Decorin as a Way to Reduce Scarring During Regeneration
Researchers here present a practical method of using decorin during wound healing in order to minimize scarring. This protein appears to influence a number of mechanisms associated with fibrosis in potentially beneficial ways, but has been challenging to make use of. It is possible that this work could have applications beyond wound healing, in other areas where tissue regeneration without scar formation is desired, such as in aged organs where fibrosis is a major issue.
Scars form when the collagen scaffolding in skin is broken apart. Instead of re-forming in their original and neat basket-weave arrangement, the collagen fibres grow back in parallel bundles that create the characteristic lumpy appearance of scars. One way to reduce scarring is to apply decorin, a skin protein involved in collagen organisation. But because decorin has a highly complex physical structure it is hard to synthesise and therefore not used in the clinic.
To get round this problem, researchers have created a simplified version of decorin. They combined a small section of the decorin protein with a collagen-binding molecule and a sticky substance secreted by mussels. The resulting glue was tested on rats with deep, 8-millimetre-wide wounds. The glue was spread over each wound and covered with clear plastic film. Rats in a control group had their wounds covered in plastic without any glue. By day 11, 99 per cent of the wound was closed in the treated rats compared with 78 per cent in the control group. By day 28, treated rats had fully recovered and had virtually no visible scarring. In comparison, control rats had thick, purple scars.
Closer inspection under the microscope confirmed that collagen fibres in the treated wounds had returned to their original basket-weave arrangement. The new skin had also developed hair follicles, blood vessels, oil glands and other structures that aren't regenerated in scars. The glue is able to promote normal collagen growth because negative charges on the decorin fragments hold the fibres apart. In doing so, the fibres are more easily able to weave in and out between each other instead of sticking together randomly. The results are impressive but there is still a way to go before this can be translated to humans. "Rats have loose skin, whereas we have tight skin, and they tend to heal better and have less scarring than we do." As a result, the glue may not be as effective in people as in rats. The glue will now be tested in pigs, whose skin better resembles our own.