A novel ex vivo model for investigation of fluid displacements in bone after endoprosthesis implantation

Tissue perfusion and mass transport in the vicinity of implant surfaces prior to integration or bonding may play a crucial role in modulating cellular activities associated with bone remodeling, in particular, at early stages of the integration process. Furthermore, fluid displacements have been postulated to transduct mechanical stress signals to bone cells via loading-dependent flow of interstitial fluid through the lacunocanalicular network of bone. Thus, an understanding and new possibilities for influencing these processes may be of great importance for implant success. An ex vivo model was developed and validated for investigation of fluid displacements in bone after endoprosthesis implantation. This model serves to explicate the effects of surgical intervention as well as mechanical loading of the implant-bone construct on load-induced fluid flow in the vicinity of the implant. Using this model, we intend to quantify perfusion and extravascular flow dynamics in the vicinity of implants and define optimal conditions for enhancing molecular transport of osteotropic agents from the implant surface to apposing bone as well as from the blood supply to the implant surface. Furthermore, the elucidation of main transport pathways may help in understanding the distribution of wear particles in bone surrounding implant, a process which has been postulated to cause osteolysis and implant loosenin

Probing two-electron multiplets in bilayer graphene quantum dots

Understanding how the electron spin is coupled to orbital degrees of freedom, such as a valley degree of freedom in solid-state systems is central to applications in spin-based electronics and quantum computation. Recent developments in the preparation of electrostatically-confined quantum dots in gapped bilayer graphene (BLG) enables to study the low-energy single-electron spectra in BLG quantum dots, which is crucial for potential spin and spin-valley qubit operations. Here, we present the observation of the spin-valley coupling in a bilayer graphene quantum dot in the single-electron regime. By making use of a highly-tunable double quantum dot device we achieve an energy resolution allowing us to resolve the lifting of the fourfold spin and valley degeneracy by a Kane-Mele type spin-orbit coupling of $\approx 65~\mu$eV. Also, we find an upper limit of a potentially disorder-induced mixing of the $K$ and $K'$ states below $20~\mu$eV.Comment: 5 Pages 5 Figure

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

Biodiesel Exhaust: The Need for Health Effects Research

BACKGROUND: Biodiesel is a diesel fuel alternative that has shown potential of becoming a commercially accepted part of the United States’ energy infrastructure. In November 2004, the signing of the Jobs Creation Bill HR 4520 marked an important turning point for the future production of biodiesel in the United States because it offers a federal excise tax credit. By the end of 2005, industry production was 75 million gallons, a 300% increase in 1 year. Current industry capacity, however, stands at just over 300 million gallons/year, and current expansion and new plant construction could double the industry’s capacity within a few years. Biodiesel exhaust emission has been extensively characterized under field and laboratory conditions, but there have been limited cytotoxicity and mutagenicity studies on the effects of biodiesel exhaust in biologic systems. OBJECTIVES: We reviewed pertinent medical literature and addressed recommendations on testing specific research needs in the field of biodiesel toxicity. DISCUSSION: Employment of biodiesel fuel is favorably viewed, and there are suggestions that its exhaust emissions are less likely to present any risk to human health relative to petroleum diesel emissions. CONCLUSION: The speculative nature of a reduction in health effects based on chemical composition of biodiesel exhaust needs to be followed up with investigations in biologic systems

Novel explant model to study mechanotransduction and cell–cell communication

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6–12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 µM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1687–1698, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55788/1/20207_ftp.pd

Facile route to conformal hydrotalcite coatings over complex architectures:a hierarchically ordered nanoporous base catalyst for FAME production

An alkali- and nitrate-free hydrotalcite coating has been grafted onto the surface of a hierarchically ordered macroporous-mesoporous SBA-15 template via stepwise growth of conformal alumina adlayers and their subsequent reaction with magnesium methoxide. The resulting low dimensional hydrotalcite crystallites exhibit excellent per site activity for the base catalysed transesterification of glyceryl triolein with methanol for FAME production

Fluid flow in the osteocyte mechanical environment : a fluid-structure interaction approach

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid–structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity (3,000με compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities (∼60.5μ m/s ) and average maximum shear stresses (∼11 Pa ) surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology

Relevance of collagen piezoelectricity to "Wolff's Law": A critical review

According to “Wolff's Law”, bone is deposited and reinforced at areas of greatest stress. From a clinical perspective, this “law” is supported by the strong association between bone density and physical activity. From a mechanistic standpoint, however, the law presents a challenge to scientists seeking to understand how osteocytes and osteoblasts sense the mechanical load. In the 1960s, collagen piezoelectricity was invoked as a potential mechanism by which osteocytes could detect areas of greater stress but piezoelectricity diminished in importance as more compelling mechanisms, such as streaming potential, were identified. In addition, accumulating evidence for the role of fluid-related shear stress in osteocyte's mechanosensory function has made piezoelectricity seemingly more obsolete in bone physiology. This review critically evaluates the role of collagen piezoelectricity (if any) in Wolff's Law—specifically, the evidence regarding its involvement in strain-generated potentials, existing alternate mechanisms, the present understanding of bone mechanosensation, and whether piezoelectricity serves an influential role within the context of this newly proposed mechanism. In addition to reviewing the literature, this review generates several hypotheses and proposes future research to fully address the relevance of piezoelectricity in bone physiology.National Center for Complementary and Alternative Medicine (U.S.) (grant K23-AT003238

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes