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Improving Muscle Function After Injury: Novel Tissue Engineering Strategies For Exercise, Surgery And Sports Medicine
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel thera ....Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel therapeutic approach to restore muscle structure and function to damaged muscles after injury or disease. Our recent research using controlled release of growth factors from biodegradable hydrogels has exciting application for muscle repairafter injury. We will utilize these cutting edge tissue engineering strategies to deliver to damaged muscles a hydrogel containing controlled delivery (slow release) microcapsules loaded with an anabolic agent (the beta-agonist, formoterol) and-or a growth factor (IL-15) designed to enhance functional muscle repair after three distinct but clinically relevant models of muscle injury: a) crush injury: A model for muscle injuries on the sports field, in the workplace, and those associated with road trauma; b) ischaemia-reperfusion injury: a model for muscle damage associated with surgical interventions, muscle transfers for functional restoration, and other injuries associated with plastic and reconstructive surgery; and c) contraction-induced injury: a model for strain injuries such as hamstring muscle tears that can occur on the sports field. After injury we will assess functional muscle repair using a comprehensive series of histological, biochemical, molecular, immunochistochemical, and physiological techniques. The research has broad application to exercise and clinical medicine; including sports, emergency and rehabilitation medicine, and plastic, reconstructive, and orthopaedic surgery.Read moreRead less
Cohort Study Of Risk Factors For Young Driver Injuries
Funder
National Health and Medical Research Council
Funding Amount
$689,830.00
Summary
Injuries impose a substantial burden on young people, both in Australia and internationally. In 1998, 70% of all deaths among young men, and 57% of deaths among young women, aged 15-24 years in Australia were due to injuries. The single largest cause of injury-related fatalities, hospital admissions and emergency department presentations among this age group is transport-related incidents. Technological advances in motor vehicle engineering and road design, and the implementation of various road ....Injuries impose a substantial burden on young people, both in Australia and internationally. In 1998, 70% of all deaths among young men, and 57% of deaths among young women, aged 15-24 years in Australia were due to injuries. The single largest cause of injury-related fatalities, hospital admissions and emergency department presentations among this age group is transport-related incidents. Technological advances in motor vehicle engineering and road design, and the implementation of various road safety measures, such as random breath testing, have led to an overall decline in the incidence of motor vehicle-related injuries in Australia in the past three decades. However, young people still have substantially higher rates of motor vehicle-related mortality than older people. This suggests that if the burden of injuries among young drivers is to be reduced to levels that are at least as comparable with those in other age-groups, then the identification of factors that are specifically associated with an increased risk of motor vehicle injury among young people, must be a priority. The current study aims to determine the role of several postulated risk factors in the incidence of young driver injuries. The specific risk factors to be examined include pre-licence road and driving exposure-experience; type, quality and quantity of driver training; and road risk perceptions and engagement in sensation seeking behaviours. The study also seeks to determine whether factors associated with increased risk of driver injury are the same for different socio-economic groups and for different ethnic and cultural groups. Information obtained in this study should provide reliable evidence about causal factors for motor vehicle crash injury among young drivers. Such information should be useful to licensing and road safety professionals, in the design of practical road safety strategies aimed at reducing the burden of young driver injuries.Read moreRead less
Multi-centre Randomised Trial Of Early Decompressive Craniectomy In Patients With Severe Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
Despite optimal neurosurgical and intensive care therapy, many trauma patients with severe brain injury (typically young males) have very poor long term neurological outcomes. Current knowledge suggests that a key contributor to secondary brain damage which occurs after injury and to poor neurological outcomes is brain swelling and subsequent increase in brain pressure. Present intensive care therapies to control brain pressure are often not effective, and favourable neurological outcomes occur ....Despite optimal neurosurgical and intensive care therapy, many trauma patients with severe brain injury (typically young males) have very poor long term neurological outcomes. Current knowledge suggests that a key contributor to secondary brain damage which occurs after injury and to poor neurological outcomes is brain swelling and subsequent increase in brain pressure. Present intensive care therapies to control brain pressure are often not effective, and favourable neurological outcomes occur in only 20-30% of these patients. Small studies suggest that a surgical operation called decompressive craniectomy (DC) may decrease brain pressure and improve neurological outcomes in these patients. DC involves temporarily surgically removing a piece of skull bone (during the swelling period) and replacing it when the swelling has subsided. DC is done under general anaesthetic in unconscious patients and is used occasionally at present, although due to insufficient research the benefits are controversial. The proposed study is a multi-centre randomised controlled study of best current therapies plus early decompressive craniectomy vs best current therapies alone in selected unconscious patients with severe head injury. The study outcome is patient neurological function measured 6 months after the injury. A study of this type is required before early DC could become a routine therapy in Australia. Next of kin will sign informed consent for the study and then also for the surgery if patients are randomised to surgery. The study will be managed at the Alfred Hospital-Monash University in Melbourne and includes fifteen collaborating ANZ neurotrauma centres over 3.0 years. There are >200 patients in Australia annually in this category with potential for DC to increase favourable outcomes in >40 patients annually. Lifetime costs for these patients with severe disability are > $2.4 million, so there may be substantial economic and social impact.Read moreRead less
Hyperbaric Oxygen In Lower Limb Trauma: A Randomised Controlled Clinical Trial
Funder
National Health and Medical Research Council
Funding Amount
$729,288.00
Summary
HOLLT is an international multi-centre randomised clinical trial aimed at assessing the impact of hyperbaric oxygen therapy (HBO) on acute complication rates and long term outcomes following severe musculoskeletal trauma. The study will enrol 250 patients with severe, open tibial fractures over a 2-3 year period. Enrolled subjects will be followed up for 2 years with radiological, clinical and quality of life measures.
Repairing The Injured Spinal Cord: Potential For Human Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult ....Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult rats can lead to limited functional recovery of hindlimb movement. We used peripheral ensheathing cells because, in humans, such cells can be obtained relatively easily and they reduce problems of tissue rejection. We found that peripheral cells are as effective as previous reports using central ensheathing cells. Our overall aim now is to advance towards the use of olfactory cells in human spinal cord injury, by trialing 3 procedures of clinical relevance: a) to test whether human olfactory cells can also support functional recovery in rats. Human cells can be obtained from the nose by a simple biopsy procedure. If they able to support regeneration, this will open the way for their use in autografts in human paraplegia. b) to delay the time when the olfactory cells are applied to the injured cord. At present, neurosurgeons are not be willing to treat the cord immediately after the injury, because of the risk of causing further damage. This trial is designed to test whether delayed treatment is still effective. c) to test the effectiveness of the cells after bruising, rather than cutting, the cord. Bruising is a more common type of injury in people, hence it is necessary to know how these cells respond to this type of damage. These procedures have been chosen to move our basic research closer to clinical application. Although treatment in humans is still a long way off, these basic studies are essential if conditions like paraplegia are eventually to become treatable.Read moreRead less
The appropriate dosing of antibiotics for patient admitted to ICU after a traumatic injury is poorly defined and based on intuition rather than evidence. Doctors need to predict which patients may develop very high antibiotic clearances and dose accordingly so that potentially life-threatening infections do not occur. Given these patients are unknown, this research seeks to identify such patients and recommend which antibiotic and which dose is appropriate to ensure adequate treatment.
Cellular And Molecular Mechanisms Of Neuronal Repair By Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$218,250.00
Summary
Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplan ....Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplantation of olfactory ensheathing cells into the injury site. Ensheathing cells normally support the nerve fibres involved in the sense of smell. Tissue culture studies show that these cells produce on their surface specific types of molecules as well as soluble growth factors that could interact with nerve fibres to promote growth. Although experiments in which ensheathing cells have been injected into rat spinal cords, have resulted in varying degrees of recovery, the question of how they are able to do this remains unknown. The study proposed here will use tissue culture and in vivo models to investigate how ensheathing cells interact with their surrounding cells. In particular we will examine how soluble factors and direct membrane contact contribute to the regeneration of nerve fibres. We will also examine the effects that ensheathing cells have on non-neuronal cells such as astrocytes and oligodendrocytes and vice-versa. A significant outcome of this project is new insight into the complex cellular interaction that occurs to bring about repair in the central nervous system. The findings will pave the way for the future development of olfactory ensheathing cells as an effective therapeutic agent of nerve repair. This could also include genetic manipulation of ensheathing cells such that their properties are optimised specifically to promote regrowth of nerve fibres.Read moreRead less