Hylaluronan-based heparin-incorporated hydrogels for generation of axially vascularized bioartificial bone tissues : in vitro and in vivo evaluation in a PLDLLA-TCP-PCL-composite system

Smart matrices are required in bone tissueengineered grafts that provide an optimal environment for cells and retain osteo-inductive factors for sustained biological activity. We hypothesized that a slow-degrading heparin-incorporated hyaluronan (HA) hydrogel can preserve BMP-2; while an arterio–venous (A–V) loop can support axial vascularization to provide nutrition for a bioartificial bone graft. HA was evaluated for osteoblast growth and BMP-2 release. Porous PLDLLA–TCP–PCL scaffolds were produced by rapid prototyping technology and applied in vivo along with HA-hydrogel, loaded with either primary osteoblasts or BMP-2. A microsurgically created A–V loop was placed around the scaffold, encased in an isolation chamber in Lewis rats. HA-hydrogel supported growth of osteoblasts over 8 weeks and allowed sustained release of BMP-2 over 35 days. The A–V loop provided an angiogenic stimulus with the formation of vascularized tissue in the scaffolds. Bone-specific genes were detected by real time RT-PCR after 8 weeks. However, no significant amount of bone was observed histologically. The heterotopic isolation chamber in combination with absent biomechanical stimulation might explain the insufficient bone formation despite adequate expression of bone-related genes. Optimization of the interplay of osteogenic cells and osteo-inductive factors might eventually generate sufficient amounts of axially vascularized bone grafts for reconstructive surgery.

Immunohistochemical analysis of structural changes in collagen for the assessment of osteoarthritis

Collagen fibrillation within articular cartilage (AC) plays a key role in joint osteoarthritis (OA) progression and, therefore, studying collagen synthesis changes could be an indicator for use in the assessment of OA. Various staining techniques have been developed and used to determine the collagen network transformation under microscopy. However, because collagen and proteoglycan coexist and have the same index of refraction, conventional methods for specific visualization of collagen tissue is difficult. This study aimed to develop an advanced staining technique to distinguish collagen from proteoglycan and to determine its evolution in relation to OA progression using optical and laser scanning confocal microscopy (LSCM). A number of AC samples were obtained from sheep joints, including both healthy and abnormal joints with OA grades 1 to 3. The samples were stained using two different trichrome methods and immunohistochemistry (IHC) to stain both colourimetrically and with fluorescence. Using optical microscopy and LSCM, the present authors demonstrated that the IHC technique stains collagens only, allowing the collagen network to be separated and directly investigated. Fluorescently-stained IHC samples were also subjected to LSCM to obtain three-dimensional images of the collagen fibres. Changes in the collagen fibres were then correlated with the grade of OA in tissue. This study is the first to successfully utilize the IHC staining technique in conjunction with laser scanning confocal microscopy. This is a valuable tool for assessing changes to articular cartilage in OA.

In situ preparation and protein delivery of silicate/alginate composite microspheres with core-shell structure

It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

Replication of the Frank-Starling response in a Mock Circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCL’s pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.

Phenomenological modeling of cell-to-cell and beat-to-beat variability in isolated Guinea Pig ventricular myocytes

Experimental action potential (AP) recordings in isolated ventricular myoctes display significant temporal beat-to-beat variability in morphology and duration. Furthermore, significant cell-to-cell differences in AP also exist even for isolated cells originating from the same region of the same heart. However, current mathematical models of ventricular AP fail to replicate the temporal and cell-to-cell variability in AP observed experimentally. In this study, we propose a novel mathematical framework for the development of phenomenological AP models capable of capturing cell-to-cell and temporal variabilty in cardiac APs. A novel stochastic phenomenological model of the AP is developed, based on the deterministic Bueno-Orovio/Fentonmodel. Experimental recordings of AP are fit to the model to produce AP models of individual cells from the apex and the base of the guinea-pig ventricles. Our results show that the phenomenological model is able to capture the considerable differences in AP recorded from isolated cells originating from the location. We demonstrate the closeness of fit to the available experimental data which may be achieved using a phenomenological model, and also demonstrate the ability of the stochastic form of the model to capture the observed beat-to-beat variablity in action potential duration.

The influence of cultural selection on strategic communication

Strategic communication is held to be a key process by which organisations respond to environmental uncertainty. In the received view articulated in the literatures of organisational communication and public relations, strategic communication results from collaborative efforts by organisational members to create shared understanding about environmental uncertainty and, as a result of this collective understanding, formulate appropriate communication responses. In this study, I explore how such collaborative efforts towards the development of strategic communication are derived from, and bounded by, culturally shared values and assumptions. Study of the influences of an organisation‟s culture on the formulation of strategic communication is a fundamental conceptual challenge for public relations and, to date, a largely unaddressed area of research. This thesis responds to this challenge by describing a key property of organisational culture – the action of cultural selection (Durham, 1992). I integrate this property of cultural selection to extend and refine the descriptive range of Weick‟s (1969, 1979) classic sociocultural model of organizing. From this integration I propose a new model, the Cultural Selection of Strategic Communication (CSSC). Underpinning the CSSC model is the central proposition that because of the action of cultural selection during organizing processes, the inherently conservative properties of an organisation‟s culture constrain development of effective strategic communication in ways that may be unrelated to the outcomes of “environmental scanning” and other monitoring functions heralded by the public relations literature as central to organisational adaptation. Thus, by examining the development of strategic communication, I describe a central conservative influence on the social ecology of organisations. This research also responds to Butschi and Steyn‟s (2006) call for the development of theory focusing on strategic communication as well as Grunig (2006) and Sriramesh‟s (2007) call for research to further understand the role of culture in public relations practice. In keeping with the explorative and descriptive goals of this study, I employ organisational ethnography to examine the influence of cultural selection on the development of strategic communication. In this methodological approach, I use the technique of progressive contextualisation to compare data from two related but distinct cultural settings. This approach provides a range of descriptive opportunities to permit a deeper understanding of the work of cultural selection. Findings of this study propose that culture, operating as a system of shared and socially transmitted social knowledge, acts through the property of cultural selection to influence decision making, and decrease conceptual variation within a group. The findings support the view that strategic communication, as a cultural product derived from the influence of cultural selection, is an essential feature to understand the social ecology of an organisation.

The mobile phone : the new communication drum of Papua New Guinea

This thesis examines the role of mobile telephony in rural communities in Papua New Guinea (PNG). It is a threshold study which reports on research conducted in the earliest stages of mobile phone adoption in these areas. It explores the ways in which this new technology changes people’s lives, social structures and relationships. The research focuses on non-urban communities, which previously had little or no access to modern communication technologies, but which are in some cases still using traditional forms of communication such as drums. It has found that the introduction of mobile telecommunications has generally been viewed positively, although several negative concerns have been strongly felt. Specific benefits related to enhanced communication with relatives and friends living away from home villages, and use of the technology in time-critical emergencies or crises. Difficulties have arisen with respect to the cost of owning and operating a handset, as well as financial and logistical challenges when recharging handset batteries, particularly in areas with no mains electricity supply. Perceived damaging effects of mobile phone access related to sex, crime and pornography. The changes taking place are described through a social lens, by foregrounding the perceptions of villagers. The perspectives of key informants, such as telecommunication company managers, are also discussed. Employing the technique of triangulation (using different methods and sources) has helped to validate the findings of the research project. The sources constantly overlap and agree on the main themes, such as those outlined above. PNG is a developing country which performs poorly on a wide range of development indicators. A large majority of the people live outside of the major towns and cities. It is therefore worthwhile investigating the introduction of mobile phone technology in rural areas. These areas often have poor access to services, including transport, health, education and banking. Until 2007, communities in such regions fell outside of mobile phone coverage areas. In the case of all ten villages discussed in this thesis, there has never been any landline telephone infrastructure available. Therefore, this research on mobile phones is in effect documenting the first ever access to any kind of phone in these communities. This research makes a unique contribution to knowledge about the role of communication in PNG, and has implications for policy, practice and theory. In the policy arena, the thesis aids understanding of the impact which communication sector competition and regulation can have on rural and relatively isolated communities. There are three practical problems which have emerged from the research: cost, battery recharging difficulties and breakage are all major obstacles to uptake and use of mobile telephony in rural communities. Efforts to reduce usage costs, enable easier recharging, and design more robust handsets would allow for increased utilisation of mobile phones for a range of purposes. With respect to the realm of theory, this research sits amongst the most recent scholarship in the mobile phone field, located within the broader communication theory area. It recommends cautionary reading of any literature which suggests that mobile phones will reduce poverty and increase incomes in poor, rural communities in developing countries. Nonetheless, the present research adds weight to mobile phone studies which suggest that the primary advantages of mobile phones in such settings are for the satisfactions of communication of itself, and for social interaction among loved ones.

Evaluation of modal analysis techniques using physical models to detect osseointegration of implants in transfemoral amputees

Non-invasive vibration analysis has been used extensively to monitor the progression of dental implant healing and stabilization. It is now being considered as a method to monitor femoral implants in transfemoral amputees. This paper evaluates two modal analysis excitation methods and investigates their capabilities in detecting changes at the interface between the implant and the bone that occur during osseointegration. Excitation of bone-implant physical models with the electromagnetic shaker provided higher coherence values and a greater number of modes over the same frequency range when compared to the impact hammer. Differences were detected in the natural frequencies and fundamental mode shape of the model when the fit of the implant was altered in the bone. The ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.

Mapping intermedia news flows : topical discussions in the Australian and French political blogospheres

The growth of technologies and tools branded as =new media‘ or =Web 2.0‘ has sparked much discussion about the internet and its place in all facets of social life. Such debate includes the potential for blogs and citizen journalism projects to replace or alter journalism and mainstream media practices. However, while the journalism-blog dynamic has attracted the most attention, the actual work of political bloggers, the roles they play in the mediasphere and the resources they use, has been comparatively ignored. This project will look at political blogging in Australia and France - sites commenting on or promoting political events and ideas, and run by citizens, politicians, and journalists alike. In doing so, the structure of networks formed by bloggers and the nature of communication within political blogospheres will be examined. Previous studies of political blogging around the world have focussed on individual nations, finding that in some cases the networks are divided between different political ideologies. By comparing two countries with different political representation (two-party dominated system vs. a wider political spectrum), this study will determine the structure of these political blogospheres, and correlate these structures with the political environment in which they are situated. The thesis adapts concepts from communication and media theories, including framing, agenda setting, and opinion leaders, to examine the work of political bloggers and their place within the mediasphere. As well as developing a hybrid theoretical base for research into blogs and other online communication, the project outlines new methodologies for carrying out studies of online activity through the analysis of several topical networks within the wider activity collected for this project. The project draws on hyperlink and textual data collected from a sample of Australian and French blogs between January and August 2009. From this data, the thesis provides an overview of =everyday‘ political blogging, showing posting patterns over several months of activity, away from national elections and their associated campaigns. However, while other work in this field has looked solely at cumulative networks, treating collected data as a static network, this project will also look at specific cases to see how the blogospheres change with time and topics of discussion. Three case studies are used within the thesis to examine how blogs cover politics, featuring an international political event (the Obama inauguration), and local political topics (the opposition to the =Création et Internet‘, or HADOPI, law in France, the =Utegate‘ scandal in Australia). By using a mixture of qualitative and quantitative methods, the study analyses data collected from a population of sites from both countries, looking at their linking patterns, relationship with mainstream media, and topics of interest. This project will subsequently help to further develop methodologies in this field and provide new and detailed information on both online networks and internet-based political communication in Australia and France.

Acoustic, mechanical and near-infrared profiling of osteoarthritic progression in bovine joints

Early-stage treatments for osteoarthritis are attracting considerable interest as a means to delay, or avoid altogether, the pain and lack of mobility associated with late-stage disease, and the considerable burden that it places on the community. With the development of these treatments comes a need to assess the tissue to which they are applied, both in trialling of new treatments and as an aid to clinical decision making. Here, we measure a range of mechanical indentation, ultrasound and near-infrared spectroscopy parameters in normal and osteoarthritic bovine joints in vitro to describe the role of different physical phenomena in disease progression, using this as a basis to investigate the potential value of the techniques as clinical tools. Based on 72 samples we found that mechanical and ultrasound parameters showed differences between fibrillated tissue, macroscopically normal tissue in osteoarthritic joints, and normal tissue, yet did were unable to differentiate degradation beyond that which was visible to the naked eye. Near-infrared spectroscopy showed a clear progression of degradation across the visibly normal osteoarthritic joint surface and as such, was the only technique considered useful for clinical application.