Biomedical subjects

Keita Ito

Publications and source records attributed to Keita Ito.

15 recordsLinked to original sources

PubMed2006

Bone regeneration during distraction osteogenesis: mechano-regulation by shear strain and fluid velocity.

Corroboration of mechano-regulation algorithms is difficult, partly because repeatable experimental outcomes under a controlled mechanical environment are necessary, but rarely available. In distraction osteogenesis (DO), a controlled displacement is used to regenerate large volumes of new bone, with predictable and reproducible outcomes, allowing to computationally study the potential mechanisms that stimulate bone formation. We hypothesized that mechano-regulation by octahedral shear strain and fluid velocity can predict the spatial and temporal tissue distributions seen during experimental DO. Variations in predicted tissue distributions due to alterations in distraction rate and frequency could then also be studied. An in vivo ovine tibia experiment evaluating bone-segment transport (distraction, 1 mm/day) over an intramedullary nail was used for comparison. A 2D axisymmetric finite element model, with a geometry originating from the experimental data, was created and included into a previously developed model of tissue differentiation. Cells migrated and proliferated into the callus, differentiating into fibroblasts, chondrocytes or osteoblasts, dependent on the biophysical stimuli. Matrix production was modelled with an osmotic swelling model to allow tissues to grow at individual rates. The temporal and spatial tissue distributions predicted by the computational model agreed well with those seen experimentally. In addition, it was observed that decreased distraction rate (0.5 mm/d vs. 0.25 mm/d) increased the overall time needed for complete bone regeneration, whereas increased distraction frequency (0.5 mm/12 h vs. 0.25 mm/6 h) stimulated faster bone regeneration, as found in experimental findings by others. Thus, the algorithm regulated by octahedral shear strain and fluid velocity was able to predict the bone regeneration patterns dependent on distraction rate and frequency during DO.

Animals↗

PubMed2006

Consistent hydration of intervertebral discs during in vitro testing.

Spinal specimens are commonly sprayed with saline solution during mechanical testing to ensure adequate hydration. However, potting of vertebrae inhibits physiological fluid exchange through the porous endplates during loading. This un-physiological flow regime may influence mechanical properties of intervertebral discs and therefore of the whole spinal unit. The objective of this study was to evaluate a new method of spinal specimen hydration through the vertebral body during in vitro testing in order to improve consistency of mechanical behaviour. Ovine lumbar anterior column units were prepared for testing. Half of the specimens were sprayed with Ringer's solution and wrapped in plastic foil. The remainder received an additional saline infusion into the centre of each vertebral body. Three consecutive compression steps were applied by a hydraulic testing machine. Average forces within four sectors of the relaxation curves were compared. Applying saline infusion improves the consistency of consecutive relaxation curves. Differences between consecutive relaxation curves were less than those for standard hydration. The forces at the beginning of the relaxation curve were also lower for the infusion method. The standard deviation between specimens of each group was lower for saline infusion of vertebrae. Hence, the new method leads to more consistent in vitro testing conditions.

Animals↗

PubMed2006

An in vitro organ culturing system for intervertebral disc explants with vertebral endplates: a feasibility study with ovine caudal discs.

STUDY DESIGN: Whole ovine caudal intervertebral discs with vertebral endplates were cultured under uniaxial diurnal loading for 7 days. OBJECTIVES: To establish and characterize an organ culture system for intervertebral discs, in which disc cells may be "maintained" in their native three-dimensional environment under load. SUMMARY OF BACKGROUND DATA: In vitro culturing of entire discs with preserved biologic and structural integrity would be a useful model to study the effects of nutrition and mechanical loading. METHODS: To maintain endplate permeability, sheep were systemically anticoagulated before death and their caudal vasculature was evacuated with saline postmortem. The first 4 caudal discs were explanted with their adjacent endplates and cultured in bioreactors under uniaxial diurnal loading (0.2 MPa for 8 hours and 0.8 MPa for 16 hours) for 4 or 7 days. Solute transport into the center of the disc was measured after 4 days of culture using a low molecular weight fluorescent marker. Cell viability, glycosaminoglycan synthesis rate, and gene expression profile were measured after 7 days of culture and compared with fresh tissue. RESULTS: Fluorescent images showed that solutes could diffuse into the disc under both static and diurnal loading, but penetration through the endplate increased with diurnal loading. Cell viability and glycosaminoglycan synthesis rates remained unchanged after 7 days of culture. Expression of catabolic genes was significantly up-regulated, whereas anabolic genes tended to be down-regulated after 7 days. CONCLUSIONS: With this novel preparation and culturing technique, endplate permeability could be maintained, which allowed culturing of intact disc explants with endplates for up to 7 days.

Animals↗

PubMed2006

Corroboration of mechanoregulatory algorithms for tissue differentiation during fracture healing: Comparison with in vivo results.

Several mechanoregulation algorithms proposed to control tissue differentiation during bone healing have been shown to accurately predict temporal and spatial tissue distributions during normal fracture healing. As these algorithms are different in nature and biophysical parameters, it raises the question of which reflects the actual mechanobiological processes the best. The aim of this study was to resolve this issue by corroborating the mechanoregulatory algorithms with more extensive in vivo bone healing data from animal experiments. A poroelastic three-dimensional finite element model of an ovine tibia with a 2.4 mm gap and external callus was used to simulate the course of tissue differentiation during fracture healing in an adaptive model. The mechanical conditions applied were similar to those used experimentally, with axial compression or torsional rotation as two distinct cases. Histological data at 4 and 8 weeks, and weekly radiographs, were used for comparison. By applying new mechanical conditions, torsional rotation, the predictions of the algorithms were distinguished successfully. In torsion, the algorithms regulated by strain and hydrostatic pressure failed to predict healing and bone formation as seen in experimental data. The algorithm regulated by deviatoric strain and fluid velocity predicted bridging and healing in torsion, as observed in vivo. The predictions of the algorithm regulated by deviatoric strain alone did not agree with in vivo data. None of the algorithms predicted patterns of healing entirely similar to those observed experimentally for both loading modes. However, patterns predicted by the algorithm based on deviatoric strain and fluid velocity was closest to experimental results. It was the only algorithm able to predict healing with torsional loading as seen in vivo.

Animals↗

PubMed2005

Internal strains in healthy and degenerated lumbar intervertebral discs.

STUDY DESIGN: A biomechanical study investigating the intradiscal mechanics of human lumbar intervertebral discs (IVDs). OBJECTIVES: To assess the relationship between nucleus pulposus migration and intradiscal strains as a function of degeneration. SUMMARY OF BACKGROUND DATA: Intradiscal deformation studies have documented the nucleus pulposus migration capabilities during bending but without assessing subsequent intradiscal strains of the anulus fibrosus. Degenerated IVDs show higher anular laxity, hypermobility, and, perhaps, segmental instability. It is unknown if nucleus pulposus migration might be the cause of increased intradiscal anular strains and if such a phenomenon is modulated by IVD degeneration. METHODS: Eighteen healthy and degenerated IVDs were subjected to compression, extension, flexion, and lateral bending. Craniocaudal radiographs at unloaded and loaded steps documented positions of wires placed within and beads glued to the external surface in the mid-transverse plane. Circumferential and radial strains from the anterior, lateral, and posterolateral regions during load were compared between healthy and degenerated IVDs. RESULTS: The nucleus pulposus migrated to the opposite side of bending regardless of bending direction and significantly more in degenerated IVDs. The highest nucleus pulposus migration was observed during lateral bending. Circumferential tensile strains were significantly higher in the posterolateral regions of degenerative IVDs during all loads. Degeneration significantly increased radial tensile and compressive strains during all bending loads. CONCLUSIONS: Increased nucleus pulposus migration in degenerated IVDs may result in increased shifting of the IVD pivot point during bending movements as well as intradiscal anular strains, particularly in the posterolateral anulus. This phenomenon may explain the segmental instability observed in degenerated segments as well as the associated anular tears present in the posterolateral region before IVD failure.

Aged↗

PubMed2005

Significance of the mechanical environment during regeneration of the intervertebral disc.

The prevalence of low back pain is high, and the intervertebral (IV) disc is regarded as one of the major causes. Various approaches have been reported to either slow down disc degeneration or to repair/regenerate the disc. So far, the effect of the mechanical environment has not been addressed in these approaches, although several investigations have shown its influence on other mesenchymal tissues. In this paper, we propose that the biophysical stimuli from the mechanical environment can directly influence cell type, as well as their metabolic activity during repair/regeneration of the IV disc. To demonstrate the potential of this idea, data from the literature, as well as explorative experimental results, are presented.

Animals↗

PubMed2005

Comparison of biophysical stimuli for mechano-regulation of tissue differentiation during fracture healing.

Most long-bone fractures heal through indirect or secondary fracture healing, a complex process in which endochondral ossification is an essential part and bone is regenerated by tissue differentiation. This process is sensitive to the mechanical environment, and several authors have proposed mechano-regulation algorithms to describe it using strain, pore pressure and/or interstitial fluid velocity as biofeedback variables. The aim of this study was to compare various mechano-regulation algorithms' abilities to describe normal fracture healing in one computational model. Additionally, we hypothesized that tissue differentiation during normal fracture healing could be equally well regulated by the individual mechanical stimuli, e.g. deviatoric strain, pore pressure or fluid velocity. A biphasic finite element model of an ovine tibia with a 3mm fracture gap and callus was used to simulate the course of tissue differentiation during normal fracture healing. The load applied was regulated in a biofeedback loop, where the load magnitude was determined by the interfragmentary movement in the fracture gap. All the previously published mechano-regulation algorithms studied, simulated the course of normal fracture healing correctly. They predicted (1) intramembranous bone formation along the periosteum and callus tip, (2) endochondral ossification within the external callus and cortical gap, and (3) creeping substitution of bone towards the gap from the initial lateral osseous bridge. Some differences between the effects of the algorithms were seen, but they were not significant. None of the volumetric components, i.e. pore pressure or fluid velocity, alone were able to correctly predict spatial or temporal tissue distribution during fracture healing. However, simulation as a function of only deviatoric strain accurately predicted the course of normal fracture healing. This suggests that the deviatoric component may be the most significant mechanical parameter to guide tissue differentiation during indirect fracture healing.

Algorithms↗

PubMed2005

2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc degeneration was evaluated by morphologic appearance, magnetic resonance imaging, and by biochemical matrix composition. Caliber and distribution of openings of the adjacent vertebral osseous endplates were measured. OBJECTIVES: Correlation between occlusion of vertebral endplate openings and intervertebral disc degeneration was quantified. SUMMARY OF BACKGROUND DATA: Calcifications of vertebral endplates with disease and age have suggested insufficient nutrition as a mechanism for intervertebral disc degeneration. It has been proposed that occlusion of endplate openings, which contain vascular sources for the disc, may limit the transport of nutrients, leading to disc degeneration. METHODS: Fresh magnetic resonance images from 39 human lumbar discs were scored. Sectioned discs with endplates were morphologically graded. Samples of nuclear and anular regions were evaluated for proteoglycan and collagen contents. Backlight microscopic images of 4 endplate regions were obtained, and caliber and distribution of endplate openings for each disc were measured. Analysis of variance regression models were used to assess correlation between endplate openings and disc degeneration. RESULTS: The decrease in opening density significantly correlated to morphologic degeneration grade, best for openings with 20 to 50 im equivalent diameter and in the nuclear region. Although the density of 20 to 50 im openings also significantly indirectly correlated to age, it was not as strong as the correlation to degeneration grade. Opening density was also significantly correlated to proteoglycan content in all regions. However, all other biochemical parameters as well as the T2 intensity score showed only weak or no correlation to opening density. CONCLUSIONS: A high indirect correlation between the density of openings in the osseous endplate (particularly of the size of the capillary buds) and the morphologic degeneration grade of the disc support the hypothesis that occlusion of these openings may deprive the cells of nutrients, leading to insufficient maintenance of the extracellular matrix and disc degeneration.

Adult↗

PubMed2004

Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration.

UNLABELLED: Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays. However, their correlation to morphological and biochemical changes is not well established. In this study, radiological and MRI parameters of DDD were assessed and compared with morphological and biochemical findings of disc degeneration. Thirty-nine human lumbar discs (L1-S1), age 19-86 years, were harvested from eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and biplanar radiographs of intact spines were obtained. Individual discs with endplates were then sectioned in the mid-sagittal plane and graded according to the morphological appearance. Samples from the nucleus of each disc were harvested for biochemical analysis including water and proteoglycan contents. On MRIs, T2-signal intensity, Modic changes, disc extension beyond the interspace (DEBIT), nucleus pulposus shape, annular tears, osteophytes and endplate integrity were graded. On radiographs, an independent observer classified the parameters disc height, endplate sclerosis, osteophytes, Schmorl's nodes, intradiscal calcifications and endplate shape. General linear-regression models were used for statistical analysis. Backward elimination with a 10% significance cut-off level was used to identify the most significant parameters, which then were summed to create composite scores for radiography, MRI and the combination of both methods. The grading was performed by three observers, and a reliability analysis using Cronbach's alpha model was used to control interobserver agreement. The three radiographic parameters height-loss, osteophytes and intradiscal calcifications correlated significantly with the morphological degree of degeneration (p<0.001, R2=642). Significant differences of even one morphological grade could also be differentiated in the composite radiological score (p<0.05), except at the extremes between grades 1 and 2 and grades 4 and 5. All MRI parameters correlated significantly with the morphological grade (p<0.05); however Modic changes, T2-intensity and osteophytes accounted for 83% of the variation in the data. T2-signal intensity correlated significantly with H2O and proteoglycan content (p<0.001), and was best for detecting highly degenerated discs. Regression showed that the combined score was better correlated with the morphological grade (p<0.001, R2=775) than either the composite radiographic (p<0.001, R2=642) or composite MRI (p<0.001, R2=696) alone. Based on the combined score, a backwards elimination of the regression was performed, in which the parameters Modic changes, and T2-intensity loss (MRI) as well as calcifications (X-ray) accounted for 87% of the variability. The interobserver validation showed a high correlation for all three scores (Cronbach's alpha values ranging from 0.95 to 0.97). CONCLUSION: Selective imaging parameters and a newly created scoring scheme were found to correlate with disc degeneration as determined in a morphological manner. Surprisingly, radiographic parameters were able to distinguish different stages of degeneration, whereas MRI could only detect advanced stages of disc degeneration. We conclude that X-rays may remain a cost-effective, non-invasive in vivo-grading method to detect early disc degeneration, and, combined with MRI, correlate best with morphological and biochemical assessment of disc degeneration.

Adult↗

PubMed2004

Fluid flow and convective transport of solutes within the intervertebral disc.

Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc. An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa. Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.

Animals↗

PubMed2004

Histopathologic features of the acetabular labrum in femoroacetabular impingement.

This paper summarizes clinical and histopathologic findings derived from 25 patients who had surgery for symptomatic femoroacetabular impingement. We explored if observed pathologic features were consistent with hypothesized mechanisms of injury, if severity of osteoarthritis and labral degeneration were associated, and if labral refixation would present an alternative. Clinically, all patients presented with limited range of motion at the hip attributable to pain and a positive impingement test. Magnetic resonance arthrography and surgical observations showed degenerated or ruptured labra or both in the anterior and/or superior regions of the acetabular rim (24 of 25 specimens) which correlated with pain provocation, limited range of motion, and anatomic deformities. Histologically, labra were mostly hyperplastic with disorganized cystic matrices. No inflammation was observed. Spatial distribution of degenerated labral matrices was not different for the two femoroacetabular impingement mechanisms. Labral degeneration and severity of osteoarthritis observed on radiographs did not correlate. In patients having only joint debridement, the labral matrix at the tip, near its vascular supply, was normal. Femoroacetabular impingement is a gentle chronic irritation of the labra located at the site of rupture that elicits a degenerative reaction. In early stages of the disease, the labral tip is not involved, providing the possibility of labral refixation after resection of the degenerated portion.

Acetabulum↗

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

The effect of roughness on biophysical stimuli at the bone-cartilage interface.

Numerical simulations are often used to investigate the effect of mechanical environment on fracture healing. Although these models exhibit biologically relevant mechanical parameters at the bone-callus interface, this interface is modelled as perfectly smooth when in fact it is rough. In this study, a macro-micro-two-scale finite element model was used to determine if roughness significantly alters calculated local mechanical parameters. An idealized fracture healing poroelastic model with a small micro-modelled sub-domain of cartilaginous callus adjacent to rough bone was subjected to cyclic loading. The shear stress, tangential fluid velocity, and pore pressure were investigated. With roughness similar to that at the growth plate, solid matrix shear stress differed substantially with interface roughness, whereas interstitial fluid velocity and pore pressure were only slightly affected. Hence, when modelling local micro-mechanical environments near hard-soft tissue interfaces, interface roughness should be considered.

Animals↗

PubMed2002

Muscle MRI findings of HTLV-1-associated myelopathy.

We report here the muscle MRI findings in two patients with human T-cell lymphotropic virus type I-associated myelopathy (HAM). It is known that thigh muscles are vulnerable in HAM patients, but detailed information about the affected muscles has not been available. Muscle MRI findings of these patients showed that thigh muscles, especially adductor magnus, and semimembranosus muscles were severely affected, but lower leg muscles were comparatively preserved. In these affected muscles, neurogenic changes were observed by EMG. We concluded that muscle MRI is very useful to estimate the affected muscles in HAM patients.

Aged↗

PubMedDate not supplied

Plate stabilization with bone rivets: an alternative method for internal fixation of fractures.

OBJECTIVES: Bone rivets were developed as an alternative method to fasten plates during internal fixation of fractures when screw anchorage may be inadequate. This study examined whether such rivets allow proper fracture healing without eliciting adverse bone remodelling and whether they can be removed safely. METHODS: A proximal diaphyseal fracture of the tibia was stabilized with a conventional plate (low-contact dynamic compression plate, Synthes) in 10 sheep. The distal fragment was anchored using bicortical screws, and the proximal fragment (1-2.5 mm thick cortex) with 3 rivets following screw stripping. Postoperative care included immediate weight bearing and biweekly radiographs. After 12 weeks, implants were removed from 6 sheep and the tibial strength measured. Tibiae with empty and filled rivet holes (at 12 and 24 weeks) were examined histologically. RESULTS: In all sheep, secondary bone healing was observed without length and angulation deformities. All fracture gaps were bridged and filled with new bone. The average torsional strength after 12 weeks was 75 +/- 11% of the intact tibia (mean +/- SD), and failure never occurred through an empty rivet hole. After 12 weeks, there was intensive cortical remodelling at the rivets correlating with slight to moderate nonprogressive periosteal radiolucency around 55% of the rivets. However, there was also endosteal appositional bone growth at 85% of the rivets. There was no observable macroscopic or microscopic osseous damage after implant removal. After 24 weeks, remodelling activity had decreased and was noted only sporadically. CONCLUSIONS: In this study, the efficacy of bone rivets for the internal fixation of a fracture with plates, where anchorage of screws may be difficult and/or insufficient, was demonstrated.

Animals↗