Application of a human bone engineering platform to an in vitro and in vivo breast cancer metastasis model

Breast cancer in its advanced stage has a high predilection to the skeleton. Currently, treatment options of breast cancer-related bone metastasis are restricted to only palliative therapeutic modalities. This is due to the fact that mechanisms regarding the breast cancer celI-bone colonisation as well as the interactions of breast cancer cells with the bone microenvironment are not fully understood, yet. This might be explained through a lack of appropriate in vitro and in vivo models that are currently addressing the above mentioned issue. Hence the hypothesis that the translation of a bone tissue engineering platform could lead to improved and more physiological in vitro and in vivo model systems in order to investigate breast cancer related bone colonisation was embraced in this PhD thesis. Therefore the first objective was to develop an in vitro model system that mimics human mineralised bone matrix to the highest possible extent to examine the specific biological question, how the human bone matrix influences breast cancer cell behaviour. Thus, primary human osteoblasts were isolated from human bone and cultured under osteogenic conditions. Upon ammonium hydroxide treatment, a cell-free intact mineralised human bone matrix was left behind. Analyses revealed a similar protein and mineral composition of the decellularised osteoblast matrix to human bone. Seeding of a panel of breast cancer cells onto the bone mimicking matrix as well as reference substrates like standard tissue culture plastic and collagen coated tissue culture plastic revealed substrate specific differences of cellular behaviour. Analyses of attachment, alignment, migration, proliferation, invasion, as well as downstream signalling pathways showed that these cellular properties were influenced through the osteoblast matrix. The second objective of this PhD project was the development of a human ectopic bone model in NOD/SCID mice using medical grade polycaprolactone tricalcium phosphate (mPCL-TCP) scaffold. Human osteoblasts and mesenchymal stem cells were seeded onto an mPCL-TCP scaffold, fabricated using a fused deposition modelling technique. After subcutaneous implantation in conjunction with the bone morphogenetic protein 7, limited bone formation was observed due to the mechanical properties of the applied scaffold and restricted integration into the soft tissue of flank of NOD/SCID mice. Thus, a different scaffold fabrication technique was chosen using the same polymer. Electrospun tubular scaffolds were seeded with human osteoblasts, as they showed previously the highest amount of bone formation and implanted into the flanks of NOD/SCID mice. Ectopic bone formation with sufficient vascularisation could be observed. After implantation of breast cancer cells using a polyethylene glycol hydrogel in close proximity to the newly formed bone, macroscopic communication between the newly formed bone and the tumour could be observed. Taken together, this PhD project showed that bone tissue engineering platforms could be used to develop an in vitro and in vivo model system to study cancer cell colonisation in the bone microenvironment.

Innovative approaches to teaching engineering drawing at tertiary institutions

This paper arises from our concern for the level of teaching of engineering drawing at tertiary institutions in Australia. Little attention is paid to teaching hand drawing and tolerancing. Teaching of engineering drawing is usually limited to computer-aided design (CAD) using AutoCAD or one of the solid-modelling packages. As a result, many engineering graduates have diffi culties in understanding how views are produced in different projection angles, are unable to produce engineering drawings of professional quality, or read engineering drawings, and unable to select fits and limits or surface roughness. In the Faculty of Built Environment and Engineering at the Queensland University of Technology new approaches to teaching engineering drawing have been introduced. In this paper the results of these innovative approaches are examined through surveys and other research methods.

Lateral movements in composite high-rise buildings under seismic action

Daring human nature has already led to the construction of high-rise buildings in naturally challenging geological regions and in worse environments of the world. However; literature review divulges that there is a lag in research of certain generic principles and rules for the prediction of lateral movement in multistorey construction. The present competitive trend orders the best possible used of available construction material and resources. Hence; the mixed used of reinforced concrete with structural steel is gaining prevalence day by day. This paper investigates the effects of Seismic load on composite multistorey building provided with core wall and trusses through FEM modelling. The results showed that increased rigidity corresponds to lower period of vibration and hence higher seismic forces. Since Seismic action is a function of mass and response acceleration, therefore; mass increment generate higher earthquake load and thus cause higher impact base shear and overturning movement. Whereas; wind force depends on building exposed, larger the plan dimension greater is the wind impact. Nonetheless; outriggers trusses noticeably contribute, in improving the serviceability of structure subjected to wind and earthquake forces.

Collaborative efforts to enhance power engineering education in Australia

A review of the issues for supporting learning of power engineering in Australia is presented in this paper. The learning needs of students and the support available in blended learning and through distance educations are explored in this review. Specific software tools to assist the learning environment are appraised and the relevance for the next generation of power engineers assessed.

Preparing for coastal change

Coastal areas are dynamic environments that are home to billions of people worldwide and provide areas of unique natural importance. As such, coastal change is of considerable local and global interest, not only within the geological realm, but also in terms of socioeconomic and biodiversity impacts. An accurate understanding of how changes in relative sea level, geological processes and extreme events, such as storms and tsunamis, have interacted to shape and change the Earth’s coastlines over millennia is fundamental to future projections of coastal change. On the basis of this, researchers in these, and various other aspects of coastal change were brought together in late 2010 at the University of Hong Kong for the first meeting of International Geoscience Program Project 588 (IGCP588) e Preparing for Coastal Change. This special issue showcases some of the results presented at this meeting.

Acquisition modelling for heavy engineering assets in mining industry

Each year, organizations in Australian mining industry (asset intensive industry) spend substantial amount of capital (A$86 billion in 2009-10) (Statistics, 2011) in acquiring engineering assets. Engineering assets are put to use in operations to generate value. Different functions (departments) of an organization have different expectations and requirements from each of the engineering asset e.g. return on investment, reliability, efficiency, maintainability, low cost of running the asset, low or nil environmental impact and easy of disposal, potential salvage value etc. Assets are acquired from suppliers or built by service providers and or internally. The process of acquiring assets is supported by procurement function. One of the most costly mistakes that organizations can make is acquiring the inappropriate or non-conforming assets that do not fit the purpose. The root cause of acquiring non confirming assets belongs to incorrect acquisition decision and the process of making decisions. It is very important that an asset acquisition decision is based on inputs and multi-criteria of each function within the organization which has direct or indirect impact on the acquisition, utilization, maintenance and disposal of the asset. Literature review shows that currently there is no comprehensive process framework and tool available to evaluate the inclusiveness and breadth of asset acquisition decisions that are taken in the Mining Organizations. This thesis discusses various such criteria and inputs that need to be considered and evaluated from various functions within the organization while making the asset acquisition decision. Criteria from functions such as finance, production, maintenance, logistics, procurement, asset management, environment health and safety, material management, training and development etc. need to be considered to make an effective and coherent asset acquisition decision. The thesis also discusses a tool that is developed to be used in the multi-criteria and cross functional acquisition decision making. The development of multi-criteria and cross functional inputs based decision framework and tool which utilizes that framework to formulate cross functional and integrated asset acquisition decisions are the contribution of this research.

Sources of hydrochemical variability and implications associated with CSG water extraction

Coal Seam Gas (CSG) production is achieved by extracting groundwater to depressurize coal seam aquifers in order to promote methane gas desorption from coal micropores. CSG waters are characteristically alkaline, have a neutral pH (~7), are of the Na-HCO3-Cl type, and exhibit brackish salinity. In 2004, a CSG exploration company carried out a gas flow test in an exploration well located in Maramarua (Waikato Region, New Zealand). This resulted in 33 water samples exhibiting noteworthy chemical variations induced by pumping. This research identifies the main causes of hydrochemical variations in CSG water, makes recommendations to manage this effect, and discusses potential environmental implications. Hydrochemical variations were studied using Factor Analysis and this was supported with hydrochemical modelling and a laboratory experiment. This reveals carbon dioxide (CO2) degassing as the principal source of hydrochemical variability (about 33%). Factor Analysis also shows that major ion variations could also reflect changes in hydrochemical composition induced by different pumping regimes. Subsequent chloride, calcium, and TDS variations could be a consequence of analytical errors potentially committed during laboratory determinations. CSG water chemical variations due to degassing during pumping can be minimized with good completion and production techniques; variations due to sample degassing can be controlled by taking precautions during sampling, transit, storage and analysis. In addition, the degassing effect observed in CSG waters can lead to an underestimation of their potential environmental effect. Calcium precipitation due to exposure to normal atmospheric pressure results in a 23% increase in SAR values from Maramarua CSG water samples.

Coal seam gas waters - their geochemical signature and potential environmental implications

Coal Seam Gas (CSG) is a form of natural gas (mainly methane) sorbed in underground coal beds. To mine this gas, wells are drilled directly into an underground coal seam and groundwater (CSG water) is pumped out to the surface. This lowers the downhole piezometric pressure and enables gas desporption from the coal matrix. In the United States, this gas has been extracted commercially since the 1980s. The economic success of US CSG projects has inspired exploration and development in Australia and New Zealand. In Australia, Queensland’s Bowen and Surat basins have been the subject of increased CSG development over the last decade. CSG growth in other Australian basins has not matured to the same level but exploration and development are taking place at an accelerated pace in the Sydney Basin (Illawarra and the Hunter Valley, NSW) and in the Gunnedah Basin. Similarly, CSG exploration in New Zealand has focused in the Waikato region (Maramarua and Huntly), in the West Coast region (Buller, Reefton, and Greymouth), and in Southland (Kaitangata, Mataura, and Ohai). Figure 1 shows a Shcoeller diagram with CSG samples from selected basins in Australia, New Zealand, and the USA. CSG water from all of these basins exhibit the same geochemical signature – low calcium, low magnesium, high bicarbonate, low sulphate and, sometimes, high chloride. This water quality is a direct result of specific biological and geological processes that have taken part in the formation of CSG. In general, these processes include the weathering of rocks (carbonates, dolomite, and halite), cation exchange with clays (responsible for enhanced sodium and depleted calcium and magnesium), and biogenic processes (accounting for the presence of high bicarbonate concentrations). The salinity of CSG waters tends to be brackish (TDS < 30000 mg/l) with a fairly neutral pH. These particular characteristics need to be taken into consideration when assessing water management and disposal alternatives. Environmental issues associated with CSG water disposal have been prominent in developed basins such as the Powder River Basin (PRB) in the United States. When disposed on the land or used for irrigation, water having a high dissolved salts content may reduce water availability to crops thus affecting crop yield. In addition, the high sodium, low calcium and low magnesium concentrations increase the potential to disperse soils and significantly reduce the water infiltration rate. Therefore, CSG waters need to be properly characterised, treated, and disposed to safeguard the environment without compromising other natural resources.

Scaffolds for growth factor delivery as applied to bone tissue engineering

There remains a substantial shortfall in treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient, has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors; which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However cost and potential complications associated with growth factors means controlled release is an important consideration in the design of new bone tissue engineering strategies. This review will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

An exploration of the professional competencies required in engineering asset management

Engineering asset management (EAM) is a rapidly growing and developing field. However, efforts to select and develop engineers in this area are complicated by our lack of understanding of the full range of competencies required to perform. This exploratory study sought to clarify and categorise the professional competencies required of individuals at different hierarchical levels within EAM. Data from 14 interviews and 61 on-line survey participants has informed the development of an initial Professional Competency Framework. The nine competency categories indicate that Engineers working in this field need to be able to collaborate and influence others, complete objectives within organizational guidelines and be able to manage themselves effectively. Limitations and potential uses in practice and research for this framework are discussed.

Using social media to facilitate knowledge transfer in complex engineering environments : a primer for educators

While highly cohesive groups are potentially advantageous they are also often correlated with the emergence of knowledge and information silos based around those same functional or occupational clusters. Consequently, an essential challenge for engineering organisations wishing to overcome informational silos is to implement mechanisms that facilitate, encourage and sustain interactions between otherwise disconnected groups. This paper acts as a primer for those seeking to gain an understanding of the design, functionality and utility of a suite of software tools generically termed social media technologies in the context of optimising the management of tacit engineering knowledge. Underpinned by knowledge management theory and using detailed case examples, this paper explores how social media technologies achieve such goals, allowing for the transfer of knowledge by tapping into the tacit and explicit knowledge of disparate groups in complex engineering environments.

Bone tissue engineering : from bench to bedside - Review article

The drive to develop bone grafts for the filling of major gaps in the skeletal structure has led to a major research thrust towards developing biomaterials for bone engineering. Unfortunately, from a clinical perspective, the promise of bone tissue engineering which was so vibrant a decade ago has so far failed to deliver the anticipated results of becoming a routine therapeutic application in reconstructive surgery. Here we describe the analysis of long-term bone regeneration studies in preclinical animal models, exploiting methods of micro- and nano analysis of biodegradable composite scaffolds.

Bone tissue engineering

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. These standard techniques face significant disadvantages. As a result, research has focused on the development of alternative therapeutic concepts aiming to design and engineer unparalleled structural and functional bone grafts. Substantial academic and commercial interest has been sparked in bone engineering methods to stimulate, control and eventually replicate key events of bone regeneration ex vivo. Over the years, this interest has further increased and bone tissue engineering has now become a well-recognized research discipline in the area of regenerative medicine. The following chapter gives an overview of bone tissue engineering principles. It focuses on research related to the combination of scaffolds with multipotent precursor cells, such as bone marrow-derived mesenchymal stem cells or human umbilical cord perivascular cells, and the clinical applications of these tissue engineered bone constructs.