Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries perform ....Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries performed annually in Australia, with patients being committed to a prolonged convalescence. There are no drug therapies to specifically treat RC or other tendon injuries and many surgical repairs fail within 12 months. The limited treatment options for RC and other tendon disorders stems from a lack of knowledge of the molecular changes that precede and lead to rupture. It is recognised that the content of sulphated sugars or glycosaminoglycans (GAGs) on proteoglycans in tendon is the strongest predictor of the tisues strength. Accumulation of GAG is a well-recognised feature of torn tendons in man. The changes in proteoglycan synthesis and breakdown that precede and lead to tendon rupture have not been defined. We have developed a new model of shoulder tendon injury in sheep that induces regional degeneration mimicking that seen in human RC disorders. We have found changes in expression of specific proteoglycans and their degradative enzymes in early tendon disease. The current project will use this model in combination with a novel culture system and recently developed genetically modified mice to determine for the first time the changes that occur over time in proteoglycan metabolism that are responsible for tendon degeneration that leads to rupture. Successful completion of these studies will identify biomarkers to monitor disease progression and a platform for the development of new therapeutic strategies to treat this debilitating disorder.Read moreRead less
Non-invasive Electrical Nerve Stimulation To Improve Healing Of Chronic Venous Leg Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$206,210.00
Summary
Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulat ....Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulation of nerves that supply the wound. Low frequency current is passed through the skin from small battery powered stimulators. We have tested this technique in laboratory animals and in just a few older people with diabetes and have shown it is remarkably effective. We now plan to test this technique properly in a large study in older adults. If successful, the electrical stimulation could result in healing of wounds in relatively few weeks that otherwise would not heal for many months. Much suffering and expense would be avoided. As people age, nerve function deteriotes. Another part of the project will explore whether electrical nerve stimulation can improve damaged nerves themselves. This will provide interesting scientific insight about nerve repair and could lead to treatments for peripheral neuropathy that occurs in diabetes and other medical conditions. Australia needs to act on this now because the number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Many of these people will experience severe impairment of their quality of life from leg ulcers that could be avoided, or at least minimized if a successful treatment is developed and made available to them. Similarly, much unnecessary expense could be avoided.Read moreRead less
Degeneration and tearing of tendons such as the rotator cuff is a major health issue in working and ageing Australians. Tendon ruptures are preceded by degenerartive change which contributes to the poor success with surgical repair. There are very limited medical treatments available. We have developed an animal model mimicing human tendon dgeneration and will determine the utility and mechanisms of action of using a novel new therapy, stem cells in modulating degenerarion and aiding repair.
This project will develop a smart bone healing gel to bridge fragments of bone defects leading to stem cell recruitment, reduced inflammation, and blood supply for fracture healing. The design of the smart bone healing gel is based on the structures and properties of functional tissue healing hematoma in wound healing.
Activated Protein C As A Promoter Of Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physi ....The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.Read moreRead less
Function Of The Flightless Protein In Wound Repair And Scar Formation In Skin
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Scarring is the inevitable outcome of wound repair and can cover a spectrum of conditions, from normal fine lines to unsightly, restrictive and deforming scars. Each year in the world over 100 million patients acquire scars, primarily from surgical procedures. Many of these scars cause considerable problems. Over 4 million burn scars occur every year, 70% of them in children. Poor wound healing is a major clinical problem and can result in loss of movement and deformity. These are especially imp ....Scarring is the inevitable outcome of wound repair and can cover a spectrum of conditions, from normal fine lines to unsightly, restrictive and deforming scars. Each year in the world over 100 million patients acquire scars, primarily from surgical procedures. Many of these scars cause considerable problems. Over 4 million burn scars occur every year, 70% of them in children. Poor wound healing is a major clinical problem and can result in loss of movement and deformity. These are especially important considerations for children, where their growth places extra demands on healing wounds and grafts, necessitating regular surgical adjustment. Scarring is an area of largely unmet medical need and development of new treatment strategies would have significant impact on public health. Changes in cell adhesion, shape and movement are important processes in wound repair. A framework of filaments, much like guy-ropes that support a tent, help coordinate these events. Remodelling of these filaments, shortening or extending them and making new connections, allows cells to change shape and respond to stimuli. This is a crucial event in repairing wounds and the proteins that perform this are fundamentally important to wound repair. We have discovered a protein in skin, known as Flightless, that is involved in this filament remodelling process. The goal of this project is to determine what Flightless does in wound repair. By changing the amount of this protein and comparing its effect in non-scarring and scarring animal wound healing models we can gain insight into its role in wound healing and scar formation in humans. The development of new animal models in this research and the discovery of the role of Flightless in wound repair will provide exciting new opportunities to improve wound repair and reduce scarring, with significant impact on public health.Read moreRead less