Improved would healing outcomes and reduced healing time were achieved in a mouse model by incorporating a gene-suppressing agent into an over-the-counter gel, according to a study published online ahead of print in Advances in Wound Care (Oct. 25, 2018).
In 2015, researchers discovered that during the wound healing process, an enzyme called fidgetin-like 2 (FL2) delays skin cells from migrating to wounds. They hypothesized that reducing FL2 levels may enable healing cells to reach their destination faster. As such, the investigators designed small interfering RNA molecules (siRNAs) that specifically inhibit the gene that codes for FL2. When the siRNAs were packaged in nanoparticles and sprayed on cutaneous wounds in mouse models, the treated wounds healed faster than untreated wounds.
Dr. David J. Sharp said that results suggest that the combination therapy
may have future applications for the treatment on chronic wounds.
Photo by Albert Einstein College of Medicine
In the current analyses, the researchers enhanced the siRNAs’ wound-healing potential by combining them with PluroGel—a protective and antimicrobial gel that keeps wounds moist. It is used in bandages and wound dressings.
Mouse models with skin excisions or burns were used to test the hypotheses. The mice were divided into three experimental arms: mice treated with the FL2-siRNA/PluroGel combination, mice treated with only PluroGel, and mice treated with PluroGel plus siRNA that did not inhibit FL2.
Wounds were treated on the day of the skin excision or burn and again two, four, and six days later. For 14 days following the injuries, wounds were assessed by investigators blinded to which treatment the mice received.
Almost immediately, researchers observed obvious differences between the different groups.
Notably, on the fourth day, the open wound areas of mice in the two control groups were almost twice as large as the wound areas in mice treated with the FL2-siRNA/PluroGel combination.
“Not only did wound healing occur more rapidly and completely, but actual regeneration occurred, with hair follicles and the skin’s supportive collagen network restored in wounded skin—clinically important improvements that are unprecedented in wound care,” says senior author Dr. David J. Sharp, PhD, professor of physiology & biophysics at Albert Einstein College of Medicine in New York City, in a press release. “We foresee this therapy having broad application for all sorts of wounds, from playground cuts to battlefield injuries to chronic wounds.”
Dr. Sharp and his colleague, Dr. Brian O’Rourke, PhD, the paper’s co-lead author also achieved similar success in treating skin wounds in pigs, whose skin more closely resemble those of humans. The team plans to seek permission from the US Food and Drug Administration to test the wound healing combination on human models.
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