By Michael Irving, November 09, 2020
A section of skin – complete with hair follicles – regenerated by the new hydrogel Tatiana Segura Lab, Duke University
Scar tissue is an effective short-term solution to quickly patch up wounded skin, but it’s not so great long-term. Now, researchers at Duke University and UCLA have created a new hydrogel that can trigger a regenerative immune response, helping skin heal healthier and stronger without scarring.
When skin is injured, the body responds by rapidly forming scar tissue to prevent infection, pain and dehydration of the wound. The downside to that is all too familiar – a permanent unsightly blight on the skin, where hair and sweat glands will no longer grow. As such, finding ways to heal wounds without scarring is an area of science that’s attracting plenty of attention.
The new study builds on the team’s previous work from 2015, when they described a new type of biomaterial they’d developed called microporous annealed particle (MAP) hydrogels. Normally hydrogels are simply water-based dressings that protect and hydrate a wound and help speed up healing, but they still result in scar formation. MAP hydrogels, however, acted like a scaffold for skin cells to grow across the wound, healing more completely. Eventually the gel dissolves away safely, leaving healthy skin.
While the MAP hydrogels reduced scarring, it wasn’t gone completely. The team found that the new skin was lacking some of the more complex structures, such as hair follicles and sebaceous glands, so for the new study they set out to address that.
“Previously we’d seen that as the wound started to heal, the MAP gel started to lose porosity, which limited how the tissue could grow through the structure,” says Don Griffin, first author of the study. ”We hypothesized that slowing down the degradation rate of the MAP scaffold would prevent the pores from closing and provide additional support to the tissue as it grows, which would improve the tissue’s quality.”
The team identified an area where the original MAP hydrogel recipe could be improved – a certain chemical linker. This peptide sequence had been taken from structural proteins commonly found in the body, and it was arranged in a chemical orientation or “chirality” that’s also common in the body. The idea is that this sequence and orientation would prevent the gel from triggering a strong immune response and allow it to be degraded when its job is done.
“Our body has evolved to recognize and degrade this amino acid structure, so we theorized that if we flipped the structure to its mirror image, which is D chirality, the body would have a harder time degrading the scaffold,” says Tatiana Segura, lead author of the study. “But when we put the hydrogel into a mouse wound, the updated gel ended up doing the exact opposite.”
To their surprise, the team noticed that the new gel degraded even faster, but in doing so it left behind stronger skin, complete with the complex structures normally missing from scar tissue. On closer inspection, the researchers found that triggering a stronger immune response worked to their advantage.
When the new hydrogel was applied to the body, the adaptive immune system responded by creating antibodies and sending out other immune cells to attack the foreign substance. This induces a regenerative immune response that helps rebuild skin more completely.
The team says that the new hydrogel could help repair cuts, burns, diabetic ulcers and other injuries that may normally be prone to scarring. They’re also exploring whether the underlying mechanism – triggering a regenerative immune response – could be used for other purposes, such as delivering vaccines.
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