex-vivo rat subcutaneous tissue in uniaxial tension with incremental stress relaxation experiments. The elastic response of the tissue was linear, with instantaneous and equilibrium tensile moduli of 4.77 kPa and 2.75 kPa, respectively. Using a 5 parameter Maxwell solid model, material parameters micro(1) = 0.95 +/- 0.24 Ns/m and micro(2) = 8.49 +/- 2.42 Ns/m defined coefficients of viscosity related to time constants tau(1M) = 3.83 +/- 0.15 sec and tau(2M) = 30.15 +/- 3.16 sec, respectively. Using a continuous relaxation function, parameters C = 0.25 +/- 0.12, tau(1C) = 1.86 +/- 0.34 sec, and tau(2C) = 110.40 +/- 25.59 sec defined the magnitude and frequency limits of the relaxation spectrum. This study provides baseline information for the stress-strain behaviors of subcutaneous connective tissue. Our results underscore the differences in mechanical behaviors between loose and high-load bearing connective tissues and suggest that loose connective tissues may function to transmit mechanical signals to and from the abundant fibroblasts, immune, vascular, and neural cells present within these tissues.

Animals↗
PubMed2002

Enlargement of growth plate chondrocytes modulated by sustained mechanical loading.

BACKGROUND: Mechanical compression and distraction forces are known to modulate growth in vertebral growth plates, and they have been implicated in the progression of scoliosis. This study was performed to test the hypothesis that growth differences produced by sustained compression or distraction loading of vertebrae are associated with alterations in the amount of increase in the height of growth plate chondrocytes in the growth direction. METHODS: Compression or distraction force of nominally 60% of body weight was maintained for four weeks on a caudad vertebra of growing rats by an external apparatus attached, by means of transcutaneous pins, to the two vertebrae cephalad and caudad to it. Growth of the loaded and control vertebrae was measured radiographically. After four weeks, the animals were killed and histological sections of the loaded and control vertebrae were prepared to measure the height of the hypertrophic zone (average separation between zonal boundaries), the mean height of hypertrophic chondrocytes, and the amount of increase in cell height in the growth direction. RESULTS: Over the four weeks of the experiment, the growth rates of the compressed and distracted vertebrae averaged 52% and 113% of the control rates, respectively. The reduction in the growth rate of the compressed vertebrae was significant (p = 0.002). In the compressed vertebrae, the height of the hypertrophic zone, the mean chondrocyte height, and the amount of increase in cell height averaged 87%, 85%, and 78% of the control values, respectively, and all were significantly less than the corresponding control values. In the distracted vertebrae, these measurements did not differ significantly from the control values. The height of the hypertrophic zone and the mean chondrocyte height correlated with the growth rate (r (2) = 0.29 [p = 0.03] and r (2) = 0.23 [p = 0.06], respectively), when each variable was expressed as a proportion of the control value. The percentage changes in the measurements of the chondrocytic dimensions relative to the control values were smaller than the percentage changes in the growth rates, a finding that suggested that the rate of chondrocytic proliferation was also modulated by the mechanical loading. CONCLUSIONS: Mechanical loading of tail vertebrae in rats modulated their growth rate, which correlated with changes in the height of hypertrophic chondrocytes. The effects of compression were greater than those of distraction. CLINICAL RELEVANCE: Information about the growth rate and chondrocytic response to mechanical loads in rat vertebrae undergoing mechanically modulated growth will be helpful in determining how human vertebral growth might respond to altered loading states during progression or treatment of scoliosis and other growth-related angular skeletal deformities.

Animals↗
PubMed2002

Growth plate chondrocyte enlargement modulated by mechanical loading.

Mechanical compression and distraction forces are known to modulate growth in vertebral growth plates, and are implicated in the progression of scoliosis. The amount of cellular enlargement is thought to be a key variable correlating with differing growth at different anatomical sites. This work tested the hypothesis that growth differences produced by mechanical loading are associated with alterations in the amount of cell height increase in the growth direction. Compression force (3 animals) or distraction force (4 animals) of 60% bodyweight was maintained on a caudal vertebra of growing rats with an external apparatus attached to vertebrae adjacent to the experimental level via transfixing pins. Growth of loaded and control vertebrae was measured from weekly radiographs. After four weeks, animals were euthanized and the loaded vertebrae and adjacent control vertebrae were excised for histological sections from which the following were measured: height of the hypertrophic zone (the average separation between boundaries of the zone); Mean Hypertrophic chondrocytic height; slope of the linear regression of cell height vs. position in the zone, (the amount of cell enlargement). Distracted and compressed vertebra growth averaged 110% and 53% of control levels. The percentage changes in the measures of chondrocyte dimensions, relative to control values, were smaller than the percentage changes in growth velocity. Also, the effects were of smaller magnitude for distracted vertebrae than for compressed vertebrae. Growth plate zonal height, slope and mean cell height all correlated significantly (p<0.05) with growth rate (expressed as a percentage of control) (Pearson r = 0.69, 0.37 and 0.41 respectively. Thus mechanical loading of tail vertebrae modulated their growth rate, that in turn correlated with changes in the amount of hypertrophic chondrocyte height increase. The effects for compression were greater than for distraction.

Animals↗