Elucidating collagen turnover rate in scar skin using heavy water

Dr Andrew Stevenson1, Dr. Pryianka Toshniwal2, Dr. Dilnath Gurusinghe4, Dr. Owen Duncan1, Professor Harvey Millar1, Professor Fiona Wood1,3, Dr Nicolas Taylor1, Dr. Helen Douglas1,3, Dr. Mark Fear1

1University of Western Australia, Crawley, Australia, 2Minderoo Foundation, Perth, Australia, 3Fiona Stanley Hospital, Murdoch, Australia, 4NHS Liverpool, Liverpool, United Kingdom

Abstract:

The appearance of scar is a life-long consequence of burn injury. Scar tissue is not static, with extracellular matrix proteins continually being turned over. Drugs targeting collagen turnover may potentially be useful in reducing scar severity and improving appearance. However, the rate at which scar tissue collagen turnover occurs is currently unknown. This rate is critical to the potential for targeting collagen or matrix turnover in the treatment of scars.

This study aimed to measure scar collagen turnover in established scars (>18 months post-injury) by measuring the amount of deuterium incorporated into burn scar and normal skin proteins over a 6-week timeframe.

For this pilot study we recruited 5 male patients with established scars. Each participant was administered 200ml/day of 70% D2O for a period of 3 weeks. Skin and scar biopsies and blood samples were taken at 0 (pre-dose), 1, 2, 3 and 6 weeks (3 weeks after final D2O dose). Sequential protein extraction was conducted and mass-spectrometry used to identify levels of deuterium enrichment in matrix proteins. Preliminary analysis suggests collagen turnover was slower in scar tissue compared to matched normal skin. In addition, turnover appeared slower with increasing age.  Importantly, up to 20% of collagen was newly synthesised, even in scar tissue, after the 6 week period. This suggests collagen turnover, whilst altered in scar, is sufficiently dynamic for therapeutic intervention. Further work to understand matrix dynamics associated with age, gender and body site will be important to better understand long-term changes in matrix after injury.


Biography:

Dr. Stevenson is a postdoctoral researcher at the Burn Injury Research Unit at UWA. He obtained his undergraduate degree from UWA, before embarking on a research career first as research assistant, then as a PhD (graduating in 2017), and currently as a postdoc at the Burn Injury Research Unit. He is currently working on fibroblast cell biology after burn injury/fibrosis.

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