Surgical adhesions are a frequent and often life-threatening complication following open or laparoscopic abdominal surgery. These adhesions develop in the weeks following surgery as the body heals. Between 50% and 90% of abdominal surgeries, depending on the type and location of the surgery, result in adhesions. They are characterized by the formation of excessive scar tissue that causes organs and tissues to adhere to one another or to the abdominal wall. While many adhesions are asymptomatic, 5% to 20% of cases result in severe complications, including chronic pain, infertility, and life-threatening bowel obstructions. Despite their prevalence, there is no reliable method for preventing or treating these adhesions, and their associated complications cost billions of dollars annually in healthcare expenses. However, new research has shown that a gel containing an inhibitory molecule can prevent the formation of surgical adhesions in both mice and pigs.

Researchers at Stanford Medicine (Stanford, CA, USA) have been studying the mechanisms behind scar formation and adhesions for years. In 2020, they identified the biological pathway responsible for adhesion formation in both mice and humans, demonstrating that inhibiting the activity of a protein called c-Jun—produced by fibroblasts in response to injury—could significantly reduce adhesion formation in laboratory mice. The protein inhibitor, known as T-5224, was identified for its ability to regulate excessive scarring and inflammation, and it has already been tested in clinical trials for rheumatoid arthritis and animal models of cancer metastasis and inflammation. In their most recent study, the researchers aimed to determine whether they could deliver this small molecule inhibitor directly into the abdominal cavity over several days and whether it would impact adhesion formation. They developed a shear-thinning hydrogel biomaterial that behaves like a liquid under pressure—such as when being forced through a syringe—but solidifies once the pressure is released. When impregnated with T-5224, the gel releases the molecule gradually over a 14-day period.

The researchers tested the T-5224-impregnated gel in both mice and minipigs, observing a nearly 300% reduction in adhesion formation compared to control animals that either received a saline wash of the surgical site or were treated with the gel without T-5224. The gel was applied as either a spray or a wash inside the abdominal cavity immediately after surgery. Over the following two weeks, the gel continuously released T-5224, which blocked the activation of fibroblasts—the cells responsible for forming adhesions—without interfering with normal wound healing. The researchers believe that this approach could provide a simple and effective method for preventing or reducing the formation of post-surgical abdominal adhesions in humans, a condition that is currently unpreventable and largely untreatable. If successful, this method could save billions of dollars in healthcare costs each year, while also reducing the incidence of chronic pain, infertility, and bowel obstructions associated with severe adhesions. The success observed in large animals, such as pigs, is a key step toward clinical trials in humans.

“Adhesions happen primarily when you injure or interact with the bowel during surgery, whether the surgery is open or laparoscopic,” said professor of surgery Michael Longaker, MD, one of the senior authors of the study, which was published in Science Translational Medicine. “This gel reduces the likelihood of adhesions without compromising the ability of the animal to heal after surgery. And, as a surgeon, I’m already used to washing out the surgical site at the end of the procedure, so this would be easy to incorporate into our normal workflow.” 

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