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Medical & Biological Engineering &... Nov 2023The current study aims to simulate fatigue microdamage accumulation in glycated cortical bone with increased advanced glycation end-products (AGEs) using a phase field...
The current study aims to simulate fatigue microdamage accumulation in glycated cortical bone with increased advanced glycation end-products (AGEs) using a phase field fatigue framework. We link the material degradation in the fracture toughness of cortical bone to the high levels of AGEs in this tissue. We simulate fatigue fracture in 2D models of cortical bone microstructure extracted from human tibias. The results present that the mismatch between the critical energy release rate of microstructural features (e.g., osteons and interstitial tissue) can alter crack initiation and propagation patterns. Moreover, the high AGEs content through the increased mismatch ratio can cause the activation or deactivation of bone toughening mechanisms under cyclic loading. The fatigue fracture simulations also show that the lifetime of diabetic cortical bone samples can be dependent on the geometry of microstructural features and the mismatch ratio between the features. Additionally, the results indicate that the trapped cracks in cement lines in the diabetic cortical microstructure can prevent further crack growth under cyclic loading. The present findings show that alterations in the materials heterogeneity of microstructural features can change the fatigue fracture response, lifetime, and fragility of cortical bone with high AGEs contents. Cortical bone models are created from microscopy images taken from the cortical cross-section of human tibias. Increased glycation contents in the cortical bone sample can change the crack growth trajectories.
Topics: Humans; Biomechanical Phenomena; Cortical Bone; Diabetes Mellitus; Fractures, Bone; Fractures, Stress; Glycation End Products, Advanced; Glycopyrrolate; Stress, Mechanical
PubMed: 37582979
DOI: 10.1007/s11517-023-02901-3 -
Bone Nov 2023Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis....
Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1-34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER). Two groups (n = 7 each) of six-month old female New Zealand white rabbits were both administered 30 μg/kg of PTH once daily for a period of two weeks to induce remodeling. Their distal right tibiae were then imaged in vivo by in-line phase contrast micro-CT at the Canadian Light Source synchrotron. Over the following two weeks the first group (PTH) received continued daily PTH while the second withdrawal group (PTHW) was administrated 0.9 % saline. At four weeks all animals were euthanized, their distal tibiae were imaged by conventional micro-CT ex vivo and histomorphometry was performed. Matching micro-CT datasets (in vivo and ex vivo) were co-registered in 3D and LER was measured from 612 BMUs. Counter to our hypothesis, mean LER was lower (p < 0.001) in the PTH group (30.19 ± 3.01 μm/day) versus the PTHW group (37.20 ± 2.77 μm/day). Despite the difference in LER, osteonal mineral apposition rate (On.MAR) did not differ between groups indicating the anabolic effect of PTH was sustained after withdrawal. The slowing of BMU progression by PTH warrants further investigation; slowed resorption combined with elevated bone formation rate, may play an important role in how PTH enhances coupling between resorption and formation within the BMU. Finally, the prolonged anabolic response following withdrawal may have utility in terms of optimizing clinical dosing regimens.
Topics: Rabbits; Female; Animals; Parathyroid Hormone; Tibia; Bone Density; Canada; Osteoporosis; Cortical Bone
PubMed: 37574096
DOI: 10.1016/j.bone.2023.116864 -
Journal of Anatomy Dec 2023"Rauisuchia" is a non-monophyletic group of quadrupedal and carnivorous pseudosuchians that inhabited the entire world during the Middle-Upper Triassic period...
Palaeobiological inferences of "rauisuchians" Fasolasuchus tenax (Los Colorados Fm., Argentina) and Prestosuchus chiniquensis (Santa Maria Super sequence, Brazil) from the Middle-Upper Triassic of South America based on microstructural analyses.
"Rauisuchia" is a non-monophyletic group of quadrupedal and carnivorous pseudosuchians that inhabited the entire world during the Middle-Upper Triassic period (Anisian/Ladinian-Rhaetian). In South America, "rauisuchians" reached the largest sizes among continental carnivores. Despite their important ecological role, some aspects of their palaeobiology have been poorly examined. Here, we study appendicular bones, dorsal ribs and osteoderms of two genera, the Argentinean Fasolasuchus tenax (PVL 3850, holotype) and the Brazilian Prestosuchus chiniquensis (SNSB-BSPG AS XXV) respectively. The femur of F. tenax is formed by laminar fibrolamellar bone, which is composed of non-fully monorefringent woven-fibred matrix and primary osteons; the dorsal rib has a Haversian bone composition with an external fundamental system recorded and the osteoderm is formed by well-organised parallel-fibred bone. The femur, humerus and fibula of P. chiniquensis are mostly composed of strongly arranged parallel-fibred bone and a laminar vascularisation. The minimal ages obtained correspond to 9 years for F. tenax (based on the maximum number of growth marks in the osteoderm) and 4 years for P. chiniquensis (obtained from the highest count of growth marks in the femur and in the humerus). F. tenax attained somatic and skeletal maturity, while P. chiniquensis was near to reaching skeletal and sexual maturity, but it was somatically immature. The overall rapid growth rate and the high and uniform vascularisation seems to imply that these features are common in most of "rauisuchians", except in P. chiniquensis.
Topics: Brazil; Argentina; Colorado; Ribs; Femur; Fossils
PubMed: 37519277
DOI: 10.1111/joa.13937 -
American Journal of Biological... Oct 2023In modern bone biology, the term "remodeling" generally refers to internal bone turnover that creates secondary osteons. However, it is also widely used by skeletal... (Review)
Review
OBJECTIVES
In modern bone biology, the term "remodeling" generally refers to internal bone turnover that creates secondary osteons. However, it is also widely used by skeletal biologists, including biological anthropologists as a catch-all term to refer to different skeletal changes. In this review, we investigated how "remodeling" is used across topics on skeletal biology in biological anthropology to demonstrate potential problems with such pervasive use of a generalized term.
METHODS
Using PubMed and Google Scholar, we selected and reviewed 205 articles that use the term remodeling to describe skeletal processes and have anthropological implications. Nine edited volumes were also reviewed as examples of collaborative work by different experts to demonstrate the diverse and extensive use of the term remodeling.
RESULTS
Four general meanings of bone "remodeling" were identified, namely, internal turnover, functional adaptation, fracture repair, and growth remodeling. Additionally, remodeling is also used to refer to a broad array of pathological skeletal changes.
DISCUSSION
Although we initially identified four general meanings of bone remodeling, they are not mutually exclusive and often occur in combination. The term "remodeling" has become an extensively used catch-all term to refer to different processes and outcomes of skeletal changes, which inevitably lead to misunderstanding and a loss of information. Such ambiguity and confusion are potentially problematic as the field of biological anthropology becomes increasingly multidisciplinary. Therefore, we advocate for precise, context-specific definitions and explanations of bone remodeling as it continues to be used across disciplines within and beyond biological anthropology.
Topics: Anthropology; Bone and Bones; Bone Remodeling
PubMed: 37515465
DOI: 10.1002/ajpa.24825 -
Journal of the Mechanical Behavior of... Sep 2023This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To...
This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, which represented osteons and interstitial tissue, loaded in uniaxial tension. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber "families." Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created by modeling aging via the following changes to the input parameters: (i) increasing porosity from 5% to 15%, (ii) increasing the ratio of the number of osteon fibers relative to interstitial fibers from 40% to 50%, and (iii) changing the fiber material properties from representing mature bone samples to representing elderly bone samples (i.e., increased strength and decreased toughness of interstitial fibers together with decreased toughness of osteon fibers). To understand the respective contributions of these changes, additional models isolating one or two of each of these were also created. From the computed stress-strain curve for the fiber bundle, the yield point (ϵ, σ), ultimate point (ϵ, σ), and toughness (U) for the bundle as a whole were measured. We found that changes to all three input parameters were required for the model to capture the aging-related decline in cortical bone mechanical properties consistent with those previously reported in the literature. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the material properties of osteon and interstitial tissue, in order to further understanding of aging-related changes in bone.
Topics: Humans; Aged; Porosity; Bone and Bones; Cortical Bone; Aging; Models, Theoretical; Haversian System
PubMed: 37499524
DOI: 10.1016/j.jmbbm.2023.106029 -
Journal of the Mechanical Behavior of... Sep 2023Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance....
An integrated experimental-computational framework to assess the influence of microstructure and material properties on fracture toughness in clinical specimens of human femoral cortical bone.
Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance. However, the relative importance of these changes to the fracture resistance of cortical bone has not been quantified in detail. In this technical note, we developed an integrated experimental-computational framework utilizing human femoral cortical bone biopsies to advance the understanding of how fracture resistance of cortical bone is modulated due to modifications in its microstructure and material properties. Four human biopsy samples from individuals with varying fragility fracture history and osteoporosis treatment status were converted to finite element models incorporating specimen-specific material properties and were analyzed using fracture mechanics-based modeling. The results showed that cement line density and osteonal volume had a significant effect on crack volume. The removal of cement lines substantially increased the crack volume in the osteons and interstitial bone, representing straight crack growth, compared to models with cement lines due to the lack of crack deflection in the models without cement lines. Crack volume in the osteons and interstitial bone increased when mean elastic modulus and ultimate strength increased and mean fracture toughness decreased. Crack volume in the osteons and interstitial bone was reduced when material property heterogeneity was incorporated in the models. Although both the microstructure and the heterogeneity of the material properties of the cortical bone independently increased the fracture toughness, the relative contribution of the microstructure was more significant. The integrated experimental-computational framework developed here can identify the most critical microscale features of cortical bone modulated by pathological processes or pharmacological treatments that drive changes in fracture resistance and improve our understanding of the relative influence of microstructure and material properties on fracture resistance of cortical bone.
Topics: Humans; Models, Biological; Finite Element Analysis; Cortical Bone; Bone and Bones; Fractures, Bone
PubMed: 37494816
DOI: 10.1016/j.jmbbm.2023.106034 -
Acta Biomaterialia Sep 2023Osteodentin is a dominant mineralized collagenous tissue in the teeth of many fishes, with structural and histological characteristics resembling those of bone....
Osteodentin is a dominant mineralized collagenous tissue in the teeth of many fishes, with structural and histological characteristics resembling those of bone. Osteodentin, like bone, comprises osteons as basic structural building blocks, however, it lacks the osteocytes and the lacuno-canalicular network (LCN), which are known to play critical roles in controlling the mineralization of the collagenous matrix in bone. Although numerous vascular canals exist in osteodentin, their role in tooth maturation and the matrix mineralization process remain poorly understood. Here, high resolution micro-computed tomography (micro-CT) and focused ion beam-scanning electron microscopy (FIB-SEM) were used to obtain 3D structural information of osteodentin in shark teeth at multiple scales. We observed a complex 3D network of primary canals with a diameter ranging from ∼10 µm to ∼120 µm, where the canals are surrounded by osteon-like concentric layers of lamellae, with 'interosteonal' tissue intervening between neighboring osteons. In addition, numerous hierarchically branched secondary canals extended radially from the primary canals into the interosteonal tissue, decreasing in diameter from ∼10 µm to hundreds of nanometers. Interestingly, the mineralization degree increases from the periphery of primary canals into the interosteonal tissue, suggesting that mineralization begins in the interosteonal tissue. Correspondingly, the hardness and elastic modulus of the interosteonal tissue are higher than those of the osteonal tissue. These results demonstrate that the 3D hierarchical canal network is positioned to play a critical role in controlling the gradient mineralization of osteodentin, also providing valuable insight into the formation of mineralized collagenous tissue without osteocytes and LCN. STATEMENT OF SIGNIFICANCE: Bone is a composite material with versatile mechanical properties. Osteocytes and their lacuno-canalicular network (LCN) are known to play critical roles during formation of human bone. However, the bone and osteodentin of many fishes, although lacking osteocytes and LCN, exhibit similar osteon-like structure and mechanical functions. Here, using various high resolution 3D characterization techniques, we reveal that the 3D network of primary canals and numerous hierarchically branched secondary canals correlate with the mineralization gradient and micromechanical properties of osteonal and interosteonal tissues of shark tooth osteodentin. This work significantly improves our understanding of the construction of bone-like mineralized tissue without osteocytes and LCN, and provides inspirations for the fabrication of functional materials with hierarchical structure.
Topics: Humans; Animals; X-Ray Microtomography; Bone and Bones; Osteocytes; Haversian System; Sharks
PubMed: 37451657
DOI: 10.1016/j.actbio.2023.07.007 -
The Journal of Experimental Biology Aug 2023Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone...
Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone replacement resulting in secondary osteons) is thought to occur in regions of low strain as part of bone maintenance or high strain in response to microdamage. However, analyses of remodeling in primates have revealed an unappreciated association with the number of daily load cycles. We tested this relationship by raising 30 male domestic rabbits (Oryctolagus cuniculus) on disparate diets from weaning to adulthood (48 weeks), facilitating a naturalistic perspective on mandibular bone adaptation. A control group consumed only rabbit pellets and an 'overuse' group ate hay in addition to pellets. To process hay, which is tougher and stiffer, rabbits increase chewing investment and duration without increasing bite force (i.e. corpus mean peak strain is similar for the two foods). Corpus remodeling in overuse rabbits was ∼1.5 times that of controls, measured as osteon population density and percentage Haversian bone. In the same subjects, there was a significant increase in overuse corpus bone formation (ratio of cortical area to cranial length), consistent with previous reports on the same dietary manipulation and bone formation in rabbits. This is the first evidence that both modeling and remodeling are simultaneously driven by the number of load cycles, independent of strain magnitude. This novel finding provides unique data on the feeding apparatus, challenges traditional thought on Haversian remodeling, and highlights the need for experimental studies of skeletal adaptation that examine mechanical factors beyond strain magnitude.
Topics: Animals; Rabbits; Male; Bone Remodeling; Mandible; Haversian System; Lagomorpha
PubMed: 37439268
DOI: 10.1242/jeb.245942 -
Journal of Biological Engineering Jul 2023Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled...
BACKGROUND
Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue.
RESULTS
Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis.
CONCLUSIONS
The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.
PubMed: 37430290
DOI: 10.1186/s13036-023-00360-w -
Journal of the Mechanical Behavior of... Aug 2023The research focuses on the evaluation of the mechanical properties of osteonal cortical bone at the lamellar level. Elastic properties of the mid-diaphysis region of...
The research focuses on the evaluation of the mechanical properties of osteonal cortical bone at the lamellar level. Elastic properties of the mid-diaphysis region of the bovine tibia are investigated via cantilever-based nanoindentation at the submicron length scale utilizing Atomic Force Microscopy, where the force-displacement curves are used for the elastic assessment using the Derjaguin-Muller-Toropov model to calculate indentation modulus. Variations of the modulus and the directional mechanical response of the osteonal bone at different distances from the Haversian canal are investigated. Additionally, the effects of demineralization on the indentation modulus are discussed. It was found that in the axial direction, the first and last untreated thick lamella layers show a significant indentation modulus difference compared to all other layers (4.26 ± 0.4 and 4.6 ± 0.3 GPa vs ∼3.5 GPa). On the other hand, the indentation modulus of transverse thick lamella layers shows a periodic variation between ∼3 ± 0.7 GPa and ∼4 ± 0.3 GPa from near the Haversian canal to near the interstitial bone. A periodic variation in the anisotropy ratio was found. Mineral content was quantified via energy-dispersive X-ray microanalysis at different levels of mineralization and shows a positive correlation with the indentation modulus.
Topics: Animals; Cattle; Tibia; Anisotropy; Bone and Bones; Cortical Bone; Elasticity
PubMed: 37393887
DOI: 10.1016/j.jmbbm.2023.105992