The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
Involvement of the Human Retinal Endothelial Cell in Blinding Eye Disease. Endothelial cells line the blood vessels of the vascular networks that circulate blood through the tissues. The molecular constitution of each endothelial cell is different and specific to function, but may predispose to tissue-specific disease. Retinal endothelial cells ensure the nutrition and protection of a tissue critical to vision, but are key participants in retinal ischemic, inflammatory and infectious diseases th ....Involvement of the Human Retinal Endothelial Cell in Blinding Eye Disease. Endothelial cells line the blood vessels of the vascular networks that circulate blood through the tissues. The molecular constitution of each endothelial cell is different and specific to function, but may predispose to tissue-specific disease. Retinal endothelial cells ensure the nutrition and protection of a tissue critical to vision, but are key participants in retinal ischemic, inflammatory and infectious diseases that threaten vision. This project will investigate molecular activities of retinal endothelial cells that are relevant to retinal disease processes and explore future biological therapies directed against the human retinal endothelial cell that address efficacy and safety deficiencies of current treatments.Read moreRead less
Bio-MEMS eye sensor for continuous monitoring of intraocular pressure. Glaucoma is a leading cause of preventable blindness, particularly prevalent in the 60+ population, caused by elevated intraocular pressure (IOP). Current treatment to monitor and prevent glaucoma-related blindness is by lowering IOP with eye-drops, laser therapy or surgery. This project directly benefits our aging population by ensuring independence and quality of life, whilst reducing long-term medical and social costs. By ....Bio-MEMS eye sensor for continuous monitoring of intraocular pressure. Glaucoma is a leading cause of preventable blindness, particularly prevalent in the 60+ population, caused by elevated intraocular pressure (IOP). Current treatment to monitor and prevent glaucoma-related blindness is by lowering IOP with eye-drops, laser therapy or surgery. This project directly benefits our aging population by ensuring independence and quality of life, whilst reducing long-term medical and social costs. By incorporating nanotechnology with ophthalmology we will provide an economic solution to long-term, reliable, home-monitoring of IOP. An implantable IOP sensor, will identify patients requiring more invasive treatment compared with those with less aggressive disease, leading to better health resource utilisation.Read moreRead less
Understanding and Modelling Insect Motion Vision. The interdisciplinary project proposed will offer a stimulating environment for research/training into computational neuroscience, an attractive area for aspiring scientists. We have already demonstrated the feasibility of transferring physiology into applications, and expect this project to deliver functional motion vision models and devices. Our proposed work will have an impact beyond the advancement of neuro-physiology as knowledge gained is ....Understanding and Modelling Insect Motion Vision. The interdisciplinary project proposed will offer a stimulating environment for research/training into computational neuroscience, an attractive area for aspiring scientists. We have already demonstrated the feasibility of transferring physiology into applications, and expect this project to deliver functional motion vision models and devices. Our proposed work will have an impact beyond the advancement of neuro-physiology as knowledge gained is applicable in a range of areas, with applications in miniature unmanned vehicles and collision avoidance detectors in defence and civilian roles. Our project could also assist in the development of artificial intelligence and as a basis for designing implantable artificial eyes.Read moreRead less
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
A lossy compression paradigm for sensory neural coding. By applying new interdisciplinary theoretical results, this research aims to enhance our understanding of how the ear turns sounds into electrical signals in the presence of high levels of random noise. Socio-economic benefits to Australia include: (i) contributions to the knowledge base of theoretical neuroscience, and communications systems, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of European interna ....A lossy compression paradigm for sensory neural coding. By applying new interdisciplinary theoretical results, this research aims to enhance our understanding of how the ear turns sounds into electrical signals in the presence of high levels of random noise. Socio-economic benefits to Australia include: (i) contributions to the knowledge base of theoretical neuroscience, and communications systems, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of European international collaborations; (iii) outcomes that will ultimately impact on improved designs for bionic ears and future biomedical prosthetics; and (iv) commercialisation and technology transfer opportunities, via the transfer of results to wireless artificial sensor networks.Read moreRead less
Effects Of The Fatty Acid, Lauric Acid, On Energy Intake And Gut Motor And Hormonal Function In Health And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
Obesity is largely due to energy intake exceeding energy expenditure, thus, strategies that reduce energy intake will result in weight loss. We discovered recently that the fatty acid, lauric acid, markedly reduces energy intake. Our studies will determine the effects of lauric acid on energy intake and body weight reduction in obese subjects. The research is a new initiative and explores the potential of lauric acid as a novel, nutrient-based and side-effect free approach to obesity management.
Vision performance in relationship to spectacle lens design. Refractive errors such as short-sightedness, long-sightedness or presbyopia (age related decline in near vision) are the leading causes of visual impairment in the world. Of these, presbyopia affects almost 100% of the population above 45 years of age. This represents over 40% of all Australians. Although spectacles provide a safe and easy means of correcting refractive errors, they affect quality of life due to distorted vision, disco ....Vision performance in relationship to spectacle lens design. Refractive errors such as short-sightedness, long-sightedness or presbyopia (age related decline in near vision) are the leading causes of visual impairment in the world. Of these, presbyopia affects almost 100% of the population above 45 years of age. This represents over 40% of all Australians. Although spectacles provide a safe and easy means of correcting refractive errors, they affect quality of life due to distorted vision, discomfort such as head and neck ache and cosmetic effects. The goals of the project are to better understand the visual performance of young and old people who wear glasses and to develop improved spectacle lens designs to provide clear and comfortable vision over a range of distances.Read moreRead less
Surface engineering of oriented nano-layers for performance control. This research project will deliver knowledge on how to graft oriented, self assembled films from a surface, develop structure-property relationships at a nano-scale, develop a means to control these properties and develop characterization techniques at nano-scales. This research project, if successful, will deliver the ability to tailor the properties of a surface in a manner and over a range of properties that is not even cont ....Surface engineering of oriented nano-layers for performance control. This research project will deliver knowledge on how to graft oriented, self assembled films from a surface, develop structure-property relationships at a nano-scale, develop a means to control these properties and develop characterization techniques at nano-scales. This research project, if successful, will deliver the ability to tailor the properties of a surface in a manner and over a range of properties that is not even contemplated today.
In addition to the scientific benefits, there are also immediate commercial applications in Australia and worldwide for ophthalmic products (e.g. anti-fog and easy to clean lenses), if the balance of properties can be obtained.
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