Mechanisms Of Bone Formation At The Device/tissue Interface: Role Of Biomaterial Surface Chemistry Modification
Funder
National Health and Medical Research Council
Funding Amount
$489,375.00
Summary
In 1992 300,000 prosthetic devices, artificial hips and knees were implanted into patients in a global market worth $2.1 billion. Growth in this field of medicine has been exceptional with now more than 1 million implants carried out each year. In 1998-99, 38,512 artificial hips and knees were implanted in Australia alone, with approximately 10% of these replacing older, failed implants. Since joint replacements provide great benefits for the patient considerable health funding is required for j ....In 1992 300,000 prosthetic devices, artificial hips and knees were implanted into patients in a global market worth $2.1 billion. Growth in this field of medicine has been exceptional with now more than 1 million implants carried out each year. In 1998-99, 38,512 artificial hips and knees were implanted in Australia alone, with approximately 10% of these replacing older, failed implants. Since joint replacements provide great benefits for the patient considerable health funding is required for joint replacements. However, failure of the implants is a major concern to the patient and financially to our health system, especially with the ever increasing life expectancy of our population. The long-and short-term success of an implant depends on the healthy support of the surrounding bone. This study aims to find ways of improving the attachment of healthy bone to the implant by modifying the surface characteristics of the implant. We will modify the surface chemistry of biomaterials with divalent cations, such as magnesium, which is known to play a critical role in bone remodelling and skeletal development. Our goal is to improve the formation of healthy bone that will promote a rapid and permanent fixation of implant into skeletons. This study goes further to study the factors, inside the cell, on the cell surface and secreted by the cell, which promote this attachment. Once these factors are identified, it should be possible to alter implant surfaces in ways to improve stability. In this proposal we will use novel bioceramic coatings and ion beam technologies. This study will not only improve our understanding of the interactions of bone and implant but also identify ways of improving implants to benefit the patient's quality of life and reduce costs in this important heath areaRead moreRead less
At present the failure rate of joint replacement is unacceptably high and will continue to rise due to the ageing and active life styles of the baby-boomer generation, placing an increasing burden on the health budget. We have developed a new bioactive material with improved mechanical-biological properties for bone regeneration. We will modify the surface of the currently used orthopaedic implants with this bioactive material to promote permanent fixation of the prosthesis to the bone.
Peptides Bound To Commonly Used Orthopaedic And Dental Biomaterials:In Vitro And In Vivo Effect On Osteogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$273,428.00
Summary
In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, ....In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, patients morbidity is high. The major cause of long-term failure of these prosthetic replacements is aseptic loosening, the result of bone loss at the bone-device interface. Novel approaches to development of more efficient implant materials would ultimately lead to major contributions to the mobility and and quality of life for these patients. Considerable effort has been devoted to alter surface characteristics of orthopaedic implants to improve the interlocking of device and skeleton. We were the first to demonstrate that surface chemical modification of biomaterials using selected ions resulted in an enhanced bone formation. This proposal is aimed at chemically modifying the surfaces of commonly used orthopaedic and dental materials, to improve the biocompatibility of new devices and the surface coatings for existing prostheses. Furthermore, this application will build on the in vitro data showing that particular peptides specifically bind osteoblasts and therefore have the potential to provide a surface on a prosthesis that is conducive to bone formation. To date, we have coupled these peptides to metallic surfaces and will proceed to study the osteoblastic phenotype and subsequent osteogenesis. Development of these novel biocompatible surfaces is anticipated to reduce patient morbidity and result in significant health care savings.Read moreRead less
Application Of Novel Sutureless Technology For Eye Surgery
Funder
National Health and Medical Research Council
Funding Amount
$342,623.00
Summary
Corneal disease and trauma are major causes of blindness. Corneal trauma requires surgical repair and vision lost from disease may be restored with corneal transplantation. In both cases sutures are used and can have significant complications. Application of a new surgical adhesive for cost-effective, quick and easy corneal surgery with enhanced wound healing is an innovative solution to a major problem in public health with manifold implications in the field of eye surgery
Novel Strategies For The Treatment Of Bone Disease By Nutrient Activators Of Calcium-sensing Receptors
Funder
National Health and Medical Research Council
Funding Amount
$467,432.00
Summary
Osteoporosis is a major health problem in the Australian community and will worsen with an ageing population. This work aims to develop new strategies for the treatment of osteoporosis and associated fractures based on the nutritional and/or pharmacological activation of calcium-sensing receptors.
Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, litt ....Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, little is known of the response properties, structure and organization of receptors and neurones responding to, and relaying information about painful stimuli, from bone to the brain. The objectives of this project are to reveal the fundamental neural mechanisms that account for the perception of bone pain. The project will test a series of specific hypotheses in order to explain why bone pain is often poorly controlled by standard pharmacological or surgical approaches. It is expected that this study will reveal the neural mechanisms responsible for relaying sensory information, in particular, that regarding painful stimuli, from bone to the brain. It will lead to a better understanding of the mechanisms of bone pain and form the template for future studies of its treatment.Read moreRead less
Trabecular Architecture During Growth - Does It Determine Metaphyseal Peak Bone Strength In Adulthood?
Funder
National Health and Medical Research Council
Funding Amount
$165,339.00
Summary
Skeletal fragility is common is elderly people but has its origin in childhood. Strong bone established during growth will provide more protection against occurrence of fragility fracture in old age. Identifying individuals during childhood who are at high risk of skeletal fragility, and early intervention is a strategic approach managing the burden of skeletal fragility on the ageing population.
The Molecular Mechanisms Controlling Maintenance Of Osteogenic Precursor Cells And Skeletal Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bon ....Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bone resorption by osteoclasts, but may also occur through a decline in the number of bone forming cells called osteoblasts or their progenitors. Fracture non-union, prosthetic loosening and the replacement of large defects in bone are common and difficult problems. The use of autologous bone cells generated from isolated BMSSCs in combination with bio-compatible implant materials would provide a novel solution for the treatment of these problems, avoiding the use of autografts and allografts of bone with all their associated difficulties. However, large numbers of ex vivo expanded BMSSCs are currently required to heal even small bone defects in animal models. This is compounded by the decline in proliferation rates and bone forming capacity of BMSSCs during prolonged expansion in culture. An improved understanding of the genes that regulate the proliferation and differentiation of BMSSCs in vitro is therefore an essential prerequisite for the effective management of bone fracture and bone loss. We propose to genetically manipulate the expression of genes in BMSSCs, that are known to regulate cellular growth and development inorder to maintain the growth of stem cell populations in vitro and to extend their capacity to form bone when transplanted in vivo.Read moreRead less
The Role Of TWIST Family Basic Helix-Loop-Helix Transcription Factors In Bone Cell Commitment, Function And Repair
Funder
National Health and Medical Research Council
Funding Amount
$485,928.00
Summary
In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influ ....In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influence the capacity of bone cell progenitors to develop into functional bone forming cells known as osteoblasts. An understanding of the fracture healing is critical for the future advancement of fracture treatment, and for identifying the mechanisms of skeletal growth and repair as well as the causes of aging and disease. This proposal seeks to identify critical regulatory molecules that act to mediate bone cell progenitor recruitment and development during bone fracture repair.Read moreRead less
Relationships Between Human Osteoblasts And Haemopoietic Cells In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$436,450.00
Summary
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collabora ....Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts. Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However, the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to increase our understanding of the development of human osteoblasts and of the factors that cause them to be sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate bone turnover.Read moreRead less