Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically

Extending services delivery with lightweight composition

The tertiary sector is an important employer and its growth is well above average. The Texo project’s aim is to support this development by making services tradable. The composition of new or value-added services is a cornerstone of the proposed architecture. It is, however, intended to cater for build-time. Yet, at run-time unforseen exceptions may occur and user’s requirements may change. Varying circumstances require immediate sensemaking of the situation’s context and call for prompt extensions of existing services. Lightweight composition technology provided by the RoofTop project enables domain experts to create simple widget-like applications, also termed enterprise mashups, without extensive methodological skills. In this way RoofTop can assist and extend the idea of service delivery through the Texo platform and is a further step towards a next generation internet of services.

A comparative study of governmental one-stop portals for public service delivery

The continuing need for governments to radically improve the delivery of public services has led to a new, holistic government reform strategy labeled “Transformational Government” that strongly emphasizes customer-centricity. Attention has turned to online portals as a cost effective front-end to deliver services and engage customers as well as to the corresponding organizational approaches for the back-end to decouple the service interface from the departmental structures. The research presented in this paper makes three contributions: Firstly, a systematic literature review of approaches to the evaluation of online portal models in the public sector is presented. Secondly, the findings of a usability study comparing the online presences of the Queensland Government, the UK Government and the South Australian Government are reported and the relative strengths and weaknesses of the different approaches are discussed. And thirdly, the limitations of the usability study in the context of a broader “Transformational Government” approach are identified and service bundling is suggested as an innovative solution to further improve online service delivery.

Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery

Bioceramics play an important role in repairing and regenerating bone defects. Annually, more than 500,000 bone graft procedures are performed in the United states and approximately 2.2 million are conducted worldwide. The estimated cost of these procedures approaches $2.5billion per year. Around 60% of the bone graft substitutes available on the market involve bioceramics. It is reported that bioceramics in the world market increase by 9% per year. For this reason, the research of bioceramics has been one of the most active areas during, the past several years. Considering the significant importance of bioceramics, our goal was to compile this book to review the latest research advances in the field of bioceramics. The text also summarizes our work during the past 10 years in an effort to share innovative concepts, design of bioceramisc, and methods for material synthesis and drug delivery. We anticipate that this text will provide some useful information and guidance in the bioceramics field for biomedical engineering researchers and material scientists. Information on novel mesoporous bioactive glasses and silicate-based ceramics for bone regeneration and drug delivery are presented. Mesoporous bioactive glasses have shown multifunctional characteristics of bone regeneration and drug delivery due to their special mesopore structures,whereas silicated-based bioceramics, as typical third-generation biomaterials,possess significant osteostimulation properties. Silica nanospheres with a core-shell structure and specific properties for controllable drug delivery have been carefully reviewed-a variety of advanced synthetic strategies have been developed to construct functional mesoporous silica nanoparticles with a core-shell structure, including hollow, magnetic, or luminescent, and other multifunctional core-shell mesoporous silica nanoparticles. In addition, multifunctional drug delivery systems based on these nanoparticles have been designed and optimized to deliver the drugs into the targeted organs or cells,with a controllable release fashioned by virtue of various internal and external triggers. The novel 3D-printing technique to prepare advanced bioceramic scaffolds for bone tissue engineering applications has been highlighted, including the preparation, mechanical strength, and biological properties of 3D-printed porous scaffolds of calcium phosphate cement and silicate bioceramics. Three-dimensional printing techniques offer improved large-pore structure and mechanical strength. In addition , biomimetic preparation and controllable crystal growth as well as biomineralization of bioceramics are summarized, showing the latest research progress in this area. Finally, inorganic and organic composite materials are reviewed for bone regeneration and gene delivery. Bioactive inorganic and organic composite materials offer unique biological, electrical, and mechanical properties for designing excellent bone regeneration or gene delivery systems. It is our sincere hope that this book will updated the reader as to the research progress of bioceramics and their applications in bone repair and regeneration. It will be the best reward to all the contributors of this book if their efforts herein in some way help reader in any part of their study, research, and career development.

Modelling, collaboration and integration : a case study for the delivery of public buildings

An evolution in the use of digital modelling has occurred in the Queensland Department of Public Works Division of Project Services over the last 20 years from: the initial implementation of computer aided design and documentation (CADD); to experimentation with building information modelling (BIM); to embedding integrated practice (IP); to current steps towards integrated project delivery (IPD) including the active involvement of consultants and contractors in the design/delivery process. This case study is one of three undertaken through the Australian Sustainable Built Environment National Research Centre investigating past R&D investment. The intent of these cases is to inform the development of policy guidelines for future investment in the construction industry in Australia. This research is informing the activities of CIB Task Group 85 R&D Investment and Impact. The uptake of digital modelling by Project Services has been approached through an incremental learning approach. This has been driven by a strong and clear vision with a focus on developing more efficient delivery mechanisms through the use of new technology coupled with process change. Findings reveal an organisational focus on several areas including: (i) strategic decision making including the empowerment of innovation leaders and champions; (ii) the acquisition and exploitation of knowledge; (iii) product and process development (with a focus on efficiency and productivity); (iv) organisational learning; (v) maximising the use of technology; and (vi) supply chain integration. Key elements of this approach include pilot projects, researcher engagement, industry partnerships and leadership.

Mid-gestation intra-amniotic infection with Ureaplasma parvum is resolved within spiny mice (Acomys cahirinus) by term delivery: but caused chronic infection of fetal lungs and placentae

Background: Ureaplasma species in amniotic fluid at the time of second-trimester amniocentesis increases the risk of preterm birth, but most affected pregnancies continue to term (Gerber et al. J Infect Dis 2003). We aimed to model intra-amniotic (IA) ureaplasma infection in spiny mice, a species with a relatively long gestation (39 days) that allows investigation of the disposition and possible clearance of ureaplasmas in the feto-placental compartment. Method: Pregnant spiny mice received IA injections of U. parvum serovar 6 (10µL, 1x104 colony-forming-units in PBS) or 10B media (10µL; control) at 20 days (d) of gestation (term=39d). At 37d fetuses (n=3 ureaplasma, n=4 control) were surgically delivered and tissues were collected for; bacterial culture, ureaplasma mba and urease gene expression by PCR, tissue WBC counts and indirect fluorescent antibody (IFA) staining using anti-ureaplasma serovar 6 (rabbit) antiserum. Maternal and fetal plasma IgG was measured by Western blot. Results: Ureaplasmas were not detected by culture or PCR in fetal or maternal tissues but were visualized by IFA within placental and fetal lung tissues, in association with inflammatory changes and elevated WBC counts (p<0.0001). Anti-ureaplasma IgG was detected in maternal (2/2 tested) and fetal (1/2 tested) plasma but not in controls (0/3). Conclusions: IA injection of ureaplasmas in mid-gestation spiny mice caused persistent fetal lung and placental infection even though ureaplasmas were undetectable using standard culture or PCR techniques. This is consistent with resolution of IA infection, which may occur in human pregnancies that continue to term despite detection of ureaplasmas in mid-gestation.

Applying quality management to project delivery in Hong Kong : A field study of management perceptions

The concept of market-driven rather than product-driven quality management has been given prominence through the report of a recent inquiry into the performance of the Hong Kong construction industry. The report submitted to the Government of Hong Kong in 2001 establishes a new vision of ‘an integrated industry that is capable of continuous improvement towards excellence in the market-driven environment’. Given the current economic downturn, major contractors are facing many challenges to realize this new quality oriented vision. This paper addresses the critical and timely issue of applying quality management to the project delivery process in Hong Kong. The paper attempts to capture and critically examine management perceptions of quality management aspects as applied to a local large-scale road construction project. Based on the analysis of questionnaire feedback and face-to-face interviews, the paper reveals key attributes of a successful application of quality management approaches, and identifies a mechanism for facilitating such implementation.

Stakeholder engagement by governance networks : a study of stakeholder engagement by road delivery network in Queensland

This thesis explores how governance networks prioritise and engage with their stakeholders, by studying three exemplars of “Regional Road Group” governance networks in Queensland, Australia. In the context of managing regionally significant road works programs, stakeholder prioritisation is a complex activity which is unlikely to influence interactions with stakeholders outside of the network. However, stakeholder priority is more likely to influence stakeholder interactions within the networks themselves. Both stakeholder prioritisation and engagement are strongly influenced by the way that the networks are managed, and in particular network operating rules and continuing access to resources.

Delivery of dimethyloxallyl glycine in mesoporous bioactive glass scaffolds to improve angiogenesis and osteogenesis of human bone marrow stromal cells

Development of hypoxia-mimicking bone tissue engineering scaffolds is of great importance in stimulating angiogenesis for bone regeneration. Dimethyloxallyl glycine (DMOG) is a cell-permeable, competitive inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression. The aim of this study was to develop hypoxia-mimicking scaffolds by delivering DMOG in mesoporous bioactive glass (MBG) scaffolds and to investigate whether the delivery of DMOG could induce a hypoxic microenvironment for human bone marrow stromal cells (hBMSC). MBG scaffolds with varied mesoporous structures (e.g. surface area and mesopore volume) were prepared by controlling the contents of mesopore-template agent. The composition, large-pore microstructure and mesoporous properties of MBG scaffolds were characterized. The effect of mesoporous properties on the loading and release of DMOG in MBG scaffolds was investigated. The effects of DMOG delivery on the cell morphology, cell viability, HIF-1α stabilization, vascular endothelial growth factor (VEGF) secretion and bone-related gene expression (alkaline phosphatase, ALP; osteocalcin, OCN; and osteopontin, OPN) of hBMSC in MBG scaffolds were systematically investigated. The results showed that the loading and release of DMOG in MBG scaffolds can be efficiently controlled by regulating their mesoporous properties via the addition of different contents of mesopore-template agent. DMOG delivery in MBG scaffolds had no cytotoxic effect on the viability of hBMSC. DMOG delivery significantly induced HIF-1α stabilization, VEGF secretion and bone-related gene expression of hBMSC in MBG scaffolds in which DMOG counteracted the effect of HIF-PH and stabilized HIF-1α expression under normoxic condition. Furthermore, it was found that MBG scaffolds with slow DMOG release significantly enhanced the expression of bone-related genes more than those with instant DMOG release. The results suggest that the controllable delivery of DMOG in MBG scaffolds can mimic a hypoxic microenvironment, which not only improves the angiogenic capacity of hBMSC, but also enhances their osteogenic differentiation.

Verification of patient position and delivery of IMRT by electronic portal imaging

Background and purpose: The purpose of the work presented in this paper was to determine whether patient positioning and delivery errors could be detected using electronic portal images of intensity modulated radiotherapy (IMRT). Patients and methods: We carried out a series of controlled experiments delivering an IMRT beam to a humanoid phantom using both the dynamic and multiple static field method of delivery. The beams were imaged, the images calibrated to remove the IMRT fluence variation and then compared with calibrated images of the reference beams without any delivery or position errors. The first set of experiments involved translating the position of the phantom both laterally and in a superior/inferior direction a distance of 1, 2, 5 and 10 mm. The phantom was also rotated 1 and 28. For the second set of measurements the phantom position was kept fixed and delivery errors were introduced to the beam. The delivery errors took the form of leaf position and segment intensity errors. Results: The method was able to detect shifts in the phantom position of 1 mm, leaf position errors of 2 mm, and dosimetry errors of 10% on a single segment of a 15 segment IMRT step and shoot delivery (significantly less than 1% of the total dose). Conclusions: The results of this work have shown that the method of imaging the IMRT beam and calibrating the images to remove the intensity modulations could be a useful tool in verifying both the patient position and the delivery of the beam.

Verification of patient position and delivery of IMRT by electronic Portal Imaging

We have taken a new method of calibrating portal images of IMRT beams and used this to measure patient set-up accuracy and delivery errors, such as leaf errors and segment intensity errors during treatment. A calibration technique was used to remove the intensity modulations from the images leaving equivalent open field images that show patient anatomy that can be used for verification of the patient position. The images of the treatment beam can also be used to verify the delivery of the beam in terms of multileaf collimator leaf position and dosimetric errors. A series of controlled experiments delivering an IMRT anterior beam to the head and neck of a humanoid phantom were undertaken. A 2mm translation in the position of the phantom could be detected. With intentional introduction of delivery errors into the beam this method allowed us to detect leaf positioning errors of 2mm and variation in monitor units of 1%. The method was then applied to the case of a patient who received IMRT treatment to the larynx and cervical nodes. The anterior IMRT beam was imaged during four fractions and the images calibrated and investigated for the characteristic signs of patient position error and delivery error that were shown in the control experiments. No significant errors were seen. The method of imaging the IMRT beam and calibrating the images to remove the intensity modulations can be a useful tool in verifying both the patient position and the delivery of the beam.