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Time Heals All Wounds – Eventually But U of U-Developed Hydrogels Heal Them Faster

July 1, 2002 — Time may heal all wounds-but not as fast as two hydrogel dressings developed by University of Utah medical researchers.

If the hydrogels work as well in people as they have in mice, millions of diabetics, elderly, burn victims and surgical patients may benefit from faster-healing diabetic ulcers, skin grafts, surgical incisions and other wounds. The researchers-from the U colleges of pharmacy, engineering and medical school-reported their findings in the September 2002 issue of the journal Biomaterials.

The hydrogels-which look like a piece of clear, thin plastic when dry, but expand six times in volume and become pliable when wet-are cousins to biopolymer hydrogels already developed by U of U scientists. Those hydrogels have the potential for a range of uses, from the delivery of anti-fever medication to timed release of insulin in diabetics.

Trials with mice show hydrogel wound dressings accelerate healing in the epithelium-the outer layer of skin-in young, healthy mice by up to 33 percent, with complete healing of deep wounds in five to seven days. If the success in young, healthy mice is indicative, the U researchers say the hydrogels would help older, less healthy mice, or people, even more profoundly.

“This portends that we have something important,” said Jane Shelby, Ph.D., associate professor of surgery.

The researchers-Glenn D. Prestwich, Ph.D., acting chair and professor of medicinal chemistry; Shelby; Kelly R. Kirker, a U doctoral student in bioengineering; Yi Luo, Ph.D., former research assistant professor, medicinal chemistry department, and J. Harte Nielson, B.S., formerly of the surgery department-hope to gain U.S. Food and Drug Administration approval to begin human trials of the hydrogels by early next year.

Conventional dressings and bandages serve mainly to keep moisture in and germs out as a wound heals. But hydrogel dressings slowly break down and reintegrate into the wound and
extracellular matrix (ECM) that surrounds human cells, according to Prestwich, who led the project.

“The hydrogel actually becomes integrated into the wound,” Prestwich said. “It’s a scaffolding that enhances healing.”

The U researchers developed hydrogels using two aminosugar polysaccharides: hyaluronan (HA) and chondroitin sulfate (CS). Both HA and CS occur naturally in the ECM of all vertebrates. HA is associated with tissue healing, but the role of CS in the process is not well established.

The U scientists mixed HA and CS with a reactive version of a waxy polymer called polyethylene glycol (PEG). Within seconds of being mixed, the substances crosslinked-a chemical process akin to weaving cloth-and within minutes they became gels.

The researchers conducted trials with mice that compared wound healing using HA hydrogel, CS hydrogel and a conventional dressing. Incisions dressed with the CS and HA hydrogels showed 33 percent more re-epithelialization after seven days and 25 percent more after 10 days. In short, wounds dressed with HA and CS hydrogels healed better.

“We jump-started the healing process,” Kirker said.
Both the CS and HA hydrogels were applied in conjunction with a conventional bandage.

Perhaps the biggest surprise of the trials was the efficacy of CS hydrogel. Researchers did not know what results to expect from it, and used it like a placebo in the trials, Prestwich said. The CS hydrogel actually aided healing slightly faster than the HA hydrogel-but the U researchers haven’t yet figured out why it works.

Shark cartilage could provide an ample supply of CS because it is readily available and cheap, Prestwich said. CS already is used as a pain reliever for people with osteoarthritis in their joints.

Patients with chronic diabetic ulcers, or wounds and cuts that won’t heal, would be the largest group to benefit from hydrogels, Shelby said. Burn patients would be the second-largest beneficiaries, followed by people recovering from surgery.

“We’d see a more profound effect in the elderly and diabetics because they’re slow healers,” Shelby said.

The U of U College of Pharmacy is an international pioneer in hydrogel research. Distinguished professors Sung Wan Kim, Ph.D., and Jindrich “Henry” Kopecek, Ph.D., D.Sci., co-directors of the Center for Controlled Chemical Delivery, developed hydrogels with potential uses ranging from releasing medicines at specific times and places in the human body to releasing insulin in diabetics. Those hydrogels are in a class of “smart biopolymers” that swell or shrink depending on temperature, sugar levels or in response to other stimuli.

The hydrogel wound dressings don’t respond to stimuli, but are biologically interactive, Prestwich said.

“This is a different direction altogether,” he said.