Biomedical subjects

Elise F Morgan

Publications and source records attributed to Elise F Morgan.

9 recordsLinked to original sources

PubMed2005

Relationships between tissue dilatation and differentiation in distraction osteogenesis.

Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

Animals↗

PubMed2005

Sensitivity of multiple damage parameters to compressive overload in cortical bone.

Damage accumulation plays a key role in weakening bones prior to complete fracture and in stimulating bone remodeling. The goal of this study was to characterize the degradation in the mechanical properties of cortical bone following a compressive overload. Longitudinally oriented, low-aspect ratio specimens (n=24) of bovine cortical bone were mechanically tested using an overload-hold-reload protocol. No modulus reductions greater than 5% were observed following overload magnitudes less than 0.73% strain. For each specimen, changes in strength and Poisson's ratio were greater (p=0.02) than that in modulus by 10.8- and 26.6-fold, respectively, indicating that, for the specimen configuration used in this study, longitudinal elastic modulus is one of the least sensitive properties to a compressive overload. Residual strains were also proportionately greater by 6.4-fold (p=0.01) in the transverse than axial direction. These results suggest that efforts to relate microcrack density and morphology to changes in compressive mechanical properties of cortical bone may benefit from considering alternative parameters to modulus reductions.

Adaptation, Physiological↗

PubMed2004

Transient changes in oxygen tension inhibit osteogenic differentiation and Runx2 expression in osteoblasts.

Vascular disruption following bony injury results in a hypoxic gradient within the wound microenvironment. Nevertheless, the effects of low oxygen tension on osteogenic precursors remain to be fully elucidated. In the present study, we investigated in vitro osteoblast and mesenchymal stem cell differentiation following exposure to 21% O(2) (ambient oxygen), 2% O(2) (hypoxia), and <0.02% O(2) (anoxia). Hypoxia had little effect on osteogenic differentiation. In contrast, short-term anoxic treatment of primary osteoblasts and mesenchymal precursors inhibited in vitro bone nodule formation and extracellular calcium deposition. Cell viability assays revealed that this effect was not caused by immediate or delayed cell death. Microarray profiling implicated down-regulation of the key osteogenic transcription factor Runx2 as a potential mechanism for the anoxic inhibition of differentiation. Subsequent analysis revealed not only a short-term differential regulation of Runx2 and its targets by anoxia and hypoxia, but a long-term inhibition of Runx2 transcriptional and protein levels after only 12-24 h of anoxic insult. Furthermore, we present evidence that Runx2 inhibition may, at least in part, be because of anoxic repression of BMP2, and that restoring Runx2 levels during anoxia by pretreatment with recombinant BMP2 rescued the anoxic inhibition of differentiation. Taken together, our findings indicate that brief exposure to anoxia (but not 2% hypoxia) down-regulated BMP2 and Runx2 expression, thus inhibiting critical steps in the osteogenic differentiation of pluripotent mesenchymal precursors and committed osteoblasts.

3T3 Cells↗

PubMed2004

Postoperative rhabdomyolysis following laparoscopic gastric bypass in the morbidly obese.

HYPOTHESIS: Laparoscopic approaches for weight reduction in the morbidly obese have become common with more than 50,000 bariatric surgical procedures being performed in 2001. The objective of this article is to raise awareness among surgeons of a new complication of rhabdomyolysis from this frequent procedure. DESIGN: Case series extracted from surgical database from January 2, 2001, through December 31, 2002. PATIENTS AND METHODS: We identified 5 cases of postoperative rhabdomyolysis in morbidly obese patients who underwent laparoscopic duodenal switch procedures with parietal gastrectomy. The cause, pathogenesis, and clinical features are reviewed and discussed. RESULTS: Postoperative rhabdomyolysis developed in 5 of 353 morbidly obese patients who underwent consecutive laparoscopic duodenal switch procedures, an incidence of 1.4%. All 5 patients were male, had a mean peak serum creatine kinase level of 19 680 U/L, and reported muscle pain in either the buttock, hip, or shoulder regions during the early postoperative period. CONCLUSIONS: We hypothesized that morbidly obese patients develop critical surface and deep tissue pressures during bariatric surgery, increasing their risk for tissue injury and rhabdomyolysis. Unexplained elevations in the serum creatinine level or reports of buttock, hip, or shoulder pain in the postoperative period should raise the possibility of rhabdomyolysis and prompt clinical investigation. We recommend routine preoperative and postoperative measurements of the serum creatine kinase and serum creatinine levels to aid detection. Surgeons need to keep a low index of suspicion because early diagnosis and treatment are the cornerstones of successful management of rhabdomyolysis.

Acute Kidney Injury↗

PubMed2004

Contribution of inter-site variations in architecture to trabecular bone apparent yield strains.

Apparent yield strains for trabecular bone are uniform within an anatomic site but can vary across site. The overall goal of this study was to characterize the contribution of inter-site differences in trabecular architecture to corresponding variations in apparent yield strains. High-resolution, small deformation finite element analyses were used to compute apparent compressive and tensile yield strains in four sites (n = 7 specimens per site): human proximal tibia, greater trochanter, femoral neck, and bovine proximal tibia. These sites display differences in compressive, but not tensile, apparent yield strains. Inter-site differences in architecture were captured implicitly in the model geometries, and these differences were isolated as the sole source of variability across sites by using identical tissue properties in all models. Thus, the effects inter-site variations in architecture on yield strain could be assessed by comparing computed yield strains across site. No inter-site differences in computed yield strains were found for either loading mode (p > 0.19), indicating that, within the context of small deformations, inter-site variations in architecture do not affect apparent yield strains. However, results of ancillary analyses designed to test the validity of the small deformation assumption strongly suggested that the propensity to undergo large deformations constitutes an important contribution of architecture to inter-site variations in apparent compressive yield strains. Large deformations substantially reduced apparent compressive, but not tensile, yield strains. These findings indicate the importance of incorporating large deformation capabilities in computational analyses of trabecular bone. This may be critical when investigating the biomechanical consequences of trabecular thinning and loss.

Adult↗

PubMed2004

Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue.

The ability to determine trabecular bone tissue elastic and failure properties has biological and clinical importance. To date, trabecular tissue yield strains remain unknown due to experimental difficulties, and elastic moduli studies have reported controversial results. We hypothesized that the elastic and tensile and compressive yield properties of trabecular tissue are similar to those of cortical tissue. Effective tissue modulus and yield strains were calibrated for cadaveric human femoral neck specimens taken from 11 donors, using a combination of apparent-level mechanical testing and specimen-specific, high-resolution, nonlinear finite element modeling. The trabecular tissue properties were then compared to measured elastic modulus and tensile yield strain of human femoral diaphyseal cortical bone specimens obtained from a similar cohort of 34 donors. Cortical tissue properties were obtained by statistically eliminating the effects of vascular porosity. Results indicated that mean elastic modulus was 10% lower (p<0.05) for the trabecular tissue (18.0+/-2.8 GPa) than for the cortical tissue (19.9+/-1.8 GPa), and the 0.2% offset tensile yield strain was 15% lower for the trabecular tissue (0.62+/-0.04% vs. 0.73+/-0.05%, p<0.001). The tensile-compressive yield strength asymmetry for the trabecular tissue, 0.62 on average, was similar to values reported in the literature for cortical bone. We conclude that while the elastic modulus and yield strains for trabecular tissue are just slightly lower than those of cortical tissue, because of the cumulative effect of these differences, tissue strength is about 25% greater for cortical bone.

Aged↗

PubMed2003

Trabecular bone modulus-density relationships depend on anatomic site.

One outstanding issue regarding the relationship between elastic modulus and density for trabecular bone is whether the relationship depends on anatomic site. To address this, on-axis elastic moduli and apparent densities were measured for 142 specimens of human trabecular bone from the vertebra (n=61), proximal tibia (n=31), femoral greater trochanter (n=23), and femoral neck (n=27). Specimens were obtained from 61 cadavers (mean+/-SD age=67+/-15 years). Experimental protocols were used that minimized end-artifact errors and controlled for specimen orientation. Tissue moduli were computed for a subset of 18 specimens using high-resolution linear finite element analyses and also using two previously developed theoretical relationships (Bone 25 (1999) 481; J. Elasticity 53 (1999) 125). Resultant power law regressions between modulus and density did depend on anatomic site, as determined via an analysis of covariance. The inter-site differences were among the leading coefficients (p<0.02), but not the exponents (p>0.08), which ranged 1.49-2.18. At a given density, specimens from the tibia had higher moduli than those from the vertebra (p=0.01) and femoral neck (p=0.002); those from the trochanter had higher moduli than the vertebra (p=0.02). These differences could be as large as almost 50%, and errors in predicted values of modulus increased by up to 65% when site-dependence was ignored. These results indicate that there is no universal modulus-density relationship for on-axis loading. Tissue moduli computed using methods that account for inter-site architectural variations did not differ across site (p>0.15), suggesting that the site-specificity in apparent modulus-density relationships may be attributed to differences in architecture.

Aged↗

PubMed2002

Quantitative computed tomography estimates of the mechanical properties of human vertebral trabecular bone.

The objective of this study was to report our quantitative computed tomography (QCT) density-mechanical property regressions for trabecular bone for use in biomechanical modelling of the human spine. Cylindrical specimens of human vertebral trabecular bone (from T10 to L4) were cored from 32 cadavers (mean +/- SD age = 70.1 +/- 16.8; 13 females, 19 males) and scanned using QCT. Mechanical tests were conducted using a protocol that minimized end-artifacts over the apparent density range tested (0.09-0.38 g/cm3). To account for the presence of multiple specimens per donor in this data set, donor was treated as a random effect in the regression model. Mean modulus (319 +/- 189 MPa) was higher and mean yield strain (0.78 +/- 0.06%) was lower than typical values reported previously due to minimization of the end-artifact errors. QCT density showed a strong positive correlation with modulus (n = 76) and yield stress (r2 = 0.90-0.95, n = 53, p < 0.001). There was a weak positive linear correlation with yield strain (r2 = 0.58, n = 53, p = 0.07). Prediction errors, incurred when estimating modulus or strength for specimens from a new donor, were 30-36% of the mean values of these properties. Direct QCT density-mechanical property regressions gave more precise predictions of mechanical properties than if physically measured wet apparent density was used as an intermediate variable to predict mechanical properties from QCT density. Use of these QCT density-mechanical property regressions should improve the fidelity of QCT-based biomechanical models of the human spine for whole bone and bone-implant analyses.

Adult↗

PubMedDate not supplied

Damage in trabecular bone at small strains.

Evidence that damage decreases bone quality, increases fracture susceptibility, and serves as a remodeling stimulus motivates further study of what loading magnitudes induce damage in trabecular bone. In particular, whether damage occurs at the smaller strains characteristic of habitual, as opposed to traumatic, loading is not known. The overall goal of this study was to characterize damage accumulation in trabecular bone at small strains (0.20 - 0.45% strain). A continuum damage mechanics approach was taken whereby damage was quantified by changes in modulus and residual strain. Human vertebral specimens (n = 7) were tested in compression using a multi-cycle load - unload protocol in which the maximum applied strain for each cycle, epsilonmax, was increased incrementally from epsilonmax = 0.20% on the first loading cycle to epsilonmax = 0.45% on the last cycle. Modulus and residual strain were measured for each cycle. Both changes in modulus and residual strains commenced at small strains, beginning as early as 0.24 and 0.20% strain, respectively. Strong correlations between changes in modulus and residual strains were observed (r = 0.51 - 0.98). Fully nonlinear, high-resolution finite element analyses indicated that even at small apparent strains, tissue-level strains were sufficiently high to cause local yielding. These results demonstrate that damage in trabecular bone occurs at apparent strains less than half the apparent compressive yield strain reported previously for human vertebral trabecular bone. Further, these findings imply that, as a consequence of the highly porous trabecular structure, tissue yielding can initiate at very low apparent strains and that this local failure has detectable and negative consequences on the apparent mechanical properties of trabecular bone.

Biomechanical Phenomena↗