On day 14 of treatment, a burn treated with nanoparticles carrying FL2 inhibitor (on the right) already looks like normal skin (on the left). The untreated burn (in the middle) does not.
Image credit: Vera DesMarais/Albert Einstein College of Medicine
The team, from the Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, has tested the experimental nanoparticle therapy on mice and showed it cut the time it takes for skin wounds to heal by half compared with no treatment.
They report how they developed and tested the therapy in the Journal of Investigative Dermatology.
David J. Sharp, professor of physiology and biophysics at Einstein, co-led the study and explains the new therapy's potential:
"We envision that our nanoparticle therapy could be used to speed the healing of all sorts of wounds, including everyday cuts and burns, surgical incisions, and chronic skin ulcers, which are a particular problem in the elderly and people with diabetes."
Reducing FL2 enzyme makes healing cells travel to wound more quickly
The new study builds on previous work where the team found an enzyme called fidgetin-like 2 (FL2) slows skin cells down as they migrate toward a wound to heal it.
FL2 belongs to a family of enzymes that play various roles in the development and activity of cells.
After their discovery, the researchers wondered if reducing levels of FL2 would make the healing cells move faster toward the wound.
So in this latest study, they developed a drug that blocks the gene that codes for FL2, loaded it into tiny nanoparticle capsules and applied them to skin wounds on mice.
They found that - compared with untreated wounds - the skin wounds on the mice healed faster with the help of the nanoparticles containing the FL2-inhibitor.
In the next stage of the study, the researchers found suppressing FL2 activity in human cells in tissue culture - where they could measure wound-healing features like cell migration and proliferation - caused the cells to move unusually fast.
siRNAs in nanoparticles silenced FL2 and sped up wound healing in mice
Meanwhile, another member of the team, Joshua Nosanchuk, professor of medicine at Einstein and attending physician, infectious diseases at the College's Montefiore Medical Center, was developing a wound healing therapy that suppresses FL2 using silencing RNA molecules (siRNAs).
The siRNAs switch genes off by binding to the gene's messenger RNA, effectively blocking its ability to code for proteins.
But there was a problem, as Prof. Sharp explains:
"siRNAs on their own won't be effectively taken up by cells, particularly inside a living organism. They will be quickly degraded unless they are put into some kind of delivery vehicle."
The study team included members who had been working on a way of developing nanoparticles that protect molecules like siRNA and stop them being degraded as they ferry them to their targets.
So, in the final stage of the study, the combined team put the FL2-silencing siRNAs inside the protective nanoparticles and applied them to mice with either skin cuts or burns.
In both cases, the treated wounds healed in half the time it took untreated wounds to heal. Prof. Sharp notes:
"We saw normal, well-orchestrated regeneration of tissue, including hair follicles and the skin's supportive collagen network."
In the next few months, Prof. Sharp is planning to test the nanoparticle wound therapy on pigs, as their skin is similar to that of humans.
Funds for the research came from the National Institutes of Health (NIH), the Women's Dermatologic Society, and the US Army Medical Research and Materiel Command (USAMRMC).
In another study that Medical News Today reported in January 2015, researchers found collagen from fish skin may promote safer wound healing than the more conventional pig or cow collagen, which carries a small risk of disease.