An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Integrated sustainable urban infrastructure management: the Brisbane urban growth model

Sustainable urban development and the liveability of a city are increasingly important issues in the context of land use planning and infrastructure management. In recent years, the promotion of sustainable urban development in Australia and overseas is facing various physical, socio-economic and environmental challenges. These challenges and problems arise from the lack of capability of local governments to accommodate the needs of the population and economy in a relatively short timeframe. The planning of economic growth and development is often dealt with separately and not included in the conventional land use planning process. There is also a sharp rise in the responsibilities and roles of local government for infrastructure planning and management. This increase in responsibilities means that local elected officials and urban planners have less time to prepare background information and make decisions. The Brisbane Urban Growth Model has proven initially successful in providing a dynamic platform to ensure timely and coordinated delivery of urban infrastructure. Most importantly, this model is the first step for local governments in moving toward a systematic approach to pursuing sustainable and effective urban infrastructure management.

Brisbane urban growth model : an integrated infrastructure management framework for Brisbane, Australia

In recent years, local government infrastructure management practices have evolved from conventional land use planning to more wide ranging and integrated urban growth and infrastructure management approaches. The roles and responsibilities of local government are no longer simply to manage daily operational functions of a city and provide basic infrastructure. Local governments are now required to undertake economic planning, manage urban growth; be involved in major infrastructure planning; and even engage in achieving sustainable development objectives. The Brisbane Urban Growth model has proven initially successful to ensure timely and coordinated delivery of urban infrastructure. This model may be the first step for many local governments to move toward an integrated, sustainable and effective infrastructure management.

Delivering value for money in the procurement of public sector major infrastructure : a new first-order decision making model

The significant challenge faced by government in demonstrating value for money in the delivery of major infrastructure resolves around estimating costs and benefits of alternative modes of procurement. Faced with this challenge, one approach is to focus on a dominant performance outcome visible on the opening day of the asset, as the means to select the procurement approach. In this case, value for money becomes a largely nominal concept and determined by selected procurement mode delivering, or not delivering, the selected performance outcome, and notwithstanding possible under delivery on other desirable performance outcomes, as well as possibly incurring excessive transaction costs. This paper proposes a mind-set change in this particular practice, to an approach in which the analysis commences with the conditions pertaining to the project and proceeds to deploy transaction cost and production cost theory to indicate a procurement approach that can claim superior value for money relative to other competing procurement modes. This approach to delivering value for money in relative terms is developed in a first-order procurement decision making model outlined in this paper. The model developed could be complementary to the Public Sector Comparator (PSC) in terms of cross validation and the model more readily lends itself to public dissemination. As a possible alternative to the PSC, the model could save time and money in preparation of project details to lesser extent than that required in the reference project and may send a stronger signal to the market that may encourage more innovation and competition.

Spatial stimulus : Model making in the architectural design studio

This action research examines the enhancement of visual communication within the architectural design studio through physical model making. „It is through physical model making that designers explore their conceptual ideas and develop the creation and understanding of space,‟ (Salama & Wilkinson 2007:126). This research supplements Crowther‟s findings extending the understanding of visual dialogue to include physical models. „Architecture Design 8‟ is the final core design unit at QUT in the fourth year of the Bachelor of Design Architecture. At this stage it is essential that students have the ability to communicate their ideas in a comprehensive manner, relying on a combination of skill sets including drawing, physical model making, and computer modeling. Observations within this research indicates that students did not integrate the combination of the skill sets in the design process through the first half of the semester by focusing primarily on drawing and computer modeling. The challenge was to promote deeper learning through physical model making. This research addresses one of the primary reasons for the lack of physical model making, which was the limited assessment emphasis on the physical models. The unit was modified midway through the semester to better correlate the lecture theory with studio activities by incorporating a series of model making exercises conducted during the studio time. The outcome of each exercise was assessed. Tutors were surveyed regarding the model making activities and a focus group was conducted to obtain formal feedback from students. Students and tutors recognised the added value in communicating design ideas through physical forms and model making. The studio environment was invigorated by the enhanced learning outcomes of the students who participated in the model making exercises. The conclusions of this research will guide the structure of the upcoming iteration of the fourth year design unit.

Engaging operations management students by designing the unit with industry focus

Operations management is an area concerned with the production of goods and services ensuring that business operations are efficient in utilizing resource and effective to meet customer requirements. It deals with the design and management of products, processes, services and supply chains and considers the acquisition, development, and effective and efficient utilization of resources. Unlike other engineering subjects, content of these units could be very wide and vast. It is therefore necessary to cover the content that is most related to the contemporary industries. It is also necessary to understand what engineering management skills are critical for engineers working in the contemporary organisations. Most of the operations management books contain traditional Operations Management techniques. For example ‘inventory management’ is an important topic in operations management. All OM books deal with effective method of inventory management. However, new trend in OM is Just in time (JIT) delivery or minimization of inventory. It is therefore important to decide whether to emphasise on keeping inventory (as suggested by most books) or minimization of inventory. Similarly, for OM decisions like forecasting, optimization and linear programming most organisations now a day’s use software. Now it is important for us to determine whether some of these software need to be introduced in tutorial/ lab classes. If so, what software? It is established in the Teaching and Learning literature that there must be a strong alignment between unit objectives, assessment and learning activities to engage students in learning. Literature also established that engaging students is vital for learning. However, engineering units (more specifically Operations management) is quite different from other majors. Only alignment between objectives, assessment and learning activities cannot guarantee student engagement. Unit content must be practical oriented and skills to be developed should be those demanded by the industry. Present active learning research, using a multi-method research approach, redesigned the operations management content based on latest developments in Engineering Management area and the necessity of Australian industries. The redesigned unit has significantly helped better student engagement and better learning. It was found that students are engaged in the learning if they find the contents are helpful in developing skills that are necessary in their practical life.

A test of the job demands : resources model with HIV/AIDS volunteers

Burnout has been identified as a significant factor in HIV/AIDS volunteering. It has been associated with depression, anxiety and the loss of volunteers from the health care delivery system. The aim of this study was to test the independence of the health and motivational processes hypothesized within the Job Demands – Resources model of burnout in HIV/AIDS volunteers. Participants were 307 HIV/AIDS volunteers from state AIDS Councils throughout Australia who completed self-report measures pertaining to role ambiguity and role conflict, social support, burnout, intrinsic and organizational satisfaction, and depression. Findings suggested that the independence of the dual processes hypothesized by the model was only partially supported. These findings provide a model for burnout which gives a framework for interventions at both the individual and organizational level which would contribute to the prevention of burnout, depression, and job dissatisfaction in HIV/AIDS volunteers.

Limitations and challenges in MSC delivery for bone regeneration

Objective: Regeneration of osseous defects by tissue-engineering or cell delivery approach provides a novel means of treatment utilizing cell biology, materials sciences, and molecular biology. The concept of in vitro explanted mesenchymal stem cells (MSCs) with an ability to induce new bone formation has been demonstrated in some small animal models. However, contradictory results have been reported regarding the regenerative capacity of MSCs after ex vivo expansion due to the lack of the understanding of microenvironment for MSC differentiation in vivo. ----- ----- Methods: In our laboratory tissue-derived and bone marrow-derived MSCs have been investigated in their osteogenesis. Cell morphology and proliferation were studied by microscopy, confocal microscopy, FACS and cell counting. Cell differentiation and matrix formation were analysed by matrix staining, quantitative PCR, and immunohistochemistry. A SCID skull defect model was used for cell transplantation studies.----- ----- Results: It was noted that tissue-derived and bone marrow-derived MSCs showed similar characteristics in cell surface marker expression, mesenchymal lineage differentiation potential, and cell population doubling. MSCs from both sources could initiate new bone formation in bone defects after delivery into a critical size defects. The bone forming cells were from both transplanted cells and endogenous cells from the host. Interestingly, the majority of in vitro osteogenic differentiated cells did not form new bone directly even though mineralized matrix was synthesized in vitro by MSCs. Furthermore, no new bone formation was detected when MSCs were transplanted subcutaneously.----- ----- Conclusion: This study unveiled the limitations of MSC delivery in bone regeneration and proposed that in vivo microenvironment needs to be optimized for MSC delivery in osteogenesis.

In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for BMP-7 gene delivery

Introduction and aims: For a scaffold material to be considered effective and efficient for tissue engineering it must be biocompatible as well as bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue-conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue-inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteo-inductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and methods: Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50) and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. Results: In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3 week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting significantly enhanced new bone formation. Conclusions: Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.

An example of developing a business model for information and communication technologies (ICT) adoption on construction projects – the National Museum of Australia project

Effective use of information and communication technologies (ICT) is necessary for delivering efficiency and improved project delivery in the construction industry. Convincing clients or contracting organisations to embrace ICT is a difficult task, there are few templates of an ICT business model for the industry to use. ICT application in the construction industry is relatively low compared to automotive and aerospace industries. The National Museum of Australia project provides a unique opportunity for investigating and reporting on this deficiency in publicly available knowledge. Concentrates on the business model content and objectives, briefly indicates the evaluation framework that was used to evaluate ICT effectiveness.

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Drug diffusion from polymeric delivery devices : a problem with two moving boundaries

An existing model for solvent penetration and drug release from a spherically-shaped polymeric drug delivery device is revisited. The model has two moving boundaries, one that describes the interface between the glassy and rubbery states of polymer, and another that defines the interface between the polymer ball and the pool of solvent. The model is extended so that the nonlinear diffusion coefficient of drug explicitly depends on the concentration of solvent, and the resulting equations are solved numerically using a front-fixing transformation together with a finite difference spatial discretisation and the method of lines. We present evidence that our scheme is much more accurate than a previous scheme. Asymptotic results in the small-time limit are presented, which show how the use of a kinetic law as a boundary condition on the innermost moving boundary dictates qualitative behaviour, the scalings being very different to the similar moving boundary problem that arises from modelling the melting of an ice ball. The implication is that the model considered here exhibits what is referred to as ``non-Fickian'' or Case II diffusion which, together with the initially constant rate of drug release, has certain appeal from a pharmaceutical perspective.

Asymptotic and numerical results for a model of solvent-dependent drug diffusion through polymeric spheres

A model for drug diffusion from a spherical polymeric drug delivery device is considered. The model contains two key features. The first is that solvent diffuses into the polymer, which then transitions from a glassy to a rubbery state. The interface between the two states of polymer is modelled as a moving boundary, whose speed is governed by a kinetic law; the same moving boundary problem arises in the one-phase limit of a Stefan problem with kinetic undercooling. The second feature is that drug diffuses only through the rubbery region, with a nonlinear diffusion coefficient that depends on the concentration of solvent. We analyse the model using both formal asymptotics and numerical computation, the latter by applying a front-fixing scheme with a finite volume method. Previous results are extended and comparisons are made with linear models that work well under certain parameter regimes. Finally, a model for a multi-layered drug delivery device is suggested, which allows for more flexible control of drug release.

Hyaluronic acid : evaluation as a potential delivery vehicle for vitronectin:growth factor complexes in wound healing applications

We have previously reported that novel vitronectin:growth factor (VN:GF) complexes significantly increase re-epithelialization in a porcine deep dermal partial-thickness burn model. However, the potential exists to further enhance the healing response through combination with an appropriate delivery vehicle which facilitates sustained local release and reduced doses of VN:GF complexes. Hyaluronic acid (HA), an abundant constituent of the interstitium, is known to function as a reservoir for growth factors and other bioactive species. The physicochemical properties of HA confer it with an ability to sustain elevated pericellular concentrations of these species. This has been proposed to arise via HA prolonging interactions of the bioactive species with cell surface receptors and/or protecting them from degradation. In view of this, the potential of HA to facilitate the topical delivery of VN:GF complexes was evaluated. Two-dimensional (2D) monolayer cell cultures and 3D de-epidermised dermis (DED) human skin equivalent (HSE) models were used to test skin cell responses to HA and VN:GF complexes. Our 2D studies revealed that VN:GF complexes and HA stimulate the proliferation of human fibroblasts but not keratinocytes. Experiments in our 3D DED-HSE models showed that VN:GF complexes, both alone and in conjunction with HA, led to enhanced development of both the proliferative and differentiating layers in the DED-HSE models. However, there was no significant difference between the thicknesses of the epidermis treated with VN:GF complexes alone and VN:GF complexes together with HA. While the addition of HA did not enhance all the cellular responses to VN:GF complexes examined, it was not inhibitory, and may confer other advantages related to enhanced absorption and transport that could be beneficial in delivery of the VN:GF complexes to wounds.