Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.

Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels.

A decoupled whole-building simulation engine for rapid exhaustive search of low-carbon and low-energy building refurbishment options

This paper presents the development of a new building physics and energy supply systems simulation platform. It has been adapted from both existing commercial models and empirical works, but designed to provide expedient exhaustive simulation of all salient types of energy- and carbon-reducing retrofit options. These options may include any combination of behavioural measures, building fabric and equipment upgrades, improved HVAC control strategies, or novel low-carbon energy supply technologies. We provide a methodological description of the proposed model, followed by two illustrative case studies of the tool when used to investigate retrofit options of a mixed-use office building and primary school in the UK. It is not the intention of this paper, nor would it be feasible, to provide a complete engineering decomposition of the proposed model, describing all calculation processes in detail. Instead, this paper concentrates on presenting the particular engineering aspects of the model which steer away from conventional practise. © 2011 Elsevier Ltd.

Exploring the process of whole system design

This paper explores the adoption of a whole system approach to a more sustainable and innovative design. A case study methodology was utilised to gain improved understanding of whole system design and those factors that substantially influence its success. The paper presents a framework of those factors including the requirement for trans-disciplinary skills, the dynamics of a flattened hierarchy and the need to identify relationships between parts of the system to ultimately optimise the whole. Knowing the factors that influence the process of whole system design provides designers with the knowledge necessary to more effectively work within, manage and facilitate that process. This paper uses anecdotes taken from operational cases, across design contexts, to demonstrate those factors. © 2010 Elsevier Ltd. All rights reserved.

A whole-life value based assessment and optimisation model for high-performance glazed facades'

Façade design is a complex and multi-disciplinary process. One major barrier to devising optimal façade solutions is the lack of a systematic way of evaluating the true social, economic and environmental impacts of a design. Another barrier is the lack of automated design aids to assist decision-making. In this paper, we present our on-going study in developing a whole-life value based multi-objective optimisation model for high-performance façades. The principal outcome of this paper is a multi-objective optimisation model for early-stage façade design. The optimisation technique coupled with other 3rd party software and/or specially developed scripts provide façade designers with an integrated design tool of wide applicability.

Characteristics of blood flow in microchannels and relevant impact on modelling blood behaviour in biochip separators

This paper reports a perspective investigation of computational modelling of blood fluid in microchannel devices as a preparation for future research on fluid-structure interaction (FSI) in biofluid mechanics. The investigation is carried out through two aspects, respectively on physical behaviours of blood flow in microchannels and appropriate methodology for modelling. The physics of blood flow is targeted to the challenges for describing blood flow in microchannels, including rheology of blood fluid, suspension features of red blood cells (RBCs), laminar hydrodynamic influence and effect of surface roughness. The analysis shows that due to the hyperelastic property of RBC and its comparable dimension with microchannels, blood fluid shows complex behaviours of two phase flow. The trajectory and migration of RBCs require accurate description of RBC deformation and interaction with plasma. Following on a discussion of modelling approaches, i.e. Eulerian method and Lagrangian method, the main stream modelling methods for multiphase flow are reviewed and their suitability to blood flow is analysed. It is concluded that the key issue for blood flow modelling is how to describe the suspended blood cells, modelled by Lagrangian method, and couple them with the based flow, modelled by Eulerian method. The multiphase flow methods are thereby classified based on the number of points required for describing a particle, as follows: (i) single-point particle methods, (ii) mutli-point particle methods, (iii) functional particle methods, and (iv) fluid particle methods. While single-point particle methods concentrate on particle dynamic movement, multipoint and functional particle methods can take into account particle mechanics and thus offer more detailed information for individual particles. Fluid particle methods provide good compromise between two phases, but require additional information for particle mechanics. For furthermore detailed description, we suggest to investigate the possibility using two domain coupling method, in which particles and base flow are modelled by two separated solvers. It is expected that this paper could clarify relevant issues in numerical modelling of blood flow in microchannels and induce some considerations for modelling blood flow using multiphase flow methods. © 2012 IEEE.

Progress towards the design and numerical analysis of a 3D microchannel biochip separator

This paper reports the design and numerical analysis of a three-dimensional biochip plasma blood separator using computational fluid dynamics techniques. Based on the initial configuration of a two-dimensional (2D) separator, five three-dimensional (3D) microchannel biochip designs are categorically developed through axial and plenary symmetrical expansions. These include the geometric variations of three types of the branch side channels (circular, rectangular, disc) and two types of the main channel (solid and concentric). Ignoring the initial transient behaviour and assuming that steady-state flow has been established, the behaviour of the blood fluid in the devices is algebraically analysed and numerically modelled. The roles of the relevant microchannel mechanisms, i.e. bifurcation, constriction and bending channel, on promoting the separation process are analysed based on modelling results. The differences among the different 3D implementations are compared and discussed. The advantages of 3D over 2D separator in increasing separation volume and effectively depleting cell-free layer fluid from the whole cross section circumference are addressed and illustrated. © 2011 John Wiley & Sons, Ltd.

Short-term in vitro responses of human peripheral blood monocytes to ferritic stainless steel fiber networks.

Beneficial effects on bone-implant bonding may accrue from ferromagnetic fiber networks on implants which can deform in vivo inducing controlled levels of mechanical strain directly in growing bone. This approach requires ferromagnetic fibers that can be implanted in vivo without stimulating undue inflammatory cell responses or cytotoxicity. This study examines the short-term in vitro responses, including attachment, viability, and inflammatory stimulation, of human peripheral blood monocytes to 444 ferritic stainless steel fiber networks. Two types of 444 networks, differing in fiber cross section and thus surface area, were considered alongside austenitic stainless steel fiber networks, made of 316L, a widely established implant material. Similar high percent seeding efficiencies were measured by CyQuant® on all fiber networks after 48 h of cell culture. Extensive cell attachment was confirmed by fluorescence and scanning electron microscopy, which showed round monocytes attached at various depths into the fiber networks. Medium concentrations of lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-α) were determined as indicators of viability and inflammatory responses, respectively. Percent LDH concentrations were similar for both 444 fiber networks at all time points, whereas significantly lower than those of 316L control networks at 24 h. All networks elicited low-level secretions of TNF-α, which were significantly lower than that of the positive control wells containing zymosan. Collectively, the results indicate that 444 networks produce comparable responses to medical implant grade 316L networks and are able to support human peripheral blood monocytes in short-term in vitro cultures without inducing significant inflammatory or cytotoxic effects.