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Biomedical subjects

L J Gibson

Publications and source records attributed to L J Gibson.

34 records · Page 2Linked to original sources

The tensile behavior of demineralized bovine cortical bone.

Bone is frequently modeled as a two-phase composite of hydroxyapatite mineral crystals dispersed throughout an organic collagen matrix. However, because of the numerous limitations (e.g. small sample size, poor strain measuring techniques, rapid demineralization with acids) of previous mechanical tests of bone with its hydroxyapatite chemically removed, we have determined new, accurate data on the material properties of the demineralized bone matrix for use in these composite models. We performed tensile tests on waisted specimens of demineralized bovine cortical bone from six humeral diaphyses. Specimens were demineralized over 14 days with a 0.5 M disodium EDTA solution that was replaced daily. Atomic absorption spectrophotometry was used to track the demineralization process and to determine the effectiveness of our demineralization protocol. Mechanical tests were performed at room temperature under displacement control at an approximate strain rate of 0.5% per s. We imposed nine preconditioning cycles before a final ramp to failure, and measured gauge length displacements using a non-invasive optical technique. The resulting stress-strain curves were similar to the tensile behavior observed in mechanical tests of other collagenous tissues, exhibiting an initial non-linear 'toe' region, followed by a linear region and subsequent failure without evidence of yielding. We found an average modulus, ultimate stress, and ultimate strain of 613 MPa (S.D. = 113 MPa), 61.5 MPa (S.D. = 13.1 MPa), and 12.3% (S.D. = 0.5%), respectively. Our average modulus is approximately half the value frequently used in current composite bone analyses. These data should also have clinical relevance because the early strength of healing fractured bone depends largely on the material properties of the collagen matrix.

Analysis of Variance↗

Effects of selected thermal variables on the mechanical properties of trabecular bone.

Osteoarticular allografts are commonly used in the treatment of segmental bone loss due to a wide resection of tumour. While the use of such grafts has met with considerable clinical success, fractures are a recognized complication of allograft use. Although trabecular bone can play an important structural role in the function of segmental allografts, few data exist on the effects of common storage and sterilization procedures on the mechanical properties of trabecular bone. To this end, we investigated with these experiments the effects of freezing at -20 degrees C, freezing at -70 degrees C, eight freeze-thaw cycles at -20 degrees C, freeze-drying, boiling and autoclaving on the compressive modulus and strength of bovine trabecular bone. Of these treatments, boiling and autoclaving were the only treatments to alter the properties of bovine trabecular bone, resulting in 26 and 58% reductions in strength, respectively. Autoclaving also significantly reduced the compressive modulus by 59%. From these data, freezing at temperatures between -20 and -70 degrees C does not appear to compromise the structural integrity of trabecular bone.

Animals↗

Improving the cost, quality, and access to healthcare in community hospitals through the use of reorganized integrated delivery systems and implementation of sophisticated clinical information systems: an organizational experience.

It is well recognized that health care is undergoing fundamental and necessary change. These changes rival, if not exceed, changes that have occurred in other industries. The factors underlying the changes are varied, but fundamentally, the economics of health care have altered. A new economic model is evolving that is disciplined by the marketplace and/or regulatory determination of "price" on a per capita basis. Success in this new model will require integrated delivery systems (IDS) serving local communities linked to purchasers through affiliations that span broader geographic areas. The demands of this model are placing unparalleled requirements for change on health care providers including the need to develop new forms of delivery systems and implement sophisticated new information systems that allow collection and detailed analysis of important clinical and financial data in an effort to achieve better value in health care. A case study of the Health and Hospital Services, Inc. (HHS) integrated delivery system and information system strategy will be discussed.

Community Health Planning↗

Compressive creep behavior of bovine trabecular bone.

There are almost no published data that describe the creep behavior of trabecular bone (at the specimen level), even though the creep behavior of cortical bone has been well documented. In an effort to characterize the creep behavior of trabecular bone and to compare it with that of cortical bone, we performed uniaxial compressive creep tests on 24 cylindrical specimens of trabecular bone taken from 19 bovine proximal tibiae. Six different load levels were used, with the applied stress normalized by the specimen modulus measured prior to creep loading. We found that trabecular bone exhibits the three creep regimens (primary, secondary, and tertiary) associated with metals, ceramics, and cortical bone. All specimens eventually fractured at strains less than 3.8%. In addition, the general shape of the creep curve was independent of apparent density. Strong and highly significant power law relationships (r2 > 0.82, p < 0.001) were found between the normalized stress sigma/E0 and both time-to-failure tf and steady-state creep rate d epsilon/dt: tf = 9.66 x 10(-33) (sigma/E0)-16.18; d epsilon/dt = 2.21 x 10(33) (sigma/E0)17.65. These data indicate that the creep behaviors of trabecular and cortical bone are qualitatively similar. In addition, the strength of trabecular bone can be reduced substantially if relatively large stresses (i.e. stresses approximately half the ultimate strength) are applied for 5 h. Such strength reductions may play a role in the etiology of progressive, age-related spine fractures if adaptive bone remodeling does not arrest creep deformations.

Aging↗

Finite element modeling of damage accumulation in trabecular bone under cyclic loading.

A two-dimensional finite element model of an idealized trabecular bone specimen was developed to study trabecular bone damage accumulation during cyclic compressive loading. The specimen was modeled as a two-dimensional honeycomb-like structure made up of an array of hexagonal cells. Each trabecula was modeled as a linearly elastic beam element with the same material properties as cortical bone. Initial microcracks were assumed to exist within the oblique trabeculae and to grow according to the Paris law. Forces and moments were computed in each trabecula and the microcracks were allowed to propagate until fracture occurred. Between cycles, fractured trabeculae were removed from the finite element mesh, and force and moment distributions were calculated for the next cycle. This iterative process was continued until the simulated trabecular bone specimen showed a 10% reduction in modulus. Creep failure was also studied using a single cell analysis, in which a closed-form solution was obtained after prescribing the creep properties of the trabeculae. The results of the crack propagation analysis showed that fractures of only a small number of individual trabeculae can cause a substantial reduction in the modulus of the trabecular bone specimen model. Statistical tests were performed to compare the slopes and intercepts of the S-N curves of our model predictions to those of experimentally derived S-N curves for bovine trabecular bone. There was no significant difference (p > 0.2 for both slope and intercept) between our model predictions and the experimentally derived S-N curves for the low-stress, high-cycle range. For the high-stress, low-cycle range, the crack propagation model overestimated the fatigue life for a given stress level (for slope, p < 0.001), while the creep analysis agreed well with the experimental data (for slope, p > 0.2). These findings suggest that the primary failure mechanism for low-stress, high-cycle fatigue of trabecular bone is crack growth and propagation, while the primary failure mechanism for high-stress, low-cycle fatigue is creep deformation and fracture. Furthermore, our results suggest that the modulus of trabecular bone at the specimen level may be highly sensitive to fractures of individual trabeculae.

Algorithms↗

Static circumferential tangential modulus of human atherosclerotic tissue.

The mechanical properties of atherosclerotic plaque may be of critical importance to the processes of plaque rupture, the most common antecedent of myocardial infarction. To investigate the effects of plaque structure and applied tensile stress on the static circumferential tangential modulus of atherosclerotic plaque, the stress-strain behavior of 26 human aortic intimal plaques was studied. Intimal plaques were collected during routine autopsies of 21 patients from the abdominal (n = 19) and thoracic (n = 2) aorta and were classified by histological analysis as cellular (n = 12), hypocellular (n = 9), and calcified (n = 5). At a physiologic applied circumferential tensile stress of 25 kPa, the tangential moduli of cellular, hypocellular, and calcified specimens were 927 +/- 468 kPa, 2312 +/- 2180 kPa, and 1466 +/- 1284 kPa, respectively. There was a nonsignificant difference in tangential modulus at 25 kPa stress between specimens classified as cellular and hypocellular (p = 0.098), cellular and calcified (p = 0.410), and hypocellular and calcified (p = 0.380). This is in marked contrast to the previously measured radial compressive behavior of plaque tissue, which showed that cellular, hypocellular, and calcified plaques were significantly different in their modulus. In tension, all 26 plaques tested demonstrated a statistically significant increase in tangential modulus with increasing applied circumferential stress. We conclude that the static circumferential tangential modulus of atherosclerotic plaque, unlike its radial compressive modulus, is not significantly affected by the degree of cellularity and calcification determined by histological characterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Mutational analysis of human papillomavirus E4 proteins: identification of structural features important in the formation of cytoplasmic E4/cytokeratin networks in epithelial cells.

We have previously demonstrated that human papillomavirus type 1 (HPV 1) and 16 (HPV 16) E4 proteins form cytoplasmic filamentous networks which specifically colocalize with cytokeratin intermediate-filament (IF) networks when expressed in simian virus 40-transformed keratinocytes. The HPV 16 (but not the HPV 1) E4 protein induced the collapse of the cytokeratin networks. (S. Roberts, I. Ashmole, G. D. Johnson, J. W. Kreider, and P. H. Gallimore, Virology 197:176-187, 1993). The mode of interaction of E4 with the cytokeratin IFs is unknown. To identify E4 sequences important in mediating this interaction, we have constructed a large panel of mutant HPV (primarily HPV 1) E4 proteins and expressed them by using the same simian virus 40-epithelial expression system. Mutation of HPV 1 E4 residues 10 to 14 (LLGLL) abrogated the formation of cytoplasmic filamentous networks. This sequence corresponds to a conserved motif, LLXLL, found at the N terminus of other E4 proteins, and similar results were obtained on deletion of the HPV 16 motif, LLKLL (residues 12 to 16). Our findings indicate that this conserved motif is likely to play a central role in the association between E4 and the cytokeratins. An HPV 1 E4 mutant protein containing a deletion of residues 110 to 115 induced the collapse of the cytokeratin IFs in a manner analogous to the HPV 16 E4 protein. The sequence deleted, DLDDFC, is highly conserved between cutaneous E4 proteins. HPV 1 E4 residues 42 to 80, which are rich in charged amino acids, appeared to be important in the cytoplasmic localization of E4. In addition, we have mapped the N-terminal residues of HPV 1 E4 16-kDa and 10/11-kDa polypeptides expressed by using the baculovirus system and shown that they begin at tyrosine 16 and alanine 59, respectively. Similar-sized E4 proteins are also found in vivo. N-terminal deletion proteins, which closely resemble the 16-kDa and 10/11-kDa species, expressed in keratinocytes were both cytoplasmic and nuclear but did not form cytoplasmic filamentous networks. These findings support the postulate that N-terminal proteolytic processing of the E1-- E4 protein may modulate its function in vivo.

Adult↗

Mechanical properties of model atherosclerotic lesion lipid pools.

Structural analysis of atherosclerotic coronary arteries has suggested that stress concentrations are associated with plaque rupture and that these stress concentrations are critically dependent on the geometry and mechanical properties of the fibrous cap and lipid pool. Recent clinical trials of lipid-lowering therapy have shown a significant reduction in cardiac events associated with plaque rupture perhaps because of the changing composition of subintimal lipid pools. To test the hypothesis that changes in lipid composition can change the mechanical properties of lipid pools, we measured the dynamic shear moduli of combinations of cholesterol monohydrate crystals, phospholipids, and triglycerides similar to those found in atherosclerotic lesions. Increasing the cholesterol monohydrate concentration from 0% to 50% increased the real component of the dynamic shear modulus (storage modulus or stiffness) by 4.5 times at a frequency of 1 Hz (P < .001). All specimens demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.1 to 3 Hz. We conclude that the stiffness of model atherosclerotic plaque lipid pools is related to the concentration of cholesterol monohydrate crystals. Because the relative concentration of cholesterol monohydrate increases during early regression of experimental atherosclerosis, the resultant stiffening of the lipid pool may reduce stresses in plaque caps. However, the magnitude of the contribution of changing lipid stiffness to the reduction of cardiac events seen in clinical studies is unclear.

Arteriosclerosis↗

Trabecular bone modulus and strength can depend on specimen geometry.

We performed a series of uniaxial compression tests on wet bovine trabecular bone to compare both modulus and strength when measured using 2:1 aspect ratio (10 mm long, 5 mm diameter) cylinders (n = 30) and 5 mm cubes (n = 29). We also compared the correlation coefficients in the resulting modulus-density and strength-density regressions and the standard errors of the estimate. When comparing the mean values of modulus and strength for each group, the confounding variations in apparent density were accounted for with an analysis of covariance. The Fisher's Z transformation was used to compare the correlation coefficients statistically. Results from the analysis of covariance indicated that the modulus and strength of the cubes were higher by 36% (p < 0.01) and 18% (p < 0.05), respectively, with respect to the 2:1 cylinder values. The correlation coefficients in the modulus-density and strength-density regressions were not sensitive to the regression model (linear versus power law). However, correlation coefficients for both modulus-density and strength-density regressions were higher (p < 0.05) for the 2:1 cylinders (r = 0.90, modulus; r = 0.94, strength) than for the cubes (r = 0.57, modulus; r = 0.82, strength). In addition, the standard errors of the estimate in both modulus and strength were substantially lower for the 2:1 cylinders. These data indicate that both modulus and strength can depend on the specimen geometry when using conventional compression testing techniques. We conclude, therefore, that inter-study comparisons of modulus and strength may be invalid if these confounding effects of different specimen geometries are not addressed. Our data also indicate that density can better explain the observed variance in modulus and strength when 2:1 cylinders are used as opposed to cubes. Using this phenomenon as a rationale for choosing a standard specimen gometry, we recommend that the 2:1 cylinder be used as a standard specimen in studies designed to determine the effects of various treatments on the uniaxial compressive modulus and strength of trabecular bone.

Animals↗

Frontal lobe functioning in conduct disordered juveniles: preliminary findings.

This investigation assessed the hypothesis that conduct disordered juveniles may suffer from a maturational lag in the development of behaviors believed associated with the frontal cortex. Twenty conduct disorder (CD) juveniles and 20 normal comparison subjects were compared on nine Lurian tasks that measure behavior attributed to frontal lobe functioning. A three-way ANOVA, with gender, race, and group as factors of interest, revealed significant differences on the verbal conflict task, verbal retroactive inhibition task, and on a measure of receptive vocabulary. Using receptive vocabulary as a covariate, an ANCOVA showed no significant differences between the groups on any of the tasks. These findings appear to support the potential impact that language dysfunction can have in the development of disinhibitory behavior. Other interpretations of the findings are presented.

Journal Article↗

The mechanical behaviour of cancellous bone.

Cancellous bone has a cellular structure: it is made up of a connected network of rods and plates. Because of this, its mechanical behaviour is similar to that of other cellular materials such as polymeric foams. A recent study on the mechanisms of deformation in such materials has led to an understanding of how their mechanical properties depend on their relative density, cell wall properties and cell geometry. In this paper, the results of this previous study are applied to cancellous bone in an attempt to further understand its mechanical behaviour. The results of the analysis agree reasonably well with experimental data available in the literature.

Animals↗

Compressive fatigue behavior of bovine trabecular bone.

We studied the fatigue behavior of bovine trabecular bone specimens under stress control using a sinusoidal uniaxial compressive load profile with a frequency of 2 Hz. The stress range was determined from the corresponding initial global platen-to-platen strain range, where the maximum initial strain was between 0.8 and 2.1% and the minimum strain was 0.6%. The local strain distribution was measured on the same type of specimen by affixing glass spheres and photographing them in the unloaded and loaded positions using multiple exposures. The number of cycles to failure (defined as a 5% decrease in secant modulus) was strongly correlated with the initial global maximum strain (r2 = 0.78) and ranged from 20 cycles at 2.1% strain to 400,000 cycles at 0.8% strain. All of the fatigue specimens showed a region of transverse failure approximately 1 mm from the end of the specimen. Microscopic examination of the failure zones revealed two failure modes: a straight transverse brittle-like fracture through the trabeculae, most often found in trabeculae transverse to the loading direction, and buckling-like failure, common in oblique trabeculae, involving bending and splitting. The local strain increased towards the ends of the specimens to a value 2-4 times that in the middle. Modulus degradation with the number of cycles was distinctively different for high-cycle and low-cycle fatigue, suggesting the possibility that both creep and damage accumulation contribute to fatigue failure of trabecular bone.

Animals↗

Theoretical analysis of the experimental artifact in trabecular bone compressive modulus.

A theoretical analysis was performed to characterize potential experimental artifacts in conventional compression testing of trabecular bone, where strains are based on the relative displacements of the two loading platens. We assumed that the total experimental artifact for modulus was the sum of a damage and friction artifact and derived equations to describe these artifacts. The two unknown constants in these equations were found using a combination of data derived from linear finite element analyses and in vitro uniaxial compression tests. Subsequent finite element analyses allowed estimation of the artifacts for a wide range of specimens (cube, 1:4-3:1 aspect ratio cylinders). If friction is completely eliminated at the specimen-platen interface, the Young's modulus of a 5 mm sized (1:1 aspect ratio dimension) specimen which has a damage artifact due to machining may be underestimated by at least 45% regardless of specimen geometry; otherwise, the platens modulus may vary from less than 30 to over 175% of the Young's modulus, depending upon the specimen geometry and Poisson's ratio of the bone. Increasing the specimen size reduces the artifact only slightly. Since Poisson's ratio can be large for trabecular bone and is rarely known a priori, the precision of the conventional compression test will, therefore, be poor unless friction is completely eliminated at the specimen-platen interface. However, without friction at the interface, the platens modulus will always underestimate Young's modulus, thereby reducing the accuracy of this test. There was also evidence that the strength may be affected by these artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗

Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium.

Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells.

Actins↗