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Peptide-Infused Gel Shown to Heal Chronic Wounds

Milica Radisic

Milica Radisic (NSERC, University of Toronto)

15 December 2016. A tissue engineering group developed a gel material infused with a synthetic peptide that in lab cultures and animals healed chronic diabetic wounds faster than a current commercial treatment. A team from the lab of chemical engineering professor Milica Radisic at University of Toronto published its findings earlier this year in Proceedings of the National Academy of Sciences (paid subscription required).

Radisic and colleagues are seeking better treatments for chronic wounds that result from diabetes, which are often slow to heal due to reduced blood flow to the legs and feet, leading to nerve damage as well as slower healing of wounds. CDC says in 2010, some 73,000 Americans required amputation of a leg or foot because of complications from diabetes. While malnutrition and immune deficiencies can also cause chronic wounds, CDC says people with diabetes are 8 times more likely to lose a leg or foot than people without diabetes.

In this case, the researchers focused on the breakdown in cell functioning in blood vessels that impedes healing. The team adapted a synthetic peptide — a short chain of amino acids — with the acronym QHREDGS describing its chemical composition, from angiopoietin-1, a key protein in developing blood vessels. Their tests of QHREDGS show the peptide protected and promoted the growth of keratinocytes making up the bulk of human skin cells, but also activates proteins that encourage cell survival and proliferation. Radisic’s lab used QHREDGS previously in studies with stem and heart cells, as well as fibroblast cells in connective tissue.

The team developed a hydrogel material to deliver the peptide to wounds. To the hydrogel, made of water and biocompatible polymers, the researchers added collagen, a basic and abundant protein found in skin, bones, and other connective tissue, and chitosan, a natural soluble sugar found in the hard outer skeleton of shellfish and used in wound dressings to stop bleeding.

The researchers tested the hydrogel, laden with QHREDGS peptides, on keratinocyte skin cells in the lab from both healthy individuals and older people with diabetes. They found the treated tissue developed new skin cells faster than untreated tissue. In tests with lab mice induced with diabetic skin wounds, the QHREDGS hydrogel closed wounds 200 times faster than non-treated tissue.

The team also tested the hydrogel against ColActive, a commercial wound healing product, made by Covalon Technologies Ltd in Mississauga, Ontario, a collaborator with Radisic’s lab on skin and bone tissue regeneration. Results show the QHREDGS hydrogel closed wounds 60 percent faster in the mice than wounds treated with ColActive, a collagen-based product.

In their tests with lab cultures and mice, researchers saw the healing skin cells migrate toward each other in a form of crawling motion. “We thought that if we were able to use our peptide to both promote survival and give these skin cells a substrate so they could crawl together, they would be able to close the wound more quickly,” says Radisic in a university statement. “But even the diabetic cells traveled much faster — that’s huge.”

The following graphic shows time-lapsed photos of skin cells, from left, without the research team’s peptide-hydrogel treatment, cells treated with a low dose, and cells treated with a high dose. Skin cells migrate together fastest with a high dose of the peptide-hydrogel material.

Skin cell migration graphic

(Radisic lab, University of Toronto)

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