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
Biothermosetting Bone Filler: An Injectable Osteoconductive Repair Material
Funder
National Health and Medical Research Council
Funding Amount
$601,698.00
Summary
Bone injury is a common and profoundly debilitating issue, and is responsible for extended partial or complete loss of mobility and associated economic impact during slow healing. There is strong demand for technology that reduces the time taken for bone repair. There is still a paucity of clinically effective biocompatible materials for treatment. We have developed a novel approach for a thermoresponsive hydrogel with unique properties suitable for rapid bone filling and regeneration.
Relationship Of The Anabolic And Catabolic Responses In Healing A Critical Sized Defect In Rats
Funder
National Health and Medical Research Council
Funding Amount
$329,750.00
Summary
Delayed bone healing after trauma is a large clinical problem. Figures suggest up to 60,000 fractures result in a delay in healing in Australia per year. Bone healing can also fail to occur in other circumstances, such as after an operation. Research effort into new approaches to solving these problems is clearly justified. We believe that in some situations, bone healing fails due to the body's healing response, the anabolic response, being insufficient. In some other situations, the body's bon ....Delayed bone healing after trauma is a large clinical problem. Figures suggest up to 60,000 fractures result in a delay in healing in Australia per year. Bone healing can also fail to occur in other circumstances, such as after an operation. Research effort into new approaches to solving these problems is clearly justified. We believe that in some situations, bone healing fails due to the body's healing response, the anabolic response, being insufficient. In some other situations, the body's bone resorbing response, the catabolic response, may be too high and prevent healing from occurring. In normal bone healing, there is a balance between the anabolic and catabolic response. In disordered bone healing, these responses are out of balance. Several reasonably new treatments are available which can increase the anabolic response or decrease the catabolic response. We have preliminary results showing that with these agents we can bring these elements into better control, and thus drive bone healing. We have optimised an animal model where both the anabolic and catabolic responses can be controlled. In this project, we explore the optimisation of the timing and magnitude of anabolic and catabolic responses in bone healing.Read moreRead less
Skeletal Disease In A Dish: Using Novel In Vitro Disease Models Produced From Patient Induced Pluripotent Stem Cells To Reveal Pathogenic Mechanisms And Explore Treatments For Genetic Skeletal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$808,551.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and a new in vitro cell reprogramming technology to induce them to form cartilage and bone cells to produce mutation-specific “disease in a dish” models. These models will allow us to answer questions about how specific mutations cause disease and test novel drug therapies
Preclinical Optimisation Of Intrauterine Transplantation Of Fetal Mesenchymal Stem Cells For Osteogenesis Imperfecta.
Funder
National Health and Medical Research Council
Funding Amount
$600,932.00
Summary
Osteogenesis imperfecta is a genetic disorder causing brittle bones and fractures. Currently there is no good treatment. Transplanting stem cells before birth should allow them to build healthy bones early in life. Despite promising effects in animals, stem cell uptake is too low to prevent all fractures and ameliorate pain and deformity. We are studying how to improve the uptake of stem cells given to the fetus and neonate, in order to develop a treatment suitable for eventual use in humans.
This project is a biochemical investigation of collagen, which is the principle protein of bone, joints, blood vessels and skin. More than 200 mutations have been identified in the genes for type I collagen that result in Osteogenesis Imperfecta (OI), otherwise known as brittle-bone disease, in children and adults. However, very little is known about how these mutations cause bones to be brittle and why the disease varies so widely in severity. Our experiments are directed towards a better under ....This project is a biochemical investigation of collagen, which is the principle protein of bone, joints, blood vessels and skin. More than 200 mutations have been identified in the genes for type I collagen that result in Osteogenesis Imperfecta (OI), otherwise known as brittle-bone disease, in children and adults. However, very little is known about how these mutations cause bones to be brittle and why the disease varies so widely in severity. Our experiments are directed towards a better understanding of how bone cells respond to the mutant collagen and how these mutations actually result in brittle bones. We know that the majority of OI-causing mutations typically lead to a severe OI because the mutant collagen interferes with normal functioning of the matrix and effectively weakens it. We will examine how the mutant collagen disrupts normal cell function using bone and skin cell lines in which we have added a mutated collagen gene. The mutations we will introduce are the same ones that cause OI in patients. The experiments cannot be carried out with OI cell lines isolated from humans because it is very difficult to identify the mutant collagen in the matrix. Instead we have engineered a marker into the mutant collagen to allow the mutant collagen to be easily tracked. We will then examine how the presence of the mutant collagen affects matrix integrity, turnover and the formation of mutant matrix. In the second part of the study we will make a transgenic mouse that carries a specific collagen mutation. This will allow us to examine the fate of mutant collagen in a whole animal. As with the engineered cells described above, the mutant collagen will be altered to allow easy tracking. Collectively, these experiments will provide valuable information about how the presence mutant collagen disprupts integrity of the extracellular matrix of skin and bone.Read moreRead less
Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.