Flow modeling in a novel non-perfusion conical bioreactor

We have developed a bioreactor vessel design which has the advantages of simplicity and ease of assembly and disassembly, and with the appropriately determined flow rate, even allows for a scaffold to be suspended freely regardless of its weight. This article reports our experimental and numerical investigations to evaluate the performance of a newly developed non-perfusion conical bioreactor by visualizing the flow through scaffolds with 45° and 90° fiber lay down patterns. The experiments were conducted at the Reynolds numbers (Re) 121, 170, and 218 based on the local velocity and width of scaffolds. The flow fields were captured using short-time exposures of 60 µm particles suspended in the bioreactor and illuminated using a thin laser sheet. The effects of scaffold fiber lay down pattern and Reynolds number were obtained and correspondingly compared to results obtained from a computational fluid dynamics (CFD) software package. The objectives of this article are twofold: to investigate the hypothesis that there may be an insufficient exchange of medium within the interior of the scaffold when using our non-perfusion bioreactor, and second, to compare the flows within and around scaffolds of 45° and 90° fiber lay down patterns. Scaffold porosity was also found to influence flow patterns. It was therefore shown that fluidic transport could be achieved within scaffolds with our bioreactor design, being a non-perfusion vessel. Fluid velocities were generally same of the same or one order lower in magnitude as compared to the inlet flow velocity. Additionally, the 90° fiber lay down pattern scaffold was found to allow for slightly higher fluid velocities within, as compared to the 45° fiber lay down pattern scaffold. This was due to the architecture and pore arrangement of the 90° fiber lay down pattern scaffold, which allows for fluid to flow directly through (channel-like flow).

In vitro characterization of natural and synthetic dermal matrices cultured with human dermal fibroblasts

The ideal dermal matrix should be able to provide the right biological and physical environment to ensure homogenous cell and extracellular matrix (ECM) distribution, as well as the right size and morphology of the neo-tissue required. Four natural and synthetic 3D matrices were evaluated in vitro as dermal matrices, namely (1) equine collagen foam, TissuFleece®, (2) acellular dermal replacement, Alloderm®, (3) knitted poly(lactic-co-glycolic acid) (10:90)–poly(-caprolactone) (PLGA–PCL) mesh, (4) chitosan scaffold. Human dermal fibroblasts were cultured on the specimens over 3 weeks. Cell morphology, distribution and viability were assessed by electron microscopy, histology and confocal laser microscopy. Metabolic activity and DNA synthesis were analysed via MTS metabolic assay and [3H]-thymidine uptake, while ECM protein expression was determined by immunohistochemistry. TissuFleece®, Alloderm® and PLGA–PCL mesh supported cell attachment, proliferation and neo-tissue formation. However, TissuFleece® contracted to 10% of the original size while Alloderm® supported cell proliferation predominantly on the surface of the material. PLGA–PCL mesh promoted more homogenous cell distribution and tissue formation. Chitosan scaffolds did not support cell attachment and proliferation. These results demonstrated that physical characteristics including porosity and mechanical stability to withstand cell contraction forces are important in determining the success of a dermal matrix material.

Investigating the effects of preinduction on human adipose-derived precursor cells in an athymic rat model

The osteogenic potential of human adipose-derived precursor cells seeded on medical-grade polycaprolactone-tricalcium phosphate scaffolds was investigated in this in vivo study. Three study groups were investigated: (1) induced—stimulated with osteogenic factors only after seeding into scaffold; (2) preinduced—induced for 2 weeks before seeding into scaffolds; and (3) uninduced—cells without any introduced induction. For all groups, scaffolds were implanted subcutaneously into the dorsum of athymic rats. The scaffold/cell constructs were harvested at the end of 6 or 12 weeks and analyzed for osteogenesis. Gross morphological examination using scanning electron microscopy indicated good integration of host tissue with scaffold/cell constructs and extensive tissue infiltration into the scaffold interior. Alizarin Red histology and immunostaining showed a heightened level of mineralization and an increase in osteonectin, osteopontin, and collagen type I protein expression in both the induced and preinduced groups compared with the uninduced groups. However, no significant differences were observed in these indicators when compared between the induced and preinduced groups.

Bone response to unloaded titanium implants in the fibula, iliac crest, and scapula: an animal study in the Yorkshire pig

The reconstruction of extended maxillary and mandibular defects with prefabricated free flaps is a two stage procedure, that allows immediate function with implant supported dentures. The appropriate delay between prefabrication and reconstruction depends on the interfacial strength of the bone–implant surface. The purpose of this animal study was to evaluate the removal torque of unloaded titanium implants in the fibula, the scapula and the iliac crest. Ninety implants with a sandblasted and acid-etched (SLA) surface were tested after healing periods of 3, 6, and 12 weeks, respectively. Removal torque values (RTV) were collected using a computerized counterclockwise torque driver. The bicortical anchored 8 mm implants in the fibula revealed values of 63.73 Ncm, 91.50 Ncm, and 101.83 Ncm at 3, 6, and 12 weeks, respectively. The monocortical anchorage in the iliac crest showed values of 71.40 Ncm, 63.14 Ncm, and 61.59 Ncm with 12 mm implants at the corresponding times. The monocortical anchorage in the scapula demonstrated mean RTV of 62.28 Ncm, 97.63 Ncm, and 99.7 Ncm with 12 mm implants at 3, 6, and 12 weeks, respectively. The study showed an increase of removal torque with increasing healing time. The interfacial strength for bicortical anchored 8 mm implants in the fibula was comparable to monocortical anchored 12 mm implants in the iliac crest and the scapula at the corresponding times. The resistance to shear seemed to be determined by the type of anchorage (monocortical vs. bicortical) and the length of the implant with greater amount of bone–implant interface.

Vitrification as a prospect for cryopreservation of tissue-engineered constructs

Cryopreservation plays a significant function in tissue banking and will presume yet larger value when more and more tissue-engineered products will routinely enter the clinical arena. The most common concept underlying tissue engineering is to combine a scaffold (cellular solids) or matrix (hydrogels) with living cells to form a tissue-engineered construct (TEC) to promote the repair and regeneration of tissues. The scaffold and matrix are expected to support cell colonization, migration, growth and differentiation, and to guide the development of the required tissue. The promises of tissue engineering, however, depend on the ability to physically distribute the products to patients in need. For this reason, the ability to cryogenically preserve not only cells, but also TECs, and one day even whole laboratory-produced organs, may be indispensable. Cryopreservation can be achieved by conventional freezing and vitrification (ice-free cryopreservation). In this publication we try to define the needs versus the desires of vitrifying TECs, with particular emphasis on the cryoprotectant properties, suitable materials and morphology. It is concluded that the formation of ice, through both direct and indirect effects, is probably fundamental to these difficulties, and this is why vitrification seems to be the most promising modality of cryopreservation

The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive polycaprolactone scaffolds

Our strategy entails investigating the influence of varied concentrations (0, 10, 100 and 1000 ng/ml) of human recombinant bone morphogenetic protein-2 (rhBMP-2) on the osteogenic expression of canine osteoblasts, seeded onto poly-caprolactone 20% tricalcium phosphate (PCL-TCP) scaffolds in vitro. Biochemical assay revealed that groups with rhBMP-2 displayed an initial burst in cell growth that was not dose-dependent. However, after 13 days, cell growth declined to a value similar to control. Significantly less cell growth was observed for construct with 1000 ng/ml of rhBMP-2 from 20 days onwards. Confocal microscopy confirmed viability of osteoblasts and at day 20, groups seeded with rhBMP-2 displayed heightened cell death as compared to control. Phase contrast and scanning electron microscopy revealed that osteoblasts heavily colonized surfaces, rods and pores of the PCL-TCP scaffolds. This was consistent for all groups. Finally, Von Kossa and osteocalcin assays demonstrated that cells from all groups maintained their osteogenic phenotype throughout the experiment. Calcification was observed as early as four days after stimulation for groups seeded with rhBMP-2. In conclusion, rhBMP-2 seems to enhance the differentiated function of canine osteoblasts in a non-dose dependent manner. This resulted in accelerated mineralization, followed by death of osteoblasts as they underwent terminal differentiation. Notably, PCL-TCP scaffolds seeded only with canine osteoblasts could sustain excellent osteogenic expression in vitro. Hence, the synergy of PCL with bioactive TCP and rhBMP-2 in a novel composite scaffold, could offer an exciting approach for bone regeneration.

Reliability prediction using the non-parametric explicit hazard model : a case study

Survival probability prediction using covariate-based hazard approach is a known statistical methodology in engineering asset health management. We have previously reported the semi-parametric Explicit Hazard Model (EHM) which incorporates three types of information: population characteristics; condition indicators; and operating environment indicators for hazard prediction. This model assumes the baseline hazard has the form of the Weibull distribution. To avoid this assumption, this paper presents the non-parametric EHM which is a distribution-free covariate-based hazard model. In this paper, an application of the non-parametric EHM is demonstrated via a case study. In this case study, survival probabilities of a set of resistance elements using the non-parametric EHM are compared with the Weibull proportional hazard model and traditional Weibull model. The results show that the non-parametric EHM can effectively predict asset life using the condition indicator, operating environment indicator, and failure history.

Political theory and theoretical physics

This paper argues, somewhat along a Simmelian line, that political theory may produce practical and universal theories like those developed in theoretical physics. The reasoning behind this paper is to show that the theory of ‘basic democracy’ may be true by way of comparing it to Einstein’s Special Relativity – specifically concerning the parameters of symmetry, unification, simplicity, and utility. These parameters are what make a theory in physics as meeting them not only fits with current knowledge, but also produces paths towards testing (application). As the theory of ‘basic democracy’ may meet these same parameters, it could settle the debate concerning the definition of democracy. This will be argued firstly by discussing what the theory of ‘basic democracy’ is and why it differs from previous work; secondly by explaining the parameters chosen (as in why these and not others confirm or scuttle theories); and thirdly by comparing how Special Relativity and the theory of ‘basic democracy’ may match the parameters.

Modeling the stepped potential discharge of primary alkaline battery cathodes

A novel model for the potentiostatic discharge of primary alkaline battery cathodes is presented. The model is used to simulate discharges resulting from the stepped potential electrochemical spectroscopy (SPECS) of primary alkaline battery cathodes cathodes, and the results are validated with experimental data. We show that a model based on a single (or mean) reaction framework can be used to simulate multi-reaction discharge behaviour and we develop a consistent functional modification to the kinetic equation of the model that allows for this to occur. The model is used to investigate the effects that the initial exchange current density, i00, and the diffusion coefficient for protons in electrolytic manganese dioxide (EMD), DH+, have on SPECS discharge. The behaviour observed is consistent with the idea that individual reduction reactions, within the multi-reaction, reduction behaviour of EMD, have distinct i00 and DH+ values.

Corona ions from overhead transmission voltage powerlines : effect on DC e-field and ambient particle concentration levels

Along with their essential role in electricity transmission and distribution, some powerlines also generate large concentrations of corona ions. This study aimed at comprehensive investigation of corona ions, vertical dc e-field, ambient aerosol particle charge and particle number concentration levels in the proximity of some high/sub-transmission voltage powerlines. The influence of meteorology on the instantaneous value of these parameters, and the possible existence of links or associations between the parameters measured were also statistically investigated. The presence of positive and negative polarities of corona ions was associated with variation in the mean vertical dc e-field, ambient ion and particle charge concentration level. Though these variations increased with wind speed, their values also decreased with distance from the powerlines. Predominately positive polarities of ions were recorded up to a distance of 150 m (with the maximum values recorded 50 m downwind of the powerlines). At 200 m from the source, negative ions predominated. Particle number concentration levels however remained relatively constant (103 particle cm-3) irrespective of the sampling site and distance from the powerlines. Meteorological factors of temperature, humidity and wind direction showed no influence on the electrical parameters measured. The study also discovered that e-field measurements were not necessarily a true representation of the ground-level ambient ion/particle charge concentrations.

Derivation of motor vehicle tailpipe particle emission factors suitable for modelling urban fleet emissions and air quality assessments

Background, aim, and scope Urban motor vehicle fleets are a major source of particulate matter pollution, especially of ultrafine particles (diameters < 0.1 µm), and exposure to particulate matter has known serious health effects. A considerable body of literature is available on vehicle particle emission factors derived using a wide range of different measurement methods for different particle sizes, conducted in different parts of the world. Therefore the choice as to which are the most suitable particle emission factors to use in transport modelling and health impact assessments presented as a very difficult task. The aim of this study was to derive a comprehensive set of tailpipe particle emission factors for different vehicle and road type combinations, covering the full size range of particles emitted, which are suitable for modelling urban fleet emissions. Materials and methods A large body of data available in the international literature on particle emission factors for motor vehicles derived from measurement studies was compiled and subjected to advanced statistical analysis, to determine the most suitable emission factors to use in modelling urban fleet emissions. Results This analysis resulted in the development of five statistical models which explained 86%, 93%, 87%, 65% and 47% of the variation in published emission factors for particle number, particle volume, PM1, PM2.5 and PM10 respectively. A sixth model for total particle mass was proposed but no significant explanatory variables were identified in the analysis. From the outputs of these statistical models, the most suitable particle emission factors were selected. This selection was based on examination of the statistical robustness of the statistical model outputs, including consideration of conservative average particle emission factors with the lowest standard errors, narrowest 95% confidence intervals and largest sample sizes, and the explanatory model variables, which were Vehicle Type (all particle metrics), Instrumentation (particle number and PM2.5), Road Type (PM10) and Size Range Measured and Speed Limit on the Road (particle volume). Discussion A multiplicity of factors need to be considered in determining emission factors that are suitable for modelling motor vehicle emissions, and this study derived a set of average emission factors suitable for quantifying motor vehicle tailpipe particle emissions in developed countries. Conclusions The comprehensive set of tailpipe particle emission factors presented in this study for different vehicle and road type combinations enable the full size range of particles generated by fleets to be quantified, including ultrafine particles (measured in terms of particle number). These emission factors have particular application for regions which may have a lack of funding to undertake measurements, or insufficient measurement data upon which to derive emission factors for their region. Recommendations and perspectives In urban areas motor vehicles continue to be a major source of particulate matter pollution and of ultrafine particles. It is critical that in order to manage this major pollution source methods are available to quantify the full size range of particles emitted for traffic modelling and health impact assessments.

Comparing charge transport predictions for a ternary electrolyte using the Maxwell–Stefan and Nernst–Planck equations

In this work, we investigate and compare the Maxwell–Stefan and Nernst–Planck equations for modeling multicomponent charge transport in liquid electrolytes. Specifically, we consider charge transport in the Li+/I−/I3−/ACN ternary electrolyte originally found in dye-sensitized solar cells. We employ molecular dynamics simulations to obtain the Maxwell–Stefan diffusivities for this electrolyte. These simulated diffusion coefficients are used in a multicomponent charge transport model based on the Maxwell– Stefan equations, and this is compared to a Nernst–Planck based model which employs binary diffusion coefficients sourced from the literature. We show that significant differences between the electrolyte concentrations at electrode interfaces, as predicted by the Maxwell–Stefan and Nernst–Planck models, can occur. We find that these differences are driven by a pressure term that appears in the Maxwell–Stefan equations. We also investigate what effects the Maxwell–Stefan diffusivities have on the simulated charge transport. By incorporating binary diffusivities found in the literature into the Maxwell–Stefan framework, we show that the simulated transient concentration profiles depend on the diffusivities; however, the simulated equilibrium profiles remain unaffected.

A model for mesoscale patterns in motile populations

Experimental observations of cell migration often describe the presence of mesoscale patterns within motile cell populations. These patterns can take the form of cells moving as aggregates or in chain-like formation. Here we present a discrete model capable of producing mesoscale patterns. These patterns are formed by biasing movements to favor a particular configuration of agent–agent attachments using a binding function f(K), where K is the scaled local coordination number. This discrete model is related to a nonlinear diffusion equation, where we relate the nonlinear diffusivity D(C) to the binding function f. The nonlinear diffusion equation supports a range of solutions which can be either smooth or discontinuous. Aggregation patterns can be produced with the discrete model, and we show that there is a transition between the presence and absence of aggregation depending on the sign of D(C). A combination of simulation and analysis shows that both the existence of mesoscale patterns and the validity of the continuum model depend on the form of f. Our results suggest that there may be no formal continuum description of a motile system with strong mesoscale patterns.

Nonlinear diffusion and exclusion processes with contact interactions

Exclusion processes on a regular lattice are used to model many biological and physical systems at a discrete level. The average properties of an exclusion process may be described by a continuum model given by a partial differential equation. We combine a general class of contact interactions with an exclusion process. We determine that many different types of contact interactions at the agent-level always give rise to a nonlinear diffusion equation, with a vast variety of diffusion functions D(C). We find that these functions may be dependent on the chosen lattice and the defined neighborhood of the contact interactions. Mild to moderate contact interaction strength generally results in good agreement between discrete and continuum models, while strong interactions often show discrepancies between the two, particularly when D(C) takes on negative values. We present a measure to predict the goodness of fit between the discrete and continuous model, and thus the validity of the continuum description of a motile, contact-interacting population of agents. This work has implications for modeling cell motility and interpreting cell motility assays, giving the ability to incorporate biologically realistic cell-cell interactions and develop global measures of discrete microscopic data.