Effects Of Pin Biomechanics, Coating Material And Surface Roughness On The Pin-bone Interface In External Repair
Funder
National Health and Medical Research Council
Funding Amount
$470,000.00
Summary
Some fractures require external fixation, anchored with metal pins in the bone fragments. The reatment is generally successful, although the pin tracts often loosen and become infected. This complication may jeopardise fracture healing and must be treated. The purpose of this project is to determine what aspects of pin design predispose to these problems at the pin-bone interface. Is it the way the pins are initially inserted, perhaps not tightly enough so that the pin is unstable, or perhaps to ....Some fractures require external fixation, anchored with metal pins in the bone fragments. The reatment is generally successful, although the pin tracts often loosen and become infected. This complication may jeopardise fracture healing and must be treated. The purpose of this project is to determine what aspects of pin design predispose to these problems at the pin-bone interface. Is it the way the pins are initially inserted, perhaps not tightly enough so that the pin is unstable, or perhaps too tight, causing microcracks in the bone? Is it the material of the pin, which might be improved with a bioactive coating? Is it the surface roughness which causes different responses of bone cells? Would it help to have an antibiotic pin? This proposal is designed to answer these questions. The biomechanics of the pin will first be studied with computer models and then tested in the laboratory. The loosening and infection associated with different types of pin will then be studied biologically. The results of the study will clarify the roles of pin biomechanics, coating and surface roughness, leading to improvements in design and better outcomes in fracture patients.Read moreRead less
Development And Validation Of A Finite Element Model For Orthopaedic Screw Insertion Into Trabecular Bone
Funder
National Health and Medical Research Council
Funding Amount
$420,454.00
Summary
Osteoporosis is a disease of the bones that results in reduced bone strength and susceptibility to fragility fractures. Due to the spongy nature of osteoporotic bone, surgeons face major difficulties in obtaining secure fixation of bone screws. Our aim is to develop and validate a computer model of orthopaedic screw insertion into trabecular bone based on micro-computed tomography image data. This will allow an assessment of the most appropriate screw designs for stable fixation of implants.
Osteal Macrophages As Therapeutic Targets For Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$618,015.00
Summary
Fragility fracture associated with osteoporosis is a substantial health problem costing $1.62 billion to treat in 2012 in Australia. There is no approved therapy to improve and accelerate fracture healing to help reduce this increasing health burden. This research will advance understanding of fracture repair in healthy and osteoporotic bone and progress development of a fracture therapy to improve bone repair by promoting specialised immune cells.
Delayed bone healing can be a considerable problem in both children and adults. Up to 10% of fractures fail to heal properly. An advanced understanding of the cellular responses in bone repair and their manipulation could improve the lives of many patients with orthopaedic problems. These studies will advance out knowledge of interventions to promote bone healing which could be translated rapidly into clinical care.
Role Of The Osteoclast In Endochondral Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$310,136.00
Summary
Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endo ....Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endochondral ossification) during which the early soft cartilaginous callus is replaced by hard mineralised callus. Our preliminary studies lead us to believe that endochondral ossification can indeed proceed without osteoclast activity. If we can safely eliminate osteoclast function early in the early stages of fracture repair, a number of therapeutic options open up for the augmentation of bone healing. The return of osteoclast function is necessary in the long term, so our strategy will also need to take this into account. This study will establish which systems are pivotal in endochondral ossification and therefore which interventions we should explore.Read moreRead less
The Role Of Muscle And The Application Of Muscle-cell Therapies In Bone Repair
Funder
National Health and Medical Research Council
Funding Amount
$438,936.00
Summary
Muscle is often close to bone and we have found that muscle cells can directly contribute to bone repair. We are examining importance of muscle cells in orthopaedic repair and whether new methods for mobilizing muscle cells can improve healing.
Twist-1 Inhibits MSC Osteoblast Differentiation During Osteoporosis Via Direct Regulation Of The Wnt Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$482,704.00
Summary
There is a predicted dramatic increase in the number of orthopaedic related problems that require surgical intervention and rehabilitation therapy in the coming decade associated with higher incidences of bone diseases as a consequence of an aging population. This proposal seeks to determine whether the transcription factor, Twist-1 plays a central role in regulating the growth and differentiation of skeletal progenitors during bone loss following the onset of osteoporosis.
Assessment Of The Properties Of Mesenchymal Stem Cells And Their Role In Skeletal Tissue Repair And Disease
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
Prostaglandin G/H Synthase-2 (PGHS-2) Is A Key Regulator Of Skeletal Adaptation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$301,018.00
Summary
Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inh ....Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inhibition of PGHS-2 by recent anti-inflammatory drugs avoids formation of gastric ulcers, but their influence on normal bone remodelling and fracture repair is not known and must be investigated. Many such inhibitors are in advanced clinical trials, but their effect on bone metabolism has not been published. This project is important because it employs novel experimental models to advance our knowledge of prostaglandin biology in skeletal adaptation, and elucidates important clinical consequences for specific inhibition of PGHS-2 in the skeleton. This project will investigate the regulation of prostaglandin production by PGHS enzymes following mechanical loading in vivo. It will use cell, molecular and histochemical techniques to determine if the genes that regulate the enzymes are influenced by mechanical stimuli, and if they are dependent on other molecules, associated with structural proteins (stress fibres) within the cell. It will investigate if inhibition of PGHS-2 by antiinflammatory drugs or stress-fibre inhibitors, depresses normal bone turnover and healing responses. The outcome of these experiments could indicate new approaches to stimulate bone formation, preserve bone mass, or minimise adverse skeletal effects of anti-inflammatory treatments related to orthopaedic or dental procedures.Read moreRead less
Novel Therapeutic Interventions For The Orthopaedic Complications Of Neurofibromatosis Type 1 (NF1).
Funder
National Health and Medical Research Council
Funding Amount
$628,422.00
Summary
Children with the genetic disease NF1 can develop fractures that fail to unite and this can lead to amputation. We have advanced models of NF1-deficient bone cells and fracture healing that we will use to test new pharmaceutical treatments for NF1.