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Ozan Akkus

Publications and source records attributed to Ozan Akkus.

10 recordsLinked to original sources
PubMed2006

The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade.

The temporal and spatial fluctuations in the dynamics of secondary osteonal remodeling impart heterogeneity to the compositional quality of bone. Bone mineral density (BMD) fails to reflect this heterogeneity as being a single score, and thus it cannot resolve the overlap between healthy individuals and those who experience fractures. Such information on tissue heterogeneity is lacking in the literature. In the current study, specimens were prepared from mid-diaphyseal portions of human femora (N=16, age range 52-85 years old) and grouped based on the anatomical location (anterior, lateral, medial and posterior quadrants). Raman microscopy was used to obtain multiple measurements from each specimen which allowed the construction of histograms of mineralization, crystallinity and carbonation. The coefficient of variation (COV) and skewness were extracted from histograms as measures of heterogeneity. Results demonstrated that average mineralization of the medial quadrant and the data pooled over quadrants significantly increased with age. The mean carbonation increased within the observed age range for the pooled data. The variations of values about the mean became tighter for mineralization, crystallinity and type-B carbonation with age, indicating an overall reduction in compositional heterogeneity of aging femoral cortex. Skewness values indicated that the distributions of histograms were not Gaussian. We conclude that age-related changes in mean tissue composition are confounded with changes in the variation of tissue make-up about the mean. Future studies will establish as to whether compositional heterogeneity correlates with the mechanical strength of bone.

Aged↗
PubMed2005

Sterilization by gamma radiation impairs the tensile fatigue life of cortical bone by two orders of magnitude.

Cortical bone grafts are utilized frequently for skeletal reconstruction, spinal fusion and tumor surgery. Due to its efficacy and convenience terminal sterilization by gamma radiation is often essential to minimize disease transmission and infection. However, the impairment in the material properties of bone tissue secondary to gamma radiation sterilization is a concern since the mechanical functionality of a bone graft is of primary importance. While the extent of this impairment is well investigated for monotonic loading conditions, there does not seem to exist any information on the effects of gamma radiation sterilization on cortical bone's fatigue properties, the physiologically relevant mode of loading. In this study we investigated the degradation in the high-cycle and low-cycle tensile fatigue lives of cortical bone tissue secondary to gamma radiation sterilization at a dose of 36.4 kGy which approximately falls in the higher end of the standard dose range used in tissue banking. The high-cycle and the low-cycle fatigue tests were conducted under load control at initial strain levels of 0.2% and 0.4%, respectively. Monotonic tensile tests were also conducted to compare the impairment of fatigue properties with the impairment of monotonic properties. Results demonstrated that the impairment in both the high-cycle and the low-cycle fatigue lives were two orders of magnitude following sterilization, a change much more pronounced than that observed for monotonic loading. In conclusion, the results suggest that the impairment of the mechanical function of gamma radiation sterilized allografts is even worse in fatigue than monotonically. Therefore, grafts should be designed to minimize functional strains and avoid stress raisers to prevent premature fatigue failures.

Adult↗
PubMed2005

Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue.

Terminal sterilization of bone allografts by gamma radiation is often essential prior to their clinical use to minimize the risk of infection and disease transmission. While gamma radiation has efficacy superior to other sterilization methods it also impairs the material properties of bone allografts, which may result in premature clinical failure of the allograft. The mechanisms by which gamma radiation sterilization damages bone tissue are not well known although there is evidence that the damage is induced via free radical attack on the collagen. In the light of the existing literature, it was hypothesized that gamma radiation induced biochemical damage to bone's collagen that can be reduced by scavenging for the free radicals generated during the ionizing radiation. It was also hypothesized that this lessening of the extent of biochemical degradation of collagen will be accompanied by alleviation in the extent of biomechanical impairment secondary to gamma radiation sterilization. Standardized tensile test specimens machined from human femoral cortical bone and specimens were assigned to four treatment groups: control, scavenger treated-control, irradiated and scavenger treated-irradiated. Thiourea was selected as the free radical scavenger and it was applied in aqueous form at the concentration of 1.5 M. Monotonic and cyclic mechanical tests were conducted to evaluate the mechanical performance of the treatment groups and the biochemical integrity of collagen molecules were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native mechanical properties of bone tissue did not change by thiourea treatment only. The effect of thiourea treatment on mechanical properties of irradiated specimens were such that the post-yield energy, the fracture energy and the fatigue life of thiourea treated-irradiated treatment group were 1.9-fold, 3.3-fold and 4.7-fold greater than those of the irradiated treatment group, respectively. However, the mechanical function of thiourea treated and irradiated specimens was not to the level of unirradiated controls. The damage occurred through the cleavage of the collagen backbone as revealed by SDS PAGE analysis. Irradiated specimens did not exhibit a noteworthy amount of intact alpha-chains whereas those irradiated in the presence of thiourea demonstrated intact alpha-chains. Results demonstrated that free radical damage is an important pathway of damage, caused by cleaving the collagen backbone. Blocking the activity of free radicals using the scavenger thiourea reduces the extent of damage to collagen, helping to maintain the mechanical strength of sterilized tissue. Therefore, free radical scavenger thiourea has the potential to improve the functional life-time of the allograft component following transplantation.

Adult↗
PubMed2005

Elastic deformation of mineralized collagen fibrils: an equivalent inclusion based composite model.

Mineralized collagen fibrils are the basic building blocks of bone tissue at the supramolecular level. Several disease states, manipulation of the expression of specific proteins involved in biomineralization, and treatment with different agents alter the extent of mineralization as well as the morphology of mineral crystals which in turn affect the mechanical function of bone tissue. An experimental assessment of mineralized fibers' mechanical properties is challenged by their small size, leaving analytical and computational models as a viable alternative for investigation of the fibril-level mechanical properties. In the current study the variation of the elastic stiffness tensor of mineralized collagen fibrils with changing mineral volume fraction and mineral aspect ratios was predicted via a micromechanical model. The partitioning of applied stresses between mineral and collagen phases is also predicted for normal and shear loading of fibrils. Model predictions resulted in transversely isotropic collagen fibrils in which the modulus along the longer axis of the fibril was the greatest. All the elastic moduli increased with increasing mineral volume fraction whereas Poisson's ratios decreased with the exception of v12 (=v21). The partitioning of applied stresses were such that the stresses acting on mineral crystals were about 1.5, 15, and 3 times greater than collagen stresses when fibrils were loaded transversely, longitudinally, and in shear, respectively. In the overall the predictions were such that: (a) greatest modulus along longer axis; (b) the greatest mineral/collagen stress ratio along the longer axis of collagen fibers (i.e., greatest relief of stresses acting on collagen); and (c) minimal lateral contraction when fibers are loaded along the longer axis. Overall, the pattern of mineralization as put forth in this model predicts a superior mechanical function along the longer axis of collagen fibers, the direction which is more likely to experience greater stresses.

Animals↗
PubMed2004

Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone.

The measures of bone mass and architecture need to be supplemented with physicochemical and compositional measures for better assessment of fracture risk. In the current studies, we investigated the effects of physicochemical properties of mineral crystals on tissue and organ-level mechanical function of aging rat cortical bone. Our hypothesis was that age-related changes in physicochemical properties of mineral crystals are related to impaired elastic deformability of cortical bone tissue. Raman microspectroscopy was used to investigate the age-related changes in mineralization (relative amounts of mineral and organic matrix), the substitution of carbonate ions in phosphate positions (type-B carbonate substitution) and mineral crystallinity (the orderliness of crystal lattice) of femurs from young adult (3-month old), middle-aged (8-month old) and aged (24-month old) female Sprague-Dawley rats. Cross-sectional properties, the area and the moment of inertia at the mid-diaphysis, were histomorphometrically quantified and the elastic deformation capacity of femurs was quantified via three-point bending tests. It was observed that the elastic deformation capacity of aged rats was significantly impaired both at the tissue and the organ levels with increasing age. In parallel with this impairment in the elastic deformability and in support of our hypothesis, we found that increasing mineralization, increasing crystallinity and increasing type-B carbonate substitution were significantly correlated with decreasing elastic deformation capacity with age. We conclude that the measure of bone mass needs to be supplemented with measures reflecting the physicochemical status of mineral crystals for improved assessment of fracture susceptibility.

Aging↗
PubMed2004

Fracture mechanics of cortical bone tissue: a hierarchical perspective.

The performance of bone tissue in the presence of flaws is a highly remarkable one. Bone tissue is the outcome of an adaptive evolutionary process; thus, insight into the mechanisms by which it fails would provide valuable information not only for development of mechanically superior biomimetic materials but also for development of treatment modalities to prevent debilitating bone fractures. Clinically, fractures of skeletal organs occur as a result of aging, disease, overuse, and trauma. Fracture mechanics, a sub-discipline of solid mechanics that investigates the performance of cracked materials, has been employed extensively in characterizing the mechanisms by which bone tissue fractures. At present the fracture mechanisms at the macroscale are better characterized than at the microscale. On the other hand, a mechanistic understanding of damage evolution at the submicroscopic scale is largely limited to postulations with little experimental insight. The challenge of skeletal fragility will be dealt with more efficiently with deeper understanding of the fracture process at each hierarchical size scale. The most recent review on this subject matter was a decade ago, and there have been numerous developments in the fracture mechanics of bone since then. This review recaps the existing literature with an emphasis on the hierarchical nature of the fracture process in bone, entailing the supramolecular, microscopic, and macroscopic scales.

Animals↗
PubMed2003

Relationship between damage accumulation and mechanical property degradation in cortical bone: microcrack orientation is important.

The accumulation of damage and the associated degradation of the mechanical properties of cortical bone are postulated to contribute to age-, disease-, overuse-, and disuse-related skeletal fragilities. Therefore, gaining insight into the relationship between damage and degradation processes is essential in understanding the etiology of skeletal fractures. In investigating this relationship, the damage measure ideally needs to account for the size, the distribution density, and the orientation of microcracks. Existing measures of damage address the size and distribution density of microcracks; however, the orientation of cracks has not been well-investigated. Because the overall orientation of microcracks determines the material axis along which the greatest degradation will be experienced, we hypothesized that the incorporation of the relative orientation between microcracks and loading direction will improve the significance of the relationship between damage accumulation and material property degradation. A three-cycle damage protocol was used to induce tensile damage and to quantify the degradation of the elastic modulus of specimens from human donor femoral cortical bone (a 24-year-old and a 72-year-old man). Microcracks were evaluated by en bloc basic fuchsin staining of specimens after testing. The length (L(i)) and the orientation with respect to the loading direction (beta(i)) of each crack were quantified by a video microscopy system. Three damage measures were quantified for each specimen: the number of linear microcracks (Cr #), the sum of the crack lengths (SigmaL(i)) accounting for the microcrack size alone, and the sum of the projected crack length [SigmaL(Pi) = SigmaL(i)cos(beta(i))] accounting for both crack size and orientation. Inclusion of the orientation parameter improved the coefficient of determination between damage accumulation and the degradation of the elastic modulus: the coefficient of determination of the sum of the projected crack length (R(2) = 0.239) was 60% greater than that of the sum the projected crack length (R(2) = 0.149) and 33% greater than that of the number of linear microcracks (R(2) = 0.180). We conclude that microcrack orientation is an essential physical variable in the relationship between damage accumulation and degradation of mechanical properties of cortical bone tissue.

Adult↗
PubMed2003

Aging of microstructural compartments in human compact bone.

Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the osteons and similar to the "fully mineralized" stage of primary bone. The results of this study demonstrated that unremodeled compartments of bone grow older through maturation and growth of mineral crystals in a protracted fashion. However, the secondary osteonal remodeling impedes this aging process and maintains the mean tissue age fairly constant over decades. Therefore, slowing of remodeling may lead to brittle bone tissue through accumulation of fully mineralized tissue fragments.

Adolescent↗
PubMedDate not supplied

Microcracks colocalize within highly mineralized regions of cortical bone tissue.

While much work has been performed to quantify the extent of bone damage, its effects on the mechanical integrity of the tissue and its biological impact, the set of factors which gives forth to microdamage are nebulous, particularly the compositional properties local to microdamage. In this context, the current study tested the hypothesis that microcracks initiate within more mineralized regions of bone. Cortical bone specimens were taken from human male donors aged 31, 38, 53, 64, 71, and 84 years at the mid femoral diaphysis in a plane parallel to the osteonal orientation. The mineralization was assessed in a spatially resolved manner using Raman microspectroscopy. Arrays of measurements were taken over the entire area (i.e. global scans) of each sample followed by measurements in the vicinity of microcracks (i.e. local scans). Histograms of mineralization were constructed for global and local scans to determine whether the mineralization of damaged loci differed from the mean overall mineralization. Statistical analysis of this data revealed that the mean mineralization of damaged loci was significantly greater (P < 0.05) than the overall mineralization for each donor, indicating that there exists a highly-mineralized 'brittle volume' in bone. The presence of this damage prone 'brittle volume' has future implications for the assessment of fracture susceptibility.

Adult↗