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Biomedical subjects

J C Lotz

Publications and source records attributed to J C Lotz.

At least 19 recordsLinked to original sources

Disc regeneration: why, when, and how.

There is increasing acknowledgment that patients with back pain who are candidates for surgery, will benefit over the long term from less invasive procedures that facilitate dynamic stabilization, rather than fusion. Dynamic stabilization can be addressed by providing assistance using mechanical devices, or relying on biologic processes such as tissue regeneration and repair. The concept of biologic disc repair has grown in recent years because of improved understanding of the cellular and molecular events of disc aging and degeneration. This article describes approaches to cell therapy, reviews relevant studies, and discusses ways to maximize clinical efficacy. Tissue engineering approaches for disc regeneration and healing have significant clinical potential.

Guided Tissue Regeneration↗

Biaxial testing of human annulus fibrosus and its implications for a constitutive formulation.

Internal pressure in the healthy human annulus fibrosus leads to multiaxial stress in vivo, yet uniaxial tests have been used exclusively to characterize its in vitro mechanical response and to determine its elastic strain energy function (W). We expected that biaxial tension tests would provide unique and necessary data for characterizing the annular material response, and thereby, for determining W. We performed uniaxial and biaxial tests on specimens of annulus, then developed an objective methodology for defining an appropriate form for W that considers data from multiple experiments simultaneously and allows the data to dictate more directly the form and the number of parameters needed. We found that the stresses attained in the biaxial tests were higher, while the strains were considerably lower, than those observed in the uniaxial tests. A comparison of strain energy functions determined from the different data sets demonstrated that constitutive models derived from uniaxial data could not predict annulus behavior in biaxial tension and vice versa. Since the annulus is in a state of multaxial stress in vivo, we conclude that uniaxial tests alone are insufficient to prescribe a physiologically relevant W for this tissue.

Adult↗

Mechanobiology of the intervertebral disc.

Intervertebral disc degeneration has been linked in humans to extreme spinal loading regimens. However, mechanisms by which spinal force influences disc cellularity, morphology and consequently biomechanical function are unclear. To gain insight into mechanobiological interactions within the disc, we developed an in vivo murine tail-compression model. Results from this model demonstrate how deviations in spinal stress induce a cycle of altered cell function and morphology as the disc remodels to a new homoeostatic configuration.

Aging↗

Acute biomechanical and histological effects of intradiscal electrothermal therapy on human lumbar discs.

STUDY DESIGN: Human cadaver lumbar spines were used to assess the acute effects of intradiscal electrothermal therapy in vitro. OBJECTIVE: To determine whether intradiscal electrothermal therapy produces acute changes in disc histology and motion segment stability. SUMMARY OF BACKGROUND DATA: Intradiscal electrothermal therapy has been introduced as an alternative for the treatment of discogenic low back pain. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested including shrinkage of the nucleus or sealing of the anulus fibrosus by contraction of collagen fibers, and thermal ablation of sensitive nerve fibers in the outer anulus. METHODS: Intradiscal electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh, frozen human lumbar cadaver specimens. In a separate study, eight specimens were tested biomechanically and instrumented to map the thermal distribution, whereas five specimens were tested only biomechanically, both before and after intradiscal electrothermal therapy. Six additional specimens were heated with intradiscal electrothermal therapy, and the resulting canal was backfilled with a silicone rubber compound to allow colocalization of the catheter and anular architecture. RESULTS: A consistent pattern of increased motion and decreased stiffness was observed. For the specimens in which only biomechanical measurements were taken, a 10% increase in the motion, on the average, at 5 Nm torque was observed after intradiscal electrothermal therapy. No apparent alteration of the anular architecture was observed around the catheter site in the intradiscal electrothermal therapy-treated discs. CONCLUSION: The data from this study suggest that the temperatures developed during intradiscal electrothermal therapy are insufficient to alter collagen architecture or stiffen the treated motion segment acutely.

Adult↗

Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro.

STUDY DESIGN: Twelve lumbar intervertebral disc specimens were imaged with magnetic resonance imaging to estimate relaxation constants, T1 and T2, and tissue water diffusion, before and after applying compression. OBJECTIVES: The objectives of the study were to measure T1, T2, and water diffusion for differences with loading state, region of the disc (anulus fibrosus or nucleus pulposus), and grade of degeneration. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging can be used qualitatively to estimate water content and degeneration of the intervertebral disc. Beyond structural information of images, the relaxation times T1 and T2 may contain information on the changes occurring with degeneration. A modified spin-echo sequence can be used to estimate tissue water diffusion in cartilage and disc specimens with the ability to measure anisotropy. METHODS: Specimens were imaged in a 1.5-Tesla clinical scanner. T1, T2, and water diffusion were estimated from midsagittal images. Magnetic resonance imaging parameters were calculated before and after axial loading. The measured T1, T2, and D (diffusion coefficient) were compared before and after compression, and for the diffusion data, also by direction to consider anisotropy. RESULTS: For the T1 data, a significant difference was found by region, nucleus > anulus, and loading state, loaded > unloaded. For the T2 values, there was a significant difference by region, nucleus > anulus, and Thompson grade. For diffusion, significant differences were found by region, nucleus > anulus, Thompson grade, direction of diffusion, and state of compression, loaded > unloaded. CONCLUSIONS: This study demonstrated that magnetic resonance imaging can be used to measure significant changes in T1, T2, or diffusion in intervertebral disc specimens by region, loading condition, or Thompson grade.

Adolescent↗

Effect of frozen storage on the creep behavior of human intervertebral discs.

STUDY DESIGN: A biomechanical study of the compressive creep behavior of the human intervertebral disc before and after frozen storage. OBJECTIVES: To determine whether frozen storage alters the time-dependent response of the intact human intervertebral disc. SUMMARY OF BACKGROUND DATA: The biomechanical properties of the intervertebral disc are generally determined using specimens that have been previously frozen. Although it is well established that freezing does not alter the elastic response of the disc, recent data demonstrate that freezing permanently alters the time-dependent mechanical behavior of porcine discs. METHODS: Twenty lumbar motion segments from 10 human spines were harvested between 12 and 36 hours postmortem. The specimens were randomly assigned to one of two groups: Group 1 was tested promptly, stored frozen for 3 weeks, then thawed, and tested a second time; Group 2 was stored frozen for 3 weeks, thawed, and then tested. Each specimen was subjected to 5 cycles of compressive creep under 1 MPa for 20 minutes, followed by a 40-minute recovery under no load. After testing each specimen was graded on a degeneration scale. A fluid transport model was used to parameterize the creep data. RESULTS: There was no statistically significant effect of freezing on the elastic or creep response of the discs. The degree of pre-existing degeneration had a significant effect on the creep response, with the more degenerated discs appearing more permeable. CONCLUSIONS: Frozen storage for a reasonable time with a typical method does not significantly alter the creep response of human lumbar discs. Freezing may produce subtle effects, but these potential artifacts do not appear to alter the discs' time-dependent behavior in any consequential way. These results may not apply to tissue kept frozen for long durations and with poor packaging.

Artifacts↗

Parametric finite element analysis of vertebral bodies affected by tumors.

The vertebral column is the most frequent site of metastatic involvement of the skeleton. Due to the proximity to the spinal cord, from 5% to 10% of all cancer patients develop neurologic manifestations. As a consequence, fracture risk prediction has significant clinical importance. In this study, we model the metastatically involved vertebra so as to parametrically investigate the effects of tumor size, material properties and compressive loading rate on vertebral strength. A two-dimensional axisymmetric finite element model of a spinal motion segment consisting of the first lumbar vertebral body (no posterior elements) and adjacent intervertebral disc was developed to allow the inclusion of a centrally located tumor in the vertebral body. After evaluating elastic, mixed, and poroelastic formulations, we concluded that the poroelastic representation was most suitable for modeling the metastatically involved vertebra's response to compressive load. Maximum principal strains were used to localize regions of potential vertebral trabecular bone failure. Radial and axial vertebral body displacements were used as relative indicators of spinal canal encroachment and endplate failure. Increased tumor size and loading rate, and reduced trabecular bone density all elevated axial and radial displacements and maximum tensile strains. The results of this parametric study suggest that vertebral tumor size and bone density contribute significantly to a patients risk for vertebral fracture and should be incorporated in clinical assessment paradigms.

Biomechanical Phenomena↗

Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading.

STUDY DESIGN: An in vivo study of the toxic consequences of static compressive stress on the intervertebral disc. OBJECTIVES: To determine whether disc cell death is correlated with the magnitude and duration of spinal compressive loading. SUMMARY OF BACKGROUND DATA: Static compression in vivo has been demonstrated to induce cell death. Cell death, in turn, has been associated with disc degeneration in humans. There are currently no tolerance criteria for the intervertebral disc that combine both biomechanical and biologic factors, although both have been implicated in cases of accelerated degeneration. METHODS: Mouse tail discs were loaded in vivo with an external compression device. Compressive stress was applied at one of two magnitudes (0.4 and 0.8 MPa) for 7 days, and at one additional magnitude (1.3 MPa) for 1, 3, and 7 days. Midsagittal sections of the discs were stained for apoptosis using the TdT-dUTP terminal nick-end labeling (TUNEL) reaction. Quantal analysis was used to correlate the extent of cell death to the magnitude and duration of loading. RESULTS: The probit transformation of the percentage of dying cells was proportional to the sum of the logarithmic transformations of the compressive stress and the time of loading. CONCLUSIONS: The results of this study demonstrate the feasibility of developing a quantitative correlation between spinal loading and disc degeneration. Such a correlation may be coupled in the future to existing engineering models that predict spinal loading in response to physical exposures and lead to improved definition of the bounds of healthy and unhealthy spinal loading, and ultimately, refined guidelines for low back safety.

Animals↗

Tibial plateau fracture as a measure of early estrogen-dependent bone fragility in rats.

The goals of this study were to develop a protocol to induce a compressive fracture at the tibial plateau of the rat knee in vitro and to determine if the biomechanical parameters provided a sensitive assessment of the early skeletal changes induced by estrogen deficiency. Sixty-one rats underwent an ovariectomy (n = 36) or sham operation (n = 25) and were maintained for 50 days after the procedure. Just before death, the proximal tibia of each animal was scanned with high-resolution x-ray tomography. From the three-dimensional images, the mean trabecular bone volume, thickness, and separation and the number of trabeculae were calculated. The knees were then harvested and mounted into a servohydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture. The fracture load of the ovariectomized rats was 24% less than that of the rats that had the sham operation. Similarly, the structural stiffness of the ovariectomized knees was decreased by 22%. Both of these differences were statistically significant (p < 0.01) and were explained by differences in trabecular bone volume (r = 0.56, p < 0.0001 and r = 0.42, p < 0.005, respectively). The other measures of trabecular bone structure were correlated with the volume and did not improve the prediction by the biomechanical parameters. These data demonstrate that biomechanical testing of the tibial plateau in rats can quantify the structural consequences of estrogen deficiency at an early time point before they become apparent at other bone sites, such as the lumbar spine.

Animals↗

[Effects of early estrogen replacement therapy on bone stability of ovariectomized rats. A biomechanical and radiologic study of the tibial plateau].

Postmenopausal osteoporosis leads to a significant increase in bone fragility. In this study we used the rat tibia plateau fracture model to investigate the efficiency of estrogen replacement therapy (ERT) to mitigate the post-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 animals underwent sham operation. The ovariectomized animals were either untreated (n = 35) or treated with estrogen injections (10 micrograms/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days post surgery. Before starting ERT and at 50 days post surgery, the trabecular structure of the right proximal tibial metaphysis of each animal was imaged non-invasively using high resolution X-ray topography. The animals were then sacrificed and the right knee from each animal was harvested and mounted into a servo-hydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administration was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham group, though this difference did not reach statistical significance. Across all groups, the failure load and stiffness were significantly correlated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.

Animals↗

Anisotropic shear behavior of the annulus fibrosus: effect of harvest site and tissue prestrain.

We used a shear protocol to investigate the time-independent, anisotropic structural behavior of 30 cube and 56 sheet specimens of human annulus fibrosus from six non-degenerate lumbar spines. The specimen sides were aligned with the natural collagen lamellar architecture. For the cube specimens, simple shear was applied sequentially in three orthogonal directions defined by the cube axes. The sheets were also tested in simple shear, with the stress applied in either the anatomic axial or circumferential directions. With the sheet specimens we also investigated the contribution of annular collagen to the shear modulus by applying a tensile prestrain (0, 5 or 10 percent) perpendicular to the direction of applied shear stress. Our cube data indicated that the shear modulus was anisotropic, being 56.04+/-36.3 kPa in the plane of the lamellae and approximately half that in the orthogonal directions. The sheet specimens demonstrated that shear modulus increased progressively by a factor of between 3 and 5 from the inner to outer annulus. The ratio of the axial to circumferential shear modulus for the sheets increased from being near unity for the inner annulus to near 2 for the outer annulus. Finally, the addition of a 10 percent tensile prestrain increased the shear modulus by between 1.5 and 2.5 times for the middle and outer annulus. The shear anisotropy we report is consistent with prior anatomical observations of this tissue and appears to develop through separate contributions from the matrix, the collagen fibers, and collagen fiber interactions.

Adult↗

Biphasic material properties of lytic bone metastases.

It is necessary to prescribe the mechanical properties of tumor tissue when modeling the metastatically involved skeleton for clarifying the mechanisms of fracture. This study provides mechanical property data for lytic bone metastases. Specimens of human lytic tumor were tested under a confined compression uniaxial creep protocol and the mechanical behavior of the tumor tissue was modeled using linear biphasic theory. The tumor tissue was found to have an aggregate modulus (HA) of 3.6 +/- 1.6 kPa and a hydraulic permeability (k) of 0.59 +/- 0.46mm4 N(-1) s(-1). Tumors with a higher percentage of stromal content were found to be stiffer and more permeable than those with a more cellular composition. No significant differences in aggregate modulus or hydraulic permeability were found between lytic metastases of different types. These data are useful for the development of models to simulate the behavior of the metastatically involved skeleton using theoretical or finite-element analysis techniques and also have significance for developing effective tumor-drug-transport models. We anticipate that specification of the mechanical behavior of this tissue may help to better focus future treatment of lytic bony metastases through better assessment of fracture risk and improved drug delivery.

Biomechanical Phenomena↗

A special theory of biphasic mixtures and experimental results for human annulus fibrosus tested in confined compression.

A finite deformation mixture theory is used to quantify the mechanical properties of the annulus fibrosus using experimental data obtained from a confined compression protocol. Certain constitutive assumptions are introduced to derive a special mixture of an elastic solid and an inviscid fluid, and the constraint of intrinsic incompressibility is introduced in a manner that is consistent with results obtained for the special theory. Thirty-two annulus fibrosus specimens oriented in axial (n = 16) and radial (n = 16) directions were obtained from the middle-lateral portion of intact intervertebral discs from human lumbar spines and tested in a stress-relaxation protocol. Material constants are determined by fitting the theory to experimental data representing the equilibrium stress versus stretch and the surface stress time history curves. No significant differences in material constants due to orientation existed, but significant differences existed due to the choice of theory used to fit the data. In comparison with earlier studies with healthy annular tissue, we report a lower aggregate modulus and a higher initial permeability constant. These differences are explained by the choice of reference configuration for the experimental studies.

Biomechanical Phenomena↗

Application of a fiber-reinforced continuum theory to multiple deformations of the annulus fibrosus.

Accurate tissue stress predictions for the annulus fibrosus are essential for understanding the factors that cause or contribute to disc degeneration and mechanical failure. Current computational models used to predict in vivo disc stresses utilize material laws for annular tissue that are not rigorously validated against experimental data. Consequently, predictions of disc stress resulting from physical activities may be inaccurate and therefore unreliable as a basis for defining mechanical-biologic injury criteria. To address this need we present a model for the annulus as an isotropic ground substance reinforced with two families of collagen fibers, and an approach for determining the material constants by simultaneous consideration of multiple experimental data sets. Two strain energy functions for the annulus are proposed and used in the theory to derive the constitutive equations relating the stress to pure stretch deformations. These equations are applied to four distinct experimental protocols and the material constants are determined from a simultaneous, nonlinear regression analysis. Good agreement between theory and experiment is achieved when the invariants are included within multiple, separate exponentials in the strain energy function.

Animals↗

Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study.

STUDY DESIGN: An in vivo study of the biologic and biomechanical consequences of static compressive loading on the mouse tail intervertebral disc. OBJECTIVES: To determine whether static compression in vivo alters the biologic activity of the disc and leads to diminished biomechanical performance. SUMMARY OF BACKGROUND DATA: Static compressive stress that exceeds the disc's swelling pressure is known to change hydration and the intradiscal stress distribution. Alterations in hydration and stress have been associated with changes in disc cell activity in vitro and in other collagenous tissues in vivo. METHODS: Mouse tail discs were loaded in vivo with an external compression device. After 1 week at one of three different stress levels, the discs were analyzed for their biomechanical performance, morphology, cell activity, and cell viability. A second group of mice were allowed to recuperate for 1 month after the 1-week loading protocol to assess the disc's ability to recover. As an aid to interpreting the histologic and biologic data, finite-element analysis was used to predict region-specific changes in tissue stress caused by the static loading regimen. RESULTS: With increasing compressive stress, the inner and middle anulus became progressively more disorganized, and the percentage of cells undergoing apoptosis increased. The expression of Type II collagen was suppressed at all levels of stress, whereas the expression of aggrecan decreased at the highest stress levels in apparent proportion to the decreased nuclear cellularity. Compression for 1 week did not affect the disc bending stiffness or strength but did increase the neutral zone by 33%. As suggested by the finite-element model, during sustained compression, tension is maintained in the outer anulus and lost in the inner and middle regions where the hydrostatic stress was predicted to increased nearly 10-fold. Discs loaded at the lowest stress recovered anular architecture but not cellularity after 1 month of recuperation. Discs loaded at the highest stress did not recover anular architecture, displaying islands of cartilage cells in the middle anulus at sites previously populated by fibroblasts. CONCLUSIONS: The results of the current project demonstrate that static compressive loading initiates a number of harmful responses in a dose-dependent way: disorganization of the anulus fibrosus; an increase in apoptosis and associated loss of cellularity; and down regulation of collagen II and aggrecan gene expression. The finite element model used in this study predicts loss of collagen fiber tension and increased matrix hydrostatic stress in those anular regions observed to undergo programmed cell death after 1 week of loading and ultimately become populated by chondrocytes after one month of recuperation. This correspondence conforms with the suggestions of others that the cellular phenotype in collagenous tissues is sensitive to the dominant type of tissue stress. Although the specific mechanisms by which alterations in tissue stress lead to apoptosis and variation in cell phenotype remain to be identified, our results suggest that maintenance of appropriate stress within the disc may be an important basis for strategies to mitigate disc degeneration and initiate disc repair.

Aggrecans↗

Use of ultrasound in spinal arthrodesis. A rabbit model.

STUDY DESIGN: The biomechanical and histologic characteristics of posterolateral spinal fusion in a rabbit model with and without the application of low-intensity ultrasound were analyzed. OBJECTIVES: To evaluate the use of ultrasound to improve the spinal fusion rate and biomechanical characteristics of the fusion mass in a rabbit model. SUMMARY OF BACKGROUND DATA: This is the first study in which the benefits of ultrasound in spinal fusion have been assessed. Posterolateral intertransverse process fusion in the rabbit has a pseudarthrosis rate similar to that recorded in humans (5-40%). METHODS: Fourteen New Zealand White rabbits were randomly assigned to each of two groups to undergo spinal fusion using autologous bone with ultrasound or autologous bone without ultrasound. A specially designed plastic constraint was used to focus the ultrasound over the rabbits' lumbar spine 20 minutes per day. Animals were killed at 6 weeks for biomechanical and histologic testing. RESULTS: The rate of pseudarthrosis, evaluated radiographically and manually in a blinded fashion, decreased at a statistically significant rate (from 35% to 7%) with ultrasound. Biomechanical analysis of the fusion mass showed that ultrasound resulted in statistically significant increases in stiffness (33%; P = 0.03), area under the load displacement curve (25%; P = 0.05), and load to failure of the fusion mass (24%; P = 0.04). Qualitative histologic assessment showed increased bone formation in those fusions exposed to ultrasound. CONCLUSIONS: Lumbar spinal fusion is a complex biologic process. The results of the current study demonstrate the reproducibility of a rabbit fusion model and the ability of ultrasound to induce a statistically significant increase in fusion rate, stiffness, area under the load displacement curve, and load to failure of the fusion mass. These results provide a basis for continued evaluation of biologic improvement of spinal arthrodesis with the use of ultrasound.

Animals↗

Effect of the pedicle and posterior arch on vertebral body strength predictions in finite element modeling.

STUDY DESIGN: A finite element study to predict the contribution of the pedicles and the posterior arch to vertebral body strength. OBJECTIVE: To determine the effect of the pedicle and posterior arch on strain distributions occurring within the vertebral body under axial compressive loading. SUMMARY OF BACKGROUND DATA: Posterior vertebral body fracture can arise from high-impact or normal loading in bones compromised by osteoporosis or neoplasm and can result in spinal canal encroachment. Anatomically, the pedicles and posterior arch have a potential role as a structural buttress to the posterior vertebral body wall. However, most finite element models used to investigate vertebral body strength have neglected these structures. METHODS: Three 3-dimensional finite element models were developed of L1, incorporating anatomic curvature, with varying degrees of posterior element inclusion (no pedicle, pedicle, and pedicle and posterior arch). Three cases were analyzed with each model: 25% dehydrated disc, normal healthy disc, and uniform pressure loading. Outcome variables were the maximum von Mises strains and the displacement of the posterior wall into the spinal canal. RESULTS: Inclusion of the posterior arch resulted in substantial decreases in maximum strain and posterior wall displacement under all loading configurations using transversely isotropic trabecular bone properties. No changes in maximum strains or displacements were recorded in the pedicle model, compared with that observed in the no-pedicle baseline case. CONCLUSIONS: The pedicle functions as a structural buttress, providing support to the posterior wall of the vertebral body when constrained through the posterior arch. To yield more accurate vertebral body strength predictions from finite element modeling, the posterior arch should be included.

Biomechanical Phenomena↗