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Understanding the mechanisms of spontaneous and skin-grafted wound repair: the path to engineered skin grafts

02 December 2023
Volume 2023 · Issue 3


Spontaneous wound repair is a complex process that involves overlapping phases of inflammation, proliferation and remodelling, co-ordinated by growth factors and proteases. In extensive wounds such as burns, the repair process would not be achieved in a timely fashion unless grafted. Although spontaneous wound repair has been extensively described, the processes by which wound repair mechanisms mediate graft take are yet to be fully explored. This review describes engraftment stages and summarises current understanding of molecular mechanisms which regulate autologous skin graft healing, with the goal of directing innovation in permanent wound closure with skin substitutes. Graftability and vascularisation of various skin substitutes that are either in the market or in development phase are discussed. In doing so, we cast a spotlight on the paucity of scientific information available as to how skin grafts (both autologous and engineered) heal a wound bed. Better understanding of these processes may assist in developing novel methods of wound management and treatments.

Extensive research is ongoing to better understand wound repair processes with the intention of improving scarring outcomes and avoiding injury conversion to hard-to-heal (chronic) wounds.1 The focus is largely on the development of novel drug therapies to promote repair and regeneration. In the surgical literature, it is recognised that timely application of skin grafts to a skin defect will modulate inflammation and close the wound. For burn wounds, the depth of injury and increased time to either spontaneous wound repair or wound closure with grafts is related to likelihood of excessive scarring.2 While skin grafting is a routinely available and widely used and reliable treatment for many wounds, this is not always the case. In extensive injuries, donor sites for graft harvest may not be available: in other cases, unsuitable wound beds may be responsible for graft failure.

There is thus a need to understand the prerequisites for successful engraftment, the cellular and molecular mechanisms associated with grafting and how spontaneous wound repair is modulated by grafting. In addition, this understanding can inform the development of reliable and effective synthetic bioengineered skin grafts, that may ultimately do away with the need for the skin graft donor site.3

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