Arizona State University (ASU) bioengineers have developed a multistep strategy that applies different nanomaterials to diabetic wounds at different times to support both early- and late-stage healing. Their work showed this method outperformed a common wound dressing in a diabetic mouse model, closing wounds faster and producing more robust skin tissue. The researchers’ analysis also suggests that their approach unexpectedly activated an immune cell population not normally seen in wounds that can resolve inflammation, which highlights a new potential avenue to accelerate healing.
For the first step, the team fabricated a silk nanomaterial dressing embedded with gold nanorods. Because gold nanoparticles readily convert light to heat, the team was able to direct a laser at dressings placed over fresh wounds in mice, producing heat that quickly sealed them in place and provided a high level of protection. The strategy, which the researchers previously found success with, creates something akin to an instantaneous scab, said Jordan Yaron, PhD, a bioengineering assistant research professor at ASU. This time around, the authors added histamine to the mix, a natural biochemical produced by the immune system that plays important roles in inflammation, blood vessel development, and allergic reactions.
Inflammation dominates the body’s initial response to injuries, but eventually subsides to allow the body to rebuild. However, diabetic wounds can get stuck in first gear, maintaining persistent, low-grade inflammation, which can inhibit the healing process.
“Since the wound is stalled, we wanted to co-deliver histamine with the dressing, to give a push and bring the inflammation stage to a resolution,” said Kaushal Rege, PhD, a chemical engineering professor at ASU. “Then we could introduce another strategy to take care of the subsequent phases of healing.”
The authors monitored the wounded mice for 11 days and found that animals treated with a combination of the nanomaterial dressing and histamine healed at the fastest rate compared to those treated with the standard dressing with histamine or the nanomaterial dressing alone. The researchers mechanically tested the healed skin as well, finding that the tissue treated with both the nanomaterial and histamine was strongest and most similar to unwounded skin.
The investigators’ next step in the study was to see if they could improve healing further by accelerating the post-inflammation phase wherein cells proliferate and remodel skin tissue. In a second set of mice, the authors followed up their initial treatment with a pair of nanoparticles they previously developed that were derived from 2 particular growth factors—proteins native to the body that promote the formation of skin tissue.
The team injected the nanoparticles at various time points into the nanomaterial-dressed wound bed, finding that delivery on day 6 had the best outcomes with regard to wound closure and tissue strength. This time point corresponds to a transitionary phase in which cells begin proliferating and remodeling tissue. With promising results in mice behind them, the researchers are now testing their strategy in larger animal models more relevant to human health, such as pigs.
