The skeleton's osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the ...cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles.
The osteocyte lacunar-canalicular system (LCS) serves as a mechanotransductive core where external loading applied to the skeleton is transduced into mechanical signals (e.g., fluid shear) that can ...be sensed by mechanosensors (osteocytes). The fluid velocity and shear stress within the LCS are affected by various loading parameters. However, the interactive effect of distinct loading parameters on the velocity and shear stress in the LCS remains unclear. To address this issue, we developed a multiscale modeling approach, combining a poroelastic finite element (FE) model with a single osteocytic LCS unit model to calculate the flow velocity and shear stress within the LCS. Next, a sensitivity analysis was performed to investigate individual and interactive effects of strain magnitude, strain rate, number of cycles, and intervening short rests between loading cycles on the velocity and shear stress around the osteocyte. Lastly, we developed a relatively simple regression model to predict those outcomes. Our results demonstrated that the strain magnitude or rate alone were the main factors affecting the velocity and shear stress; however, the combination of these two was not directly additive, and addition of a short rest between cycles could enhance the combination of these two related factors. These results show highly interactive effects of distinct loading parameters on fluid velocity and shear stress in the LCS. Specifically, our results suggest that an enhanced fluid dynamics environment in the LCS can be achieved with a brief number of load cycles combined with short rest insertion and high strain magnitude and rate.
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•A multiscale model was developed to determine fluid dynamics within the lacunar-canalicular system (LCS)•Interactive effect of various loading parameters on velocity and shear stress in the LCS was examined•Significant interactions were found between strain magnitude, strain rate and short rest•A few load cycles with rest insertion, high strain magnitude and rate are beneficial to LCS flow
The skeleton accommodates changes in mechanical environments by increasing bone mass under increased loads and decreasing bone mass under disuse. However, little is known about the adaptive changes ...in micromechanical behavior of cancellous and cortical tissues resulting from loading or disuse. To address this issue, in vivo tibial loading and hindlimb unloading experiments were conducted on 16-week-old female C57BL/6J mice. Changes in bone mass and tissue-level strains in the metaphyseal cancellous and midshaft cortical bone of the tibiae, resulting from loading or unloading, were determined using microCT and finite element (FE) analysis, respectively. We found that loading- and unloading-induced changes in bone mass were more pronounced in the cancellous than cortical bone. Simulated FE-loading showed that a greater proportion of elements experienced relatively lower longitudinal strains following load-induced bone adaptation, while the opposite was true in the disuse model. While the magnitudes of maximum or minimum principal strains in the metaphyseal cancellous and midshaft cortical bone were not affected by loading, strains oriented with the long axis were reduced in the load-adapted tibia suggesting that loading-induced micromechanical benefits were aligned primarily in the loading direction. Regression analyses demonstrated that bone mass was a good predictor of bone tissue strains for the cortical bone but not for the cancellous bone, which has complex microarchitecture and spatially-variant strain environments. In summary, loading-induced micromechanical benefits for cancellous and cortical tissues are received primarily in the direction of force application and cancellous bone mass may not be related to the micromechanics of cancellous bone.
The rapid growth in the field of metal-organic frameworks (MOFs) over recent years has highlighted their high potential in a variety of applications. For biological and environmental applications ...MOFs with low toxicity are vitally important to avoid any harmful effects. For this reason, Ca-based MOFs are highly desirable owing to their low cost and high biocompatibility. Useful Ca MOFs are still rare owing to the ionic character and large size of the Ca2+ ion tending to produce dense phases. Presented here is a novel Ca-based MOF containing 2,3-dihyrdoxyterephthalate (2,3-dhtp) linkers Ca(2,3-dhtp)(H2O) (SIMOF-4). The material undergoes a phase transformation on heating, which can be followed by variable temperature powder X-ray diffraction. The structure of the high temperature form was obtained using single-crystal X-ray diffraction. The electrochemical properties of SIMOF-4 were also investigated for use in a Na ion battery.
•John Currey studied how bone adapts to mechanical loading during an individual’s lifetime and over evolutionary time.•Extant vertebrate bones or fossils’ bony structures can reveal effects of ...long-term trends in loading history and natural selection.•Load predictability is a major consideration for bone adaptation broadly across an evolutionary timescale.•Bones with highly predictable load patterns demonstrate more precise design with lower safety factors.•Exposure to rare loading events with high costs of failure, leads to structures with very high safety factor.
Much is known about skeletal adaptation in relation to the mechanical functions that bones serve. This includes how bone adapts to mechanical loading during an individual’s lifetime as well as over evolutionary time. Although controlled loading in animal models allows us to observe short-term bone adaptation (epigenetic mechanobiology), examining an assemblage of extant vertebrate bones or a group of fossils’ bony structures can reveal the combined effects of long-term trends in loading history and the effects of natural selection. In this survey we examine adaptations that take place over both time scales and highlight a few of the extraordinary insights first published by John Currey. First, we provide a historical perspective on bone adaptation control mechanisms, followed by a discussion of safety factors in bone. We then summarize examples of structural- and material-level adaptations and mechanotransduction, and analyze the relationship between these structural- and material-level adaptations observed in situations where loading modes are either predictable or unpredictable. We argue that load predictability is a major consideration for bone adaptation broadly across an evolutionary timescale, but that its importance can also be seen during ontogenetic growth trajectories, which are subject to natural selection as well. Furthermore, we suggest that bones with highly predictable load patterns demonstrate more precise design with lower safety factors, while bones that experience less predictable loads or those that are less capable of repair and adaptation are designed with a higher safety factor. Finally, exposure to rare loading events with high potential costs of failure leads to design of structures with very high safety factor compared to everyday loading experience. Understanding bone adaptations at the structural and material levels, which take place over an individual’s lifetime or over evolutionary time has numerous applications in translational and clinical research to understand and treat musculoskeletal diseases, as well as to permit the furthering of human extraterrestrial exploration in environments with altered gravity.
The influence of loading history on in vivo strains within a given specie remains poorly understood, and although in vivo strains have been measured at the hindlimb bones of various species, strains ...engendered during modes of activity other than locomotion are lacking, particularly in non-human species. For commercial egg-laying chickens specifically, there is an interest in understanding their bones' mechanical behaviour, particularly during youth, to develop early interventions to prevent the high incidence of osteoporosis in this population. We measured in vivo mechanical strains at the tibiotarsus midshaft during steady activities (ground, uphill, downhill locomotion) and non-steady activities (perching, jumping, aerial transition landing) in 48 pre-pubescent female (egg-laying) chickens from two breeds that were reared in three different housing systems, allowing varying amounts and types of physical activity. Mechanical strain patterns differed between breeds, and were dependent on the activity performed. Mechanical strains were also affected by rearing environment: chickens that were restricted from performing dynamic load bearing activity due to caged-housing generally exhibited higher mechanical strain levels during steady, but not non-steady activities, compared to chickens with prior dynamic load-bearing activity experience. Among chickens with prior experience of dynamic load bearing activity, those reared in housing systems that allowed more frequent physical activity did not exhibit lower mechanical strains. In all groups, the tibiotarsus was subjected to a loading environment consisting of a combination of axial compression, bending, and torsion, with torsion being the predominant source of strain. Aerial transition landing produced the highest strain levels with unusual strain patterns compared to other activities, suggesting it may produce the strongest anabolic response. These results exemplify how different breeds within a given specie adapt to maintain different patterns of mechanical strains, and how benefits of physical activity in terms of resistance to strain are activity-type dependent and do not necessarily increase with increased physical activity. These findings directly inform controlled loading experiments aimed at studying the bone mechanoresponse in young female chickens and can also be associated to measures of bone morphology and material properties to understand how these features influence bone mechanical properties in vivo.
•Genetics influenced in vivo strain patterns that tibiotarsi adapt to maintain.•More active loading history did not coincide with decreased in vivo strains.•The mechanical environment of the tibiotarsus was dominated by torsion-induced shear.
Metal-organic frameworks (MOFs) are well known for their ability to adsorb various gases. The use of MOFs for the storage and release of biologically active gases, particularly nitric oxide (NO) and ...carbon monoxide (CO), has been a subject of interest. To elucidate the binding mechanisms and geometry of these gases, an in situ single crystal X-ray diffraction (scXRD) study using synchrotron radiation at Diamond Light Source has been performed on a set of MOFs that display promising gas adsorption properties. NO and CO, were introduced into activated Ni-CPO-27 and the related Co-4,6-dihydroxyisophthalate (Co-4,6-dhip). Both MOFs show strong binding affinity towards CO and NO, however CO suffers more from competitive co-adsorption of water. Additionally, we show that morphology can play an important role in the ease of dehydration for these two systems.
Abstract Bone loss occurs during adulthood in both women and men and affects trabecular bone more than cortical bone. The mechanism responsible for trabecular bone loss during adulthood remains ...unexplained, but may be due at least in part to a reduced mechanoresponsiveness. We hypothesized that trabecular and cortical bone would respond anabolically to loading and that the bone response to mechanical loading would be reduced and the onset delayed in adult compared to postpubescent mice. We evaluated the longitudinal adaptive response of trabecular and cortical bone in postpubescent, young (10 week old) and adult (26 week old) female C57Bl/6J mice to axial tibial compression using in vivo microCT (days 0, 5, 10, and 15) and dynamic histomorphometry (day 15). Loading elicited an anabolic response in both trabecular and cortical bone in young and adult mice. As hypothesized, trabecular bone in adult mice exhibited a reduced and delayed response to loading compared to the young mice, apparent in trabecular bone volume fraction and architecture after 10 days. No difference in mechanoresponsiveness of the cortical bone was observed between young and adult mice. Finite element analysis showed that load-induced strain was reduced with age. Our results suggest that trabecular bone loss that occurs in adulthood may in part be due to a reduced mechanoresponsiveness in this tissue and/or a reduction in the induced tissue deformation which occurs during habitual loading. Therapeutic approaches that address the mechanoresponsiveness of the bone tissue may be a promising and alternate strategy to maintain trabecular bone mass during aging.
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