Burns research & reconstructive surgery

Children's Hospital Burns Research Instiute

Macrophage contribution to hypertrophic scarring in paediatric burns

Medbury H., Taran S., Guiffre A., Fetcher J. and Holland A.

Each year in Australia, 6000 children present to emergency centres due to a burn; with 10% of these being admitted to hospital. Up to 35% of children who are hospitalised with a scald burn will subsequently develop severe scarring, known as a hypertrophic scar (HTS). In addition to considerable cosmetic and psychological sequelae, scars are often inflamed, itchy, and can result in functional impairment that may permanently disable the child. Even children that appear to heal well at a young age may develop functional sequelae later as they grow. Children often require multiple and prolonged ongoing care, which may include further surgery. In spite of continuous improvements in the management of acute burns, therapeutic strategies to treat HTS remain limited and we are basically left with supportive management and delayed reconstructive surgery. It is thus vital that the process of HTS be understood so that its formation can be prevented.

HTS results from excessive and irregular / abnormal deposition of collagen and other extracellular matrix molecules during a prolonged remodeling phase of tissue repair. A relatively recently described macrophage phenotype -the fibrocyte- has been shown to contribute to collagen synthesis in tissue repair and fibrosis in a variety of conditions such as asthma, scleroderma and, as shown by our collaborators, in atherosclerosis and intimal hyperplasia. Recently, we have shown that fibrocytes are associated with the development of HTS in the healing of paediatric burns. The fibrocytes were detected in a skin biopsy taken at time of debridement and skin grafting, indicating that though HTS arises weeks to months post burn injury, the likelihood of its development may be determined very early on in the wound healing process.

Given the strong correlation between the presence of fibrocytes and HTS, it can be speculated that if fibrocyte formation or function could be inhibited, HTS may be able to be prevented. We are now extending our studies to investigate the role of other macrophage subgroups (e.g. inflammatory or immune regulatory subgroups) in the healing burn. The role of these subgroups in the healing burn remains largely unknown. Given that macrophages that can be sequentially converted from one phenotype to another however, it may be possible to inhibit HTS through modulating monocyte/ macrophage transformation away from the ‘fibrocyte’ phenotype. It is thus important to define monocyte/macrophage contribution to HTS as it may enable us to develop treatments to modulate their transformation to limit, or even prevent, HTS formation.

A New Model for Hypertrophic Scarring

Bertinetti M., Medbury H., Harvey J. and Holland A.

Children who sustain deep burn injuries frequently suffer severe scarring which maybe disfiguring, painful and itchy. The development of this process is called hypertrophic scarring (HTS). Our experience and some studies have suggested that the longer a burn wound takes to heal, the greater the chance of HTS occurring. This is one of the reasons why most burns surgeons recommend grafting a burn wound if it has not healed by 14 days. Scientific evidence for this remains scant however, with limited evidence and no consensus regarding the optimal timing of split skin grafting to minimise scarring. To investigate this concept further we have developed a new model of HTS. Using this model we have compared the effect of duration of thermal contact on the depth of the burn caused and assessed the subsequent scarring. Results indicate that 20 seconds thermal contact is required to re recreate a deep dermal burn and subsequently HTS.

We are now aiming to build on this pilot study to assess the optimal time to graft a deep dermal burn.